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Abstract There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner

In this work, ginsenoside CK was confirmed as an EGFR tyrosine kinase inhibitor, with an IC50 value of 32.58 ± 0.09 μM. Molecular docking showed that ginsenoside CK could fit into EGFR binding pocket, thereby acting as a ligand for EGFR. Ginsenoside CK inhibited proliferation of A549 cells as well as induced its apoptosis via downregulating anti-apoptotic factors and upregulating apoptosis induction factors. Ginsenoside CK alone and combined with gefitinib inhibited the tumor progression of A549 lung cancer xenografts in BALB/c nude mice. ELISA assay showed that ginsenoside CK combined with gefitinib alleviated the inflammatory response by suppressing the release of pro-inflammatory cytokines, indicating better inhibitory effects than ginsenoside CK or gefitinib alone. This work further confirmed that ginsenoside CK regulated the EGFR/MAPK/ERK signaling both in vitro and in vivo. In conclusion, ginsenoside CK can exhibit the anti-lung cancer effect via acting as an EGFR tyrosine kinase inhibitor.

Fine particulate matter (PM2.5) may disrupt women's reproductive hormones, posing potential reproductive risks. However, the exact compositions of PM2.5 responsible for these effects remain unclear. Our investigation explored the long-term impacts of PM2.5 constituents on reproductive hormones, based on a large longitudinal assisted reproductive cohort study in Anhui, China. We included 24,396 reproductive hormone samples from 19,845 women attending assisted reproductive technologies (ART) between 2014 and 2020. Using high-resolution gridded data (1-km resolution), we calculated the residence-specified PM2.5 constituents during the year before the month of hormone testing. Relationships between PM2.5 constituents [organic matter (OM), chloride (Cl-), sulfate (SO42-), ammonium (NH4+), black carbon, and nitrate] and reproductive hormones were investigated using the linear mixed model with subject-specific intercepts. The constituent-proportion model and the constituent-residual model were also constructed. Additionally, cubic spline analysis was used to examine the potential non-linear exposure-response relationship. We found that per interquartile range (IQR) increment in OM was associated with a 5.31 % (3.74 %, 6.89 %) increase in estradiol, and per IQR increment in Cl- and NH4+ were associated with 13.56 % (7.63 %, 19.82 %) and 9.07 % (4.35 %, 14.01 %) increases in luteinizing hormone. Conversely, per IQR increment in OM and Cl- were associated with −7.27 % (-9.34 %, −5.16 %) and −8.52 % (-10.99 %, −5.98 %) decreases in progesterone, and per IQR increment in SO42- was associated with a −9.15 % (-10.31 %, −7.98 %) decrease in testosterone. These associations were held in both proportional and residual models. Moreover, exposure-response curves for estradiol and progesterone with PM2.5 constituents exhibited approximately U-shaped. These results suggested that specific PM2.5 constituents might disrupt reproductive hormone homeostasis in women attending ART, providing new evidence for formulating PM2.5 pollution reduction strategies that could benefit women's reproductive health.

Abstract Physical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical exercise can downregulate the S‐nitrosylation of gephyrin (SNO‐gephyrin) in the basolateral amygdala (BLA) to exert anxiolytic effects. It is found that the level of SNO‐gephyrin is significantly increased in the BLA of high‐anxiety rats and a downregulation of SNO‐gephyrin at cysteines 212 and 284 produced anxiolytic effect. Mechanistically, inhibition of SNO‐gephyrin by either Cys212 or Cys284 mutations increased the surface expression of GABAAR γ2 and the subsequent GABAergic neurotransmission, exerting anxiolytic effect in male rats. On the other side, overexpression of neuronal nitric oxide synthase in the BLA abolished the anxiolytic‐like effects of physical exercise. This study reveals a key role of downregulating SNO‐gephyrin in the anxiolytic effects of physical exercise, providing a new explanation for protein post‐translational modifications in the brain after exercise.

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage.

Abstract Background Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. Methods Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. Results Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. Conclusions This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. Trial registration ISRCTN65203415.

Abstract Background Coronary inflammation plays crucial role in type 2 diabetes mellitus (T2DM) induced cardiovascular complications. Both glucose-lowering drug interventions (GLDIS) and glycemic control (GC) status potentially correlate coronary inflammation, as indicated by changes in pericoronary adipose tissue (PCAT) attenuation, and thus influence cardiovascular risk. This study evaluated the impact of GLDIS and GC status on PCAT attenuation in T2DM patients. Methods This retrospective study collected clinical data and coronary computed tomography angiography (CCTA) images of 1,342 patients, including 547 T2DM patients and 795 non-T2DM patients in two tertiary hospitals. T2DM patients were subgroup based on two criteria: (1) GC status: well: HbA1c 9%; (2) GLDIS and non-GLDIS. PCAT attenuations of the left anterior descending artery (LAD-PCAT), left circumflex artery (LCX-PCAT), and right coronary artery (RCA-PCAT) were measured. Propensity matching (PSM) was used to cross compare PCAT attenuation of non-T2DM and all subgroups of T2DM patients. Linear regressions were conducted to evaluate the impact of GC status and GLDIS on PCAT attenuation in T2DM patients. Results Significant differences were observed in RCA-PCAT and LCX-PCAT between poor GC-T2DM and non-T2DM patients (LCX: − 68.75 ± 7.59 HU vs. – 71.93 ± 7.25 HU, p = 0.008; RCA: − 74.37 ± 8.44 HU vs. − 77.2 ± 7.42 HU, p = 0.026). Higher PCAT attenuation was observed in LAD-PCAT, LCX-PCAT, and RCA-PCAT in non-GLDIS T2DM patients compared with GLDIS T2DM patients (LAD: − 78.11 ± 8.01 HU vs. − 75.04 ± 8.26 HU, p = 0.022; LCX: − 71.10 ± 8.13 HU vs. − 68.31 ± 7.90 HU, p = 0.037; RCA: − 78.17 ± 8.64 HU vs. − 73.35 ± 9.32 HU, p = 0.001). In the linear regression, other than sex and duration of diabetes, both metformin and acarbose were found to be significantly associated with lower LAD-PCAT (metformin: β coefficient = − 2.476, p=0.021; acarbose: β coefficient = − 1.841, p = 0.031). Conclusion Inadequate diabetes management, including poor GC and lack of GLDIS, may be associated with increased coronary artery inflammation in T2DM patients, as indicated by PCAT attenuation on CCTA, leading to increased cardiovascular risk. This finding could help healthcare providers identify T2DM patients with increased cardiovascular risk, develop improved cardiovascular management programs, and reduce subsequent cardiovascular related mortality.

Abstract Key message The forest canopy gaps, formed by natural or anthropogenic factors, have been found to reduce soil carbon content and increase nutrient availability. The magnitudes of these effects have been observed to increase with gap age and size, and are largely influenced by changes in temperature, precipitation, and solar radiation. Context Local studies have illustrated the influence of canopy gaps on the spatial heterogeneity of soil carbon and nutrients, playing a pivotal role in driving forest regeneration and succession. Nevertheless, it remains largely unknown whether the response of soil carbon and nutrient content to gap formation is consistent across forest ecosystems at global scale. Aims The aim of this paper is to assess the homogeneity of the observed responses of soil carbon and nutrients following gap formation among a wide array of forest ecosystems and climatic regions. Methods We performed a meta-analysis synthesizing 2127 pairwise observations from 52 published articles to quantify the changes in in soil physical, chemical, and microbial variables resulting from gap creation in natural forests and plantations spanning tropical to boreal regions. Results Canopy gaps resulted in significant decrease of soil organic carbon (C org) and microbial carbon (C mic). The concentrations of ammonium (NH4 +), nitrate (NO3 −), and available phosphorus (available P) increased following gap creation. These changes mainly occurred in the growing season and in the mineral soil layer, becoming more pronounced with increasing gap age and size. The change in C org was negatively regulated by mean annual precipitation, and was associated with the changes in Nt and N mic . The change in NH4 + was positively regulated by mean annual temperature, and was associated with the changes in available P and oxidoreductases (Ox-EEAs). The model explaining the change in soil carbon content exhibited a higher explanatory power than the one accounting for changes in soil nutrient availability. Conclusion The results indicated that forest canopy gaps resulted in a reduction in soil carbon content and an increase in nutrient availability. These findings contribute to a better understanding of the role of small-scale disturbances as drivers of forest ecosystem succession.

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis.Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness.Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated.Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

ABSTRACT Platinum-based chemotherapy failure represents a significant challenge in the management of ovarian cancer (OC) and contributes to disease recurrence and poor prognosis. Recent studies have shed light on the involvement of the gut microbiota in modulating anticancer treatments. However, the precise underlying mechanisms, by which gut microbiota regulates the response to platinum-based therapy, remain unclear. Here, we investigated the role of gut microbiota on the anticancer response of cisplatin and its underlying mechanisms. Our results demonstrate a substantial improvement in the anticancer efficacy of cisplatin following antibiotic-induced perturbation of the gut microbiota in OC-bearing mice. 16S rRNA sequencing showed a pronounced alteration in the composition of the gut microbiome in the cecum contents following exposure to cisplatin. Through metabolomic analysis, we identified distinct metabolic profiles in the antibiotic-treated group, with a notable enrichment of the gut-derived metabolite 3-methylxanthine in antibiotic-treated mice. Next, we employed a strategy combining transcriptome analysis and chemical–protein interaction network databases. We identified metabolites that shared structural similarity with 3-methylxanthine, which interacted with genes enriched in cancer-related pathways. It is identified that 3-methylxanthinesignificantly enhances the effectiveness of cisplatin by promoting apoptosis both in vivo and in vitro. Importantly, through integrative multiomics analyses, we elucidated the mechanistic basis of this enhanced apoptosis, revealing a dopamine receptor D1-dependent pathway mediated by 3-methylxanthine. This study elucidated the mechanism by which gut-derived metabolite 3-methylxanthine mediated cisplatin-induced apoptosis. Our findings highlight the potential translational significance of 3-methylxanthine as a promising adjuvant in conjunction with cisplatin, aiming to improve treatment outcomes for OC patients.IMPORTANCEThe precise correlation between the gut microbiota and the anticancer effect of cisplatin in OC remains inadequately understood. Our investigation has revealed that manipulation of the gut microbiota via the administration of antibiotics amplifies the efficacy of cisplatin through the facilitation of apoptosis in OC-bearing mice. Metabolomic analysis has demonstrated that the cecum content from antibiotic-treated mice exhibits an increase in the levels of 3-methylxanthine, which has been shown to potentially enhance the therapeutic effectiveness of cisplatin by an integrated multiomic analysis. This enhancement appears to be attributable to the promotion of cisplatin-induced apoptosis, with 3-methylxanthine potentially exerting its influence via the dopamine receptor D1-dependent pathway. These findings significantly contribute to our comprehension of the impact of the gut microbiota on the anticancer therapy in OC. Notably, the involvement of 3-methylxanthine suggests its prospective utility as a supplementary component for augmenting treatment outcomes in patients afflicted with ovarian cancer.

With the proposal of ''Carbon peaking and carbon neutrality'', Adiabatic Compressed Air Energy Storage (A-CAES) has emerged as a significant component within China's energy storage infrastructure. But its thermodynamic efficiency and economical return need yet to be raised. The present paper proposed a modified system coupling with thermal power plant to utilize the excess compression heat. Utilizing advanced transient modeling software, an A-CAES plant is modeled and validated. The operation performance of the coupled system is compared with non-coupled system, which shows that the system efficiency is raised from 54.8 % to 76.7 % and the investment return rate is improved from 9.18 % to 10.43 %.

Given the physiological function and anatomical location of the reproductive tract, studying the upper reproductive tract microbiota may be essential for studying male infertility and other male diseases. This study aimed to characterize the microbiota of the upper reproductive tract male rats and investigate whether specific microbial compositions are associated with sperm parameters. 16S rRNA gene sequencing was used to characterize the microbial composition in the testis, epididymis, seminal vesicles, vas deferens and prostate tissues of the rats. The results showed significant enrichment of Methyloperoxococcus spp. in testicular tissues, Jeotgalicoccus spp. in epididymal tissues. Spearman's correlation analysis revealed that the abundance of several bacterial genera in epididymal, testicular, and seminal vesicle gland tissues correlated with several sperm activity parameters. Our findings provide detailed information on characterizing the upper reproductive tract microbiome in male rats, as well as a potentially crucial link between the reproductive system microbiota and sperm quality.

Sirtuin 5 (Sirt5), a member of the Sirtuin family, is involved in various intracellular biological processes. However, the function of Sirt5 in oocyte maturation has not been clearly elucidated. In this study, we observed that Sirt5 was persistently expressed during the meiotic division of mouse oocytes, with a notable decline in expression in aging oocytes. Sirt5 inhibition led to the failure of the first polar body extrusion and induced cell cycle arrest, indicative of unsuccessful oocyte maturation. Furthermore, Sirt5 inhibition was associated with the extrusion of abnormally large polar bodies, suggesting disrupted asymmetric oocyte division. Mechanistically, the inhibition of Sirt5 resulted in aberrant spindle assembly and disordered chromosome alignment in oocytes. Moreover, Sirt5 inhibition caused the spindle to be centrally located in the oocyte without migrating to the cortical region, consequently preventing the formation of the actin cap. Further investigation revealed that Sirt5 inhibition notably diminished the expression of phosphorylated cofilin and profilin1, while increasing cytoplasmic F-actin levels. These findings suggest that Sirt5 inhibition during oocyte maturation adversely affects spindle assembly and chromosome alignment and disrupts actin dynamics impairing spindle migration and contributing to the failure of symmetric oocyte division and maturation.

The use of bisphenol A (BPA) has been restricted due to its endocrine-disrupting effects. As a widely used alternative to BPA today, environmental levels of bisphenol Z (BPZ) continue to rise and accumulate in humans. Oocyte quality is critical for a successful pregnancy. Nevertheless, the toxic impacts of BPZ on the maturation of mammalian oocytes remain unexplored. Therefore, the impacts of BPZ and BPA on oocyte meiotic maturation were compared in an in vitro mouse oocyte culture model. Exposure to 150 μM of both BPZ and BPA disrupted the assembly of the meiotic spindle and the alignment of chromosomes, and BPZ exerted stronger toxicological effects than BPA. Furthermore, BPZ resulted in aberrant expression of F-actin, preventing the formation of the actin cap. Mechanistically, BPZ exposure disrupted the mitochondrial localization pattern, reduced mitochondrial membrane potential and ATP content, leading to impaired mitochondrial function. Further studies revealed that BPZ exposure resulted in oxidative stress and altered expression of genes associated with anti-oxidative stress. Moreover, BPZ induced severe DNA damage and triggered early apoptosis in oocytes, accompanied by impaired lysosomal function. Overall, the data in this study suggest that BPZ is not a safe alternative to BPA. BPZ can trigger early apoptosis by affecting mitochondrial function and causing oxidative stress and DNA damage in oocytes. These processes disrupt cytoskeletal assembly, arrest the cell cycle, and ultimately inhibit oocyte meiotic maturation.

Abstract Background Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural networks to identify cell-free DNA (cfDNA) carrying aberrant methylation offers an appealing and non-invasive approach for HCC detection. However, some limitations exist in traditional methylation detection technologies and models, which may impede their performance in the read-level detection of HCC. Methods We developed a low DNA damage and high-fidelity methylation detection method called No End-repair Enzymatic Methyl-seq (NEEM-seq). We further developed a read-level neural detection model called DeepTrace that can better identify HCC-derived sequencing reads through a pre-trained and fine-tuned neural network. After pre-training on 11 million reads from NEEM-seq, DeepTrace was fine-tuned using 1.2 million HCC-derived reads from tumor tissue DNA after noise reduction, and 2.7 million non-tumor reads from non-tumor cfDNA. We validated the model using data from 130 individuals with cfDNA whole-genome NEEM-seq at around 1.6X depth. Results NEEM-seq overcomes the drawbacks of traditional enzymatic methylation sequencing methods by avoiding the introduction of unmethylation errors in cfDNA. DeepTrace outperformed other models in identifying HCC-derived reads and detecting HCC individuals. Based on the whole-genome NEEM-seq data of cfDNA, our model showed high accuracy of 96.2%, sensitivity of 93.6%, and specificity of 98.5% in the validation cohort consisting of 62 HCC patients, 48 liver disease patients, and 20 healthy individuals. In the early stage of HCC (BCLC 0/A and TNM I), the sensitivity of DeepTrace was 89.6 and 89.5% respectively, outperforming Alpha Fetoprotein (AFP) which showed much lower sensitivity in both BCLC 0/A (50.5%) and TNM I (44.7%). Conclusions By combining high-fidelity methylation data from NEEM-seq with the DeepTrace model, our method has great potential for HCC early detection with high sensitivity and specificity, making it potentially suitable for clinical applications. DeepTrace: https://github.com/Bamrock/DeepTrace

Stepwise photopolymerization is a miraculous strategy modulating the polymer skeleton and electro-optical properties of light modulators based on liquid crystal/polymer composites. However, owing to the indistinct polymerization mechanism and curing condition discrepancy, the required polymer structures and electro-optical properties are hard to be controlled precisely. Herein, a novel polymer-stabilized liquid crystal film based on acrylate/epoxy resin is proposed, fabricated and the relationships between preparation process, polymer content, polymer morphology and electro-optical properties are studied. The in-situ photopolymerization of acrylate/epoxy resin liquid crystalline polymer is fulfilled using cation photo-initiator UV 6976. The distinct photopolymerization speed between acrylate and epoxy resin benefits the polymer morphology control, and with accurate containment of the polymerization process and polymer composition, the superior electro-optical properties at a higher polymer content are acquired. The polymer morphology and electro-optical properties are influenced by the polymer content and mass ratio between acrylate and epoxy resin. The best electro-optical properties among samples are attained by controlling the mass ratio between acrylate and epoxy resin to 1:1, integrating higher densities of scattering centers and lower anchoring effect. With higher polymer content, the strategy of increasing the mass ratio of E6M benefits the improvement of E-O properties for alleviating polymer density. This work provides insights to stepwise polymerization of liquid crystalline monomers and offers a fancy strategy for the preparation of novel liquid crystal dimming films.

As an indispensable part of the power transmission system, insulators are of great importance to the safe and stable operation of power grids in terms of their healthy and reliable operation. To realize real-time monitoring of insulator defects under a complex environment, this paper proposes an insulator defect detection method based on the You Only Look Once version 7-tiny (YOLOv7-tiny) algorithm. Then an edge device-unmanned aerial vehicle (UAV) inspection system is developed to verify the real-time performance of the algorithm. By introducing the structure intersection over union (SIoU) loss function to the YOLOv7-tiny model, the regression speed of the anchor frame can be effectively accelerated on the basis of the miniature model, to accelerate the model operation. Thereafter, a smooth sigmoid linear unit (SiLU) activation function is used in the network neck to improve the nonlinear representation ability; After that, an edge computing device based on NVIDIA Jetson Xavier NX is established to verify the real-time performance of the method. Experimental results reveal mean average precision (mAP) of insulators and their missing series defects is as high as 98.31%. Besides, the detection speed of the designed model deployed to mobile edge devices can reach 35 frames per second (FPS), with real-time and accurate detection performance of insulators and their missing series defects.

Summary: Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan–Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423–1.262) in the azvudine group 0.802 (0.435–1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805–3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546–3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the “National Key R&D Program of China” (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Abstract Background Neurotransmitter release depends on the fusion of synaptic vesicles with the presynaptic membrane and is mainly mediated by SNARE complex assembly. During the transition of Munc18-1/Syntaxin-1 to the SNARE complex, the opening of the Syntaxin-1 linker region catalyzed by Munc13-1 leads to the extension of the domain 3a hinge loop, which enables domain 3a to bind SNARE motifs in Synaptobrevin-2 and Syntaxin-1 and template the SNARE complex assembly. However, the exact mechanism of domain 3a extension remains elusive. Results Here, we characterized residues on the domain 3a hinge loop that are crucial for the extension of domain 3a by using biophysical and biochemical approaches and electrophysiological recordings. We showed that the mutation of residues T323/M324/R325 disrupted Munc13-1-mediated SNARE complex assembly and membrane fusion starting from Munc18-1/Syntaxin-1 in vitro and caused severe defects in the synaptic exocytosis of mouse cortex neurons in vivo. Moreover, the mutation had no effect on the binding of Synaptobrevin-2 to isolated Munc18-1 or the conformational change of the Syntaxin-1 linker region catalyzed by the Munc13-1 MUN domain. However, the extension of the domain 3a hinge loop in Munc18-1/Syntaxin-1 was completely disrupted by the mutation, leading to the failure of Synaptobrevin-2 binding to Munc18-1/Syntaxin-1. Conclusions Together with previous results, our data further support the model that the template function of Munc18-1 in SNARE complex assembly requires the extension of domain 3a, and particular residues in the domain 3a hinge loop are crucial for the autoinhibitory release of domain 3a after the MUN domain opens the Syntaxin-1 linker region.

Upper tract urothelial carcinoma (UTUC) is a relatively rare malignant neoplasm of the urinary system. Due to its highly aggressiveness, the tumor has already undergone invasive growth when most UTUC patients are diagnosed. In addition, the most common cause of fever in cancer patients is infection, and cancer patients with neoplastic fever are relatively rare. We reported a 58-year-old man with invasive high-grade UTUC accompanied by hyperthermia.

Summary: The dorsal root ganglion (DRG) is characterized by the dense clustering of primary sensory neuron bodies, with their axons extending to target tissues for sensory perception. The close physical proximity of DRG neurons facilitates the integration and amplification of somatosensation, ensuring normal physiological functioning. However, the mechanism underlying DRG neuron aggregation was unclear. In our study, we culture DRG neurons from newborn rats on substrates with varying stiffness and observe that the aggregation of DRG neurons is influenced by mechanical signals arising from substrate stiffness. Moreover, we identify Piezo1 as the mechanosensor responsible for DRG neurons’ ability to sense different substrate stiffness. We further demonstrate that the Piezo1-calpain-integrin-β1/E-cadherin signaling cascade regulates the aggregation of DRG neurons. These findings deepen our understanding of the mechanisms involved in histogenesis and potential disease development, as mechanical signals arising from substrate stiffness play a crucial role in these processes.

BackgroundA few observational studies revealed that amyotrophic lateral sclerosis (ALS) was tightly connected with osteoporosis. However, the results of previous studies were inconsistent, and the causal effect of ALS on osteoporosis has not been investigated. To do so, the two-sample Mendelian randomization (MR) method was employed to estimate the causality.MethodsThe instrumental variables (IVs) for ALS were selected from one GWAS summary dataset (27,205 ALS cases and 110,881 controls), and bone mineral density (BMD) in the femoral neck (FN), lumbar spine (LS), and forearm, extracted from another large-scale GWAS summary database (53,236 cases), were used as phenotypes for osteoporosis. Random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were conducted to evaluate the causality. Sensitivity analyses were further performed to explore heterogeneity and pleiotropy.ResultsA total of 10 qualified SNPs were finally selected as proxies for ALS. The results of random effects from IVW revealed that ALS has no causal effect on FN-BMD (beta: −0.038, 95% CI: −0.090 to 0.015, SE: 0.027, p = 0.158), LS-BMD (beta: −0.015, 95% CI: −0.076 to 0.046, SE: 0.031, p = 0.629), and forearm BMD (beta: 0.044, 95% CI: −0.063 to 0.152, SE: 0.055, p = 0.418). These results were confirmed using the MR-Egger, weighted median, simple model, and weighted model. No heterogeneity or pleiotropy was detected (p > 0.05 for all).ConclusionContrary to previous observational studies, our study figured out that no causal effect existed between ALS and osteoporosis. The disparity in results is probably attributed to secondary effects such as physical inactivity and muscle atrophy caused by ALS.

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) can colonize the gastrointestinal tract and cause bloody diarrhea in children. Previous studies showed that its pathogenesis could be mediated by metabolites from both the host and microbiota. L-Glutamine (Gln) was found to be depleted in intestinal tissues as the main energy source according to previous studies. Hence, we aimed to determine the effects of Gln on EHEC infection and its underlying mode of action. In this study, a Gln-limited signal was found to activate the type 3 secretion system (T3SS), which is crucial for EHEC infection via perturbation of central metabolism. By shifting the phosphorylation of NtrC, a key regulator in bacterial nitrogen metabolism, Gln stimulates ler transcripts in a σS-PchA-dependent manner. Our in vivo experiments further demonstrated that Gln supplementation can reduce EHEC colonization in the gastrointestinal tract by repressing T3SS. Moreover, Gln could further attenuate bacterial infection by boosting host defense, which might be dependent on multiple pathways. Besides, our experiments demonstrated that Gln did not induce Shiga-like toxin (Stx) production or cause impairment of gut flora. In conclusion, our study presented evidence that Gln could act against EHEC infection by reducing bacterial virulence and strengthening host defense. Therefore, Gln serves as a promising therapeutic agent for EHEC infection. IMPORTANCE The type 3 secretion system (T3SS) was obtained in many Gram-negative bacterial pathogens, and it is crucial for their pathogenesis. Environmental signals were found to be involved in the expression regulation of T3SS, which was vital for successful bacterial infection in the host. Here, we discovered that L-glutamine (Gln), the most abundant amino acid in the human body, could repress enterohemorrhagic Escherichia coli (EHEC) T3SS expression via nitrogen metabolism and therefore had potential as an antivirulence agent. Our in vitro and in vivo evidence demonstrated that Gln could decline EHEC infection by attenuating bacterial virulence and enhancing host defense simultaneously. We repurpose Gln as a potential treatment for EHEC infection accordingly.

Background Acne vulgaris (AV) is a common skin disease. Fire needle is a method of quickly piercing the local skin lesions with red-hot needles for AV. This work aimed to evaluate the efficacy and safety of fire needle combined with chemical peels for AV. Methods Eight databases including PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Internet, Wanfang, Sinomed, and VIP databases were searched to enrolled randomized controlled trials (RCTs) comparing fire needle therapy combined with chemical peels with chemical peels alone. The risk of bias was evaluated by the Cochrane Collaboration’s tool. Statistical analysis was completed by RevMan 5.3 and Stata 14.0. Results Altogether 18 studies including 1213 patients were enrolled. Compared with chemical peels alone, fire needle adjuvant chemical peels therapy improved the total effective rate (RR = 1.37,95% CI [1.26,1.48], p

Summary: Maintaining cellular viability relies on the integrity of the plasma membrane, which must be repaired upon damage. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion is a crucial mechanism involved in membrane repair. In C. elegans epidermal cell hyp 7, syntaxin-2 (SYX-2) facilitates large membrane wound repair; however, the underlying molecular mechanism remains unclear. Here, we found that SNAP-25 protein RIC-4 and synaptobrevin protein SEC-22 are required for SYX-2 recruitment at the wound site. They interact to form a SNARE complex to promote membrane repair in vivo and fusion in vitro. Moreover, we found that SEC-22 localized in multiple intracellular compartments, including endosomes and the trans-Golgi network, which recruited to the wounds. Furthermore, inhibition of RAB-5 disrupted SEC-22 localization and prevented its interaction with SYX-2. Our findings suggest that RAB-5 facilitates the formation of the RIC-4/SEC-22/SYX-2 SNARE complex and provides valuable insights into the molecular mechanism of how cells repair large membrane wounds.

Halophytes play a crucial role in the ecological restoration of saline and alkaline land and hold promising benefits to food security in China. Although a variety of aspects of halophytes have been extensively addressed, there is still a lack of overall understanding of the leaf nitrogen (N) and phosphorus (P) stoichiometric characteristics, especially at a national scale. We compiled a national dataset of 311 observations from 113 sampling sites across China to explore the changing trends and influencing factors on leaf N and P concentrations, and N:P ratio of halophytes. The results showed that leaf N concentration decreased significantly with increasing latitude (LAT), which was mainly driven by the mean annual temperature (MAT) and mean annual precipitation (MAP). The leaf P concentration increased remarkably with increasing longitude (LON), which was induced by the variation in soil total P (TP) content. The leaf N:P ratio increased as LAT increased and LON decreased, which was potentially regulated by the MAT, MAP, and soil TP content. The scaling exponents of the N-P relationship differed significantly among halophyte types and were 0.40, 0.87, and 1.39 for euhalophyte, pseudohalophyte, and recretohalophyte, respectively. The leaf N concentration exhibited significant differences among ecosystem types and halophyte types, whereas the leaf P concentration and N:P ratio remained relatively stable. In summary, the leaf N concentration and N-P scaling exponent might be the classification criteria for halophyte types from the perspective of plant nutrient resource allocation. Moreover, this study characterized the spatial distribution and allocation strategy of leaf N and P stoichiometry in halophytes by data integration analysis, providing the basic information for nutrient management in the processes of the future domestication and introduction of halophytes.

Abstract Exosomes play crucial roles in local and distant cellular communication and are involved in various physiological and pathological processes. Tumour‐derived exosomes are pivotal to tumorigenesis, but the precise mechanisms underlying their secretion remain elusive. In particular, the SNARE proteins that mediate the fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) in tumour cells are subject to debate. In this study, we identified syntaxin‐4, SNAP‐23, and VAMP‐7 as the SNAREs responsible for exosome secretion in MCF‐7 breast cancer cells and found that a SNARE complex consisting of these SNAREs can drive membrane fusion in vitro. Deletion of any of these SNAREs in MCF‐7 cells did not affect MVB biogenesis and transportation, indicating their specific involvement in MVB–PM fusion. In addition, syntaxin‐4, SNAP‐23, and VAMP‐7 play equivalent roles in exosome secretion in both HeLa cervical cancer cells and A375 melanoma cells, suggesting their conserved function in exosome secretion. Furthermore, deletion of VAMP‐7 in 4T1 mammary carcinoma cells efficiently inhibited exosome secretion and led to significant attenuation of tumour growth and lung metastasis in mouse models, implying that VAMP‐7 may hold promise as a novel therapeutic target for breast cancer.

IntroductionIn early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC).MethodsFrom the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method.ResultsMore ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range.DiscussionNeither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy.

In this work, an automated microfluidic chip that uses negative pressure to sample and analyze solutions with high temporal resolution was developed. The chip has a T-shaped channel for mixing the sample with a fluorescent indicator, a flow-focusing channel for generating droplets in oil, and a long storage channel for incubating and detecting the droplets. By monitoring the fluorescence intensity of the droplets, the device could detect changes in solution accurately over time. The chip can generate droplets at frequencies of up to 42 Hz with a mixing ratio of 1:1 and a temporal resolution of 3–6 s. It had excellent linearity in detecting fluorescein solution in the concentration range 1–5 μM. This droplet microfluidic chip provides several advantages over traditional methods, including high temporal resolution, stable droplet generation, and faster flow rates. This approach could be applied to monitoring calcium ions with a dynamic range from 102 to 107 nM and a detection limit of 10 nM.

Technical indicators and mining sequence are often optimized separately when optimizing metal mine production. This approach ignores the mutual influence between indicators and mining sequence, and the optimization results may not reach the global optimum. This study focuses on the entire production process of a metal mine and establishes a model and creates an algorithm for the simultaneous dynamic optimization of the technical indicators and mining sequence of a metal mine. A model of the dynamic relationships between technical indicators is initially created in order to derive an optimization model that dynamically optimizes both the technical indicators and the mining sequence of a metal mine. A hybrid coding AADE algorithm is developed to solve the optimization equation. A test case of the Huogeqi copper mine is presented to demonstrate the use of the model and the algorithm. The simultaneous dynamic optimization of technical indicators and mining sequence produced greater NPV in the test case than the optimization of technical indicators alone; NPV increased by 1161.01 104 CNY. In addition, the hybrid coding AADE algorithm was compared with hybrid coding GA, DE and ADE algorithms. The hybrid coding AADE algorithm performed searches significantly better than the other three hybrid coding algorithms in solving the simultaneous dynamic optimization for technical indicators and mining sequence.

Uterine corpus endometrial cancer (UCEC) is the sixth most common female cancer worldwide, with an increasing incidence. Improving the prognosis of patients living with UCEC is a top priority. Endoplasmic reticulum (ER) stress has been reported to be involved in tumor malignant behaviors and therapy resistance, but its prognostic value in UCEC has been rarely investigated. The present study aimed to construct an ER stress-related gene signature for risk stratification and prognosis prediction in UCEC. The clinical and RNA sequencing data of 523 UCEC patients were extracted from TCGA database and were randomly assigned into a test group (n = 260) and training group (n = 263). An ER stress-related gene signature was established by LASSO and multivariate Cox regression in the training group and validated by Kaplan-Meier survival analysis, Receiver Operating Characteristic (ROC) curves and nomograms in the test group. Tumor immune microenvironment was analyzed by CIBERSORT algorithm and single-sample gene set enrichment analysis. R packages and the Connectivity Map database were used to screen the sensitive drugs. Four ERGs (ATP2C2, CIRBP, CRELD2 and DRD2) were selected to build the risk model. The high-risk group had significantly reduced overall survival (OS) (P < 0.05). The risk model had better prognostic accuracy than clinical factors. Tumor-infiltrating immune cells analysis depicted that CD8+ T cells and regulatory T cells were more abundant in the low-risk group, which may be related to better OS, while activated dendritic cells were active in the high-risk group and associated with unfavorable OS. Several kinds of drugs sensitive to the high-risk group were screened out. The present study constructed an ER stress-related gene signature, which has the potential to predict the prognosis of UCEC patients and have implications for UCEC treatment.

Abstract Background Ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of controlled ovarian stimulation. Frozen-embryo transfer (ET) is prompted to be performed in the next menstrual cycles after cancellation of fresh-ET after occurrence of OHSS. However, effects of frozen-ET in the second menstrual cycle have never been investigated. Therefore, this study aimed to assess this in the menstrual cycle after OHSS. Methods The OHSS group included 342 women with moderate-severe OHSS who underwent the first frozen-ET in the second menstrual cycle in the First Affiliated Hospital of Anhui Medical University from June 2018 to September 2019. A total of 342 women without OHSS who received frozen-ET in the second menstrual cycle were selected as control group matched by age, body mass index, fertility history, ovulation induction scheme. Uni- and multi-variable conditional logistic regression was used to estimate the association between moderate-severe OHSS and pregnancy outcomes. Results There were no significant differences in maternal outcomes (miscarriage, preterm birth and pregnancy complications including gestational diabetes mellitus, pregnancy-induced hypertension, placenta previa, premature rupture of membranes and postpartum hemorrhage) and in neonatal outcome (birth-weight and body length, neonatal congenital diseases and other complications) between the two groups in either uni- or multi-variable models. Conclusions Frozen-ET in the menstrual cycle after OHSS has similar maternal and neonatal outcomes as in women without OHSS. This study indicates that frozen-ET could be performed in the second menstrual cycle in women who recovered from moderate-severe OHSS.

Precise matching of reaction rate and electric potential of electrodes in paired electrolysis is challenging. Here, the authors develop paired-electrolysis-enabled nickel-catalyzed enantioselective reductive cross-coupling of α-chloroesters and aryl bromides.

Neurotransmitter release by Ca2+‐triggered synaptic vesicle exocytosis is essential for information transmission in the nervous system. The soluble N‐ethylmaleimide sensitive factor attachment protein receptors (SNAREs) syntaxin‐1, SNAP‐25, and synaptobrevin‐2 form the SNARE complex to bring synaptic vesicles and the plasma membranes together and to catalyze membrane fusion. Munc18‐1 and Munc13‐1 regulate synaptic vesicle priming via orchestrating neuronal SNARE complex assembly. In this review, we summarize recent advances toward the functions and molecular mechanisms of Munc18‐1 and Munc13‐1 in guiding neuronal SNARE complex assembly, and discuss the functional similarities and differences between Munc18‐1 and Munc13‐1 in neurons and their homologs in other intracellular membrane trafficking systems.

Background: Previously, research has reported associations of lipid and lipoprotein imbalances with carcinogenesis and cancer progression, so they have been considered as promising prognostic biomarkers for cancer in recent years. However, the correlation of preoperative serum triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) with non-small cell lung carcinoma (NSCLC) prognosis remains under exploration. Here, the study investigated the prognostic function of TG/HDL-C for NSCLC. Methods: The total combined group of this retrospective study enrolled 479 NSCLC patients from two tertiary referral hospitals, of which 223 patients were defined as the training group (Nanchang) and the remaining 256 were defined as the validation group (Wuhan). The cut-off of preoperative TG/HDL-C was determined through ROC curve in the training group and verified in the validation and combined groups subsequently. With one Cox proportional hazards model and K-M survival curves, a survival analysis was conducted. Results: In the training group, the optimal cut-off of TG/HDL-C was 1.02. Furthermore, the data based on the training group revealed a greater, shorter, overall survival (OS) in patients having a high TG/HDL-C (>1.02) than those having low TG/HDL-C (≤1.02). Meanwhile, in univariate and multivariate analysis, for prognostic OS among NSCLC patients, TG/HDL-C acted as one independent factor. All the results above were confirmed in the validation and combined groups. Conclusion: NSCLC patients with a comparatively low preoperative serum TG/HDL-C level had a correlation with well OS. TG/HDL-C possibly acted as one novel, effective prognostic biomarker for NSCLC patients.

Some major construction projects require materials that can quickly and easily obtain high mechanical properties. Nowadays sulfoaluminate cement (SAC) has attracted attention for such projects due to its fast hardening rate, high early strength, and low alkalinity. Added early strength agents are commonly used to improve the early strength of Ultra-high performance concrete (UHPC). Most early-strength agent research has focused on Portland cement systems. Due to the different components of SAC and Portland cement, the compatibility between different early strength agents and SAC needs to be further explored.This paper selected three inorganic early-strength agents, calcium formate (Ca(HCOO)2), aluminum sulfate (Al2(SO4)3), and lithium carbonate (Li2CO3), and an organic early-strength agent, triethanolamine (TEA), which are commonly used. Experimental studies were carried out for single and compound early-strength agent systems in a SAC-based Ultra-high performance concrete (UHPC) system with a low water-cement ratio of 0.23. The results showed three inorganic early-strength agents reduced the setting time and improved the strength of the UHPC. The 4 h compressive strength of UHPC with 0.4 % Ca(HCOO)2 increased from 22.1 MPa to 41.2 MPa due to the improved microstructure and denser matrix.The composite mixture of Ca(HCOO)2 and Li2CO3 had a good synergistic effect in the early and middle stages, the compressive strength can reach 88.7 when curing 3 days. Different from Portland cement system, TEA had an adverse effect in the both single and compound systems.

To clarify the copyrights of 3D models of oblique photography (3DMOP) and guarantee their security, a novel security protection scheme of 3DMOP was proposed in this study by synergistically applying digital watermarking and data encryption. In the proposed scheme, point clouds were clustered first, and then the centroid and feature points of each cluster were calculated and extracted, respectively. Afterward, the watermarks were embedded into the point clouds cluster-by-cluster, taking distances between feature points and centroids as the embedding positions. In addition, the watermarks were also embedded using texture coordinates of 3DMOP to further enhance the robustness of the watermarking algorithm. Furthermore, Arnold transformation was performed on texture images of 3DMOP for security protection of classified or sensitive information. Experimental results have verified the strong imperceptibility and robustness of the proposed watermarking algorithm, as well as the high security of the designed data encryption algorithm. The outcomes of this work can refine the current security protection methods of 3DMOP and thus further expand their application scope.

A polymer-stabilized liquid crystal (PSLC) device has been a promising candidate in several scenarios like smart vehicle windows and glass curtain walls in recent years due to its remarkable features like a fast switch from the initial transparent state to the scattering state with a rather low driving voltage, high transmittance at off-state, and broad viewing angle. The electro-optical characteristics of PSLC devices are determined by the synergistic attributions of liquid crystal (LC) molecules and the influence of the polymer network exerted on the movement of LC molecules. A systematic study of the influence of the polymer network on the movement of LC molecules is conducted, with the polymer network formed by methoxy/cyano/carboxyl monomers and diacrylate C6M. The polymer network morphology of PSLC film is greatly affected by the molecular structures and content of monoacrylic monomers. Additionally, the electro-optical performance and peel strength of PSLC films could be improved by modulating the molecular structures and morphology of polymer networks. PSLC devices containing carboxyl monomers show enhanced electro-optical performance and peel strength due to their directional filiform topology. This study might provide guidance for optimizing the performance of PSLC devices and establishing the relationship between the molecular structure, polymer network morphology, and electro-optical performance of reverse-mode dimming films.

Abstract Gas explosions or coal and gas outbursts can cause transient destruction of combined coal–rock, and the dynamic mechanical response of combined coal–rock masses plays a key role in accident failure, but we now know little about the dynamic mechanical responses of combined coal–rock. In this article, we selected three rocks (limestone, shale, sandstone) and two coals (bituminous coal and anthracite coal) to form combined coal–rock, and analyze their dynamic mechanical properties by using the SHPB system. We find that the dynamic compressive strength and elastic modulus of combined rock–coal are lower than the average value of single rock and coal, while the ultimate strain and strain rate of combined coal–rock are higher than the average values of single rock and coal. Compressive strength and elastic modulus of the combined body increase gradually with increasing confining pressure, and the strain decreases accordingly. The dynamic stress–strain curve demonstrates an obvious double-peak at high strain rate (85.55 s−1 and above in the present work), while there is no obvious double-peak of the curve at low strain rate. Dynamic compressive strength of combined coal–rock body increases significantly with increasing confining pressure at low strain rate, but it increases more smoothly at higher strain rate. The elastic modulus also increases with increasing confining pressure, and it seems to be stable as confining pressure increases at low strain rate. The ultimate strain decreases gradually with increasing confining pressure but more gently compared with that at low strain rate. Besides, longitudinal fractures of combined coal–rock bodies include penetrating fractures, partially penetrating fractures, and interrupted fractures stopped at the coal–rock interface. The dynamic mechanical response of combined coal–rock is of guiding significance for maintaining the stability of the roadway and formulating the support measures for the roadway.

Taking the influence of lithological characteristics differences on the genesis of pores in migmatite reservoirs as the main line, the genesis and characteristics of pores were analyzed from the perspective of the relationship between rock fabric and grain deposition. (1) Based on hydrodynamic conditions, mineral assemblage and rock structure characteristics, and taking three endmembers of clastic particles, clay minerals and carbonate minerals for classification, the "sweet spots" in the Lucaogou Formation are mainly composed of tuffaceous sandy dolomite, tuffaceous feldspar detrital siltstone, tuffaceous dolomitic sandstone and tuffaceous dolomitic siltstone. The migmatites have mixed sources, and various types of migmatite layers can be superimposed on each other vertically to form facies marginal mixing. (2) Based on the spherical accumulation model, when the content of debris particles is lower than 52.4%, the porosity decreases with the increase of particle content. When the content of clastic particles reaches 52.4%, if the content of clastic particles[JP]continues to increase, large number of ntergranular pores will appear, and the porosity will increase rapidly, gradually evolving into a conventional sandstone reservoir. (3) According to the relationship between the three end components of clastic particles, clay minerals and carbonate minerals and the pore types, the pores of the migmatites in the Lucaogou Formation can be classified into three types including intergranular pore, intragranular dissolved pore and intercrystalline pore. The pores in tuffaceous sandy dolomites and tuffaceous feldspar detrital siltstones are mainly intergranular and intragranular dissolved ones supported by particles, while those in tuffaceous dolomitic sandstones and tuffaceous dolomitic siltstones are mainly intercrystalline ones. The development of high-quality migmatite reservoirs is mainly controlled by the content of clastic particle components, and the content of soluble clastic components and dissolution effect can improve the physical properties of the reservoirs.

Taking the influence of lithological characteristics differences on the genesis of pores in migmatite reservoirs as the main line, the genesis and characteristics of pores were analyzed from the perspective of the relationship between rock fabric and grain deposition. (1) Based on hydrodynamic conditions, mineral assemblage and rock structure characteristics, and taking three endmembers of clastic particles, clay minerals and carbonate minerals for classification, the "sweet spots" in the Lucaogou Formation are mainly composed of tuffaceous sandy dolomite, tuffaceous feldspar detrital siltstone, tuffaceous dolomitic sandstone and tuffaceous dolomitic siltstone. The migmatites have mixed sources, and various types of migmatite layers can be superimposed on each other vertically to form facies marginal mixing. (2) Based on the spherical accumulation model, when the content of debris particles is lower than 52.4%, the porosity decreases with the increase of particle content. When the content of clastic particles reaches 52.4%, if the content of clastic particles[JP]continues to increase, large number of ntergranular pores will appear, and the porosity will increase rapidly, gradually evolving into a conventional sandstone reservoir. (3) According to the relationship between the three end components of clastic particles, clay minerals and carbonate minerals and the pore types, the pores of the migmatites in the Lucaogou Formation can be classified into three types including intergranular pore, intragranular dissolved pore and intercrystalline pore. The pores in tuffaceous sandy dolomites and tuffaceous feldspar detrital siltstones are mainly intergranular and intragranular dissolved ones supported by particles, while those in tuffaceous dolomitic sandstones and tuffaceous dolomitic siltstones are mainly intercrystalline ones. The development of high-quality migmatite reservoirs is mainly controlled by the content of clastic particle components, and the content of soluble clastic components and dissolution effect can improve the physical properties of the reservoirs.

Pyroxasulfone (PYS) is an isoxazole herbicide favored for its high activity. However, the metabolic mechanism of PYS in tomato plants and the response mechanism of tomato to PYS are still lacking. In this study, it was found that tomato seedlings had a strong ability to absorb and translocate PYS from roots to shoots. The highest accumulation of PYS was in the apex tissue of the tomato shoots. Using UPLC-MS/MS, five metabolites of PYS were detected and identified in tomato plants, and their relative contents in different parts of tomato plants varied greatly. The serine conjugate, DMIT [5, 5-dimethyl-4, 5-dihydroisoxazole-3-thiol (DMIT)] &Ser, was the most abundant metabolites of PYS in tomato plants. In tomato plants, the conjugation of thiol-containing metabolic intermediates of PYS to serine may mimic the cystathionine β-synthase-catalyzed condensation of serine and homocysteine (in the pathway sly00260 sourced from KEGG database). This study ground breakingly proposed that serine may play an important role in plant metabolism of PYS and fluensulfone (whose molecular structure is similar to PYS). PYS and atrazine (whose toxicity profile is similar to PYS but not conjugate with serine) produced different regulatory outcomes for endogenous compounds in the pathway sly00260. Differential metabolites in tomato leaves exposed to PYS compared with the control, including amino acids, phosphates, and flavonoids, may play important roles in tomato response to PYS stress. This study provides inspiration for the biotransformation of sulfonyl-containing pesticides, antibiotics and other compounds in plants.

Background: Osteosarcoma is most prevalently found primary malignant bone tumors, with primary metastatic patients accounting for approximately 25% of all osteosarcoma patients, yet their 5-year OS remains below 30%. Bilirubin plays a key role in oxidative stress-associated events, including malignancies, making the regulation of its serum levels a potential anti-tumor strategy. Herein, we investigated the association of osteosarcoma prognosis with serum levels of TBIL, IBIL and DBIL, and further explored the mechanisms by which bilirubin affects tumor invasion and migration. Methods: ROC curve was plotted to assess survival conditions based on the determined optimal cut-off values and the AUC. Then, Kaplan-Meier curves, along with Cox proportional hazards model, was applied for survival analysis. Inhibitory function of IBIL on the malignant properties of osteosarcoma cells was examined using the qRT-PCR, transwell assays, western blotting, and flow cytometry. Results: We found that, versus osteosarcoma patients with pre-operative higher IBIL (>8.9 μmol/L), those with low IBIL (≤8.9 μmol/L) had shorter OS and PFS. As indicated by the Cox proportional hazards model, pre-operative IBIL functioned as an independent prognostic factor for OS and PFS in total and gender-stratified osteosarcoma patients (P

Objectives: Osteoporosis and Parkinson's disease (PD) are both aging-related diseases. PD patients with comorbid osteoporosis are vulnerable to the risk of fracture, which leads to a serious public health burden to the whole society. Therefore, this study sought to reveal the clinical and genetic correlations between PD and osteoporosis based on a cross-sectional study and bioinformatics analysis. Methods: A cross-sectional study of 95 PD patients and 99 healthy controls was conducted. Ordinal logistic regression analysis was utilized to investigate the clinical correlations between PD and osteoporosis. Two microarray datasets (GSE20292, GSE35958) including PD, osteoporosis and normal control samples were retrieved from the GEO database for GO analysis, KEGG pathway analysis and PPI network. Results: PD patients had lower 25(OH)VitD, FN BMD, BMD and T-score of the LS and TH, as well as poorer bone mass diagnosis, yet higher PINP compared to healthy controls. Both age and UPDRS II score of PD patients were adversely correlated with BMD of LS and TH. PD diagnosis acted as an independent risk factor of osteoporosis, and PD patients had approximately double risk for osteoporosis. Bioinformatics analysis further revealed that SNAP25, AQP4, SV2B, KCND3, and ABCA2 had important diagnostic value and risk prediction value for both PD and osteoporosis. Conclusions: PD diagnosis can be used as an independent risk factor for osteoporosis. Moreover, SNAP25, AQP4, SV2B, KCND3 and ABCA2 as the top 5 hub genes have important diagnostic and risk predictive value for both PD and osteoporosis.

ObjectiveRecent knowledge concerning the significance of long non-coding RNA (lncRNA)-mediated ceRNA networks provides new insight into their possible roles as specific biomarkers for the treatment of osteosarcoma (OS). Thus, this study aims to clarify the functional relevance and mechanistic actions of lncRNA LBX2-AS1 in OS.MethodsDifferential analysis was performed by integrating the TCGA and GTEx databases. Cox regression analysis was then employed to assess the prognostic value of the model. The expression of lncRNA LBX2-AS1 and miR-597-3p was quantified in OS cell lines by qRT-PCR. The proliferation, migration, invasion, and apoptosis of OS cell lines in response to manipulated lncRNA LBX2-AS1 were evaluated by MTT, colony formation, transwell, Western blot, and flow cytometry assays. Luciferase activity was assayed to validate the reciprocal regulation between lncRNA LBX2-AS1 and miR-597-3p. The protein levels of BRD4 and EMT-related factors were examined by Western blot assay. Finally, tumor growth in response to LBX2-AS1 knockdown was evaluated in xenograft-bearing nude mice.ResultsBy integrating the GTEx and TCGA databases, we identified 153 differentially expressed lncRNAs. Among them, 5 lncRNAs, RP11-535M15.1, AC002398.12, RP3-355L5.4, LBX2-AS1, and RP11.47A8.5, were selected to establish a model, which predicted the prognosis of OS. Higher lncRNA LBX2-AS1 expression was noted in OS tissues relative to that in normal tissues. Silencing lncRNA LBX2-AS1 facilitated apoptosis and curtailed proliferative, migratory, and invasive capacities of OS cells. Mechanistically, lncRNA LBX2-AS1 could elevate the expression of BRD4, an oncogene, by competitively binding to miR-597-3p. More importantly, knockdown of lncRNA LBX2-AS1 increased the sensitivity of OS cells to the BRD4 inhibitor JQ-1. Finally, the tumor growth of OS cell xenografts was constrained in vivo in the presence of lncRNA LBX2-AS1 knockdown.ConclusionIn conclusion, lncRNA LBX2-AS1 promotes the growth of OS and represses the sensitivity to JQ-1 by sponging miR-597-3p to elevate the expression of BRD4.

IntroductionChina is one of the largest consumers of agricultural antibiotics in the world. While the Chinese government has been tightening its regulations to control antimicrobial resistance (AMR) from animal sources in recent years, the extent of antimicrobial oversight and the practices of antibiotic use in animal agriculture in China has not yet been explored. This study describes the practices of antimicrobial management in eastern China and current scenarios of antibiotic use in commercial farms and smallholder backyard farming.Methods33 semi-structured interviews were conducted with government agriculture officials, veterinary drug sellers, farmers and smallholders in two contrasting areas of rural Zhejiang and Jiangsu provinces, China. Interview transcripts were analyzed in NVivo12 using a thematic approach.ResultsFindings revealed that although the governance of antibiotic use has made progress, especially in controlling irrational antibiotic use in commercial farms, smallholders are under-regulated due to a lack of resources and assumptions about their marginal role as food safety governance targets. We also found that smallholders resort to human antibiotics for the treatment of backyard animals because of economic constraints and lack of access to professional veterinary services.DiscussionMore attention needs to be devoted to the local structural needs of farmers to reduce antibiotic misuse. Considering the extensive links of AMR exposure under the One Health framework, efforts to integrate smallholders in antibiotic governance are required to address the AMR burden systematically in China.

Due to the superior thermal conductivity and high uranium density, U3Si2 is an excellent candidate for conventional UO2 nuclear fuel and shows great potential application in accident-tolerant fuel (ATF) assembly of light water reactors (LWRs). Currently, the behavior of Xe bubbles with internal or applied stress is rarely investigated, restricting further understanding of swelling in U3Si2. The mesoscopic phase-field method has been developed in this work to study the spatial and temporal Xe bubble evolution in U3Si2. The results show that the bubble density and its average size increase as the fission rate increases. Applied stress accelerates the nucleation and growth of gas bubbles, reshaping the bubbles’ morphology from spherical in a stress-free state into elongated along the applied direction in a stressed state. The gas bubbles in a local dislocation stress field nucleate preferentially at stress-concentrated sites and spread over the whole system in succession, and the bubble coarsening is controlled by the stress overlap of the dislocation pair. The results show a practical phase-field method for Xe bubble evolution study in U3Si2, which can be expanded into swelling behavior investigation in other fuels and lay a solid foundation for the development of ATF assembly.