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Jeonghoon Ha,1 Hansang Baek,1 Chaiho Jeong,2 Hyunsam Kim,3 Ki-Hyun Baek,4 Moo Il Kang,1 Dong-Jun Lim1 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea; 3Department of Internal Medicine, Dongshin Hospital, Seoul, Korea; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, KoreaCorrespondence: Dong-Jun LimDivision of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, KoreaEmail ldj6026@catholic.ac.krPurpose: Studies investigating the association between vitamin D and metabolic parameters have reported inconsistent results depending on the characteristics of the subjects. We aimed to investigate the association between vitamin D levels and various metabolic indicators in healthy Korean adults by using nationally representative data.Methods: A total of 3640 participants were included after excluding subjects who were ≤ 19 years of age and had a history of treatment for dyslipidemia, hypertension, or diabetes and a history of other chronic diseases such as liver and kidney diseases. After dividing the 25-hydroxyvitamin D (25(OH)D) level into quartiles, the risk of having each metabolic parameter higher than the median value was determined according to the 25(OH)D quartile by using regression analysis.Results: In a multivariate regression analysis, a higher 25(OH)D quartile tended to have a significantly lower risk of having a triglyceride (TG) level higher than the median value (103.1 mg/dl). As the quartile increased, the risk of having a waist circumference or body mass index higher than the median value also decreased, but the difference was not statistically significant. No significant changes were observed in fasting glucose or glycated hemoglobin level according to quartile.Conclusion: We demonstrated that subjects with a higher 25(OH)D quartile exhibited a significantly lower risk of having a TG level higher than the median value in a representative Korean population. More evidence from a prospective study on whether vitamin D supplementation improves serum TG levels in healthy adults is needed.Keywords: 25-hydroxyvitamin D, triglyceride, glucose, body mass index, waist circumference

Jayanta Kumar Patra,1 Kwang-Hyun Baek2 1Research Institute of Biotechnology and Medical Converged Science, Dongguk University-Seoul, Ilsandong-gu, Gyeonggi-do, 2Department of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk, South Korea Abstract: The aim of this study was to compare the biological synthesis of gold nanoparticles (AuNPs) generated using the aqueous extracts of outer oriental melon peel (OMP) and peach. The synthesized OMP-AuNPs and peach extract (PE)-AuNPs were characterized by ultraviolet–visible spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray analysis, X-ray powder diffraction, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The surface plasmon resonance spectra were obtained at 545 nm and 540 nm for OMP-AuNPs and PE-AuNPs, respectively. The estimated absolute crystallite size of the synthesized AuNPs was calculated to be 78.11 nm for OMP-AuNPs and 39.90 nm for PE-AuNPs based on the Scherer equation of the X-ray powder diffraction peaks. Fourier transform infrared spectroscopy results revealed the involvement of bioactive compounds present in OMP and peach extracts in the synthesis and stabilization of synthesized AuNPs. Both the OMP-AuNPs and PE-AuNPs showed a strong antibacterial synergistic activity when combined with kanamycin (9.38–20.45 mm inhibition zones) and rifampicin (9.52–25.23 mm inhibition zones), and they also exerted a strong synergistic anticandidal activity (10.09–15.47 mm inhibition zones) when combined with amphotericin B against five pathogenic Candida species. Both the OMP-AuNPs and PE-AuNPs exhibited a strong antioxidant potential in terms of 1,1-diphenyl-2-picrylhydraxyl radical scavenging, nitric oxide scavenging, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging, and a reducing power, along with a strong proteasome inhibitory potential that could be useful in cancer drug delivery and cancer treatments. The PE-AuNPs showed comparatively higher activity than OMP-AuNPs, which could be attributed to the presence of rich bioactive compounds in the PE that acted as reducing and capping agents in the synthesis of PE-AuNPs. Overall, the results of the current investigation highlighted a novel green technology for the synthesis of AuNPs using food waste materials and their potential applications in the biomedical, pharmaceutical, and cosmetic industries. Keywords: antibacterial, anticandidal, antioxidant, Cucumis melo, gold nanoparticles, proteasome inhibitor, Prunus persica

Jayanta Kumar Patra, Kwang-Hyun Baek School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk, Republic of Korea Abstract: Biological synthesis of nanoparticles using nontoxic, eco-friendly approaches is gaining importance owing to their fascinating biocompatibility and environmentally benign nature. This study describes the green synthesis approach for synthesis of gold nanoparticles (ANPs) using aqueous extract of the rind of watermelon as a fruit waste and evaluate its biopotential in terms of proteasome inhibitory activity, antibacterial, and antioxidant potential. The synthesized ANPs were characterized using UV–vis spectroscopy, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The surface plasmon resonance spectra of ANPs were obtained at 560 nm. Scanning electron microscopy image revealed that particles had a spherical shape and have a size distribution of 20–140 nm, followed by the elemental analysis by energy-dispersive X-ray spectroscopy. X-ray diffraction analysis confirmed the crystallite nature of the ANPs and Fourier-transform infrared spectroscopy revealed the involvement of bioactive compounds from watermelon rind in the synthesis, capping, and stabilization of ANPs. ANPs exhibited potential antibacterial activity against five different foodborne pathogenic bacteria with diameter of inhibition zones ranged between 9.23 and 11.58 mm. They also displayed strong synergistic antibacterial activity together with kanamycin (11.93–21.08 mm inhibition zones) and rifampicin (10.32–24.84 mm inhibition zones). ANPs displayed strong antioxidant activity in terms of DPPH radical scavenging (24.69%), nitric oxide scavenging (25.62%), ABTS scavenging (29.42%), and reducing power. Significantly high proteasome inhibitory potential of the ANPs (28.16%) could be highly useful for cancer treatment and targeted cancer drug delivery. Overall, results highlight a potential low-cost green method of synthesizing ANPs from food waste materials. Significant biopotentials of synthesized ANPs could make it a potential candidate for its application in the biomedical, pharmaceutical, cosmetics, and food sectors. Keywords: antibacterial, antioxidant, gold nanoparticles, proteasome inhibitor, watermelon peel, green synthesis, biosynthesis

Sei Won Kim,1 Jong Min Lee,1 Jick Hwan Ha,1 Hyeon Hui Kang,1 Chin Kook Rhee,1 Jin Woo Kim,1 Hwa Sik Moon,1 Ki Hyun Baek,2 Sang Haak Lee1 1Division of Pulmonology, Critical Care and Sleep Medicine, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Background: Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD. Patients and methods: In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed. Results: Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20–6.48, P=0.018) compared with carriers in the dominant model. Conclusion: Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD. Keywords: chronic obstructive pulmonary disease, osteoporosis, vitamin D receptor gene, polymorphism, haplotype

Purpose: This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16., Methods: 457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck. Safety, PD, PK, and immunogenicity were evaluated throughout the study period., Results: Mean percent changes from baseline in lumbar spine, total hip, and femoral neck BMD at Month 18 were comparable across treatment groups, indicating comparable efficacy between SB16 and DEN. The mean percent change in lumbar spine BMD was 6.8 % (SB16 + SB16), 6.2 % (DEN+SB16), and 6.8 % (DEN+DEN). Total hip BMD increased by 4.4 %, 3.5 %, and 4.0 %, and femoral neck BMD by 3.4 %, 3.1 %, and 2.7 % for SB16 + SB16, DEN+SB16, and DEN+DEN, respectively. Safety profiles were similar among groups, with no new safety concerns identified after switching. Only one patient in the DEN+SB16 group developed non-neutralizing anti-drug antibodies by Month 18, indicating a low immunogenicity risk for SB16., Conclusion: Switching from DEN to SB16 demonstrated comparable efficacy, safety, PD, PK, and immunogenicity in PMO patients relative to those who continued DEN. SB16 was well tolerated over 18 months, demonstrating comparable outcomes to DEN., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoon-sok Chung reports a relationship with Amgen that includes: speaking and lecture fees. Yoon-sok Chung reports a relationship with Samsung Bioepis that includes: consulting or advisory and funding grants. Bente Langdahl reports a relationship with Amgen that includes: consulting or advisory and speaking and lecture fees. Bente Langdahl reports a relationship with UCB that includes: consulting or advisory and speaking and lecture fees. Bente Langdahl reports a relationship with Gedeon-Richter that includes: speaking and lecture fees. Bente Langdahl reports a relationship with Astellas that includes: speaking and lecture fees. Bente Langdahl reports a relationship with AstraZeneca that includes: speaking and lecture fees. Bente Langdahl reports a relationship with Samsung Bioepis that includes: funding grants. Rafal Plebanski reports a relationship with Samsung Bioepis that includes: funding grants. Edward Czerwinski reports a relationship with Amgen that includes: consulting or advisory and speaking and lecture fees. Edward Czerwinski reports a relationship with Samsung Bioepis that includes: funding grants. Eva Dokoupilova reports a relationship with AbbVie that includes: funding grants. Eva Dokoupilova reports a relationship with Eli Lilly that includes: funding grants. Eva Dokoupilova reports a relationship with GSK that includes: funding grants. Eva Dokoupilova reports a relationship with Novartis that includes: funding grants. Eva Dokoupilova reports a relationship with Biopharma SPRL that includes: funding grants. Eva Dokoupilova reports a relationship with Pfizer that includes: funding grants. Eva Dokoupilova reports a relationship with Sanofi that includes: funding grants. Eva Dokoupilova reports a relationship with Hexal AG that includes: funding grants. Eva Dokoupilova reports a relationship with Gilead that includes: funding grants. Eva Dokoupilova reports a relationship with Janssen that includes: funding grants. Eva Dokoupilova reports a relationship with Galapagos that includes: funding grants. Eva Dokoupilova reports a relationship with Samsung Bioepis that includes: funding grants. Jerzy Supronik reports a relationship with Samsung Bioepis that includes: funding grants. Jan Rosa reports a relationship with Samsung Bioepis that includes: funding grants. Andrzej Mydlak reports a relationship with Samsung Bioepis that includes: funding grants. Rafal Sapula reports a relationship with Zamosc Rehabilitation Clinic that includes: employment. Rafal Sapula reports a relationship with Polish Rehabilitation Society that includes: board membership. Rafal Sapula reports a relationship with Medical Rehabilitation for Lublin Region that includes: consulting or advisory. Rafal Sapula reports a relationship with Samsung Bioepis that includes: funding grants. Anna Rowinska-Osuch reports a relationship with Samsung Bioepis that includes: funding grants. Ki-Hyun Baek reports a relationship with Samsung Bioepis that includes: funding grants. Audrone Urboniene reports a relationship with Samsung Bioepis that includes: funding grants. Robert Mordaka reports a relationship with Samsung Bioepis that includes: funding grants. Sohui Ahn reports a relationship with Samsung Bioepis that includes: employment. Sohui Ahn reports a relationship with Samsung Biologics that includes: equity or stocks. Young Hee Rho reports a relationship with Samsung Bioepis that includes: employment. Young Hee Rho reports a relationship with Samsung Biologics that includes: equity or stocks. Jisuk Ban reports a relationship with Samsung Bioepis that includes: employment. Jisuk Ban reports a relationship with Samsung Biologics that includes: equity or stocks. Richard Eastell reports a relationship with AstraZeneca that includes: consulting or advisory. Richard Eastell reports a relationship with Immunodiagnostic Systems that includes: consulting or advisory. Richard Eastell reports a relationship with Sandoz that includes: consulting or advisory. Richard Eastell reports a relationship with Samsung Bioepis that includes: consulting or advisory. Richard Eastell reports a relationship with CL Bio that includes: consulting or advisory. Richard Eastell reports a relationship with CureTeQ that includes: consulting or advisory. Richard Eastell reports a relationship with Biocon that includes: consulting or advisory. Richard Eastell reports a relationship with Grunenthal that includes: consulting or advisory. Richard Eastell reports a relationship with Takeda that includes: consulting or advisory. Richard Eastell reports a relationship with Theramex that includes: consulting or advisory. Richard Eastell reports a relationship with UCB that includes: consulting or advisory. Richard Eastell reports a relationship with Pharmacosmos that includes: speaking and lecture fees. Richard Eastell reports a relationship with Alexion that includes: speaking and lecture fees. Richard Eastell reports a relationship with Radius that includes: speaking and lecture fees. Richard Eastell reports a relationship with UCB that includes: speaking and lecture fees. Richard Eastell reports a relationship with Amgen that includes: speaking and lecture fees. Richard Eastell reports a relationship with Samsung Bioepis that includes: travel reimbursement. Richard Eastell reports a relationship with CL Bio that includes: travel reimbursement. Richard Eastell reports a relationship with Alexion that includes: funding grants. Richard Eastell reports a relationship with CL Bio that includes: funding grants. Richard Eastell reports a relationship with Osteolabs that includes: funding grants. Richard Eastell reports a relationship with DSMB for Biocon that includes: Chairman. Richard Eastell reports a relationship with DSMB for CureTeQ that includes: Chairman. Richard Eastell reports a relationship with DSMB for STOPFOP that includes: Chairman. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, we report rapid activation of a solution-processed aluminum oxide gate dielectric film to reduce its processing time under ambient atmosphere. Aluminum precursor films were exposed to a high energy light-pulse and completely converted into dielectric films within 30 seconds (450 pulses). The aluminum oxide gate dielectric film irradiated using intense pulsed light with 450 pulses exhibits a smooth surface and a leakage current density of less than 10 -8 A cm -2 at 2 MV cm -1 . Moreover, dielectric constants of the aluminum oxide layer were calculated to be approximately 7. Finally, we fabricated a solution-processed indium gallium zinc oxide thin-film transistor with AlO x using intense pulsed light irradiation, exhibiting a field-effect mobility of 2.99 cm 2 V -1 s -1 , threshold voltage of 0.73 V, subthreshold swing of 180 mV per decade and I on / I off ratio of 3.9 × 10 6 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5 mg annual dose for osteoporosis in breast cancer patients, is limited., Materials and Methods: In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5 mg dose of zoledronic acid and monitored over 12 months for changes in bone mineral density (BMD), fracture rates, and biochemical markers., Results: Initially, the AI group was the oldest, averaging 59.1 ± 8.7 years. At baseline, no significant differences in variables, except age, were observed. After 12 months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12 months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups., Conclusion: A single infusion of 5 mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest that could affect the impartiality of the reported research., (© 2024. The Japanese Society Bone and Mineral Research.)

The global human population is growing and demand for food is increasing. Global agriculture faces numerous challenges, including excessive application of synthetic pesticides, emergence of herbicide-and pesticide-resistant pathogenic microbes, and more frequent natural disasters associated with global warming. Searches for valuable endophytes have increased, with the aim of making agriculture more sustainable and environmentally friendly. Endophytic microbes are known to have a variety of beneficial effects on plants. They can effectively transfer nutrients from the soil into plants, promote plant growth and development, increase disease resistance, increase stress tolerance, prevent herbivore feeding, reduce the virulence of pathogens, and inhibit the growth of rival plant species. Endophytic microbes can considerably minimize the need for agrochemicals, such as fertilizers, fungicides, bactericides, insecticides, and herbicides in the cultivation of crop plants. This review summarizes current knowledge on the roles of endophytes focusing on their mechanisms of disease control against phytopathogens through the secretion of antimicrobial substances and volatile organic compounds, and the induction of systemic resistance in plants. Additionally, the beneficial roles of these endophytes and their metabolites in the control of postharvest diseases in plants have been summarized., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Glucagon-like peptide-1(GLP-1) is a hormone often measured in the short-term following Roux-en-Y gastric bypass (RYGB) due to its elevation and association with improvement of glucose metabolism. We examined the durability of this effect in patients with type 2 diabetes mellitus (DM) in the long term after RYGB., Methods: Obese patients with type 2 DM who had received RYGB 10 years ago (n = 10) were enrolled and a meal tolerance test (MTT) was performed. A matched control group with type 2 DM (n = 5) underwent MTT., Results: Glucose levels during the MTT did not differ between patients with RYGB and the nonsurgical group. Insulin, C-peptide and GLP-1 levels during MTT were significantly higher in patients with RYGB compared with the nonsurgical group (Area under the curve [AUC] of insulin; 57.4 ± 22.9 vs. 27.7 ± 11.1 mIU/L•hr, P = 0.008; AUC of total GLP-1; 189.4 ± 74.72 vs. 52.13 ± 10.23 pM •hr, P = 0.002), and in particular, peak insulin, C-peptide and GLP-1 levels observed 30-45 min after eating were markedly different from those in the nonsurgical group. Bile acids (BAs) and fibroblast growth factor 19 (FGF-19) levels during MTT were higher in patients with RYGB compared with the nonsurgical group. Peak BAs and FGF-19 levels tended to be higher in the RYGB., Conclusions: An enhanced GLP-1 response was noted 10 years after RYGB, strongly suggesting a durability of this effect. BAs and FGF-19 were increased in the RYGB group, but not as much as the pronounced increase in GLP-1 secretion., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Inflammation is associated with multiple life-threatening conditions. Desmidorchis flava is an edible plant and traditionally used for managing various diseases. Three novel molecules, namely desmiflavaside-C ( 1 ), nizwaside ( 2 ), and desmiflanoside ( 3 ) were isolated from Desmidorchis flava , and their structures were confirmed by mass spectrometry and through reported literature. These compounds were in vivo examined for antinociceptive (tonic visceral nociception) and anti-inflammatory (carrageenan induced paw edema) activities. Significant antinociceptive potential was demonstrated by compound 1 at 0.5 and 1 mg/kg doses followed by compounds 2 and 3 . At similar doses, significant anti-inflammatory activity was noted for all the tested compounds. Their antinociceptive and anti-inflammatory activities were comparable to the reference standards. In silico predicted binding modes suggests that these compounds may target allosteric sites of COX-1 and COX-2 enzymes to elicit their anti-inflammatory activities. These isolated natural products may have therapeutic potential in conditions afflicted with pain and inflammation.

Clavibacter michiganensis subsp. michiganensis (Cmm) and C. michiganensis subsp. capsici (Cmc) are phytopathogenic bacteria that cause bacterial canker disease in tomatoes and peppers, respectively. Bacterial canker disease poses serious challenges to solanaceous crops, causing significant yield losses and economic costs. Effective management necessitates the development of sustainable control strategies employing nanobiotechnology. In this study, the antibacterial effects of four Aspergillus sojae-mediated nanoformulations, including cobalt oxide nanoparticles (Co 3 O 4 NPs), zinc oxide nanoparticles (ZnO NPs), cobalt ferrite nanoparticles (CoFe 2 O 4 NPs), and CoFe 2 O 4 /functionalized multi-walled carbon nanotube (fMWCNT) bionanocomposite, were evaluated against Cmm and Cmc. The diameters of the zone of inhibition of A. sojae-mediated Co 3 O 4 NPs, ZnO NPs, CoFe 2 O 4 NPs, and CoFe 2 O 4 /fMWCNT bionanocomposite against Cmm and Cmc were 23.60 mm, 22.09 mm, 27.65 mm, 22.51 mm, and 19.33 mm, 17.66 mm, 21.64 mm, 18.77 mm, respectively. The broth microdilution assay was conducted to determine the minimal inhibitory and bactericidal concentrations. The MICs of Co 3 O 4 NPs, ZnO NPs, CoFe 2 O 4 NPs, and CoFe 2 O 4 /fMWCNT bionanocomposite against Cmm were 2.50 mg/mL, 1.25 mg/mL, 2.50 mg/mL, and 2.50 mg/mL, respectively. While, their respective MBCs against Cmm were 5.00 mg/mL, 2.50 mg/mL, 5.00 mg/mL, and 5.00 mg/mL. The respective MICs of Co 3 O 4 NPs, ZnO NPs, CoFe 2 O 4 NPs, and CoFe 2 O 4 /fMWCNT bionanocomposite against Cmc were 2.50 mg/mL, 1.25 mg/mL, 5.00 mg/mL, and 5.00 mg/mL. While, their respective MBCs against Cmc were 5.00 mg/mL, 2.50 mg/mL, 10.00 mg/mL, and 10.00 mg/mL. The morphological and ultrastructural changes of Cmm and Cmc cells were observed using field-emission scanning and transmission electron microscopy before and after treatment with sub-minimal inhibitory concentrations of the nanoformulations. Nanoformulation-treated bacterial cells became deformed and disrupted, displaying pits, deep cavities, and groove-like structures. The cell membrane detached from the bacterial cell wall, electron-dense particles accumulated in the cytoplasm, cellular components disintegrated, and the cells were lysed. Direct physical interactions between the prepared nanoformulations with Cmm and Cmc cells might be the major mechanism for their antibacterial potency. Further research is required for the in vivo application of the mycosynthesized nanoformulations as countermeasures to combat bacterial phytopathogens., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia)., Objective: This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (PMO; NCT04664959)., Design: The study included 457 PMO patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at Month 0 and Month 6. At Month 12, patients were re-randomized to continue with the assigned treatment or switch from DEN to SB16 up to Month 18. This report includes results up to Month 12., Methods: The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for Month 12), total hip and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen [CTX] and procollagen type I N-terminal propeptide [P1NP]), safety, and immunogenicity profiles were measured up to Month 12., Results: The least-squares mean differences in percent change from baseline in lumbar spine BMD at Month 12 were 0.33% (90% confidence interval [CI]: -0.25, 0.91) in the full analysis set and 0.39% (95% CI: -0.36, 1.13) in the per-protocol set; both within the pre-defined equivalence margin. The secondary endpoints were comparable between the two treatment groups., Conclusion: The reported efficacy, PK, PD, safety, and immunogenicity data support the biosimilarity of SB16 to DEN., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Cancer-associated cognitive decline may result in difficulties in maintaining daily life activities for older patients with cancer. It is, therefore, critical to identify changes in cognitive function throughout illness trajectories., Aim: To determine the longitudinal patterns and factors associated with cognitive function among older cancer survivors., Methods: A secondary analysis was conducted using data from the 2012 to 2020 Korean Longitudinal Study of Aging database. A total of 207 cancer survivors aged 60 years and above were included in the analysis. Latent class growth modeling was employed to identify the trajectories of self-reported cognitive function, and logistic regression analysis was used to identify factors associated with these trajectories., Results: The cognitive function of older adults with cancer was divided into 2 distinct trajectories, characterized by differences in intercept (8) and slope (0.7): the "low and declining class" and the "high and sustainable class." The proportion of individuals belonging to the "high and sustainable class" (n = 153, 73.9%) was significantly and considerably higher than those in the "low and declining class" (n = 54, 26.1%). Individuals with low and declining cognitive function were more likely to be older, have a lower education level, live in rural areas, have poor handgrip strength, experience depression, and have lower social participation compared to those with high and sustainable cognitive function., Conclusions: Our findings can help health care professionals develop tailored interventions for older cancer survivors with low cognitive function based on their physical and mental health status, as well as their environmental backgrounds., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types., Methods: This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene., Results: SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31-0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42-0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42-0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70-1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects., Conclusion: SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.

The liver has a unique ability to regenerate in response to injury or disease with hepatocytes and biliary epithelial cells (BECs) driving the regenerative response. Liver progenitor cells (LPCs) also play role in regeneration with the ability to differentiate into either hepatocytes or BECs. However, during chronic liver disease, the regenerative capacity of the liver is impaired. The use of LPCs is a promising therapeutic strategy for patients with chronic liver diseases. LPCs can be expanded in vitro as self-renewing organoids, however, most approaches to LPC organoids do not include critical cells from the LPC niche in 3D organoid cultures. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche, in supporting the hepatobiliary organoids in long-term culture even in the absence of defined growth supplements, such as Wnt agonists. Furthermore, LiECs alter the gene expression profile of hepatobiliary organoids involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine manner. Our findings expand the role of LiECs for regulating stemness of LPCs and elucidate a role for niche cells in a LPC organoid co-culture model with a reduction in growth supplements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This comprehensive review critically examines the detrimental impacts of endocrine-disrupting chemicals (EDCs) on bone health, with a specific focus on substances such as bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, and dioxins. These EDCs, by interfering with the endocrine system's normal functioning, pose a significant risk to bone metabolism, potentially leading to a heightened susceptibility to bone-related disorders and diseases. Notably, BPA has been shown to inhibit the differentiation of osteoblasts and promote the apoptosis of osteoblasts, which results in altered bone turnover status. PFASs, known for their environmental persistence and ability to bioaccumulate in the human body, have been linked to an increased osteoporosis risk. Similarly, phthalates, which are widely used in the production of plastics, have been associated with adverse bone health outcomes, showing an inverse relationship between phthalate exposure and bone mineral density. Dioxins present a more complex picture, with research findings suggesting both potential benefits and adverse effects on bone structure and density, depending on factors such as the timing and level of exposure. This review underscores the urgent need for further research to better understand the specific pathways through which EDCs affect bone health and to develop targeted strategies for mitigating their potentially harmful impacts.

Introduction: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice., Methods: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety., Results: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m 2 , glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks., Conclusion: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function., Trial Registration Number: NCT05107063 submitted October 27, 2021., (© 2024. The Author(s).)

Objective: We aim to investigate the association between bone mineral density (BMD) measurement and fragility fractures and assess the predictive value of combining BMD measurement and frailty for fracture risk assessment., Methods: This retrospective cohort study analyzed data from 5126 rural Koreans in the Chungju Metabolic Disease Cohort study. Frailty was defined using Fried's frailty phenotype. Fractures were assessed via structured medical interviews. Adjusted odds ratios (ORs) were calculated considering age, sex, body mass index, behavior, BMD, handgrip strength, medications, and comorbidities., Results: The study cohort consisted of 5126 participants comprising 1955 (38.1%) males and 3171 (61.9%) females. Osteoporosis significantly increased the fracture risk across all types, except vertebral fracture, with adjusted OR (95% CI) of 1.89 (1.23-3.47) for any fracture, 2.05 (1.37-2.98) for hip fracture, 2.18 (1.06-4.50) for other fracture, and 1.71 (1.03-3.63) for major osteoporotic fracture (MOF). Frail individuals exhibited significantly increased risk for any fracture (OR 2.12; 95% CI, 1.21-3.71), vertebral fracture (2.48; 1.84-3.61), hip fracture (2.52; 1.09-3.21), other fracture (2.82; 1.19-8.53), and MOF (1.87; 1.01-3.47). The combination of frailty and BMD further increased the risks, with frail individuals demonstrating elevated ORs across BMD categories. In subgroup analyses, men showed a significant association between frailty with osteoporosis in hip fracture and MOF. Frail women with osteoporosis exhibited the highest risks for all fractures, particularly vertebral (OR 5.12; 95% CI, 2.07-9.68) and MOF (OR 5.19; 95% CI, 2.07-6.61). Age-specific analysis revealed that individuals aged 70 and older exhibited markedly higher fracture risks compared with those under 70. The combination of frailty and low BMD further elevated the fracture risk. Frailty was applied with BMD and demonstrated superior risk prediction for MOF compared with that with either score alone (area under the curve 0.825; P = .000)., Conclusions: Combining frailty with BMD provides a more accurate fracture risk assessment for individuals over 50 years., Competing Interests: Conflict of interest: The authors have no conflicts of interest to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com 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 journals.permissions@oup.com.)

Aims: To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI)., Materials and Methods: We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching., Results: During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI., Conclusions: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: Despite improvements in multiple myeloma (MM) survival rates, data on cardiovascular outcomes in long-term survivors remain lacking., Methods: This retrospective case-control study utilized the Korean National Health Insurance Service database (2009-2020) to compare the incidence of cardiovascular disease (CVD) between patients with MM and a matched control group, focusing on long-term (> 5 years) survivors. A preliminary case cohort (n = 15,402 patients with MM) and a matched control cohort (n = 123,216 patients without MM) were established based on birth year and sex. Following 1:1 propensity score matching, the final matched cohorts each comprised 15,402 participants., Results: The case and control cohorts were comparable in mean age (66.2 ± 11.5 years vs. 66.1 ± 11.3 years), sex, age distribution, and comorbidities. By the 8-year follow-up, the cumulative incidence of CV events (12.5% vs. 22.1%) and CVD risk were significantly lower in the case cohort. The 5-year landmark analysis revealed significant differences in CVD incidence between the cohorts (7.8% [case cohort] vs. 9.8% [control cohort]), with variations across age groups and sex, highlighting a significantly higher CVD risk among patients aged < 50 years in the case cohort (P < 0.001)., Conclusions: These findings underscore the need for vigilant CVD monitoring in MM long-term survivors, particularly those aged < 50 years at first diagnosis., Implication for Cancer Survivors: This study highlights the importance of integrating cardiovascular monitoring and risk management into long-term care for MM survivors, with a focus on younger patients and personalized interventions., (© 2024. The Author(s).)

Plants being sessile are exposed to different environmental challenges and consequent stresses associated with them. With the prerequisite of minerals for growth and development, they coordinate their mobilization from the soil through their roots. Phosphorus (P) and iron (Fe) are macro- and micronutrient; P serves as an important component of biological macromolecules, besides driving major cellular processes, including photosynthesis and respiration, and Fe performs the function as a cofactor for enzymes of vital metabolic pathways. These minerals help in maintaining plant vigor via alterations in the pH, nutrient content, release of exudates at the root surface, changing dynamics of root microbial population, and modulation of the activity of redox enzymes. Despite this, their low solubility and relative immobilization in soil make them inaccessible for utilization by plants. Moreover, plants have evolved distinct mechanisms to cope with these stresses and coregulate the levels of minerals (Fe, P, etc.) toward the maintenance of homeostasis. The present study aims at examining the uptake mechanisms of Fe and P, and their translocation, storage, and role in executing different cellular processes in plants. It also summarizes the toxicological aspects of these minerals in terms of their effects on germination, nutrient uptake, plant-water relationship, and overall yield. Considered as an important and indispensable component of sustainable agriculture, a separate section covers the current knowledge on the cross-talk between Fe and P and integrates complete and balanced information of their effect on plant hormone levels.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes life-threatening and persistent infections in immunocompromised patients. It is the culprit behind a variety of hospital-acquired infections owing to its multiple tolerance mechanisms against antibiotics and disinfectants. Biofilms are sessile microbial aggregates that are formed as a result of the cooperation and competition between microbial cells encased in a self-produced matrix comprised of extracellular polymeric constituents that trigger surface adhesion and microbial aggregation. Bacteria in biofilms exhibit unique features that are quite different from planktonic bacteria, such as high resistance to antibacterial agents and host immunity. Biofilms of P. aeruginosa are difficult to eradicate due to intrinsic, acquired, and adaptive resistance mechanisms. Consequently, innovative approaches to combat biofilms are the focus of the current research. Nanocomposites, composed of two or more different types of nanoparticles, have diverse therapeutic applications owing to their unique physicochemical properties. They are emerging multifunctional nanoformulations that combine the desired features of the different elements to obtain the highest functionality. This review assesses the recent advances of nanocomposites, including metal-, metal oxide-, polymer-, carbon-, hydrogel/cryogel-, and metal organic framework-based nanocomposites for the eradication of P. aeruginosa biofilms. The characteristics and virulence mechanisms of P. aeruginosa biofilms, as well as their devastating impact and economic burden are discussed. Future research addressing the potential use of nanocomposites as innovative anti-biofilm agents is emphasized. Utilization of nanocomposites safely and effectively should be further strengthened to confirm the safety aspects of their application., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The present article describes the muscle relaxant and antipyretic effects of pentacyclic triterpenes, oleanolic acid ( OA ), ursolic acid ( UA ) and betulinic acid ( BA ) isolated from roots of Diospyros lotus in animal models. The muscle relaxant effects of isolated pentacyclic triterpenes were determined by chimney and inclined plane tests. In the chimney test, pretreatment of pentacyclic triterpenes evoked significant dose dependent influence on muscle coordination. When administered intraperitoneally (i.p.) to mice at 10 mg/kg for 90 min, OA , UA , and BA exhibited muscle relaxant effects of 66.72 %, 60.21 %, and 50.77 %, respectively. Similarly, OA , UA, and BA (at 10 mg/kg) illustrated 65.74 %, 59.84 % and 51.40 % muscle relaxant effects in the inclined plane test. In the antipyretic test, significant amelioration was caused by pretreatment of all compounds in dose dependent manner. OA , UA, and BA (at 5 mg/kg) showed 39.32 %, 34.32 % and 29.99 % anti-hyperthermic effects, respectively 4 h post-treatment, while at 10 mg/kg, OA , UA, and BA exhibited 71.59 %, 60.99 % and 52.44 % impact, respectively. The muscle relaxant effect of benzodiazepines is well known for enhancement of GABA receptors. There may exist a similar mechanism for muscle relaxant effect of pentacyclic triterpenes. The in-silico predicted binding pattern of all the compounds reflects good affinity of compounds with GABA A receptor and COX-2. These results indicate that the muscle relaxant and antipyretic activities of these molecules can be further improved by structural optimization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Authors Ajmal Khan and Sobia Ahsan Halim are working as associate editor in section “Pharmaceutical Sciences” of this journal., (© 2024 The Authors.)

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of -8.5, -8.3, and -8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein-ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes.

The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis (VL), a potentially fatal disease if left untreated. Given the limitations of current therapies, there is an urgent need for new, safe, and effective drugs. To discover novel antileishmanial compounds from previously unexplored chemical spaces, we conducted a high-throughput screening (HTS) of 2562 natural compounds, assessing their activity against L. donovani promastigotes and intracellular amastigotes. Utilizing the criteria of ≥70% parasite growth inhibition and ≥70% host cell (THP-1) viability, we selected 100 inhibitors for half-maximal inhibitory concentration (IC 50 ) value determination. Twenty-six compounds showed activities in both forms of Leishmania with a selectivity index of over 3. Clustering analysis resulted in four chemical clusters with scaffolds of lycorine (cluster 1), 5-hydroxy-9,10-dihydro-4 H ,8 H -pyrano[2,3- f ]chromene-4,8-dione (cluster 2), and semi-synthetic derivatives of ansamycin macrolide (cluster 4). The enantiomer of lycorine, BMD-NP-00820, showed the highest anti-amastigote activity with an IC 50 value of 1.74 ± 0.27 μM and a selectivity index (SI) > 29. In cluster 3, the most potent compound had an IC 50 value of 2.20 ± 0.29 μM with an SI > 23, whereas in cluster 4, with compounds structurally similar to the tuberculosis drug rifapentine, BMD-NP-02085 had an IC 50 value of 1.76 ± 0.28 μM, but the SI value was 7.5. Taken together, the natural products identified from this study are a potential source for the discovery of antileishmanial chemotypes for further development.

Accumulating data suggest that ribosomal protein S6 kinase 1 (S6K1), an effector in the mammalian target of rapamycin (mTOR) pathway, plays pleiotropic roles in tumor progression. However, to date, while the tumorigenic function of S6K1 in tumor cells has been well elucidated, its role in the tumor stroma remains poorly understood. We recently showed that S6K1 mediates vascular endothelial growth factor A (VEGF-A) production in macrophages, thereby supporting tumor angiogenesis and growth. As macrophage-derived VEGF-A is crucial for both tumor cell intravasation and extravasation across the vascular endothelium, our previous findings suggest that stromal S6K1 signaling is required for tumor metastatic spread. Therefore, we aimed to determine the impact of host S6K1 depletion on tumor metastasis using a murine model of pulmonary metastasis (S6k1 -/- mice implanted with B16F10 melanoma). The ablation of S6K1 in the host microenvironment significantly reduced the metastasized B16F10 melanoma cells on the lung surface in both spontaneous and intravenous lung metastasis mouse models without affecting the incidence of metastasis to distant lymph nodes. In addition, stromal S6K1 loss decreased the number of tumor cells circulating in the peripheral blood of mice bearing B16F10 xenografts without affecting the vascular leakage induced by VEGF-A in vivo. These observations demonstrate that S6K1 signaling in host cells other than endothelial cells is required to modulate the host microenvironment to facilitate the metastatic spread of tumors via blood circulation, thus revealing its novel role in the tumor stroma during tumor progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The adverse effects of waste generation on the environment and public health have raised global concerns. The utilization of waste as a raw material to develop products with enhanced value has opened up novel prospects for promoting environmental sustainability. Biosurfactants obtained from agro-industrial waste are noteworthy due to their sustainability and environmental friendliness. Microorganisms have been employed to generate biosurfactants as secondary metabolites by making use of waste streams. The utilization of garbage as a substrate significantly reduces the expenses associated with the process. Furthermore, apart from reducing waste and offering alternatives to artificial surfactants, they are extensively employed in bioremediation, food processing, agriculture, and various other industrial pursuits. Bioremediation of heavy metals and other metallic pollutants mitigated through the use of bacteria that produce biosurfactants which has been the more recent research area with the aim of improving its quality and environmental safety. Moreover, the production of biosurfactants utilizing agricultural waste as a raw material aligns with the principles of waste minimization, environmental sustainability, and the circular economy. This review primarily focuses on the production process and various types of biosurfactants obtained from waste biomass and feedstocks. The subsequent discourse entails the production of biosurfactants derived from various waste streams, specifically agro-industrial waste., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sundaram, Govindarajan, Vinayagam, Krishnan, Nagarajan, Gnanasekaran, Baek and Rajamani Sekar.)

Aims: We aimed to investigate weight change in patients with new-onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults., Materials and Methods: We used the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication., Results: In total, 114, 874 patients with new-onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35-2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25., Conclusion: Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new-onset type 2 diabetes mellitus, particularly for young and obese individuals., (© 2023 John Wiley & Sons Ltd.)

Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e.g., HSP10 and HSP27), HSP40, HSP60, HSP70, HSP90, and the category of large HSPs that include HSP100 and ClpB proteins. The overexpression of HSPs is induced to counteract cell stress at elevated levels in a variety of solid tumors, including anticancer chemotherapy, and is closely related to a worse prognosis and therapeutic resistance to cancer cells. HSPs are also involved in anti-apoptotic properties and are associated with processes of cancer progression and development, such as metastasis, invasion, and cell proliferation. This review outlines the previously mentioned HSPs and their significant involvement in diverse mechanisms of tumor advancement and metastasis, as well as their contribution to identifying potential targets for therapeutic interventions.

Background: Insurance reimbursement provisions in South Korea limit osteoporosis medication availability for patients with T-scores exceeding - 2.5. This study aimed to evaluate the financial impact and fracture prevention of continuous denosumab therapy until a T-score>-2.0 (Dmab-C strategy), versus discontinuation of denosumab after reaching T-score>-2.5 (Dmab-D strategy) in osteoporosis patients., Methods: A cost-consequence analysis from a Korean healthcare system perspective was performed using a newly developed Markov model. The incidence of vertebral and non-vertebral fracture, fracture-related deaths, drug costs, and fracture-treatment costs were estimated and compared between Dmab-C and Dmab-D strategy over a lifetime in eligible patients aged 55 years., Results: Base-case analysis revealed that Dmab-C prevented 32.21 vertebral fracture (VF) and 12.43 non-VF events per 100 patients over a lifetime, while reducing 1.29 fracture-related deaths. Lifetime direct healthcare cost saving per patient was KRW 1,354,655 if Dmab-C replaces Dmab-D. When productivity losses were considered, Dmab-C saved KRW 29,025,949 per patient compared to Dmab-D. The additional treatment costs of Dmab-C could be offset by the higher subsequent treatment costs and fracture treatment costs of Dmab-D. The sensitivity analysis showed consistent patterns with results of the base-case analysis., Conclusion: Continuous treatment using denosumab until osteoporosis patients achieve and maintain a T-score of -2.0 would provide greater clinical and economic benefits in terms of fracture prevention and reduced mortality risks compared to outcomes from discontinuing treatment at a T-score of -2.5 or above. This new treatment strategy would effectively lower the risk of fractures and fracture-related mortality, ultimately leading to lower medical expenses., (© 2024. The Author(s).)

Aim: This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults., Materials and Methods: In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points., Results: The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores., Conclusions: Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults., (© 2023 John Wiley & Sons Ltd.)

Lactic acid, gallic acid, and their mixture (1% each) were prepared (LA, GA, and LGA) and plasma-activated organic acids (PAOA) were produced through exposure to plasma for 1 h (PAL, PAG, and PLGA). Chicken breast and drumstick were immersed in the prepared solutions for 10 min and analyzed their antibacterial effect against Salmonella Typhimurium and Campylobacter jejuni and antioxidant activity during 12 d of storage. As a result, PAOA inactivated approximately 6.37 log CFU/mL against S. Typhimurium and 2.76, 1.86, and 3.04 log CFU/mL against C. jejuni (PAL, PAG, and PLGA, respectively). Moreover, PAOA had bactericidal effect in both chicken parts inoculated with pathogens, with PAL and PLGA displaying higher antibacterial activity compared to PAG. Meanwhile, PAOA inhibited lipid oxidation in chicken meats, and PAG and PLGA had higher oxidative stability during storage compared to PAL. This can be attributed to the superior antioxidant properties of GA and LGA, including higher total phenolic contents, ABTS + reducing activity, and DPPH radical scavenging activity, when compared to LA. In particular, when combined with plasma treatment, LGA showed the greatest improvement in antioxidant activity compared to other organic acids. In summary, PLGA not only had a synergistic bactericidal effect against pathogens on chicken, but also improved oxidative stability during storage. Therefore, PLGA can be an effective method for controlling microorganisms without adverse effect on lipid oxidation for different chicken cuts., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Conformational restriction was addressed towards the development of more selective and effective antileishmanial agents than currently used drugs for treatment of Leishmania donovani; the causative parasite of the fatal visceral leishmaniasis. Five types of cyclopentane-based conformationally restricted miltefosine analogs that were previously explored in literature as anticancer AKT-inhibitors were reprepared and repurposed as antileishmanial agents. Amongst, positions-1 and 2 cis-conformationally-restricted compound 1a and positions-2 and 3 trans-conformationally-restricted compound 3b were highly potent eliciting sub-micromolar IC 50 values for inhibition of infection and inhibition of parasite number compared with the currently used miltefosine drug that showed low micromolar IC 50 values for inhibition of infection and inhibition of parasite number. Compounds 1a and 3b eradicated the parasite without triggering host cells cytotoxicity over more than one log concentration interval which is a superior performance compared to miltefosine. In silico studies suggested that conformational restriction conserved the conformer capable of binding LdAKT-like kinase while it might be possible that it excludes other conformers mediating undesirable effects and/or toxicity of miltefosine. Together, this study presents compounds 1a and 3b as antileishmanial agents with superior performance over the currently used miltefosine drug., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pharmaceutical companies are investigating more source matrices for natural bioactive chemicals. Friedelin (friedelan-3-one) is a pentacyclic triterpene isolated from various plant species from different families as well as mosses and lichen. The fundamental compounds of these friedelane triterpenoids are abundantly found in cork tissues and leaf materials of diverse plant genera such as Celastraceae, Asteraceae, Fabaceae, and Myrtaceae. They possess many pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. Friedelin also has an anti-insect effect and the ability to alter the soil microbial ecology, making it vital to agriculture. Ultrasound, microwave, supercritical fluid, ionic liquid, and acid hydrolysis extract friedelin with reduced environmental impact. Recently, the high demand for friedelin has led to the development of CRISPR/Cas9 technology and gene overexpression plasmids to produce friedelin using genetically engineered yeast. Friedelin with low cytotoxicity to normal cells can be the best phytochemical for the drug of choice. The review summarizes the structural interpretation, biosynthesis, physicochemical properties, quantification, and various forms of pharmacological significance.

Rice ( Oryza sativa L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in domesticated rice. Ensuring high and constant rice production is vital to facilitating human food supplies, as over three billion people around the globe rely on rice as their primary source of dietary intake. However, the world's rice production and grain quality have drastically declined in recent years due to the challenges posed by global climate change and abiotic stress-related aspects, especially drought, heat, cold, salt, submergence, and heavy metal toxicity. Rice's reduced photosynthetic efficiency results from insufficient stomatal conductance and natural damage to thylakoids and chloroplasts brought on by abiotic stressor-induced chlorosis and leaf wilting. Abiotic stress in rice farming can also cause complications with redox homeostasis, membrane peroxidation, lower seed germination, a drop in fresh and dry weight, necrosis, and tissue damage. Frequent stomatal movements, leaf rolling, generation of reactive oxygen radicals (RORs), antioxidant enzymes, induction of stress-responsive enzymes and protein-repair mechanisms, production of osmolytes, development of ion transporters, detoxifications, etc., are recorded as potent morphological, biochemical and physiological responses of rice plants under adverse abiotic stress. To develop cultivars that can withstand multiple abiotic challenges, it is necessary to understand the molecular and physiological mechanisms that contribute to the deterioration of rice quality under multiple abiotic stresses. The present review highlights the strategic defense mechanisms rice plants adopt to combat abiotic stressors that substantially affect the fundamental morphological, biochemical, and physiological mechanisms.

Mungbean is known to be susceptible to waterlogging (WL) stress. Some of the wild species have the potential to tolerate this through various physiological and molecular mechanisms. Auxin Response Factor (ARF) and Auxin/Indole Acetic Acid (AUX/IAA), an early responsive gene family, has multiple functions in growth, development, and stress tolerance. Here, we report the first comprehensive analysis of the ARF and AUX/IAA gene family in mungbean. A total of 26 ARF and 19 AUX/IAA genes were identified from the mungbean genome. The ARF and AUX/IAA candidates were clearly grouped into two major clades. Further, the subgrouping within the major clades indicated the presence of significant diversity. The gene structure, motif analysis, and protein characterization provided the clue for further fundamental research. Out of the10 selected candidate genes, VrARF-5 , VrARF-11 , VrARF-25 , and VrAUX/IAA-9 were found to significantly multiple-fold gene expression in the hypocotyl region of WL-tolerant wild relatives (PRR 2008-2) provides new insight into a role in the induction of lateral root formation under WL stress. The analysis provides an insight into the structural diversity of ARF and AUX/IAA genes in mungbean. These results increase our understanding of ARF and AUX/IAA genes and therefore offer robust information for functional investigations, which can be taken up in the future and will form a foundation for improving tolerance against waterlogging stress.

Objective: We aimed to investigate the associations of body composition and the risk of fracture in postmenopausal women, stratified based on bone mineral density., Methods: A population-based cohort study using the database of the National Screening Program for Transitional Ages with women aged 66 years was performed. Bone mineral density was categorized as normal, osteopenia, and osteoporosis. The following body mass index (BMI) categories for general obesity were used: underweight (<18.5), normal (18.5-22.9), overweight (23-24.9), obese (25-29.9), and severely obese (≥30 kg/m2). Waist circumference (WC) used for central obesity assessment was categorized into 5 groups. Newly diagnosed fracture during the follow-up period defined based on ICD-10 codes was the primary outcome., Results: During 7.7 ± 1.4 years of follow-up, 41 672 (17.9%) participants experienced any fracture, 20 326 (8.7%) experienced vertebral fractures (VFs), and 2883 (1.2%) experienced hip fractures (HFs). The adjusted hazard ratios (aHRs) for any fracture showed a progressive increase with higher BMI and WC categories in individual with osteopenia and osteoporosis. Regarding VF, aHR was highest in severely obese individuals with osteoporosis (aHR [95% CI], 3.45 [2.99-3.97]) and in individuals with WC ≥ 95 cm with osteoporosis (4.79 [4.09-5.60]). The aHR [95% CI] for HF was highest in the underweight group with osteopenia (1.94 [1.16-3.27]) and osteoporosis (2.96 [2.15-4.10]). In central obesity individuals with WC ≥ 95 cm, aHR [95% CI] for HF was 2.80 [1.91-4.91]., Conclusions: General obesity and central obesity are not protective against any fracture, VF and HF in postmenopausal women with osteopenia or osteoporosis., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The side effects and safety issues tied to calcium supplementation raise questions about its necessity in osteoporosis treatment. We retrospectively evaluated 189 postmenopausal osteoporosis patients treated with denosumab for 12 months. Patients exhibited neither renal dysfunction nor compromised general dietary intake. Patients were divided into three groups as follows: group A, weekly vitamin D 7000 IU; group B, daily vitamin D 1000 IU with elemental calcium 100 mg; and group C, daily vitamin D 1000 IU with elemental calcium 500 mg. All groups showed significant increases in bone density: +6.4 ± 4.7% for the lumbar spine, +2.2 ± 3.5% for the femoral neck, and +2.4 ± 3.8% for the total hip in group A; +7.0 ± 10.9% for the lumbar spine, +2.3 ± 5.2% for the femoral neck, and +2.4 ± 3.8% for the total hip in group B; and + 6.7 ± 8.7% for the lumbar spine, +2.5 ± 8.4% for the femoral neck, and +2.3 ± 4.0% for the total hip in group C. Serum calcium levels increased over time in all three groups with no significant difference. Changes in CTX and P1NP levels did not differ between the groups (all p > 0.05). With regular dietary intake, calcium supplementation levels showed no significant effect on bone density, bone marker changes, or hypocalcemia incidence during denosumab treatment.

The ubiquitin-proteasome system (UPS) is an essential protein quality controller for regulating protein homeostasis and autophagy. Ubiquitination is a protein modification process that involves the binding of one or more ubiquitins to substrates through a series of enzymatic processes. These include ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Conversely, deubiquitination is a reverse process that removes ubiquitin from substrates via deubiquitinating enzymes (DUBs). Dysregulation of ubiquitination-related enzymes can lead to various human diseases, including cancer, through the modulation of protein ubiquitination. The most structurally and functionally studied DUB is the ubiquitin-specific protease 7 (USP7). Both the TRAF and UBL domains of USP7 are known to bind to the [P/A/E]-X-X-S or K-X-X-X-K motif of substrates. USP7 has been shown to be involved in cancer pathogenesis by binding with numerous substrates. Recently, a novel substrate of USP7 was discovered through a systemic analysis of its binding motif. This review summarizes the currently discovered substrates and cellular functions of USP7 in cancer and suggests putative substrates of USP7 through a comprehensive systemic analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In a previous study, we investigated the effects of high-temperature requirement factor A4 (HtrA4) deficiency on trophoblasts using the BeWo KO cell line. However, the effects of this deficiency on angiogenesis remain unclear. To explore the role of HtrA4 in angiogenesis, HUVECs were co-cultured with wild-type BeWo cells (BeWo WT), BeWo KO, and HtrA4-rescued BeWo KO (BeWo KO-HtrA4 rescue) cells. Dil staining and dextran analysis revealed that HUVECs co-cultured with BeWo KO formed tubes, but they were often disjointed compared to those co-cultured with BeWo WT, BeWo KO-HtrA4 rescue, and HUVECs controls. RT-PCR, ELISA, and western blot analysis were performed to assess angiogenesis-related factors at the mRNA and protein levels. HtrA4 deficiency inhibited IL-6 expression in trophoblasts, and the reduced secretion of IL-6 decreases VEGFA expression in HUVECs by modulating the JAK2/STAT3 signaling pathway to prevent tube formation. Moreover, rescuing HtrA4 expression restored the HUVEC tube formation ability. Interestingly, IL-6 expression was lower in supernatants with only cultured HUVECs than in co-cultured HUVECs with BeWo WT cells, but the HUVEC tube formation ability was similar. These findings suggest that the promoting angiogenesis-related signaling pathway differs between only HUVECs and co-cultured HUVECs, and that the deficiency of HtrA4 weakens the activation of the IL-6/JAK/STAT3/VEGFA signaling pathway, reducing the ability of tube formation in HUVECs. HtrA4 deficiency in trophoblasts hinders angiogenesis and may contribute to placental dysfunction., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)