Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

Exposure to Short- and Medium-Chain Chlorinated Paraffins and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study in Eastern China.

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group (p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL (p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C13H23Cl5 and C10H16Cl6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

Deterministic factors modulating assembly of groundwater microbial community in a nitrogen-contaminated and hydraulically-connected river-lake-floodplain ecosystem.

The river-lake-floodplain system (RLFS) undergoes intensive surface-groundwater mass and energy exchanges. Some freshwater lakes are groundwater flow-through systems, serving as sinks for nitrogen (N) entering the lake. Despite the threat of cross-nitrogen contamination, the assembly of the microbial communities in the RLFS was poorly understood. Herein, the distribution, co-occurrence, and assembly pattern of microbial community were investigated in a nitrogen-contaminated and hydraulically-connected RLFS. The results showed that nitrate was widely distributed with greater accumulation on the south than on the north side, and ammonia was accumulated in the groundwater discharge area (estuary and lakeshore). The heterotrophic nitrifying bacteria and aerobic denitrifying bacteria were distributed across the entire area. In estuary and lakeshore with low levels of oxidation-reduction potential (ORP) and high levels of total organic carbon (TOC) and ammonia, dissimilatory nitrate reduction to ammonium (DNRA) bacteria were enriched. The bacterial community had close cooperative relationships, and keystone taxa harbored nitrate reduction potentials. Combined with multivariable statistics and self-organizing map (SOM) results, ammonia, TOC, and ORP acted as drivers in the spatial evolution of the bacterial community, coincidence with the predominant deterministic processes and unique niche breadth for microbial assembly. This study provides novel insight into the traits and assembly of bacterial communities and potential nitrogen cycling capacities in RLFS groundwater.

Nuclear Factor Kappa B Promotes Ferritin Heavy Chain Expression in Bombyx mori in Response to B. mori Nucleopolyhedrovirus Infection.

Ferritin heavy chain (FerHCH) is a major component of ferritin and plays an important role in maintaining iron homeostasis and redox equilibrium. Our previous studies have demonstrated that the Bombyx mori ferritin heavy chain homolog (BmFerHCH) could respond to B. mori nucleopolyhedrovirus (BmNPV) infection. However, the mechanism by which BmNPV regulates the expression of BmFerHCH remains unclear. In this study, BmFerHCH increased after BmNPV infection and BmNPV infection enhanced nuclear factor kappa B (NF-κB) activity in BmN cells. An NF-κB inhibitor (PDTC) reduced the expression of the virus-induced BmFerHCH in BmN cells, and overexpression of BmRelish (NF-κB) increased the expression of virus-induced BmFerHCH in BmN cells. Furthermore, BmNPV infection enhanced BmFerHCH promoter activity. The potential NF-κB cis-regulatory elements (CREs) in the BmFerHCH promoter were screened by using the JASPAR CORE database, and two effective NF-κB CREs were identified using a dual luciferase reporting system and electrophoretic mobility shift assay (EMSA). BmRelish (NF-κB) bound to NF-κB CREs and promoted the transcription of BmFerHCH. Taken together, BmNPV promotes activation of BmRelish (NF-κB), and activated BmRelish (NF-κB) binds to NF-κB CREs of BmFerHCH promoter to enhance BmFerHCH expression. Our study provides a foundation for future research on the function of BmFerHCH in BmNPV infection.

Core-Shell Plasmonic Nanomaterials toward: Dual-Mode Imaging Analysis of Glutathione and Enhanced Chemodynamic Therapy.

A simple process, rich information, and intelligent response are the goals pursued by cancer diagnosis and treatment. Herein, we developed a core-shell plasmonic nanomaterial (Au@MnO2-DNA), which consisted of a AuNP core with an outer shell MnO2 nanosheet decorated with fluorophore modified DNA, to achieve the aforementioned aims. On the basis of the unique optical properties of plasmonic nanoparticles and the oxidability of the shell MnO2, scattering signal and fluorescence (FL) signal changes were both related to the expression level of glutathione (GSH), for which a dual-mode imaging analysis was successfully achieved on single optical microscope equipment with one-key switching. Meanwhile, the product of Mn2+ from the reaction between MnO2 and GSH not only served as a smart chemodynamic agent to initiate Fenton-like reaction for achieving chemodynamic therapy (CDT) of cancer cells but also relieved the side effect of intracellular GSH in cancer therapy. Therefore, the core-shell plasmonic nanomaterials with dual modal switching features and diagnostic properties act as excellent probes for achieving bioanalysis of aberrant levels of intracellular GSH and simultaneously activating the CDT of cancer cells based on the in situ reactions in cancer cells.

CS-CNTs homojunctions prepared byin situgrowth of carbon nanotubes on the surface of porous carbon spheres for lithium-sulfur batteries.

Lithium-sulfur battery is expected to become a new generation of commercial battery owing to its ultra-high theoretical specific capacity, low-cost, and environmental benign. However, the inherent insulation of sulfur and the shuttle effect of lithium polysulfide between electrodes limit the application of lithium-sulfur battery. In order to solve these problems, we focus on the design of carbon-sulfur composite structure. Herein, CS-CNTs homojunctions featured with the carbon nanotubes (CNTs)in situgrown on carbon sphere (CS) is designed and synthesized by simple polymerization and heat treatment. The composites of CS with interconnected pore networks and CNTs with high conductivity not only offer a conductive framework to promote fast electron transmission, but also provide a larger space to load sulfur and effectively capture polysulfides. The CS-CNTs@S cathode shows better electrochemical performance compared with CS-CPs@S and CS@S. The first discharge specific capacity is 1053 mAh g-1at 0.1 C. After 200 cycles, the specific capacity still remains at 427 mAh g-1.

Analysis for interaction between interleukin-35 genes polymorphisms and risk factors on susceptibility to coronary heart disease in the Chinese Han population.

BACKGROUND: The relationship between IL-35 genes polymorphism and susceptibility to coronary heart disease has not been tested in the largest Han population in China. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) of interleukin-35 (IL-35) genes and its relationship with environment on the risk of coronary heart disease (CHD). METHODS: We performed Hardy-Weinberg equilibrium test on the control group. The relationship between the four SNPs of IL-35 genes and the risk of coronary heart disease was studied by multivariate logistic regression. The best interaction was identified with generalized multifactor dimensionality reduction (GMDR). Logistic regression was used for investigation on association between four SNPs and CHD risk. RESULTS: Logistic regression analysis showed that the C allele of rs428253 and the G allele of rs2243115 were independently correlated with increased risk of CHD, and adjusted ORs (95% CI) were 1.91 (1.28-2.64) and 1.80 (1.30-2.23), respectively. However, there was no significant association between CHD and rs4740 or rs568408. GMDR model indicated a best model for CHD risk consisted of rs428253 and current smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.010). Therefore, this overall multi-dimensional model had the highest cross-validation consistency, regardless of how the data were divided. This provided an evidence of gene-environment interaction effects. We also found that current smokers with rs428253-GC/CC genotype have the highest CHD risk, compared to never smokers with rs428253-GG genotype, OR (95% CI) = 3.04 (1.71-4.41), after adjustment for age, gender, hypertension, T2DM and alcohol consumption status. CONCLUSIONS: In this study, the C allele of rs428253 and the G allele of rs2243115, and the interaction rs428253 and current smoking were correlated with increased risk of CHD.

PRMT5 and FOXP1 expression profile in invasive breast cancer patients undergoing neoadjuvant chemotherapy.

Neoadjuvant chemotherapy is the standard treatment for patients with advanced localized breast cancer, but today it has found a good place in the early stages to achieve a negative surgical margin and increase the possibility of breast preservation. Numerous studies have shown that patient survival increases with a complete pathological response in the relationship of some immunological molecules known as immunohistochemistry markers. The aim of this study was to investigate the complete pathological response in the relationship between PRMT5 and FOXP1 expression. In a cross-sectional study of breast cancer patients in stages I to III, who were treated with Neoadjuvant chemotherapy at the Breast Cancer Research Institute during the years 2018 to 2019, were examined. A complete pathological response was obtained in cases where no tumors remained in the breast and axillary tissue after surgery. Immunohistochemical analyzes for FOXP1, PRMT5, and PR and ER biomarkers of the tumor were conducted. Data were analyzed using descriptive and analytical statistics by SPSS v. 21 software. 157 patients with a mean age of 47.5 ±16.2 years were included in the study. Our results revealed that there was no significant difference between the foxp1 Positive and Negative patients, in terms of cancer stage, metastasis, being PR or ER-positive (P>0.05).  While being PRMT5+/- had a significant relationship with FOXP1 expression (p=0.001). In the case of the response to treatment, there was a significant association between a complete response and being foxp1 + (p=0.01). While in other immunohistochemistry markers, no significant association was found (P>0.05). Our study revealed no association of foxp1 and PRMT5 with other biomarkers of breast cancer and clinical progress of the disease. Our study revealed no association of foxp1 and PRMT5 with other biomarkers of breast cancer and clinical progress of the disease.

Association of genetic variants in lncRNA GAS5/miR-21/mTOR axis with risk and prognosis of coronary artery disease among a Chinese population.

BACKGROUND: Allowing for the significance of single nucleotide polymorphisms (SNPs) in reflecting disease risk, this investigation attempted to uncover whether SNPs situated in lncRNA GAS5/miR-21/mTOR axis were associated with risk and prognosis of coronary heart disease (CHD) among a Chinese Han population. METHODS: Altogether 436 patients with CHD were recruited as cases, and meanwhile, 471 healthy volunteers were included into the control group. Besides, SNPs of GAS5/MIR-21/mTOR axis were genotyped utilizing mass spectrometry. Chi-square test was applied to figure out SNPs that were strongly associated with CHD risk and prognosis, and combined effects of SNPs and environmental parameters on CHD risk were evaluated through multifactor dimensionality reduction (MDR) model. RESULTS: Single nucleotide polymorphisms of GAS5 (ie, rs2067079 and rs6790), MIR-21 (ie, rs1292037), and mTOR (rs2295080, rs2536, and rs1034528) were associated with susceptibility to CHD, and also Gensini score change of patients with CHD (P < .05). MDR results further demonstrated that rs2067079 and rs2536 were strongly interactive in elevating CHD risk (P < .05), while smoking, rs6790 and rs2295080 showed powerful reciprocity in predicting Gensini score change of patients with CHD (P < .05). CONCLUSION: Single nucleotide polymorphisms of lncRNA GAS5/miR-21/mTOR axis might interact with smoking to regulate CHD risk, which was conducive to diagnosis and prognostic anticipation of CHD.

Multicenter biomonitoring of polybrominated diphenyl ethers (PBDEs) in colostrum from China: Body burden profile and risk assessment.

Polybrominated diphenyl ethers (PBDEs) were listed in the Stockholm Convention due to their persistent and toxic nature. In utero exposure to PBDEs might affect fetal development as it is sensitive when exposed to even low dose of xenobiotic substances during the pregnancy. In this study, a multi-centre human biomonitoring study of tri-to hexa-BDEs was conducted in three Chinese cities using 60 colostrum samples from local residents. The patterns and influencing factors, correlation with the birth outcome, and potential health risks during the breastfeeding of tri-to hexa-BDEs in the colostrum samples were assessed. The median concentration of tri-to hexa-BDEs was 9.1 (Interquartile range: 3.1-19.5) ng g-1 lipid weight, and BDE-153 contributed 68% of the detected PBDEs. The PBDE levels were mostly associated with maternal age and drinking water sources, while correlations with other factors including weight gain, BMI, parity and the number of aborted pregnancies was not significant. The level of BDE-28 was positively correlated with the birth weight, while the BDE-99 was positively correlated with the head circumference, using multilinear regression. For the total hazard quotients, 60% of the infants have an estimated value higher than 1, showed potential chronic hazard for future development and possible adverse health effects to the babies from the exposure to PBDE congeners. Alternative food source seems to have a lower risk for neonates than the colostrum, but the advantages of breastfeeding undoubtedly outweigh the risks and potential adverse health effects caused by environmental PBDEs and other xenobiotic chemical exposure.

Toxic effects of chrysoidine on human serum albumin: isothermal titration calorimetry and spectroscopic investigations.

Chrysoidine is widely used in industry as a type of azo dye, and is sometimes used illegally as a food additive despite its potential toxicity. Human serum albumin (HSA) is one of the most important proteins in blood plasma and possesses major physiological functions. In the present study, the conformational and functional effects of chrysoidine on HSA were investigated by isothermal titration calorimetry (ITC), multiple spectroscopic methods, a molecular docking study and an esterase activity assay. Based on the ITC results, the binding stoichiometry of chrysoidine to HSA was estimated to be 1.5:1, and was a spontaneous process via a single hydrogen bond. The binding of chrysoidine to HSA induced dynamic quenching in fluorescence, and changes in secondary structure and in the microenvironment of the Trp-214 residue. In addition, the hydrogen bond (1.80 Å) formed between the chrysoidine molecule and the Gln-211 residue. The esterase activity of HSA decreased following the addition chrysoidine due to the change in protein structure. This study details the direct interaction between chrysoidine and HSA at the molecular level and the mechanism for toxicity as a result of the functional changes induced by HSA structural variation upon binding to chrysoidine in vitro. This study provides useful information towards detailing the transportation mechanism and toxicity of chrysoidine in vivo.

[Advanced glycated albumin induces macrophage apoptosis via activating caspase-12 pathway].

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on the activation of caspase-12, a key molecule in endoplasmic reticulum stress (ERS)-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms of macrophage apoptosis. RAW264.7 macrophages were treated with AGE-alb (2, 4 and 6 g/L), control albumin (C-alb, 4 g/L), tunicamycin (TM, 4 mg/L), or pretreated with 4-phenylbutyric acid (PBA, 5 mmol/L) for 1 h and then treated with AGE-alb (4 g/L). After incubation for 24 h, the cell viability and apoptosis were determined by using MTT assay and TUNEL detection kit, respectively. Lactate dehydrogenase (LDH) activity in media was determined by using an assay kit. The protein levels of caspase-12 were examined by Western blot analysis. The results showed that like TM (an ERS inducer), incubation with AGE-alb led to significant decrease in viability and increase in LDH activity in media and apoptotic rate in a dose-dependent manner. In addition, AGE-alb induced activation of caspase-12 especially at the concentration of 4 and 6 g/L (P < 0.01), which was similar to TM. However, PBA (an ERS inhibitor) protected RAW264.7 macrophages from AGE-alb-induced decrease in viability and increases in LDH activity and apoptosis. Moreover, PBA also inhibited the caspase-12 activation induced by AGE-alb (P < 0.05). These results suggest that AGE-alb may induce apoptosis in RAW 264.7 macrophages, and the mechanism may be related to the activation of ERS-associated apoptotic pathway mediated by caspase-12.

1-Benzyl-4-phenyl-1H-1,2,3-triazoles improve the transcriptional functions of estrogen-related receptor γ and promote the browning of white adipose.

The estrogen-related receptor γ (ERRγ) is a potential molecular target for the development of small molecules to stimulate the adipose browning process, which may represent a novel attractive strategy to treat obesity related disorders. The receptor possesses a very small ligand binding cavity and therefore identification of small molecule ERRγ modulators is a considerable challenge. We have successfully designed and synthesized a series of 1-benzyl-4-phenyl-1H-1,2,3-triazoles and demonstrated that they improve the transcriptional functions of ERRγ, potently elevating both the mRNA levels and the protein levels of ERRγ downstream targets. One of the most promising compounds, 4-(1-(4-iso-propylbenzyl)-1H-1,2,3-triazol-4-yl)benzene-1,2-diol (2e) was further shown to directly bind with the ERRγ ligand binding domain (ERRγ-LBD) in an isothermal calorimetric (ITC) assay and to thermally stabilize ERRγ-LBD protein by increasing its melting temperature (Tm) as demonstrated by circular dichroism (CD) spectroscopy. Furthermore, 2e potently stimulates the adipocyte browning process and induces mitochondrial biogenesis both in vitro and in vivo, suggesting the considerable therapeutic potential of this compound for the treatment of obesity and related disorders.

A Glimpse of Research Trends and Frontiers in the Etiology of Premature Ovarian Insufficiency via Bibliometric Analysis.

INTRODUCTION: Premature Ovarian Insufficiency (POI) is the most common reproductive aging disorder in women of reproductive age, which is characterized by decreased ovarian function in women before the age of 40. Etiology research of POI has garnered interest and attention from scholars worldwide over the past decades. METHOD: However, to the best of our knowledge, no comprehensive survey with bibliometric analysis has been conducted yet on the research trends of POI etiology. This article aimed to analyze current scientific findings on the etiology of POI, offering innovative ideas for further research. Research articles on the etiology of POI from 1994 to 2023 were collected from the Web of Science Core Collection. A total of 456 research articles were included, and the total number of publications increased annually. We used VOSviewer and bibliometric.com to analyze the keywords, terms, institution, publication country/region, author name, publication journal, and the sum of times the articles have been cited. RESULTS: This study has shown that a research hotspot is the genetic etiology of POI; however, there is still a lack of research on the impact of epigenetic alterations, iatrogenic injuries, environmental pollution, social stress, and unhealthy lifestyles on the pathogenesis of POI. CONCLUSION: The factors illustrated here represent potential future directions for POI etiology research and warrant more attention from researchers.

Flavonoids: Potential therapeutic agents for cardiovascular disease.

Flavonoids are found in the roots, stems, leaves, and fruits of many plant taxa. They are related to plant growth and development, pigment formation, and protection against environmental stress. Flavonoids function as antioxidants and exert anti-inflammatory effects in the cardiovascular system by modulating classical inflammatory response pathways, such as the TLR4-NF-ĸB, PI3K-AKT, and Nrf2/HO-1 signalling pathways. There is increasing evidence for the therapeutic effects of flavonoids on hypertension, atherosclerosis, and other diseases. The potential clinical value of flavonoids for diseases of the cardiovascular system has been widely explored. For example, studies have evaluated the roles of flavonoids in the regulation of blood pressure via endothelium-dependent and non-endothelium-dependent pathways and in the regulation of myocardial systolic and diastolic functions by influencing calcium homeostasis and smooth muscle-related protein expression. Flavonoids also have hypoglycaemic, hypolipidemic, anti-platelet, autophagy, and antibacterial effects. In this paper, the role and mechanism of flavonoids in cardiovascular diseases were reviewed in order to provide reference for the clinical application of flavonoids in the future.

Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.

BACKGROUND: Tumor metastasis represents a stepwise progression and stands as a principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration of its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within the tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in tumor metastasis. AIM OF REVIEW: This review systematically explores the roles of CAFs at eight critical stages of tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) tumor metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, and 8) premetastatic niche (PMN) formation. Additionally, we provide a compendium of extant strategies aimed at targeting CAFs in cancer therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review delineates a structured framework for the interplay between CAFs and tumor metastasis while furnishing insights for the potential therapeutic developments. It contributes to a deeper understanding of cancer metastasis within the TME, facilitating the utilization of CAF-targeting therapies in anti-metastatic approaches.

ED-71 ameliorates bone regeneration in type 2 diabetes by reducing ferroptosis in osteoblasts via the HIF1α pathway.

Eldecalcitol (ED-71), a novel active form of vitamin D, shows potential in treating osteoporosis. However, its underlying mechanisms of action remain to be determined. This study aimed to investigate the effect of ED-71 on bone regeneration and to illustrate its mode of action. The in-vitro model was developed using rat primary osteoblasts cultured under high-glucose conditions, and these cells were treated with ED-71. Additionally, an in vivo model of cranial bone defects was established in type 2 diabetic rats, and ED-71 was administered by gavage. The results demonstrated that ED-71 prevented osteoblast cell death, enhanced rat primary osteoblasts' osteogenic capacity, and attenuated the overexpression of hypoxia-inducible factor 1α (HIF1α) induced by high glucose levels. Furthermore, ED-71 increased glutathione peroxidase 4 (GPX4) levels and inhibited ferroptosis in response to hyperglycemic stimulation. Notably, interference with the HIF1α activator and ferroptosis activator Erastin significantly reduced the therapeutic effects of edetate osteolysis. These findings were further tested in vivo experiments. These results suggest that ED-71 activates the HIF1α pathway in vivo and in vitro, effectively relieving the ferroptosis induced by high glucose. Significantly, ED-71 may improve osteogenic disorders caused by diabetes.

Finding the minimum number of retrieved lymph nodes and negative lymph nodes in gastric cancer surgery: a real-world study.

BACKGROUND: Lymph node retrieval deficiency can lead to understagement and postoperative cancer recurrence, it is crucial to establish the standard number of retrieved lymph nodes (rLNs) and negative lymph nodes (nLNs) for patients undergoing gastrectomy. METHODS: Patients who has gastric adenocarcinoma and underwent either radical subtotal gastrectomy (RSG) or radical total gastrectomy (RTG) between 2000 and 2022 were retrospectively included. We utilized restricted cubic spline (RCS) analysis to determine the ideal threshold for rLNs and nLNs. Survival analysis was conducted using Kaplan-Meier (KM) curves, log-rank tests and forest plots. Propensity score matching (PSM) was utilized to balance parameters between two groups. The median follow-up time for this study was 3,095 days. RESULTS: Our study found that there are significant tumor characteristic differences between RSG and RTG. For patients with N0-N3a stage undergoing RSG, retrieving≥24 lymph nodes intraoperatively were associated with better prognosis both before and after PSM (OS: P<0.001, P=0.019); whereas for N3b stage, at least 32 rLNs were required (OS: P=0.006, P=0.023). Similarly, for patients with N0-N3a stage undergoing RTG, retrieving≥27 lymph nodes intraoperatively were associated with better prognosis both before and after PSM (OS: P<0.001, P=0.047); whereas for N3b stage, at least 34 rLNs were required (OS: P<0.001, P=0.003). Additionally, for patients undergoing RSG, having ≥21 nLNs (OS: P<0.001, P=0.013), and for those undergoing RTG, having ≥22 nLNs (OS: P<0.001, P<0.001), were also associated with better prognosis both before and after PSM. CONCLUSIONS: For patients receiving RSG, rLNs should reach 24 when lymph nodes are limited, and 32 when lymph node metastasis is more extensive, with a minimum number of nLNs ideally reaching 21. Similarly, for patients receiving RTG, rLNs should reach 27 when lymph nodes are limited, 34 when lymph node metastasis is more extensive, and a minimum number of nLNs ideally reaching 22.

Study on the Effect of Different Concentrations of SO2 on the Volatile Aroma Components of 'Beibinghong' Ice Wine.

SO2 plays an important role in wine fermentation, and its effects on wine aroma are complex and diverse. In order to investigate the effects of different SO2 additions on the fermentation process, quality, and flavor of 'Beibinghong' ice wine, we fermented 'Beibinghong' picked in 2019. We examined the fermentation rate, basic physicochemical properties, and volatile aroma compound concentrations of 'Beibinghong' ice wine under different SO2 additions and constructed a fingerprint of volatile compounds in ice wine. The results showed that 44 typical volatile compounds in 'Beibinghong' ice wine were identified and quantified. The OAV and VIP values were calculated using the threshold values of each volatile compound, and t the effect of SO2 on the volatile compounds of 'Beibinghong' ice wine might be related to five aroma compounds: ethyl butyrate, ethyl propionate, ethyl 3-methyl butyrate-M, ethyl 3-methyl butyrate-D, and 3-methyl butyraldehyde. Tasting of 'Beibinghong' ice wine at different SO2 additions revealed that the overall flavor of 'Beibinghong' ice wine was the highest at an SO2 addition level of 30 mg/L. An SO2 addition level of 30 mg/L was the optimal addition level. The results of this study are of great significance for understanding the effect of SO2 on the fermentation of 'Beibinghong' ice wine.

Synergistic Development of Natural Rubber/Butyl Rubber Composites for Improved Interfacial Bonding and Enhanced Shock-Absorbing Capabilities.

Shock-absorbing materials play a vital role in various industrial sectors, including construction and transportation. Among these materials, natural rubber (NR) stands out due to its exceptional elastic and mechanical properties, coupled with its robust crack resistance. Nevertheless, with the rising demand for enhanced damping capacities, there is a need to further optimize the damping performance of NR. One direct approach is to blend it with high-damping rubber. Butyl rubber (IIR) is a prominent member of the high-damping rubber category. Integrating IIR effectively with the NR, however, presents challenges. These challenges arise from IIR's inherent characteristics, such as its low unsaturation, slower vulcanization rate, and restricted compatibility with NR. Addressing these challenges, our study employed isoprene and isobutene to synthesize a variant of butyl rubber with a higher degree of unsaturation-achieving an unsaturation level between 4 and 6 mol %. Notably, this heightened unsaturation significantly expedited the curing time of IIR and facilitated the concurrent vulcanization of both IIR and NR. Utilizing atomic force microscopy, we observed that the introduction of unsaturated double bonds ameliorated the compatibility between NR and IIR, leading to an interfacial region extending up to 1000 nm. Our tests using a dynamic mechanical analyzer and rubber processing analyzer demonstrated the material's damping temperature range. Furthermore, there was a noticeable rise in the loss factor (tan δ) at ambient temperature, which remains over 0.1 across both a frequency window of 0.2 to 5 Hz and a strain spectrum of 10 to 200%. This tan δ enhancement ensured the potential of these rubber composites for shock-absorbing applications.