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Objective Metabolomics analyses suggest abnormal purine metabolism during the development of osteoporosis. This study aimed to investigate the role of purine metabolism-related genes in osteoporosis. Methods Three microarray datasets for osteoporosis were used in this study. Purine metabolism activity score was quantified by GSVA. Differential expression analysis and weighted Gene Co-expression Network Analysis (WGCNA) were employed to screen dysregulated purine metabolism activity-related genes in osteoporosis. Three machine learning algorithms were employed to screen potential biomarkers, and a predictive nomogram based on biomarkers was then established. Drugs that target the biomarkers were predicted based on the DGIDB database. An ovariectomized rat model causing osteoporosis was established to validate the expression of biomarkers and the purine metabolism in vivo. Results Purine metabolism activity of osteoporosis samples was significantly different from controls. Based on differential analysis and WGCNA, 122 dysregulated purine metabolism-related genes were found, and they were mainly involved in immune inflammation-related functions. PDPK1 and FOXO3 were identified as potential biomarkers, and the nomogram based on PDPK1 and FOXO3 showed well performance to predict the onset risk of osteoporosis, with a clinical net benefit greater than PDPK1 and FOXO3 each alone. Two approved drugs, resveratrol and celecoxib, were predicted to target FOXO3 and PDPK1, respectively. Expression of FOXO3 and PDPK1 was enhanced in osteoporosis both in bioinformatics analysis and in vivo experiments. Rat model showed higher serum levels of xanthine and hypoxanthine as well as high level of uric acid. Conclusion FOXO3 and PDPK1 might be biomarkers and targets for the prevention and treatment of osteoporosis. Highlights Purine metabolism activity is dysregulated in osteoporosis patients compared to that of controls Dysregulated purine metabolism-related genes in osteoporosis were involved in inflammation-related functions PDPK1 and FOXO3 were identified as two potential biomarkers in osteoporosis Resveratrol and celecoxib could target FOXO3 and PDPK1, respectively

Artemisia argyi is widely distributed in Asia, and it often becomes the dominant population in the field because of its strong ecological niche competitiveness. Allelochemicals secreted by plants are generally considered an important reason for their dominance in ecological competition. In this study, the allelochemicals in A. argyi were screened by a series of experiments and their mechanisms were explored via transcriptomics. First, the inhibitory effects of A. argyi on Echinochloa crusgalli , Setaria viridis , Portulaca oleracea and Amaranthus retroflexus were evaluated. Then, we carried out a qualitative and quantitative analysis of the chemical composition of the aqueous extract of A. argyi to screen for potential allelochemicals that can inhibit weed growth. Four potential allelochemicals were quantified: neochlorogenic acid (5-CQA), chlorogenic acid (3-CQA), cryptochlorogenic acid (4-CQA), and caffeic acid (CA). Coincidentally, their allelopathic effects on weeds seemed to be identical to their content, in the order CA>4−CQA>5−CQA>3-CQA. These findings suggested that CA might be the main allelopathic compound in the aqueous extract of A. argyi . Subsequently, the allelopathic effect and molecular mechanism of CA on S. viridis leaves were investigated. The physiological results showed that CA significantly induced reactive oxygen species (ROS) production, led to malondialdehyde (MDA) accumulation, and disrupted enzyme activities (POD, SOD, CAT) in S. viridis leaves. Moreover, transcriptome results revealed that CA inhibited S. viridis growth by downregulating multiple genes involved in gibberellin (GA) and phytoalexin biosynthesis and Mitogen-activated protein kinase (MAPK) signaling pathways. In addition, differentially expressed genes (DEGs) related to the biosynthesis and signaling pathways of phytohormones were verified by Quantitative Real-Time PCR (RT-qPCR). Taken together, this study may be the first to identify allelochemicals and explore their molecular mechanism about A. argyi . Importantly, the ecological advantages of A. argyi could be applied to ecological regulation and the development of botanical herbicides.

Background: With the update of equipment, the hospital base of this study began to adopt craniospinal irradiation (CSI) intensity-modulated radiotherapy (IMRT) in May 2018 to replace the traditional CSI conventional radiotherapy (CRT) technology. The purpose of this study was designed to compare the differences in acute hematological adverse reactions induced by CSI-IMRT and CSI-CRT. Methods: The clinical data and hematological data of 102 patients with central nervous system malignant tumors who underwent CSI treatment at the 900th Hospital of Joint Logistics Support Force of PLA from January 2008 to August 2022 were analyzed retrospectively. The patients included 63 men and 39 women, aged 3 to 56 years old. On the basis of the radiotherapy technique used, the patients were divided into the CSI-IMRT group (38 cases) and CSI-CRT group (64 cases). Acute hematological adverse reactions during radiotherapy were compared between the two groups according to the Common Terminology Criteria for Adverse Events version 4.0. The Mann-Whitney U test was used to compare the measurement data, and the χ2 test was used to compare the count data. Results: No significant difference was found between the CSI-IMRT group and the CSI-CRT group in terms of sex, histopathological type, tumor location, spinal cord invasion, surgery, and the Eastern Cooperative Oncology Group score (χ2 = 0.004 to 6.213; all P > .05). No significant difference was found in onset time of myelosuppression (11 days (interquartile range [IQR]: 7 to 14; minimum [min] to maximum [max]: 0 to 26) vs 8 days (IQR: 7 to 15; min to max: 3 to 29)) and nadir time of myelosuppression (21 days (IQR: 18 to 25; min to max: 12 to 35) vs 22 days (IQR: 15 to 25; min to max: 12 to 36)) between the CSI-IMRT group and the CSI-CRT group (Z = −0.856, −0.248; all P > .05). There were no significant differences in the incidence of decreased white blood cell counts (WBC), platelet counts, and hemoglobin concentration between the CSI-IMRT group and the CSI-CRT group, 86.8% (33/38) vs 78.1% (50/64), 57.9% (22/38) vs 42.2% (27/64), 57.9% (22/38) vs 53.1% (34/64); χ2 = 1.195, 2.357, 0.219; all P > .05. There were no significant differences in the incidence of decreased WBC, platelet counts, and hemoglobin concentration (severe myelosuppression) in grades III and IV, 23.7% (9/38) vs 21.9% (14/64), 7.9% (3/38) vs 3.1% (2/64), 5.3% (2/38) vs 9.4% (6/64); χ2 = 0.045, 1.164, 0.558; all P > .05. Conclusions: There was no significant difference in the incidence of myelosuppression and severe myelosuppression (grade III or above) induced by CSI-IMRT and CSI-CRT. CSI-IMRT is worthy of further clinical application.

The inevitable introduction of oxygen into Czochralski-method-grown single crystal silicon, facilitated by the use of quartz crucibles, can result in the failure of chips and devices. Both the size and position of the heater exert a significant influence on the oxygen concentration within the Czochralski-method-grown silicon. In this study, a novel short-type heater was designed and evaluated for its effect on melt temperature and oxygen diffusion during crystal growth. The silicon melt temperatures and oxygen diffusion coefficients in an MCZ furnace for several heater settings were simulated, and the results were implemented in experiments. From the examination of the growth process through computation, the heater and its positional adjustments were determined to be effective modulators of oxygen concentration during crystal growth, which was consequently reduced to below 4 ppma (ASTM F121-83). Finally, the simulations were validated experimentally, limitations in production were discussed, and possible improvements were outlined.

Patients with PD-L1-negative, EGFR/ALK wild-type metastatic non-small cell lung cancer (NSCLC) exhibit limited responses to immune checkpoint inhibitors (ICIs). This study evaluates the BRICS regimen-a sequential approach combining stereotactic body radiotherapy (SBRT), probiotics, PD-1 inhibitors, and low-dose chemotherapy-to overcome immunotherapy resistance. This retrospective study included 23 patients treated between 2018 to 2024. Eligibility criteria: confirmed PD-L1-negative NSCLC, no actionable mutations, and measurable lesions. The BRICS regimen comprised SBRT (24 Gy in 3 fractions) to a single lesion, oral probiotics (6 g/day), low-dose chemotherapy, and PD-1 inhibitors administered every 21 days for six cycles. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Median age was 62 years; 82.6% were male. ORR and DCR were both 95.7%. Median PFS was 16 months (95% CI: 9.11-22.89), and median OS was 32.7 months (95% CI: 11.53-53.87). In subgroup analysis based on prior treatment status, median PFS and OS were numerically longer in treatment-naïve patients compared to previously treated patients (mPFS: 20.0 vs. 13.6 months; mOS: 48.0 vs. 18.0 months), though without statistical significance (P > 0.05). Poor ECOG performance status predicted poorer PFS (HR=9.908, p=0.013) and OS (HR=26.406, p=0.008). Adverse events were predominantly grade 1 to 2 (fatigue:13.2%, rash:8.7%), with no grade ≥3 toxicities. The BRICS regimen demonstrated promising efficacy and safety in PD-L1-negative NSCLC, potentially overcoming resistance through multimodal immunomodulation. clinical benefit was observed regardless of treatment line, with a trend toward improved outcomes when administered as first-line therapy. Prospective trials are warranted to validate these findings and explore mechanisms underlying radiotherapy-microbiome-chemotherapy synergy.

Hepatocellular cancer (HCC) remained a life-threatening carcinoma. Agents for HCC imaging and therapy were expected to possess different intratumoral retention time. To construct an agent with different intratumoral retention time when applied for tumor imaging or therapy remained great values. A lasialoglycoprotein receptor (ASGPR) targeted lactobionic acid derivative (LABO) was constructed for fluorescent imaging and photodynamic therapy of HCC. 18 F labeled LABO ( 18 F-LABO) was developed for PET imaging of HCC. LABO and 18 F-LABO showed similar molecular structure. LABO exhibited characteristic of viscosity and concentration-induced intratumoral in-situ self-assembly to expand the intratumoral retention. LABO was non-fluorescent at free stage, but emitted NIR fluorescence and generated irradiation-induced ROS after self-assembly for fluorescent imaging and photodynamic therapy. ASGPR specificity of LABO and 18 F-LABO was confirmed using HepG2 cell. Biodistribution and fluorescent imaging confirmed the different tumor retention time of LABO and 18 F-LABO when used for photodynamic therapy and PET imaging. PET imaging and photodynamic therapy were performed on HepG2 tumor bearing mice, which revealed that 18 F-LABO/LABO could specifically accumulated in the HepG2 tumor for tumor location/inhibition. LABO/ 18 F-LABO with excellent HCC specificity but different intratumoral behaviors showed great values for the PET/NIR imaging and photodynamic therapy for HCC. Graphical Abstract

Understanding the variability of turbulence intensity (TI) under different wind regimes is essential for the design and safety of offshore wind turbines. The IEC Normal Turbulence Model (NTM), though widely adopted in industry, does not incorporate directional dependence or account for extreme wind events such as typhoons, which can lead to substantial underestimation of turbulence in complex offshore environments. In this study, field measurements from two coastal sites in China, Huilai and Pingtan, were analyzed. At Pingtan, two months of observations captured both normal and typhoon-affected winds, providing a unique dataset for assessing turbulence under typhoon-affected conditions. The results show that wind speeds during the typhoon-affected period were approximately 14% higher than those during normal periods. At Huilai, TI was evaluated under northeasterly and southeasterly sea breezes, revealing that the IEC NTM underestimated TI by 15–42%, with more pronounced discrepancies under northeasterly winds. Based on these findings, revised NTM parameters and correction factors are proposed for different wind conditions, enhancing the applicability of the model to offshore wind turbine design. This work underscores the importance of incorporating directional and event-specific modifications into IEC turbulence standards to ensure reliable structural assessment across diverse wind regimes.

Background Esophageal squamous cell carcinoma (ESCC), the most common type of esophageal cancer, characterized by low five-year survival rate, and concurrent chemoradiotherapy (CCRT) has been proposed to treat ESCC, while potential biomarkers for prognostic monitoring after optimized CCRT remains unknown. Methods Serum samples from 45 patients with ESCC were collected and categorized into three groups: Control (pre-CCRT), CCRT (during CCRT), and CCRT-1 M (one-month post-CCRT). The therapeutic effect was evaluated using CT imaging and established evaluation criteria. Untargeted metabolomic analysis was performed on the serum samples to identify differential metabolites caused by CCRT treatment, assessing their potential for prognostic monitoring. Results CCRT had significant therapeutic efficacy in patients with ESCC, as indicated by CT imaging and RECIST 1.1 solid tumor evaluation criteria. Notably, several metabolic markers were identified through non-targeted metabolomic analysis, highlighting changes following CCRT treatment. These differential metabolites are involved in the dysregulation of phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine, arginine, and proline metabolism, and glycine, serine, and threonine metabolism, suggesting a reduction in glucose metabolism in patients with ESCC after CCRT. Additionally, ROC analysis indicated that the AUC of these metabolites exceeded 0.661, underscoring their diagnostic value for assessing CCRT efficacy and their potential use in prognostic monitoring. Comparative metabolomic analysis identified L-phenylalanine and lysine as promising serum biomarkers for predicting therapeutic outcomes. Conclusions CCRT shows considerable therapeutic benefit in patients with ESCC, with observed reductions in glucose metabolism post-treatment. L-phenylalanine and lysine may serve as potential serum biomarkers to predict CCRT efficacy.

IntroductionReducing feed costs and promoting sustainability are key challenges in yak production. This study aimed to comprehensively evaluate the potential of four locally available agricultural by-products—pumpkin vines (PV), sweet potato vines (SPV), grape vines (GV), and pepper straw (PS)—as alternative feed resources for yaks.MethodsFirst, the chemical composition (dry matter-DM, crude protein, neutral detergent fiber-NDF, acid detergent fiber-ADF) of each by-product was analyzed. Subsequently, a 72-hour in vitro ruminal fermentation experiment was conducted to evaluate fermentation parameters. Finally, high-throughput sequencing was used to analyze associated shifts in the rumen bacterial microbiota, and Spearman correlation analysis was performed to link key microbial genera with fermentation outcomes.Results and Discussion1) GV and PV had a higher crude protein content, while PS had the highest levels of dry matter (DM), neutral detergent fiber (NDF) and acid detergent fiber (ADF, P< 0.001); 2) After 72 hours of in vitro fermentation, PV and SPV had superior gas production and nutrient degradability (DM, NDF and ADF, P< 0.001); 3) The fermentation parameters showed that SPV and GV promoted more efficient fermentation, characterized by a lower pH and a lower acetate-to-propionate ratio, but higher microbial protein (MCP) levels (P< 0.001). PV yielded the highest concentrations of volatile fatty acids (P< 0.001). 4) Rumen microbiota analysis identified distinct, diet-specific enrichments of bacterial genera (P< 0.05), including: g_Fusobacterium and g_Basfia in PV; g_Rikenellaceae_RC9_gut_group and g_Streptococcus in SPV; g_norank_f:p-251-o5 and g_Butyricicoccus in PS; g_Lachnospira and g_Pseudobutyrivibrio in GV Critically, Spearman correlation analysis linked these microbial shifts to fermentation outcomes: Genera such as g_Fusobacterium and g_Basfia were found to be positively correlated with MCP (P< 0.05), while g_Rikenellaceae_RC9_gut_group and g_Butyricicoccus were positively associated with total volatile fatty acids (P< 0.05). In conclusion, while all four by-products show potential as alternative feeds, SPV and GV show better overall feeding value for yaks, supported by their balanced nutrient composition, improved fermentability, and positive associations with rumen microbiota. This integrated assessment provides a strong basis for utilizing them to enhance the sustainability of yak production.

Background Familial hypercholesterolemia (FH) is an inherited disorder with markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. Although many mutations have been reported in FH, only a few have been identified as pathogenic mutations. This study aimed to confirm the pathogenicity of the LDL receptor (LDLR) c.2160delC variant in FH. Methods In this study, the proband and her family members were systematically investigated, and a pedigree map was drawn. High-throughput whole-exome sequencing was used to explore the variants in this family. Next, quantitative polymerase chain reaction (qPCR), western blot (WB) assays, and flow cytometry were conducted to detect the effect of the LDLR c.2160delC variant on its expression. The LDL uptake capacity and cell localization of LDLR variants were analyzed by confocal microscopy. Results According to Dutch Lipid Clinic Network (DLCN) diagnostic criteria, three FH patients were identified with the LDLR c.2160delC variant in this family. An in-silico analysis suggested that the deletion mutation at the 2160 site of LDLR causes a termination mutation. The results of qPCR and WB verified that the LDLR c.2160delC variant led to early termination of LDLR gene transcription. Furthermore, the LDLR c.2160delC variant caused LDLR to accumulate in the endoplasmic reticulum, preventing it from reaching the cell surface and internalizing LDL. Conclusions The LDLR c.2160delC variant is a terminating mutation that plays a pathogenic role in FH.