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BACKGROUND: High-grade meningiomas (HGMs) recurring after X-ray treatment show a poor prognosis. We assessed the effectiveness and safety of boron neutron capture therapy (BNCT) in patients with refractory recurrent HGMs. METHODS: This phase II investigator-led randomized controlled trial utilized an accelerator-based BNCT system to treat refractory recurrent HGMs. Patients were randomly assigned in a 2:1 ratio to the BNCT (12 patients) and control (6 patients) arms. Progression-free survival (PFS) judged by an independent third-party committee was the primary endpoint and PFS judged by the investigators and overall survival of the BNCT arm were the secondary endpoints. The control arm received rescue BNCT if they show disease progression. RESULTS: Three and two patients with World Health Organization (WHO) grade 3 disease were assigned to the BNCT and control arms, respectively; the remaining patients had WHO grade 2 disease. Median PFS (primary endpoint) was 14.4 months (95% CI: 7.9-26.4) in the BNCT arm and 1.4 months (95% CI: 1.0-9.0) in the control arm. Median PFS (secondary endpoint) was 14.7 months (95% CI: 7.6-22.8) in the BNCT arm and 1.5 months (95% CI: 1.0-9.0) in the control arm. The differences were statistically significant (log-rank test, P = 0.0157 and P = 0.0002, respectively). Five patients in the control arm received rescue BNCT. The objective response rate in the BNCT arm was 27.3%. CONCLUSIONS: Boron neutron capture therapy is an effective treatment for refractory recurrent HGMs. Compared with conventional therapy, PFS in both primary and secondary endpoints were considerably improved. © The Author(s) 2026. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

TOURMALINE-MM3 (NCT02181413) and -MM4 (NCT02312258) were phase 3 studies of fixed-duration, single-agent ixazomib maintenance in post-transplant (TOURMALINE-MM3)/transplant-ineligible (TOURMALINE-MM4) patients with newly diagnosed multiple myeloma (NDMM) that demonstrated improved median progression-free survival (PFS) for ixazomib vs placebo. We present the final overall survival (OS) analyses for each study separately. In both studies, eligible patients were randomized 3:2 to receive ixazomib maintenance (3 mg [cycles 1-4], 4 mg [from cycle 5 if tolerated]) or matching placebo for ≤26 cycles, or until progressive disease/unacceptable toxicity. At median follow-up of approximately 8 years (TOURMALINE-MM3) and 5 years (TOURMALINE-MM4), median OS was not reached in either arm in MM3 (hazard ratio [HR], 1.025; 95% confidence interval [CI], 0.789-1.332; p = 0.850), and was 64.8 (ixazomib) vs 69.5 (placebo) months in MM4 (HR, 1.090; 95% CI, 0.861-1.381; p = 0.473). No new safety signals were identified in either study; incidence of new primary malignancies was low. Despite meeting their primary endpoints (PFS), neither final OS analysis of TOURMALINE-MM3/-MM4 showed statistically significant differences between fixed-duration ixazomib maintenance and placebo in patients with NDMM. The growing number of available, highly effective salvage treatments with novel mechanisms of action make demonstrating an OS advantage in front-line myeloma studies increasingly challenging. © 2025. Takeda Development Center Americas, Inc. (TDCA).

AIM: The benzoxaborole derivative DNDI-6148 is an antiparasitic agent with activity against multiple Leishmania protozoan species, including L. infantum and L. donovani, which cause visceral leishmaniasis. We investigated the safety, tolerability and pharmacokinetics of single oral doses of DNDI-6148 in a randomized, parallel-group, placebo-controlled, first-in-human study in 64 healthy participants. METHODS: Eight cohorts of eight participants each were enrolled. DNDI-6148, formulated as a suspension in ORA-Sweet® was administered orally as single 10-380 mg doses. Pharmacokinetics (PK) and safety were assessed for four (cohorts receiving 10-80 mg DNDI-6148) or six (cohorts receiving 160-380 mg DNDI-6148) days after dosing. RESULTS: Sixteen adverse events (AEs) were experienced by 13 participants (20.3%), all mild or moderate in severity and resolved by the end of the study. No AE led to any participant withdrawal, and no fatal or serious AEs were reported. DNDI-6148 was relatively slowly absorbed (tmax ranging between 3 and 12 h) under fasting conditions, with increase in plasma concentrations modestly sub-proportional to dose. The mean half-life was between 12.80 and 25.42 h. The fraction of the dose excreted by the kidneys as unchanged DNDI-6148 was below 0.2%. Trace amounts of three metabolites (formed by oxidation, deboronation, dehydrogenation of DNDI-6148) were detected in plasma. CONCLUSION: After a single administration of up to 380 mg by oral route, DNDI-6148 had an acceptable safety and tolerability profile and a favourable PK profile. These data support further clinical development. © 2025 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Objective The clinical effectiveness of 2% crisaborole cream and amorolfine hydrochloride cream on keratinized tinea pedis is the goal of this investigation. Methods Using random numbers, 100 patients with keratotic tinea pedis were split into two groups: the observation group received 2% crisaborole ointment and amorolfine hydrochloride cream once a night for four weeks, while the control group received white vaseline and amorolfine hydrochloride cream once a night. The two groups were compared in terms of clinical efficacy, adverse reaction incidence, and improvement in the dermatological quality of life index (DLQI) score. Results Following four weeks of treatment, the observation group's overall effective rate was 98%, which was significantly higher than 82%, and the difference was statistically significant (p < 0.001). The pruritus scales were (6.12 ± 1.92) days, (12.01 ± 3.89) days, (3.92 ± 3.02) days, and (15.09 ± 3.98) days in the control group. The observation group was significantly lower than the control group at both the 2-week and 4-week treatment points (p < 0.001). The incidence of negative effects did not differ significantly between the two groups (p > 0.05). Conclusions For keratinized tinea foot, 2% crisaborole ointment can increase the effectiveness of amorolfine hydrochloride cream.

Chronic graft-versus-host disease (cGVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. We hypothesize that it is possible to decrease its risk by manipulating the immune response in late phases of transplantation. We performed a prospective randomized trial including 73 patients. Patients in the treatment arm received 4 mg of ixazomib (IXZ) every 28 days from day +100. With a median follow-up of 24 months, the cumulative incidence of moderate/severe cGVHD in the IXZ vs control groups at 1 and 2 years were: 3.23% vs 30.2% (hazard ratio [HR], 0.089; P = .02) and 13% vs 43% (HR, 0.23; P = .01), respectively. Estimates for cGVHD and relapse-free survival at 2 years were 81% for IXZ and 49% for the control group (HR, 0.30). Increased STAT3 and p38 phosphorylation in T cells, and higher proportion of B cells that have undergone immunoglobulin isotype switching and circulating plasma cells on day +180 were associated with a significantly higher risk of developing moderate/severe cGVHD. The administration of IXZ decreases the risk of moderate/severe cGVHD. It is possible to identify biological patterns by flow cytometry to predict the risk of cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT03225417. © 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

The aim of this study was to evaluate the bioequivalence and safety of a single application of crisaborole ointment to test formulation and reference formulation in healthy subjects under fasting conditions. A total of 32 subjects were included and divided into 2 groups (test-reference; reference-test). A single-center, single-dose, 2-formulation, 2-period, 2-sequence, open, randomized, and crossover trial design was adopted. Eligible healthy subjects were applied with the test preparation (domestic crisaborole ointment) or the reference preparation (original crisaborole ointment), followed by a 7-day washout period. Blood samples were collected at predetermined time points before and after administration. After the development and verification of the blood concentration detection method for this study, the third-party supplier used liquid chromatography-tandem mass spectrometry to determine the plasma concentration of crisaborole and used SAS Version 9.4 software to calculate the pharmacokinetic parameters and evaluate the bioequivalence. In this study, the 90% confidence intervals of the geometric mean ratios of maximum concentration, area under the concentration-time curve over the dosing interval, and area under the concentration-time curve from time 0 to infinity were within the acceptable range (80%-125%). During the study, 5 subjects had 8 adverse events, and no serious adverse events were reported. In this study, the tested formulation of crisaborole ointment is bioequivalent to the reference formulation, and the safety is comparable. © 2025 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.

PURPOSE: Pain consists of biological, psychological, and sociological elements that are influenced by the aging process. Pain management in older adults may be improved by multimodal strategies that impact the biopsychosocial model. Chronic musculoskeletal pain in older adults is often linked with social isolation which limits the use of in-person nonpharmacologic therapies. The purpose of this study was to compare two interactive routines delivered with artificial intelligence (AI) on pain severity, pain interference, and other outcomes in older adults with chronic musculoskeletal pain that live alone. METHODS: Adults 60 years of age and older were recruited, enrolled, and randomly assigned to the conversational voice assistant-standard or the conversational voice assistant-enhanced (CVA-E) group. Participants interacted with routines twice a day and as needed for 12 weeks in their homes. Self-reported pain and pain-related outcome data were collected at baseline and postintervention. RESULTS: A sample of N = 50 participants engaged with the interactive voice assistant routines twice daily. After 12 weeks, the participants self-reported decreased scores in pain interference, loneliness, and depression. Self-reported depression scores were significantly reduced in both intervention groups. There was a statistically significant decrease in self-reported loneliness reported by older adults in the CVA-E group. CONCLUSIONS AND IMPLICATIONS: The experience of pain can be detrimental to older adults, especially when they live alone or are socially isolated. The preliminary findings from this study suggest that prescribed routines delivered with an AI voice assistant may encourage older adults' engagement with nonpharmacologic biopsychosocial strategies, and influence pain interference in older adults. There is a need to continue exploring personalized and biopsychosocial tailored routines delivered with technology and their impact on pain and other pain-related outcomes.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is the most common type of osteoporosis. Numerous studies have shown that static magnetic fields (SMFs) can inhibit bone loss by regulating bone remodeling. However, there are currently no clinical studies on the treatment of osteoporosis with SMFs. This study aims to investigate the clinical therapeutic effects of moderate static magnetic fields (MMFs) on PMOP. METHODS: In this paper, we constructed MMF device using neodymium-iron-boron (NdFeB) materials. At the animal level, the effect of MMF exposure for 8 weeks on estrogen deficiency-induced bone loss was investigated by evaluating bone microstructure, mechanical properties, and bone conversion using ovariectomized (OVX) mice. Clinically, a single-blind randomized controlled study in patients with PMOP was designed. PMOP patients aged 55-70 years were recruited and randomized into the control and MMF treatment groups. Clinical assessments of bone mineral density (BMD), bone turnover markers (BTMs) and VAS scores were performed at baseline and day 90, respectively. RESULTS: The results showed that MMF exposure significantly improved BMD, bone mineral content (BMC), bone microarchitecture and bone strength in OVX mice. For bone turnover, MMF increased the number of osteoblasts on the bone surface of OVX mice as well as the level of serum bone formation marker P1NP, while decreasing the number of osteoclasts and the level of serum bone resorption marker β-CTX. The clinical trial's results showed that MMF treatment had a positive effect on the improvement of BMD in the lumbar spine and increased serum P1NP levels while decreased β-CTX levels. In addition, MMF treatment decreased participants' VAS scores for low back pain. CONCLUSIONS: The results of both animal and clinical studies demonstrated that MMF treatment improved bone turnover and have a positive effect on BMD improvement, as well as alleviated low back pain in PMOP patients. This study will promote the translational research and clinical application of SMF treatment for osteoporosis. TRIAL REGISTRATION: Intervention study of moderate static magnetic field on osteoporosis and iron metabolism in postmenopaus

Oral-drug based regimens are useful in certain circumstances for transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM), but few studies have compared Ixazomib based regimen with lenalidomide based regimen head-to-head. We carried out a prospective randomized, open, parallel group trial in patients with TI-NDMM in 3 China centers from March 2020 to December 2022. Sixty-three patients were available for final analysis, ICd (Ixazomib/cyclophosphamide/dexamethasone, n = 31) and RCd (lenalidomide/cyclophosphamide/dexamethasone, n = 32). The primary objective was to compare the two regimens by analyzing the overall response rate (ORR), safety profiles, progression-free survival (PFS) and overall survival (OS). We also explored clinical and the biological characteristics of the patients with primary drug resistance. Baseline characteristics were well balanced between ICd and RCd groups, with the median age 70 vs. 70 years; 12.9% vs. 12.5% of patients had stage III disease; 25.8% vs. 28.1% had high-risk cytogenetic abnormalities. The overall response rate (ORR) at the end of 4 cycles was 87.1% vs. 71.9% (odds ratio [OR], 1.212; 95% CI, 0.938-1.565; P = 0.213); the best ≥ VGPR rate was 41.9% vs. 31.2% (OR, 1.342; 95% CI 0.694-2.597; P = 0.439). Among high-risk cytogenetic patients, ORR was higher in the ICd group, 75% vs. 55.5% (P = 0.620), respectively. After 35 months follow-up, the median PFS were 22 and 23 months between ICd and RCd groups (P = 0.897). Median OS was not reached, estimated 3-year OS rate was 86.4% vs. 85.4% (P = 0.774). The most common adverse events of grade 3 or 4 were neutropenia (6.5% in the ICd group vs. 31.3% in the RCd group), anemia (19.4% vs. 18.8%), pneumonia (0 vs. 15.6%) and diarrhea (12.9% vs. 0). Treatment emergent adverse events (TEAEs) induced dose reduction and discontinuation were 22.6% vs. 37.5% and 3.2% vs. 6.3% in the ICd vs. RCd group, respectively. Exploration data showed that patients with t (4;14) were insensitive to initial RCd treatment. The ICd regimen showed a tendency towards improved ORR compared to RCd regimen. Both ICd and RCd regimens demonstrated less dose reduction and treatment discontinuation, suggestin

BACKGROUND: The effectiveness of crisaborole for proactive treatment of atopic dermatitis (AD) is not well established. OBJECTIVES: This study aims to investigate the efficacy and safety of a proactive treatment strategy with 2% crisaborole ointment for managing mild-to-moderate AD in children. PATIENTS AND METHODS: In this 16-week randomized-controlled trial, children aged 2-17 years with mild-to-moderate AD were enrolled. All participants received treatment with 0.1% mometasone furoate cream for 2 weeks. Those with an IGA score of ≤ 1 were randomly assigned in a 1:1 ratio to either the proactive treatment group, which received crisaborole combined with emollient twice daily, or the reactive treatment group, which received emollients alone, and in the event of disease relapse, both groups received 0.1% mometasone furoate cream as rescue treatment. RESULTS: Of the 153 patients screened, 142 were randomized; 73 to the proactive treatment group and 69 to the reactive treatment group. At the end of the 16-week trial, the proactive treatment group had a relapse rate of 43.84%, significantly lower than the 71.01% relapse rate in the reactive group (P = 0.001). Additionally, the proactive treatment group demonstrated a significant reduction in the need for mometasone furoate prescriptions at weeks 4, 8, 12, and 16 (P < 0.05). Improvements were also observed in IGA, EASI, PP-NRS, and POEM scores at 12 weeks (P < 0.05). No significant differences in adverse events were found between the groups (χ2 = 2.237, P = 0.135). CONCLUSIONS: Proactive treatment with crisaborole ointment for children older than 2 years with mild-to-moderate AD effectively reduces flare-ups and reliance on topical corticosteroids, demonstrating good tolerability and safety. CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2100054340 (Date of Trial Registration: 14 December 2021). © 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Hepatocellular carcinoma (HCC) is one of the most prevalent solid cancers with the highest mortality rate, despite various treatment modalities. Sodium pentaborate pentahydrate (NaB) is a boron derivative that has an effect on cell death pathways against cancer. Curcumin (Cur) is the primary bioactive substance in the plant Curcuma longa and has anti-inflammatory, antioxidant and anti-cancer activities, mostly whose bioactivity is enhanced by combining piperine (Pip). Ferroptosis is a form of cell death different from apoptosis, necrosis, and autophagy due to reactive oxygen species (ROS) and disturbance in iron homeostasis. In our current study, we evaluated the effects of a NaB, Cur, and Pip combination on ferroptosis in HCC cell lines HepG2 and Hep3B. Our findings demonstrated that this combination treatment significantly decreased glutathione peroxidase (GSH-Px) activity and also increased ROS levels and intracellular ferrous iron in HCC cells. Additionally, qRT-PCR and Western blot analyses revealed upregulation of ferroptosis-related genes and protein expressions, indicating a synergistic induction of ferroptotic pathways by NaB, Cur, and Pip. These results suggest that this combination may represent a promising strategy for inducing ferroptosis in HCC, providing a basis for preliminary research into its potential as a therapeutic approach. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Maize crop is a vital source of nutrients, but its productivity and nutritional quality are threatened by climate change-induced stresses. Among different micronutrients, zinc (Zn) has prime importance due to its role in improving growth, enzyme activation, protein synthesis, and chlorophyll production. On the other hand, iron (Fe) is essential for electron transport, respiration, energy production, and metabolic functions. Furthermore, the role of boron (B) in cell wall formation, membrane integrity, pollen germination, seed and fruit development is also vital. Previous studies have largely focused on individual micronutrient management, overlooking their synergistic roles. However, synergistic contribution of zinc, iron, and boron toward maize biofortification and yield improvement still needs investigation. This study uniquely addresses this gap by evaluating sole and consortia applications of these micronutrients to enhance yield and micronutrients (Zn, Fe, and B) in maize. A total of eight treatments, i.e., control, Fe, Zn, B, Fe + Zn, Fe + B, Zn + B, and Fe + Zn + B, were applied in soil while bed preparation for sowing of maize (Azam variety) in three replications, following a randomized complete block design (RCBD). Results demonstrate that Fe + Zn + B caused an increase in maize plant height (33.12%), 1000-grain weight (37.05%), biological yield (21.23%), grain yield (47.35%) while decrease in POD (38.77%), SOD (48.37%), CAT (48.78%), and APx (50.00%) compared to the control. Furthermore, improvement in Fe, Zn, and B concentration in leaves and grains verified the efficacious functioning of Fe + Zn + B more than the control. In conclusion, Fe + Zn + B is suggested as an effective amendment for mitigating nutritional deficiency in maize. © 2025. The Author(s).

Psoriasis is a multifactorial inflammatory disorder characterized by therapeutic resistance and high recurrence rates, with complex unmet clinical demands necessitating novel therapeutic strategies. Recently, emerging evidence has revealed pathological accumulation of senescent cells (SnCs) in psoriatic lesions, suggesting their critical involvement in disease persistence and relapse. Our previous studies demonstrated that precision photodynamic therapy (PDT) effectively eliminates SnCs and mitigates senescence-associated pathologies, positioning senotherapy as a potential breakthrough for psoriasis management. Building on these foundations, we developed SnC-targeted photosensitizers (H2O2-activated TZ0953 and β-gal-activated TZ0993) and revealed that SnC-targeted PDT significantly alleviates psoriatic pathology in psoriasis model mice. Further optimization led to a combination strategy employing TZ0953 with crisaborole, implementing dual-pathway intervention of the clearance of SnCs and inflammatory microenvironment modulation. This "dual-target" approach demonstrated superior efficacy compared to monotherapies. Our work pioneers a "dual-target/modal" strategy and addresses both cellular senescence and inflammatory cascades in psoriasis, providing a novel strategic direction for psoriasis treatment optimization.

BACKGROUND: The global emergence and spread of carbapenem-resistant Enterobacteriaceae in clinical settings have driven the search for inhibitors that can counteract carbapenemases. These enzymes include several serine β-lactamases (SBLs, such as KPC) and metallo-β-lactamases (MBLs, such as NDM) that hydrolyse almost all β-lactams including carbapenems. This endeavour has successful developed some SBL inhibitors, including the boron-containing compound vaborbactam. However, the challenge posed by MBLs remains unresolved. METHODS: A high-throughput screening was conducted on 1718 FDA-approved drugs as potential adjuvants to meropenem. The synergistic effect was determined by checkerboard assay. The underlying mechanisms were elucidated using enzyme inhibition assays, molecular docking and dynamics simulations. The safety and efficacy were evaluated using a murine model. FINDINGS: We have identified another boron-containing broad-spectrum serine and metallo-β-lactamase inhibitor, the benzoxaborole antifungal agent tavaborole. In vitro, tavaborole enhances the antibacterial activity of multiple β-lactam antibiotics against bacteria producing either SBLs or MBLs. In vivo, injectable administration of tavaborole has demonstrated good safety in mice and has restored the efficacy of meropenem against blaNDM-5 and blaKPC-2-positive bacterial infection in a mouse intraperitoneal model. Tavaborole may effectively inhibit the activity of SBLs and MBLs by covalently bonding with the active serine residue of SBLs and chelating the Zn2+ at the active center of MBLs. INTERPRETATION: Tavaborole shows good potential as an agent for use in combination with β-lactam antibiotics for treating multidrug-resistant Gram-negative bacterial infections. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Pinduoduo-China Agricultural University Research Fund.

BACKGROUND: Despite the development of novel therapeutic modalities, lung cancer persists as the leading cause of cancer-related mortality. Platinum-based treatments represent the most prominent treatment option, with cisplatin being the most frequently utilized chemotherapeutic agent. However, cisplatin has several serious side effects. A substantial body of evidence has emerged in recent years indicating that boron compounds exhibit anti-cancer properties when administered as monotherapy or in combination with chemotherapy agents. The objective of this study is to examine the anti-cancer effects of Cisplatin (Cis) and sodium pentaborate pentahydrate (NaB), both individually and in combination, on non-small cell lung cancer (NSCLC) cell line A-549 cells and small cell lung cancer (SCLC) cell line DMS-114 cells under in vitro conditions. METHODS AND RESULTS: The effects of cisplatin and NAB on cell survival, apoptosis, the cell cycle, and the expression levels of apoptotic, anti-apoptotic, and tumor suppressor genes were determined by an MTS assay, an Annexin-V assay, a cell cycle analysis, and real-time PCR (qPCR). It was found that the IC-50 value of cisplatin, which was 10 µM when used alone, decreased to 2.5 µM when combined with a non-toxic dose of NaB on the A-549 cell line. BAX and TP53 gene expression levels were elevated by the Nab-Cisplatin combination in the A-549 cell line. The combination was observed to result in an approximately 19-fold increase in CDK2 gene expression in the A-549 cell line and an approximately 6-fold increase in the DMS-114 line, which resulted in S phase and/or G2 phase arrest on the cell cycle. Gene expression levels of Survivin and Ki-67 were decreased by the combination on both cell lines when compared with cisplatin alone. The findings demonstrate that NaB exerts an anti-cancer effect on the A-549 and DMS-114 cell lines. Moreover, when combined with cisplatin, it produces a synergistic anti-cancer effect on the A-549 cell line, whereby apoptosis is activated and cell proliferation is inhibited. CONCLUSION: The combination of NaB and cisplatin represents a novel approach to the treatment of NSCLC. This is due to the fact tha

Salinity stress significantly hinders plant growth by disrupting osmotic balance and inhibiting nutrient uptake, leading to reduced biomass and stunted development. Using saponin (SAP) and boron (B) can effectively overcome this issue. Boron decreases salinity stress by stabilizing cell walls and membranes, regulating ion balance, activating antioxidant enzymes, and enhancing water uptake. SAP are bioactive compounds that have the potential to alleviate salinity stress by improving nutrient uptake, modulating plant hormone levels, promoting root growth, and stimulating antioxidant activity. That's why the current study was planned to use a combination of SAP and boron as amendments to mitigate salinity stress in sweet potatoes. Four levels of SAP (0%, 0.1%, 0.15%, and 0.20%) and B (control, 5, 10, and 20 mg/L B) were applied in 4 replications following a completely randomized design. Results illustrated that 0.15% SAP with 20 mg/L B caused significant enhancement in sweet potato vine length (13.12%), vine weight (12.86%), root weight (8.31%), over control under salinity stress. A significant improvement in sweet potato chlorophyll a (9.84%), chlorophyll b (20.20%), total chlorophyll (13.94%), photosynthetic rate (17.69%), transpiration rate (16.03%), and stomatal conductance (17.59%) contrast to control under salinity stress prove the effectiveness of 0.15% SAP + 20 mg/L B treatment. In conclusion, 0.15% SAP + 20 mg/L B is recommended to mitigate salinity stress in sweet potatoes. © 2024. The Author(s).

AIM: To evaluate the antimicrobial capability of sclareol and its derivatives against Staphylococcus aureus and its Methicillin-resistant strain (MRSA). METHODS AND RESULTS: A new series of Boron-Heck-coupled sclareol analogues were prepared by structural modifications at the C-15 terminal double bond of sclareol using ultrasonication. The structural modifications were designed to keep the stereochemistry of all the five chiral centres of sclareol intact. A two-step reaction scheme consisting of Boron-Heck coupling of sclareol followed by Wittig reaction was carried out to produce novel sclareol congeners for antimicrobial evaluation. Three compounds SAJ-1, SAJ-2 and SB-11 exhibited strong antibacterial activity against S. aureus and Methicillin-resistant strain (MRSA) with MIC values between 3 and 11 μM. Among all the screened compounds, SAJ-1 and SAJ-2 showed the best antibiofilm profiles against both strains. Moreover, SAJ-1 and SAJ-2 acted synergistically with streptomycin against S. aureus while creating varying outcomes in combination with ciprofloxacin, penicillin and ampicillin. SAJ-1 also acted synergistically with ampicillin against S. aureus, while SB-11 showed synergism with ciprofloxacin against both pathogens. Moreover, SAJ-1 and SAJ-2 also inhibited staphyloxanthin production in S. aureus and MRSA and induced postantibiotic effects against both pathogens. CONCLUSIONS: It can be inferred that SAJ-1, SAJ-2 and SB-11 may act as potential chemical entities for the development of antibacterial substances. The study revealed that SAJ-1 and SAJ-2 are the most suitable sclareol analogues for further studies towards the development of antibacterial substances. SIGNIFICANCE AND IMPACT OF THE STUDY: SAJ-1, SAJ-2 and SB-11 show promising antibacterial properties against Staphylococcus aureus. Efforts should be made and more research should be done utilizing in vivo models to determine their efficacy as antibiotics. © 2022 Society for Applied Microbiology.

The development of more effective tumor therapy remains challenging and has received widespread attention. In the past decade, there has been growing interest in synergistic tumor therapy based on supramolecular coordination complexes. Herein, we describe two triangular metallacycles (1 and 2) constructed by the formation of pyridyl boron dipyrromethene (BODIPY)-platinum coordination. Metallacycle 2 had considerable tumor penetration, as evidenced by the phenylthiol-BODIPY ligand imparting red fluorescent emission at ∼660 nm, enabling bioimaging, and transport visualization within the tumor. Based on the therapeutic efficacy of the platinum(II) acceptor and high singlet oxygen (1O2) generation ability of BODIPY, 2 was successfully incorporated into nanoparticles and applied in chemo-photodynamic tumor therapy against malignant human glioma U87 cells, showing excellent synergistic therapeutic efficacy. A half-maximal inhibitory concentration of 0.35 μM was measured for 2 against U87 cancer cells in vitro. In vivo experiments indicated that 2 displayed precise tumor targeting ability and good biocompatibility, along with strong antitumor effects. This work provides a promising approach for treating solid tumors by synergistic chemo-photodynamic therapy of supramolecular coordination complexes.

129. Rom J Morphol Embryol. 2020 Jul-Sep;61(3):967-970. doi: 10.47162/RJME.61.3.39. Letter to the Editor: Boron enhances the antiviral activity of the curcumin against SARS-CoV-2. Scorei IR(1), Biţă A, Mogoşanu GD. Author information: (1)BioBoron Research Institute, S.C. Natural Research S.R.L., Podari, Dolj County, Romania; [email protected]. DOI: 10.47162/RJME.61.3.39 PMCID: PMC8112755 PMID: 33817742 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no conflict of interests.

Preclinical and clinical investigation on proteasome as a druggable target in cancer has led to the development of proteasome inhibitors (PIs) with different pharmacodynamic and pharmacokinetic properties. For example, carfilzomib has a better safety profile and a lower risk of clinically relevant drug-drug interactions than bortezomib, whereas ixazomib can be orally administered on a weekly basis due to a very long elimination half-life and high systemic exposure. The purpose of this review article is to elucidate the quantitative and qualitative differences in potency, selectivity, pharmacokinetics, safety and drug-drug interactions of clinically validated PIs to provide useful information for their clinical use in real life setting.

Atopic dermatitis is a chronic inflammatory skin disease with a significant impact on the overall wellbeing of patients and their families. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis in multiple countries. However, in the key pivotal trials, a low proportion of the overall patient population was Asian, therefore the safety and efficacy of crisaborole in the Asian population with atopic dermatitis remains unclear. CrisADe CLEAR was a multicenter, randomized, double-blind, vehicle-controlled, phase 3 study (NCT04360187) to assess the efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis involving ≥5% treatable body surface area. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. The primary endpoint was percentage change from baseline in the Eczema Area and Severity Index total score at day 29. Additional endpoints were improvement and success per Investigator's Static Global Assessment score at day 29 and change from baseline on the Peak Pruritus Numerical Rating Scale at week 4. Safety was assessed using rates of treatment emergent adverse events, serious adverse events, and clinically significant changes in vital signs and clinical laboratory parameters. Crisaborole-treated patients showed a significantly greater reduction versus vehicle in percentage change from baseline in Eczema Area and Severity Index total score at day 29 (P = 0.0002). Response rates for achievement of Investigator's Static Global Assessment improvement and success at day 29 were significantly higher for patients treated with crisaborole versus vehicle (P = 0.0124 and P = 0.0078, respectively). Crisaborole-treated patients showed a significantly greater reduction versus vehicle in change from baseline on the Peak Pruritus Numerical Rating Scale at week 4 (P = 0.0009). No new safety signals were identified. Treatment with crisaborole was effective and well tolerated in Chinese and Japanese patients with mild-to-moderate atopic dermatitis. © 2023 The Authors. The Journal of Der

BACKGROUND: Although the bortezomib-based triple-drug therapy is considered as a front-line therapy for multiple myeloma (MM) in Chinese patients, increased level of toxicity leads to treatment dissatisfaction. Treatment with ixazomib, an oral proteasome inhibitor, has demonstrated better efficacy and safety profile without increasing the toxicity. In this study, we investigate the safety and clinical outcomes of Chinese patients with newly diagnosed MM (NDMM) who transitioned from a bortezomib-based triple-drug therapy to an ixazomib-based triple-drug therapy in a real-world clinical setting. METHODS: This will be an open-label, single-arm, multicenter, prospective, observational study will recruit Chinese patients (aged ≥ 18 years) diagnosed with NDMM using International Myeloma Working Group (IMWG) criteria and who have received a bortezomib-based triple-drug therapy for more than two cycles as initial therapy. The previous bortezomib-based triple-drug therapy may include bortezomib, cyclophosphamide, and dexamethasone or lenalidomide, bortezomib, and dexamethasone or bortezomib, doxorubicin, and dexamethasone or bortezomib, thalidomide, and dexamethasone. At the time of enrollment, patients must have achieved at least partial response as defined by IMWG criteria. Approximately 320 eligible patients at 15 top MM hospitals in China will be treated with ixazomib triple-drug therapy and followed up once every 3 months for 24 months, unless specified. The primary endpoint is to assess progression-free survival at 2 years for Chinese patients with NDMM who have transitioned from a bortezomib-based triple-drug therapy to ixazomib-based triple-drug therapy. The clinical effectiveness, safety and tolerability, patient-reported outcomes, and health economic/resource utilization will be evaluated as secondary endpoints. PLANNED OUTCOMES: The results from this study may provide evidence to verify the benefits of transitioning from bortezomib-based triple-drug therapy to ixazomib-based triple-drug therapy in Chinese patients with NDMM in a real-world clinical setting. TRIAL REGISTRATION: The study has been registered at clinicalTrials.gov (NCT05013190). © 2022. The Auth

BACKGROUND: Atopic dermatitis is highly prevalent in black/African American, Asian, and Hispanic patients, making assessment of these populations in clinical trials important. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. In two pivotal phase III clinical trials in patients aged ≥ 2 years, crisaborole was superior to vehicle in reducing global disease severity. The most common treatment-related adverse event was application site pain. OBJECTIVE: The objective of this study was to investigate the efficacy and safety of crisaborole according to patient race and ethnicity. METHODS: A pooled post hoc analysis by race and ethnicity of the two pivotal trials and a safety extension trial was performed. Race included white or nonwhite (encompassing Asian/native Hawaiian/other Pacific Islander, black/African American, and other/American Indian/Alaskan native); ethnicity included Hispanic/Latino or not Hispanic/Latino. RESULTS: In white, nonwhite, Hispanic/Latino, and not Hispanic/Latino groups at day 29, more crisaborole- than vehicle-treated patients achieved improvements in global disease severity [Investigator's Static Global Assessment of clear/almost clear with a ≥ 2-grade improvement (white: 33.5% vs. 22.3%, nominal p < 0.001; nonwhite: 30.0% vs. 21.3%, nominal p < 0.05; Hispanic/Latino: 35.4% vs. 18.2%, nominal p < 0.01; not Hispanic/Latino: 31.3% vs. 22.8%, nominal p < 0.01)]. Crisaborole treatment also improved atopic dermatitis signs/symptoms and quality of life. Frequency of crisaborole-related adverse events was 7.1-8.5% in the pivotal trials. CONCLUSION: Across races and ethnicities, crisaborole demonstrated efficacy for the treatment of mild-to-moderate atopic dermatitis, with a low frequency of treatment-related adverse events.

We report the first clinical investigation conducted in Japan to confirm the safety, tolerability, and pharmacokinetics of ixazomib alone and combined with lenalidomide-dexamethasone (Rd) in Japanese patients with relapsed/refractory multiple myeloma. Adult patients with measurable disease and ≥2 prior lines of therapy received oral ixazomib 4.0 mg on days 1, 8, 15 alone or combined with lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15, 22 in 28-day cycles. Fourteen patients who had received a median of seven prior therapies were enrolled (seven per cohort). One of six evaluable patients in each cohort experienced dose-limiting toxicities [diarrhea, nausea, hypokalemia, hypertension, thrombocytopenia, hyponatremia (ixazomib cohort); thrombocytopenia, and neutropenia (ixazomib + Rd cohort)]. The most common drug-related adverse events were neutropenia, thrombocytopenia, leukopenia, and lymphopenia. Drug-related grade ≥3 adverse events occurring in ≥3 patients per cohort were (ixazomib/ixazomib + Rd cohort, n): neutropenia (4/2), thrombocytopenia (3/2), and lymphopenia (5/2). Ixazomib was rapidly absorbed with a median T max of approximately 1-2-h post-dose, and had a geometric mean terminal half-life of 5-6 days. Of 13 response-evaluable patients, one achieved a partial response (duration ∼38 weeks; ixazomib cohort) and seven had stable disease.

BACKGROUND: The oral proteasome inhibitor ixazomib is under phase 3 clinical investigation in multiple myeloma (MM) in combination with lenalidomide-dexamethasone. This study was conducted to investigate the pharmacokinetic and safety profiles of ixazomib, administered with lenalidomide-dexamethasone, in East Asian patients with relapsed/refractory MM. METHODS: Adult patients with measurable disease who had received 1-3 prior lines of therapy received oral ixazomib on days 1, 8, and 15, lenalidomide (25 mg) on days 1-21, and dexamethasone (40 mg) on days 1, 8, 15, and 22, in 28-day cycles. Primary objectives were to characterize ixazomib plasma pharmacokinetics, determine the recommended phase 2/3 dose, and evaluate safety and tolerability. RESULTS: Forty-three patients were enrolled. No dose-limiting toxicities were reported for the first six patients receiving ixazomib (4.0 mg), confirming this as the recommended phase 2/3 dose. Ixazomib was rapidly absorbed with a median T max of 1.5 h on day 1 and 2.0 h on day 15 of cycle 1 and had a geometric mean terminal half-life of 6.1 days. Twenty-one (49%) patients had at least one drug-related grade ≥3 adverse event (AE); the most common were neutropenia (19%), diarrhea (14%), and thrombocytopenia (12%). Twenty-eight of 43 (65%) response-evaluable patients had at least a partial response. The recommended phase 2/3 dose for ixazomib was determined to be 4.0 mg. CONCLUSIONS: The all-oral combination of ixazomib plus lenalidomide-dexamethasone appeared active and well tolerated at 4.0 mg. Consequently, East Asian patients enrolled in phase 3 studies are receiving the same ixazomib dose as patients in other regions. TRIAL REGISTRATION: This study is registered at NCT01645930.

Antimicrobial resistance driven by multidrug-resistant (MDR) Gram-negative pathogens poses a major global threat, contributing to substantial morbidity and mortality. Novel β-lactam/β-lactamase inhibitor combinations, particularly meropenem-vaborbactam (M/V) and ceftazidime-avibactam (C/A), have expanded therapeutic options; however, their comparative efficacy and safety remain uncertain. This meta-analysis compared M/V and C/A in adult patients with MDR Gram-negative infections. MEDLINE, Embase, and Cochrane Central were searched for studies evaluating M/V versus C/A in hospitalized adults. Outcomes included all-cause mortality, clinical cure, and microbiological recurrence; safety was assessed qualitatively. Data were synthesized using Review Manager, with trial sequential analysis (TSA) applied to minimize random error. Five retrospective cohort studies (three full articles and two conference abstracts) comprising 3,280 patients were included, of whom 577 received M/V and 2,703 received C/A. Populations predominantly consisted of older adults aged 57-70 years, with respiratory tract infections being most common. Pooled analyses demonstrated no statistically significant differences between M/V compared to C/A in all-cause mortality (Odds ratio [OR] 0.87; 95% CI 0.69-1.11; P = 0.26; I² = 16%), clinical cure (OR 1.41; 95% CI 0.66-3.03; P = 0.37; I² = 55%), and microbiological recurrence (OR 0.67; 95% CI 0.32-1.40; P = 0.29; I² = 0%). Qualitative synthesis indicated comparable tolerability. TSA for mortality demonstrated insufficient evidence for definitive conclusions. M/V showed no statistically significant difference over C/A; therefore, selection should be guided judiciously based on clinical context. Further studies are needed to define the optimal role of each agent within antimicrobial stewardship frameworks.

With the continuous advancement of deep space exploration missions, maintaining astronaut skin health has become a critical medical issue affecting the safety and effectiveness of long-duration missions. Deep space environmental stressors, including microgravity, ionizing radiation, lunar dust exposure, and microbiome dysbiosis, can synergistically disrupt the skin barrier structure, leading to immune homeostasis imbalance and impaired wound healing. In recent years, research on skin protection in deep space has gradually evolved into a systematic "multi-dimensional integrated protective" framework. From the engineering protection perspective, optimization of multi-layer composite spacesuit structures, the use of hydrogen-rich and boron-containing shielding materials, as well as cabin temperature-humidity regulation and debris-resistant technologies, have greatly enhanced environmental defense capacity. From the biomedical protection perspective, functional hydrogels, antimicrobial dressings, and active compounds derived from traditional Chinese medicine have demonstrated remarkable potential in repairing the skin barrier, modulating immunity, and providing antioxidant defense. Meanwhile, the development of skin microecological interventions and wearable physiological monitoring systems has fostered a trend toward personalized health management. Future research should focus on elucidating the interactive mechanisms among the space environment, skin, and immune barrier, while exploring intelligent monitoring and nanotechnology-based protection strategies. Establishing a predictive and preventive skin health safeguarding system will provide comprehensive medical support for future deep space missions. Publisher: 深空探测任务的持续推进使宇航员皮肤健康成为影响长期任务安全与效能的关键医学问题。微重力、电离辐射、月尘暴露及微生物群紊乱等深空环境应激因素可协同破坏皮肤屏障结构，诱发免疫稳态失衡及创面愈合障碍。近年来，深空皮肤防护体系逐渐形成以“多维整合防护”为核心的系统化防护模式。工程防护方面，通过优化航天服多层复合结构、富氢与含硼屏蔽材料设计以及舱体温湿调控与抗碎片防护模式，显著增强了环境防御能力;医学生物防护方面，功能性水凝胶、抗菌敷料及中药活性成分在皮肤屏障修复、免疫调控及抗氧化防御中展现出显著潜力;同时，皮肤微生态干预与可穿戴生理监测系统的发展，推动了个体化健康管理模式的形成。未来研究应聚焦航天环境-皮肤-免疫屏障的交互机制，探索智能化监测与纳米防护技术，构建以预测性预防为核心的皮肤健康保障体系，为深空任务提供系统性医学支持。.

OBJECTIVE: This review evaluates the effectiveness of protective coatings in enhancing the corrosion resistance of neodynium-iron-boron (Nd2Fe14B) and samarium cobalt (SmCo5) magnets in orthodontics. METHODS: In accordance with PRISMA guidelines, a structured search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library. Eligible studies included peer-reviewed research on corrosion resistance, cytotoxicity, or durability of coated magnets. Twelve studies were assessed for bias using the QUIN tool. RESULTS: Coatings such as zirconium dioxide (ZrO2), zirconium nitride (ZrN), diamond-like carbon (DLC), silanization, parylene, and PTFE enhanced corrosion resistance, limited ion release, and maintained mechanical function. ZrO2 and ZrN had the highest resistance, while DLC provided superior durability. Parylene and epoxy resin showed lower mechanical stress resilience. The predominance of in vitro data limits clinical application. CONCLUSIONS: Coatings enhance the durability and safety of rare-earth magnets in orthodontics. However, limited in vivo evidence and inconsistencies in testing are challenges. Future research should focus on long-term studies and multifunctional coatings optimizing corrosion resistance, biocompatibility, and mechanical performance.

Topical molecular targeted therapies have recently emerged for the treatment of atopic dermatitis (AD), but their efficacy and safety, particularly in children, remain underexplored. This systematic review and meta-analysis aim to evaluate the efficacy and safety of topical targeted therapies in children with AD. We conducted a comprehensive search of the CENTRAL, MEDLINE, Embase, and ICHUSHI databases for articles published up to January 7, 2023, based on a protocol registered in PROSPERO (CRD42022366449). Randomized controlled trials (RCTs) investigating new topical targeted therapies in children (≤18 years) with AD were included. The primary outcomes were the Eczema Area and Severity Index (EASI) scores and treatment-related adverse events. Secondary outcomes included additional efficacy and safety analyses. A meta-analysis was performed using Revman 5.4, with bias risk assessed via the RoB 2 tool. Nine studies (reported in eight articles) involving 2182 patients were included, with 1469 children treated with Janus kinase inhibitors (ruxolitinib and delgocitinib) and phosphodiesterase-4 inhibitors (crisaborole, lotamilast, and difamilast). These interventions significantly improved EASI scores, with the least square mean change (mean difference: -56.67%; 95% confidence interval [-59.16% to -54.18%]). Additionally, topical targeted therapies did not increase the incidence of treatment-emergent adverse events (risk difference: 0.00; 95% confidence interval [-0.02 to 0.02]). The risk of bias was low across all outcomes. New topical targeted therapies administered over 4 weeks are effective and safe for children with atopic dermatitis aged ≤18 years. Further studies are needed to establish their long-term safety and efficacy. © 2025 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Boron neutron capture therapy (BNCT) is an emerging modality for cancer treatment. Although its concept was proposed in the last century, progress has been relatively slow because limitations in neutron source technology and boron compounds. In recent years, with the increased availability of neutron devices and improvements in boron compounds, the radiobiological effects of BNCT have been investigated more deeply, leading to a surge of research findings in the field. Therefore, a systematic review of the current status of BNCT is particularly warranted. In this review, we integrate the latest studies to provide a comprehensive and detailed description of the direct and indirect mechanisms by which BNCT induces cell killing, as well as the subsequent cellular responses. More importantly, we propose that BNCT exhibits a stronger immunologic foundation and immunogenicity than traditional radiation therapy, indicating significant potential for its combined application with immunotherapy. These results offer a robust theoretical foundation for the future clinical use of BNCT and indicate that continued investigation of BNCT in conjunction with immunotherapy may pave the way for more advanced cancer treatment strategies.