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Accelerating imaging speed in optical microscopy is often realized at the expense of image contrast, image resolution, and detection sensitivity - a common predicament for advancing high-speed and high-throughput cellular imaging. We here demonstrate a new imaging approach, called asymmetric-detection time-stretch optical microscopy (ATOM), which can deliver ultrafast label-free high-contrast flow imaging with well delineated cellular morphological resolution and in-line optical image amplification to overcome the compromised imaging sensitivity at high speed. We show that ATOM can separately reveal the enhanced phase-gradient and absorption contrast in microfluidic live-cell imaging at a flow speed as high as ∼10 m/s, corresponding to an imaging throughput of ∼100,000 cells/sec. ATOM could thus be the enabling platform to meet the pressing need for intercalating optical microscopy in cellular assay, e.g. imaging flow cytometry - permitting high-throughput access to the morphological information of the individual cells simultaneously with a multitude of parameters obtained in the standard assay. [ABSTRACT FROM AUTHOR]

Stroke is the second leading cause of death globally. Oxidative stress plays a critical role in the development of stroke. The Oxidative Balance Score (OBS) is a tool used to assess the combined impact of diet and lifestyle on the body's antioxidant capacity. The study included stroke survivors from the National Health and Nutrition Examination Survey (1999-2018), with a total of 1,781 participants and a median follow-up duration of 6.5 years, during which 786 participants (39.59%) died. The relationship between OBS and all-cause mortality was assessed using the Cox proportional hazards model. The results indicated that individuals in higher OBS quartiles had lower mortality rates. Specifically, patients in the fourth quartile had a 41% reduced risk of all-cause mortality compared to those in the first quartile (HR = 0.59, 95% CI = 0.42-0.84, p = 0.003). Restricted cubic spline analysis revealed a linear inverse relationship between OBS and all-cause mortality. Subgroup analysis further demonstrated that the inverse association persisted across various population subgroups. Overall, our study suggests that higher levels of OBS can reduce the risk of all-cause mortality in stroke survivors and provides new evidence for their diet and lifestyle., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by the NCHS Research Ethics Review Board (ERB). All participants provided written informed consent., (© 2025. The Author(s).)

Long-term exposure to air pollutants and diabetes are both linked to cancer development. However, their combined effect remains unclear. This study examined the relationship between air pollutants and cancer incidence, with diabetes as a potential mediator. Data from 10,590 participants in the 2015 China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Participants were grouped based on cancer diagnosis, and air pollutant exposure levels were estimated using satellite-based spatiotemporal models. Generalized linear regression and restricted cubic spline (RCS) analysis were used to assess the impact of air pollutants and diabetes in covariates-adjusted models. Further analyses, including conditional independence test, mediation effect and sensitivity analysis based on Bayesian networks, were performed to further analyze specific air pollutants. After adjusting for covariates, particulate matter (PM) (PM ≤ 1 μm in aerodynamic diameter [PM 1 ], PM 2.5 , ammonium (NH 4 ), nitrate (NO 3 ) and diabetes showed significant associations with cancer incidence. RCS analysis confirmed significant direct effects of PM 2.5 and PM 10 on cancer and the mediated effects of diabetes. The interaction between diabetes and both PM 2.5 and PM 10 was further supported by conditional independence tests, highlighting diabetes as a significant mediator in the PM 2.5 -cancer relationship. This study offers a novel perspective by identifying diabetes as a key intermediary in the association between PM 2.5 exposure and cancer risk, providing evidence that diabetes plays a significant mediating role in air pollutant-related cancer development., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The Medical Ethics Board Committee of Peking University granted the study an exemption from review., (© 2025. The Author(s).)

The relationship between 25-hydroxyvitamin D (25(OH)D) status and cardiovascular disease (CVD) in the diabetes population still needs to be clarified. This study aimed to explore the association of 25(OH)D with CVD and cardiometabolic risk factors in Chinese population with type 2 diabetes mellitus (T2DM). This cross-sectional study was performed with 1378 hospitalized patients with T2DM. Participants were classified into three groups according to the serum 25(OH)D levels: vitamin D adequate, vitamin D insufficiency and vitamin D deficient. Multivariate logistic regression analysis, stratified analysis and interaction analysis were performed to determine the relationship between serum 25(OH)D levels and CVD outcome. After adjusting for confounders, serum 25(OH)D levels were significantly negatively associated with cardiovascular disease in type 2 diabetic patients [OR: 0.97 (0.94, 0.99), p = 0.0131]. Taking the vitamin D-sufficient group (≥ 20 ng/mL) as a reference, the vitamin D-deficiency group (< 12 ng/mL) was associated with a significantly higher risk of cardiovascular disease, with a 1.25-fold increased risk after adjusting for all potential confounders [OR: 2.25 (1.33, 3.79), p = 0.0023]. Stratification analysis showed that the association between vitamin D deficiency and increased risk of cardiovascular disease was particularly significant in women [OR: 4.32 (1.54, 12.12), p = 0.0055], older adults [OR: 4.14 (1.10, 15.56), p = 0.0355], normal-weight [OR: 4.09 (1.51, 11.10), p = 0.0056] and obese subjects [OR: 3.66 (1.03, 13.05), p = 0.0453]. Vitamin D deficiency was significantly associated with an increased risk of overweight/obesity [OR: 1.57 (1.10, 2.24), p = 0.0134], hypertension [OR: 1.81 (1.30, 2.51), p = 0.0004], hypertriglyceridemia [OR: 1.56 (1.12, 2.16), p = 0.0078] and reduced HDL-C [OR: 1.67 (1.19, 2.35), p = 0.0033]. Serum 25(OH)D levels were significantly negatively associated with CVD in T2DM patients and vitamin D deficiency was significantly associated with an increased risk of overweight/obesity, hypertension and dyslipidemia., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University. Written informed consent to participate was obtained from all participants. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Fusarium head blight (FHB) is a severe disease worldwide that leads to substantial economic losses. Wheat‒maize cropping is the dominant system in Sichuan Province, China. However, FHB has become increasingly severe in this system, and Fusarium rot disease is also becoming a severe threat to maize. To understand the composition and pathogenicity of the Fusarium species associated with FHB, samples of typical symptomatic wheat spikes were collected from wheat‒maize cropping fields in 16 administrative districts of Sichuan Province, and Fusarium perithecia were obtained from both wheat straw and maize stubble. Based on morphological and molecular identification, 175 isolates from symptomatic wheat spikes were identified as five Fusarium species: F. asiaticum, F. avenaceum, F. graminearum, F. meridionale, and F. proliferatum. Among them, F. asiaticum and F. graminearum were the dominant pathogenic species, with isolation frequencies of 75.43% and 20.57%, respectively. Additionally, 136 single-ascospore isolates from wheat straw or maize stubble were identified as F. asiaticum, F. equiseti, F. graminearum, F. meridionale, F. proliferatum, and F. temperatum. Pathogenicity assays revealed that the Fusarium strains from all sources could successfully infect wheat and maize. F. graminearum exhibited a high degree of pathogenicity towards both crops under investigation, while F. asiaticum demonstrated significantly greater pathogenicity towards wheat than maize. This work will help understand the cyclic infection caused by Fusarium species in wheat‒maize cropping systems and provide valuable data for the effectively controlling Fusarium rot disease in both wheat and maize., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Intervertebral disc degeneration disease (IDD) is one of the leading causes of disability, and current therapies are ineffective. Phosphodiesterase 4B (PDE4B) plays essential roles in regulating the activation of the NLRP3 inflammasome. However, whether PDE4B or NLRP3 is involved in the development of IDD is unclear. This study sought to explore the role of PDE4B in IDD pathogenesis by in vivo and in vitro experiments. This results showed that PDE4B and NLRP3 were significantly upregulated in nucleus pulposus (NP) tissues from IDD-related human patients. Deletion of PDE4B in the NP resulted in downregulated JNK and NLRP3. Aberrant PDE4B expression enhanced the phosphorylation of JNK and NLRP3 expression. Furthermore, genetic ablation of the pde4b gene delayed IDD pathogenesis, and PDE4 inhibitor also can reverse the IDD pathogenesis. Our study showed that aberrant PDE4B activation in NP tissues induces pathological changes in IDD, phosphorylation of JNK and NLRP3 are involved in this process, and inhibition of aberrant PDE4B activity is a potential therapeutic strategy for IDD., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Ethics approval: was obtained from the Ethics Committee of Tongde Hospital of Zhejiang Province (No. 202122-088). Informed consent was obtained from all participants enrolled in this study. The study was conducted according to the Code of Ethics of the World Medical Association (Declaration of Helsinki). All animal procedures were approved by the Animal Care and Use Committee of Zhejiang University. Accordance: We confirmed that all experiments in this study were performed in accordance with the relevant guidelines and regulations. Arrive: All the procedure of the study is followed by the ARRIVE guidelines., (© 2025. The Author(s).)

Steatotic liver disease (SLD) is a common chronic liver disease without effective therapeutic options. Some studies suggest potential health benefits of dietary live microbes. This study aims to investigate the association between dietary live microbes intake and metabolic dysfunction-associated steatotic liver disease (MASLD) / metabolic alcohol-related liver disease (MetALD) / alcoholic liver disease (ALD) in adults. Data from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. MASLD was defined according to the latest Delphi Consensus standard. Participants were grouped based on estimated dietary live microbe intake: low (< 10 4  CFU/g), moderate (10 4 -10 7  CFU/g), and high (> 10 7  CFU/g). Multivariable logistic regression analysis was employed to assess the impact of dietary live microbes on MASLD/MetALD/ALD, along with further investigations into non-dietary probiotic/prebiotic relationships. Participants had a weighted mean age of 47.05 years (SE, 0.24) and 50.59% were female. MASLD proportions differ among low (21.76%), moderate (22.24%), and high (18.96%) microbe groups. Similarly, for MetALD, proportions are 7.75%, 6.95%, and 6.44%, and for ALD, 5.42%, 3.59%, and 2.97% in respective groups. The high dietary live microbe intake group was associated with a 16% lower risk of MASLD compared to those in the low intake group (trend test, P = 0.02), while the risk of ALD was reduced by 25% in the moderate intake group. A lack of association was identified between non-dietary prebiotic/probiotic and MASLD/MetALD/ALD. Our study suggests that a relatively high intake of live microbes diets in adults is associated with a lower risk of SLD., Competing Interests: Declarations. Ethical approval and consent to participate: The study protocols of the NHANES were approved by the National Center for Health Statistics institutional review board, with all individuals providing informed written consent. Human study considerations were exempted due to the anonymity of the data. Consent for publication: Not applicable. Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025. The Author(s).)

Given the limited research on regularization mechanisms in finite element analysis of the ultimate pullout resistance of plate anchors, particularly considering soil strain softening, this paper employs a Cosserat continuum regularization mechanism combined with a Mohr-Coulomb matched Drucker-Prager constitutive model (MC-matched DP model) to address this issue. Implementing the User-Defined Element function in ABAQUS, the numerical solution was developed and validated against existing literature to verify the accuracy of the MC-matched DP model for analyzing plate anchor pullout resistance. This study demonstrates that the Cosserat continuum model effectively resolves common issues such as numerical convergence difficulties and mesh dependency encountered in finite element calculations for softening soils. Subsequently, the model was applied to conduct a detailed analysis of the ultimate pullout resistance of plate anchors and the progressive failure process of the soil. Parametric analyses were performed to explore the combined effects of plate anchor inclination, burial depth, and degree of strain softening on ultimate resistance and failure mechanisms. Based on these analyses, an expression for the ultimate resistance coefficient N c , incorporating the influences of plate anchor inclination, burial depth, and strain softening, was formulated, providing a valuable reference for geotechnical engineers in practical applications., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The impact of neutrophil percentage-to-albumin ratio (NPAR) on the outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective cohort study was conducted in patients with ACLF treated with artificial liver support system (ALSS). The ACLF was diagnosed according to the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH ACLF) criteria. Disease severity was rated according to the COSSH ACLF score. Restricted cubic splines, linear or Cox regression models were used to investigate the relationships of baseline NPAR with disease severity and 90-day prognosis. The 90-day transplant-free and overall survival rates of 258 eligible patients were 58.5% and 66.3%, respectively. The NPAR in transplant-free survivors was lower than that in transplant or death patients (22.8 ± 4.4 vs. 25.3 ± 3.7, P < 0.001). NPAR was positively associated with COSSH ACLF score (adjusted β (95% CI) > 0, P < 0.001), transplant-free survival (adjusted HR (95% CI) for transplant or death: 1.07 (1.02-1.13), P = 0.007), and overall survival (adjusted HR (95% CI) for death: 1.09 (1.03-1.15), P = 0.003). Patients with NPAR ≥ 22.4 had poor 90-day prognosis compared to the rest (all adjusted HR (95% CI) > 1, P < 0.05). NPAR was positively associated with disease severity and poor short-term prognosis in patients with COSSH ACLF who underwent ALSS treatment. Thus, it could be used as a prognostic biomarker for COSSH ACLF., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The cohort study was approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University. All study components were performed according to the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Due to the retrospective nature of the study, the Biomedical Research Ethics Committee of West China Hospital of Sichuan University waived the need of obtaining informed consent., (© 2025. The Author(s).)

Intervertebral Disc degeneration (IDD) is one of the leading causes of disability, and current therapies are ineffective. Phosphodiesterase 4B (PDE4B) plays an essential role in regulating the activation of nuclear factor E2-related factor 2 (Nrf2), while Nrf2 regulates ferroptosis. However, it is still unknown whether PDE4B is involved in the development of IDD. In this study, we explored the role of PDE4B on ferroptosis and Nrf2 in IDD pathogenesis by in vivo and in vitro experiments. The findings suggested that the expressions of PDE4B, ASCL4, and TRFC were significantly upregulated, and the expression of Nrf2 was significantly downregulated in nucleus pulposus (NP) tissues from human IDD patients dependent on IDD degeneration. Overexpression of PDE4B (PDE4B-OE) in NP cells upregulated the expression of ASCL4 and TRFC, and downregulated the expression of Nrf2. Meanwhile, the level of cytokine and oxidative stress were upregulated. Ferroptosis inhibitor Fer-1 or Nrf2 activator dimethyl fumarate (DMF) suppressed the effect of PDE4B-OE, while ferroptosis inducer elastin enhanced the effect of PDE4B-OE. In the IDD rat model, PDE4 inhibitor roflumilast, ferroptosis inhibitor Fer-1, or Nrf2 activator dimethyl fumarate (DMF) delayed IDD pathogenesis. While administration of ferroptosis inducer elastin enhanced IDD pathogenesis. Combination with PDE4B inhibitor and ferroptosis inhibitor Fer-1 significantly synergistic reversed IDD pathogenesis. While combination with PDE4B inhibitor or Nrf2 activator and elastin also decreased the degree of the IDD. The IHC suggested PDE4 inhibitor downregulated the expression of ASCL4 and TRFC. However, the combination effect of the Nrf2 activator was not obvious. Our study suggested that aberrant PDE4B activation in NP tissues induces pathological changes in IDD mediated by ferroptosis, and PDE4 inhibitor reveres the process of IDD by suppressing ferroptosis, and has a synergic effect with ferroptosis inhibitor. So PDE4B inhibition may be a potential therapeutic strategy for IDD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Sarcopenia is an age-related muscle senescence disease that leads to functional limitations, physical disability and premature death in older adults. Atherogenic index of plasma (AIP) is a novel indicator of atherosclerotic status based on triglycerides and high-density lipoprotein cholesterol. The aim of this study was to investigate the association between AIP and new-onset sarcopenia and its components among middle-aged and older adults in a Chinese community. This cohort study included 7,992 participants who were free of sarcopenia in 2011 in the China Health and Retirement Longitudinal Study and were followed up in 2013 and 2015. Sarcopenia was assessed using the recommendations of the Asian Working Group for Sarcopenia 2019. Longitudinal associations between AIP and sarcopenia and its components were assessed using Cox proportional risk regression modeling. The results showed that AIP was negatively associated with sarcopenia [HR and 95% CI: 0.73 (0.62-0.86)]; with muscle mass [β and 95%CI: 0.49 (0.4-0.57)], skeletal muscle mass index [β and 95%CI: 0.17 (0.15-0.2)], and grip strength [β and 95% CI: 0.17 (0.15-0.2)] being positively correlated. A lower AIP was associated with a lower muscle mass and handgrip strength and higher incidence of sarcopenia. Regular measurement of AIP in the middle-aged and older population in the community can help in the early diagnosis and intervention of sarcopenia., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Participants in our study were from the China Health and Retirement Longitudinal Study (CHARLS ). CHARLS informed consent was obtained from each participant before conducting the investigation. The CHARLS study was approved by the Biomedical Ethics Committee of Peking University (approval number: IRB00001052-11015). Consent for publication: Not applicable., (© 2025. The Author(s).)

Ammonia oxidation plays a vital role in regulating soil nitrogen (N) cycle in agricultural soil, which is significantly influenced by different fertilizer regimes. However, there is still need to further investigate the effects of different fertilizer managements on rhizosphere soil ammonia-oxidizing archaea (AOA) and bacteria (AOB) community in the double-cropping rice field. Therefore, the effects of different long-term (37 years) fertilizer managements on rhizosphere soil potential nitrification activity (PNA), AOA and AOB community structure, and its relationship under the double-cropping rice system in southern of China were studied in the present paper. The field experiment included without fertilizer input as a control (CK), inorganic fertilizer (MF), rice straw and inorganic fertilizer (RF), 30% organic manure and 70% inorganic fertilizer (OM). This result indicated that rhizosphere soil organic carbon (SOC) (SOC), total N and ammonium N (NH 4 + -N) contents in paddy field with RF and OM treatments were increased. Rhizosphere soil PNA, potential nitrification rate (PNR) and abundance of AOB in paddy field with MF treatment were increased, and abundance of AOA in paddy field with RF and OM treatments were increased, respectively. The result also showed that rhizosphere soil diversity index of AOA and AOB with RF and OM treatments were enhanced, compared with CK treatment. Rhizosphere soil AOB and AOA community composition was dominated by Proteobacteria, Actinobacteria and Acidobacteria with all fertilizer treatments. There had significantly positively correlation between the abundance of AOA and SOC, total N, and NH 4 -N contents. However, there had significantly negatively correlation between soil pH and abundance of AOA, soil PNA, PNR. As a result, long-term application of rice straw and organic manure was benefit for increasing community structure of rhizosphere soil ammonia oxidizer under the double-cropping rice system in southern of China., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The efficacy of neoadjuvant therapy varies significantly with hormone receptor (HR) status for patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). Despite extensive research on HER2 + BC, the optimal neoadjuvant strategy for HR+/HER2 + BC remains inconclusive. This study aimed to identify the optimal neoadjuvant regimen for HR+/HER2 + BC treatment. We conducted a systematic search for trials comparing neoadjuvant regimens for HR+/HER2 + BC and a network meta-analysis. Odds ratios for pathological complete response (pCR) and hazard ratios for event-free survival (EFS) were calculated. Treatment regimens were ranked using the surface under the cumulative ranking curve. 20 trials with 2809 patients were included. In pCR analysis, three neoadjuvant regimens sequentially ranked at the top, namely those comprising T-DM1, pertuzumab with trastuzumab, and tyrosine kinase inhibitor with trastuzumab, demonstrating significantly higher pCR rates than monotherapies. In EFS analysis, pertuzumab with trastuzumab ranked the first while T-DM1 containing regimen ranked the last. Anthracycline-free regimens showed a marginally higher pCR rate than anthracycline-containing regimens, while carboplatin-containing regimens demonstrated a numerically higher pCR rate than carboplatin-free regimens. Significant heterogeneity was observed in endocrine therapy analysis, which may be caused by different strategies for incorporating endocrine therapy. In conclusion, trastuzumab plus pertuzumab stands out as the optimal neoadjuvant HER2-targeting regimen for HR+/HER2 + BC Furthermore, anthracycline-free carboplatin-containing chemotherapy emerges as a promising combination treatment. Further investigation is required to clarify the role of endocrine therapy in HR+/HER2 + BC to guide its clinical application., Competing Interests: Declarations. Competing interests: Hao Tang, Yajing Feng and Xin Yu are current employees of Shanghai Roche Pharmaceuticals Ltd. The remaining authors have declared no conflicts of interest., (© 2024. The Author(s).)

Immune checkpoint inhibitor (ICI) therapy is the new standard treatment for advanced or metastatic hepatocellular carcinoma (HCC); however, many patients still fail to respond. This study explored the expression and prognosis of programmed death ligand 1 (PD-L1), cluster of differentiation 24 (CD24), and cluster of differentiation 47 (CD47) in patients with hepatitis B virus-associated HCC (HBV-associated HCC). We analyzed sequencing data from the Cancer Genome Atlas (TCGA) and investigated the expression of PD-L1, CD24, and CD47 in HBV-associated HCC patients by immunohistochemistry and their relationship with prognosis and clinicopathological factors. HCC data from the TCGA database show that PD-L1 was substantially correlated with various immune cells. In 67 patients with HBV-associated HCC, high PD-L1 and CD24 expression levels were related to poor overall survival (OS) and progression-free survival (PFS). PD-L1 expression was significantly associated with the staging of HBV-associated HCC (p = 0.011) and Ki67 expression (p = 0.024). Correlation analysis between variables reveals that PD-L1 was significantly positively correlated with CD24 and CD47. High expression of PD-L1 and CD24 are risk factors for poor prognosis in HBV-associated HCC patients following curative resection. PD-L1 is significantly correlated with CD24 and CD47., Competing Interests: Declaration. Competing interests: The authors declare no competing interests. Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Fujian Provincial Hospital (Approval No. K2021-02-013)., (© 2024. The Author(s).)

Osteosarcoma (OS) is the most prevalent secondary sarcoma associated with retinoblastoma (RB). However, the molecular mechanisms driving the interactions between these two diseases remain incompletely understood. This study aims to explore the transcriptomic commonalities and molecular pathways shared by RB and OS, and to identify biomarkers that predict OS prognosis effectively. RNA sequences and patient information for OS and RB were obtained from the University of California Santa Cruz (UCSC) Xena and Gene Expression Omnibus databases. When RB and OS were first identified, a common gene expression profile was discovered. Weighted Gene Co-expression Network Analysis (WGCNA) revealed co-expression networks associated with OS after immunotyping patients. To evaluate the genes shared by RB and OS, univariate and multivariate Cox regression analysis were then carried out. Three machine learning methods were used to pick key genes, and risk models were created and verified. Next, medications that target independent prognostic genes were found using the Cellminer database. The comparison of differential gene expression between OS and RB revealed 1216 genes, primarily linked to the activation and proliferation of immune cells. WGCNA identified 12 modules related to OS immunotyping, with the grey module showing a strong correlation with the immune-inflamed phenotype. This module intersected with differential genes from RB, producing 65 RB-associated OS Immune-inflamed Genes (ROIGs). Analysis identified 6 hub genes for model construction through univariate Cox regression and three machine learning techniques. A risk model based on these hub genes was established, demonstrating significant prognostic value for OS. Genes shared between OS and RB contribute to the progression of both cancers through multiple pathways. The ROIGs risk score model independently predicts the overall survival of OS patients. Additionally, this study highlights genes with potential as therapeutic targets or biomarkers for clinical use., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Interleukin-6 (IL-6) is a major pro-inflammatory cytokine that demonstrates a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions. Our recent studies identified a novel non-canonical signaling pathway that involves prolonged activation of SRC family of kinases (SFKs) by IL-6/gp130, where genetic or pharmacological inhibition of this pathway was protective in several acute injury models. This study was designed to assess the effect of a small molecule (R159) that inhibits the non-canonical signaling in a mouse model of multimorbidity induced by chronic inflammation. Aged mice were fed a high-fat diet (HFD) to exacerbate chronic inflammation and inflammaging-related conditions, and R159 significantly decreased systemic inflammatory responses in adipose tissue and liver. R159 was protective against trabecular bone and articular cartilage loss and markedly prevented neurogenesis decline. Moreover, R159 reduced weight gain induced by HFD and increased physical activity levels. These findings suggest that selective pharmacological inhibition of SFK signaling downstream of IL6/gp130 offers a promising strategy to alleviate systemic chronic inflammation and relevant multimorbidity., Competing Interests: Declarations. Competing interests: Denis Evseenko is a co-founder and major stockholder of Carthronix Inc. All other authors declare no competing interests., (© 2024. The Author(s).)

Cuproptosis is a recently discovered form of regulated cell death triggered by mitochondrial copper accumulation and proteotoxic stress. Here, we provide the first evidence that glutathione (GSH), a major non-protein thiol in cells, acts as a cuproptosis inhibitor in pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, GSH inhibits cuproptosis by chelating copper, contrasting its role in blocking ferroptosis by inhibiting lipid peroxidation. The classical cuproptosis inducer, ES-Cu (elesclomol plus copper), increases the protein stability of the transcription factor NFE2L2 (also known as NRF2), leading to the upregulation of gene expression of glutamate-cysteine ligase modifier subunit (GCLM) and glutamate-cysteine ligase catalytic subunit (GCLC). GCLM and GCLC are rate-limiting enzymes in GSH synthesis, and increased GSH is transported into mitochondria via the solute carrier family 25 member 39 (SLC25A39) transporter. Consequently, genetic inhibition of the NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis-mediated tumor suppression in cell culture and in mouse tumor models. These findings not only reveal distinct mechanisms of GSH in inhibiting cuproptosis and ferroptosis, but also suggest a potential combination strategy to suppress PDAC tumor growth., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hypocalcemia is a common complication of thyroidectomy, particularly total thyroidectomy. The higher incidence of hypocalcemia following total thyroidectomy is primarily due to inadvertent damage to the parathyroid glands during surgery. This study aims to investigate the predictive value of intraoperative parathyroid hormone (IOPTH) in determining hypocalcemia during hospitalization and the recovery of parathyroid function after total thyroidectomy, as well as the factors that may influence IOPTH. In this retrospective study, we analyzed a cohort of 164 patients who underwent total thyroidectomy at our institution between 2018 and 2019. IOPTH was measured either 15 min after bilateral thyroidectomy combined with area VI lymph node dissection, or 15 min after bilateral thyroidectomy alone. We plotted ROC curves for IOPTH and ΔPTH% in relation to hypocalcemia during hospitalization and recovery of parathyroid function. Additionally, we explored risk factors for the development of hypocalcemia during hospitalization and factors that may influence IOPTH. IOPTH and ΔPTH% demonstrated good specificity and sensitivity for predicting hypocalcemia during hospitalization and for assessing recovery of parathyroid function. Lower preoperative PTH levels, chronic lymphocytic thyroiditis, and intraoperative parathyroid auto-transplantation were identified as risk factors for IOPTH < 15 pg/mL. IOPTH and ΔPTH% are predictive of hypocalcemia during the postoperative hospital stay and recovery of parathyroid function. Patients with chronic lymphocytic thyroiditis, intraoperative parathyroid auto-transplantation, and low preoperative PTH levels should be closely monitored for the recovery of parathyroid function after surgery., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study was approved by the Institutional Review Board of China-Japan Union Hospital of Jilin University (approval number: 2022-KYYS-078). The patients or their legal guardians signed a detailed informed consent form before surgery., (© 2024. The Author(s).)

The relationship between the oxidative balance score (OBS) and the serum Klotho level has yet to be defined. We sought to investigate the potential relationship between OBS and the serum Klotho level in the U.S. population aged 40-79 years. This study included 8,145 participants from the National Health and Nutrition Examination Surveys (NHANES) database spanning from 2007 to 2016. The OBS consisted of the dietary OBS and the lifestyle OBS, based on 16 dietary components and 4 lifestyle components. Weighted multiple linear regressions were performed to explore the association between OBS and serum Klotho level. Furthermore, nonlinear relationships were analyzed through the application of restricted cubic splines (RCS). In the multivariate linear regression model with adjustment for such as demographics, economic income and dietary intake, a higher OBS was associated with a higher serum Klotho, with the beta estimate and 95%CI of 2.85 (1.03-4.68, p < 0.01). Compared with the lowest tertile group, the highest group was associated with a higher Klotho level (30.35, 3.43-57.28, p < 0.05). Furthermore, higher dietary OBS and lifestyle OBS were similarly associated with higher Klotho level (beta (95%CI): 1.27 (0.79-3.32); 14.23 (9.53-18.92), respectively). The RCS exhibited a linear dose-response association between OBS, dietary OBS and lifestyle OBS with serum Klotho concentration (P non-linearity >0.05). The association between OBS and serum Klotho level was consistent across age, sex, education, marital status, energy intake and poverty income ratio (PIR) (P interaction >0.05). The study reported significant association between OBS and klotho, indicating that adherence to antioxidant behaviors may be linked to slower aging and better health., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study explored the comorbid mechanisms between Crohn's disease (CD) and chronic obstructive pulmonary disease (COPD) using bioinformatics analysis. From the Gene Expression Omnibus (GEO) microarray dataset, 349 common differentially expressed genes (coDEGs) were identified, and 8 shared hub genes were found: CCL2, CXCL1, TLR2, ICAM1, PTPRC, ITGAX, PTGS2, and MMP9, which were vital for immune function and regulation of inflammatory responses. In addition, the study also analyzed the association between coDEGs and immune cell infiltration using the single-sample gene set enrichment algorithm (ssGSEA). Potential drugs related to these genes were identified using the connectivity map (CMap). These findings provided new perspectives for understanding the interaction between CD and COPD., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Immune system and inflammation had a great influence on the progression of muscle atrophy. However, the causal relationship with specific immune cell traits remained uncertain. The aim of this study was to elucidate the genetic influences on these associations, providing insights into the underlying mechanisms of muscle atrophy. A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between immune cell phenotypes and muscle atrophy. Data on immune cell phenotypes were obtained from a research cohort containing data on 731 immune cell phenotypes and data on muscle atrophy were sourced from a Finnish database. MR analysis was performed using the MR-Egger method, weighted median, inverse variance weighting, heterogeneity testing, sensitivity analysis, and multiplicity analysis, with results subjected to false discovery rate(FDR) correction. Additionally, the UK Biobank cohort was utilized as an external validation. A total of 31 immune phenotypes with causal relationships with muscle atrophy were identified, including various phenotypes of conventional dendritic cells, myeloid cells, T cells/B cells/natural killer cells, regulatory cells, and T cell maturation stages. Among them, 12 immune phenotypes were identified as exhibiting a positive causal relationship with muscle atrophy, while 19 immune phenotypes were demonstrated to have a negative causal association, highlighting the complex interactions between immune cells and muscle health. The results of the reverse MR analysis indicated that a negative correlation between muscle atrophy and CD28 on secreting Treg (OR = 0.9038, 95%CI:0.8308 ~ 0.9832, P = 0.0186). A significant positive correlation was revealed by external datasets between the CD25 on IgD + CD38- immune phenotype and the risk of muscle atrophy, which was consistent with the trend observed in the training group (OR = 1.1041, 95% CI: 1.1005-1.1076, P = 0.0263). No evidence of pleiotropy was observed, and the reliability of these findings was demonstrated by the leave-one-out analysis. The findings highlight significant correlations between certain immune cell features and muscle atrophy, providing potential targets for further investigation of immunological mechanisms and therapeutic interventions for this condition., (© 2024. The Author(s).)

Salmonella enterica, a prominent foodborne pathogen, contributes significantly to global foodborne illnesses annually. This species exhibits significant genetic diversity, potentially impacting its infectivity, disease severity, and antimicrobial resistance. Whole genome sequencing (WGS) offers comprehensive genetic insights that can be utilized for virulence assessment. However, existing bioinformatic tools for studying Salmonella virulence have notable limitations. To address this gap, a Salmonella Virulence Database with a non-redundant, comprehensive list of putative virulence factors was constructed. Two bioinformatic analysis tools, Virulence Factor Profile Assessment and Virulence Factor Profile Comparison tools, were developed. The former provides data on similarity to the reference genes, e-value, and bite score, while the latter assesses the presence/absence of virulence genes in Salmonella isolates and facilitates comparison of virulence profiles across multiple sequences. To validate the database and associated bioinformatic tools, WGS data from 43,853 Salmonella isolates spanning 14 serovars was extracted from GenBank, and WGS data previously generated in our lab was used. Overall, the Salmonella Virulence database and our bioinformatic tools effectively facilitated virulence assessment, enhancing our understanding of virulence profiles among Salmonella isolates and serovars. The public availability of these resources will empower researchers to assess Salmonella virulence comprehensively, which could inform strategies for pathogen control and risk evaluations associated with human illnesses., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The stability of reservoir landslides is determined by the strength of the slide zone. Using both experimental and numerical techniques to analyze the strength of the slide zone has been widely used in the research of reservoir landslides. However, few models consider the strength of the coupling between seepage and shear. This paper aims to analyze the shear strength of slide zone soil combined with different stresses by using the directed shear test and particle flow code PFC 2D . The results indicated that slide zone soil clearly experienced the strain-hardening without seepage. While a specific strain-softening phenomenon was observed because the introduction of seepage reduced the shear strength significantly, the internal friction angle demonstrated a higher sensitivity to seepage stress compared to cohesion as the seepage stress increased. The direction and amount of flow velocity dynamically alter during the shear process, as revealed by numerical simulation results, suggesting that the shear strength was nonlinear with increasing seepage stress and changed structure. It can be assumed that seepage deterioration in the Huangtupo landslide is a dynamic process that influences the structure, strength and permeability characteristics., (© 2024. The Author(s).)

Currently, the alarm functions of existing levee seepage monitoring systems are limited to single-parameter monitoring and lack rate-of-change alarms and correlation alarms. This can lead to false alarms, missed alarms, equipment failures, or unnecessary downtime. To enhance the intelligence of levee safety monitoring and seepage alarms, a levee seepage intelligent alarm system based on a Bidirectional Long Short-Term Memory (BILSTM) network model was designed and implemented. Firstly, data cleaning and preprocessing are carried out on the engineering safety monitoring operation data to reduce the influence of dirty data such as outliers and repetitive values on the accuracy of alarms. Secondly, for the correlation between the piezometric tube water levels of the levee and the Yangtze River water levels, a correlation analysis based on Mutual Information (MI) theory was conducted to minimize the effect of piezometric tube water level change delays on correlation. Finally, the BILSTM model was used to predict trends in these potentially abnormal data intervals. Based on engineering application requirements, alarm thresholds were established, and a multi-level alarm module was developed. Field operation test results show that the proposed method can accurately predict the piezometric tube water levels of levees, achieving intelligent alarms within the engineering safety monitoring system., (© 2024. The Author(s).)

The systemic immune-inflammatory index (SII) has been identified as an independent prognostic factor for multiple diseases. However, the impact of SII on outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective study enrolled patients with ACLF treated with artificial liver support system. Restricted cubic spline (RCS) (knots at the 10th, 50th, and 90th percentiles) and Cox proportional hazards models were applied to investigate the relationship between SII and 90-day transplant-free survival and overall survival in patients with ACLF. A total of 258 patients with ACLF were included. The 90-day transplant-free survival rate and overall survival rate were 58.5% and 66.3%. The SII was 465.5 (277.3-804.4). Adjusted RCS models showed linear exposure-response relationship between SII and 90-day transplant-free survival (P for overall < 0.001, P for nonlinear = 0.154) and 90-day overall survival (P for overall < 0.001, P for nonlinear = 0.103), and adjusted Cox models confirmed the positive relationship. Compared with patients with SII < 480, patients with ≥ 480 had more serious  condition, lower 90-day transplant-free survival rate (46.8% vs. 69.7%, adjusted HR (95% CI) for transplant or death: 2.13 (1.40-3.23), P < 0.001), and lower 90-day overall survival rate (56.3% vs. 75.8%; adjusted HR (95% CI) for death: 2.26 (1.42-3.61), P = 0.001). Stratified Cox models suggested no potential modifiers in the relationship between SII and 90-day transplant-free survival. Our findings suggested SII was positively associated with poor short-term prognosis of ACLF., (© 2024. The Author(s).)

In this study, we successfully established a novel gallbladder cancer cell line, designated as GBC-X1, derived from a primary tumor of a gallbladder cancer patient. By comprehensively analyzing the cell line's phenotype, molecular characteristics, biomarkers, and histological characteristics, we confirmed that GBC-X1 serves as a valuable model for investigating the pathogenesis of gallbladder cancer and developing therapeutic agents. GBC-X1 has been continuously cultured for one year, with over 60 stable passages. Morphologically, GBC-X1 exhibits typical features of epithelial tumors. The population doubling time of GBC-X1 is 32 h. STR analysis validated a high consistency between GBC-X1 and the patient's primary tumor. Karyotype analysis revealed an abnormal hypertetraploid karyotype for GBC-X1, characterized by representative karyotypes of 98, XXXX del (4) p (12) del (5) p (21) der (10). Under suspension culture conditions, GBC-X1 efficiently forms tumor balls, while subcutaneous inoculation of GBC-X1 cells into NXG mice leads to xenograft formation with a rate of 80%. Drug sensitivity testing demonstrated that GBC-X1 is resistant to oxaliplatin and sensitive to 5-FU, gemcitabine, and paclitaxel. Immunohistochemistry revealed positive expression of CK7, CK19, E-cadherin, MMP-2, CD44, SOX2, and TP53 in GBC-X1 cells, weak positive expression of Vimentin, and a Ki67 positive rate of 35%. Our research highlights GBC-X1 as a novel gallbladder cancer cell line and emphasizes its potential as an effective experimental model for investigating the pathogenesis of gallbladder cancer and drug development., (© 2024. The Author(s).)

Soil organic carbon (SOC) plays a vital role in maintaining or enhancing soil fertility and quality of paddy field, but there is still limited information about how SOC mineralization responds to different tillage managements under the double-cropping rice (Oryza sativa L.) system in southern of China. Therefore, this study was designed to explore the changes in SOC content, soil enzyme activities (invertase, cellulose and urease), SOC mineralization at 0-10 cm and 10-20 cm layers and its relationship with 7-years tillage management under the double-cropping rice system of southern China. The experiment included four tillage managements: rotary tillage with all residues removed as a control (RTO), conventional tillage with residue incorporation (CT), rotary tillage with residue incorporation (RT), and no-tillage with residue retention (NT). The results indicated that SOC and soil labile organic carbon contents at 0-10 cm and 10-20 cm layers in paddy field with CT and RT treatments were significantly higher than the RTO treatment. Compared to the RTO treatment, SOC mineralization and accumulation at 0-10 cm and 10-20 cm layers in paddy field with CT, RT and NT treatments were increased. SOC accumulation and potential mineralization at 0-10 cm layer with NT treatment were significantly higher than the CT, RT and RTO treatments. Soil mineralization constant at 10-20 cm layer with CT treatment was significantly higher than those of RT, NT and RTO treatments. This result indicated SOC mineralization rate and accumulation at 10-20 cm layer of CT, RT, NT and RTO treatments were lower than those of treatments at 0-10 cm layer. Compared to RTO treatment, soil invertase, cellulose and urease activities with CT and RT treatments were significantly increased. Compared to RTO treatment, soil invertase, cellulose and urease activities at 0-20 cm layer of CT treatment increased by 22.6%, 46.2% and 89.0%, respectively. There was significantly positive correlation between SOC accumulation and SOC content, soil invertase, cellulose, urease activities, but SOC accumulation was significantly negative correlated with soil pH, bulk density. Therefore, CT and RT treatments were beneficial managements to improve SOC content and SOC mineralization in the double-cropping rice field of southern China., (© 2024. The Author(s).)

The first-order second-moment checking point method was introduced to judge the instability probability and evaluate the stability of the TCURM. The frequency-response stability calculation and the reliability results were compared, and a frequency-response stability and reliability analysis method was proposed. Taking the Zengziyan W12 # unstable rock mass in Nanchuan, Chongqing, China, as an example, the calculation shows that the dynamic indexes and geological indexes decrease as the stiffness of the deterioration area decreases. According to the statistical data of the laboratory test and the field investigation, reliability theory is used to evaluate the stability of the TCURM, and the failure probabilities are 80.3% and 96.27% under natural and saturated conditions, which correspond to states of poor stability and instability, respectively. The reliability evaluation results are consistent with the conclusion of the frequency-response stability analysis. The new method can provide a theoretical basis for developing the dynamic monitoring and early warning indicators of the TCURM and disaster prevention and mitigation in mountainous areas., (© 2024. The Author(s).)

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC., (© 2024. The Author(s).)

Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS&#95;SIGNALING&#95;UP pathway in AR and related to HYPOXIA, TGF&#95;BETA&#95;SIGNALING and TNFA&#95;SIGNALING&#95;VIA&#95;NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE., (© 2024. The Author(s).)

The differences between the serum albumin determined by bromocresol green (BCG) and immunonephelometry (IN) were inconsistent in past studies, and the samples were all adults. We sought to determine the differences in children and reveal the impacts of these differences on the clinical diagnosis and treatments of primary nephrotic syndrome (PNS). Repeated measurements from 576 PNS children showed that albumin measured by BCG and IN (ALB-B and ALB-I) were 19.95 (11.15) g/L and 15.30 (11.05) g/L, respectively, and the mean difference was 4.68 g/L (P < 0.001). The cut-offs we calculated for hypoalbuminemia and severe hypoalbuminemia based on the IN were 25 and 15 g/L, which were 5 g/L lower than the cut-offs recommended by KIDGO, respectively. A pair of historical control samples (206 vs. 216) with ALB-B or ALB-I showed that the proportion of severe hypoalbuminemia was 14.60% greater in IN group (75.20% vs. 60.60%, P < 0.001). The misdiagnosis rate of severe hypoalbuminemia by IN was 33.77% when 20 g/L rather than 15 g/L was used as the cut-off. Furthermore, the proportion of patients receiving albumin injections increased by 10.20%, and the average consumption increased by 97.06% (P = 0.01) along with the use of IN. So, our results suggested that the difference between ALB-B and ALB-I led to misdiagnosis and prescription abuse in PNS children., (© 2024. The Author(s).)

This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin β1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases., (© 2024. The Author(s).)

Insulin resistance (IR) has a strong association with acute ischemic stroke (AIS) occurrence and poor prognosis of afflicted patients. However, the relation between early neurological deterioration (END) risk and IR in elderly and middle-aged patients remains to be thoroughly studied. Here, we investigated the relationship between four indicators of IR and the risk of END in middle-aged patients patients with AIS. The study retrospectively analyzed 1696 elderly and middle-aged patients having AIS between January 2019 and June 2023. Within 7 days of admission, the patients were then stratified relying upon alternations in the National Institutes of Health Stroke Scale. Subsequently, we employed logistic regression analyses for assessing each index correlation with END on the basis of the tertiles of TyG index (TyGI), triglyceride to high-density lipoprotein ratio (TG/HDL), TyG-BMI, alongside IR metabolic score (METS-IR). These four indicators were significantly heightened in the END group (n = 680) in comparison to the non-END group (n = 1016). When grouping using tertiles, the four aforementioned indicators emerged as independent risk factors for END occurrence, whether or not adjusted for confounding factors. The results revealed a progressive elevation in END occurrence risk with the rise in the tertile of each indicator. Finally, we utilized receiver operating characteristic (ROC) curves for assessing the indicators' predictive power. TyG-BMI, TyGI, TG/HDL, and METS-IRs' area under the curve (AUC) were, respectively, 0.736 (95% CI: 0.712-0.761; P < 0.001), 0. 694 (95% CI: 0.668-0.721; P < 0.001), 0.684 (95% CI: 0.658-0.711; P < 0.001), and 0.722 (95% CI: 0.697-0.747; P < 0.001). IR is associated with END risk in middle-aged AIS patients. TyG-BMI, TyGI, TG/HDL, and METS-IR are independent risk factors of END in elderly and middle-aged AIS patients. Simultaneously, these four IR indicators have significant predictive power for END., (© 2024. The Author(s).)

In order to improve the ability of intelligent reasoning and prediction of 3DR27 model which presented in our previous work, enhance the usability of this model, and better fulfill the demands of real applications for spatial database, we focused on the problem of reasoning with the inverse of 3D cardinal direction relations between spatial objects. In order to realize automated reasoning, an algorithm for computing the inverse of 3D cardinal direction relations based on matrices is proposed on the basis of the mapping between the 3D rectangular cardinal direction relations and 3D interval relation matrix. This algorithm improves the power of reasoning for this model by means of the excellent properties of matrix operations. Theorems are provided to prove formally that our algorithm is correct and complete. This study realized the automatic inference and calculation of the inverse of the 3D cardinal direction relations based on 3DR27 model and further improved the ability of spatial reasoning and spatial analysis of spatial database., (© 2024. The Author(s).)

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression. Statistical analyses revealed 1038, 1244, and 3125 significantly altered genes (P < 0.05, abs (log 2 fold change) > log 2 1.5) between control and MCT-exposed rats during the first, second, and third week, respectively. Pathway enrichment analyses revealed involvement of cell cycle and innate immune system for the upregulated genes, GPCR and VEGF signaling for the downregulated genes. Furthermore, qRT-PCR validated upregulation of representative genes associated with cell cycle including Cdc25c (cell division cycle 25C), Cdc45, Top2a (topoisomerase IIα), Ccna2 (cyclin A2) and Ccnb1 (cyclin B1). Western blot and immunofluorescence analysis confirmed increases in PCNA, Ccna2, Top2a, along with other proliferation markers in the lung tissue of MCT-treated rats. In summary, RNA sequencing data highlights the significance of cell proliferation in progression of rodent PH., (© 2024. The Author(s).)

The resolution of traffic congestion and personal safety issues holds paramount importance for human's life. The ability of an autonomous driving system to navigate complex road conditions is crucial. Deep learning has greatly facilitated machine vision perception in autonomous driving. Aiming at the problem of small target detection in traditional YOLOv5s, this paper proposes an optimized target detection algorithm. The C3 module on the algorithm's backbone is upgraded to the CBAMC3 module, introducing a novel GELU activation function and EfficiCIoU loss function, which accelerate convergence on position loss l box , confidence loss l obj , and classification loss l cls , enhance image learning capabilities and address the issue of inaccurate detection of small targets by improving the algorithm. Testing with a vehicle-mounted camera on a predefined route effectively identifies road vehicles and analyzes depth position information. The avoidance model, combined with Pure Pursuit and MPC control algorithms, exhibits more stable variations in vehicle speed, front-wheel steering angle, lateral acceleration, etc., compared to the non-optimized version. The robustness of the driving system's visual avoidance functionality is enhanced, further ameliorating congestion issues and ensuring personal safety., (© 2024. The Author(s).)

Degradation of bond strength due to corrosion of steel strands is of great importance for serviceability of prestressed concrete structures. An analytical model is proposed to demonstrate the effect of corrosion of steel strand on reduction of bond strength. Corrosion expansion force generated by steel strand corrosion before and after corrosion cracking is firstly estimated. Then, the reduced gripping effect of the concrete, change of friction coefficient between the corroded strand and reduction force on the bearing face are considered in calculating the pre-rib extrusion force. Finally, the enhancement of bond strength due to transverse confinement of stirrups is considered and the ultimate bond strength of corroded steel strand is calculated. Comparison of results between the prediction and experimental result shows the proposed model can be used to reasonably evaluate the bond strength. The prediction result of the bond strength model is affected by the degree of strand corrosion, but almost not by the drawing method., (© 2024. The Author(s).)

Based on the dual response of RhB@UiO-67 (1:6) to Cu 2+ and Fe 3+ , a proportional fluorescent probe with (I 392 /I 581 ) as the output signal was developed to recognize Cu 2+ and Fe 3+ . Developing highly sensitive and selective trace metal ions probes is crucial to human health and ecological sustainability. In this work, a series of ratio fluorescent probes (RhB@UiO-67) were successfully synthesized using a one-pot method to enable fluorescence sensing of Cu 2+ and Fe 3+ at low concentrations. The proportional fluorescent probe RhB@UiO-67 (1:6) exhibited simultaneous quenching of Cu 2+ and Fe 3+ , which was found to be of interest. Furthermore, the limits of detection (LODs) for Cu 2+ and Fe 3+ were determined to be 2.76 μM and 0.76 μM, respectively, for RhB@UiO-67 (1:6). These values were significantly superior to those reported for previous sensors, indicating the probe's effectiveness in detecting Cu 2+ and Fe 3+ in an ethanol medium. Additionally, RhB@UiO-67 (1:6) demonstrated exceptional immunity and reproducibility towards Cu 2+ and Fe 3+ . The observed fluorescence quenching of Cu 2+ and Fe 3+ was primarily attributed to the mechanisms of fluorescence resonance energy transfer (FRET), photoinduced electron transfer (PET), and competitive absorption (CA). This work establishes a valuable foundation for the future study and utilization of Cu 2+ and Fe 3+ sensing technologies., (© 2024. The Author(s).)

Agricultural products are pivotal to the national economy, and a comprehensive analysis of brand competitiveness significantly contributes to the support of agricultural structural adjustment and modernization. Focusing on the Yangtze River Delta region of China, this study develops an evaluation index system encompassing four dimensions: core brand competitiveness, brand management, market competitiveness, and innovation in branding. Utilizing a DEMATEL-ISM model, this research elucidates the intrinsic relationships among factors that influence brand competitiveness, resulting in a four-tier hierarchical model. The analysis delineates key factors at superficial, intermediate, and profound levels that influence brand competitiveness. Notably, regional production bases, along with innovations in brand technology and systems, emerge as profound influencers. Drawing on these findings, the study recommends strategies to enhance production foundations, accurately define development trajectories, spearhead technological innovation to foster collective reform efforts, and advocate for institutional advancements to bolster healthy brand growth., (© 2024. The Author(s).)

The impact of aging on diabetic retinopathy (DR) remains underestimated. The current study aimed to investigate the association between biological aging and DR, in contrast to chronological age (CA). Using the National Health and Nutrition Survey data from 2005 to 2008. Biological aging was evaluated through the biological age (BA) and phenotypic age (PA), which were calculated from clinical markers. DR was identified in participants with diabetes mellitus (DM) when they exhibited one or more retinal microaneurysms or retinal blot hemorrhages under retinal imaging, with or without the presence of more severe lesions. Survey-weighted multivariable logistic regression was performed, and the regression model was further fitted using restricted cubic splines. The discriminatory capability and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Based on weighted analyses, of the 3100 participants included in this study, of which 162 had DR. In the adjusted model, BA (odds ratio [OR] = 1.12, 95% CI, 1.06-1.18) and PA (OR = 1.11, 95% CI, 1.07-1.14) were associated with DR, while CA was not significantly (OR = 1.01, 95% CI, 0.99-1.03). Narrowing the analysis to DM participants and adjusting for factors like insulin showed similar results. ROC and DCA analyses indicate that BA/PA predicted DR better than CA and offer greater clinical utility. The positive association between BA/PA and DR was consistent across subgroups despite potential interactions. Biological aging heightens DR risk, with BA/PA showing a stronger association than CA. Our findings underscored the importance of timely anti-aging interventions for preventing DR., (© 2024. The Author(s).)

Chemotherapy resistance poses clinical challenges in pancreatic cancer treatment. Developing cell lines resistant to chemotherapy is crucial for investigating drug resistance mechanisms and identifying alternative treatment pathways. The genetic and biological attributes of pancreatic cancer depend on its aetiology, racial demographics and anatomical origin, underscoring the need for models that comprehensively represent these characteristics. Here, we introduce PDAC-X2, a pancreatic cancer cell line derived from Chinese patients. We conducted a comprehensive analysis encompassing the immune phenotype, biology, genetics, molecular characteristics and tumorigenicity of the cell line. PDAC-X2 cells displayed epithelial morphology and expressed cell markers (CK7 and CK19) alongside other markers (E-cadherin, Vimentin, Ki-67, CEA and CA19-9). The population doubling time averaged around 69 h. In vivo, PDAC-X2 cells consistently maintained their tumorigenicity, achieving a 100% tumour formation rate. Characterised by a predominantly tetraploid karyotype, this cell line exhibited a complex genetic markup. Notably, PDAC-X2 cells demonstrated resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil and oxaliplatin. In conclusion, PDAC-X2 presents an invaluable preclinical model. Its utility lies in facilitating the study of drug resistance mechanisms and the exploration of alternative therapeutic approaches aimed at enhancing the prognosis of this tumour type., (© 2024. The Author(s).)

Although the death of hepatocytes is a crucial trigger of liver ischemia-reperfusion (I/R) injury, the regulation of liver I/R-induced hepatocyte death is still poorly understood. Phosphoglycerate mutase 5 (PGAM5), a mitochondrial Serine/Threonine protein phosphatase, regulates mitochondrial dynamics and is involved in the process of both apoptosis and necrotic. However, it is still unclear what role PGAM5 plays in the death of hepatocytes induced by I/R. Using a PGAM5-silence mice model, we investigated the role of PGAM5 in liver I/R injury and its relevant molecular mechanisms. Our data showed that PGAM5 was highly expressed in mice with liver I/R injury. Silence of PGAM5 could decrease I/R-induced hepatocyte death in mice. In subcellular levels, the silence of PGAM5 could restore mitochondrial membrane potential, increase mitochondrial DNA copy number and transcription levels, inhibit ROS generation, and prevent I/R-induced opening of abnormal mPTP. As for the molecular mechanisms, we indicated that the silence of PGAM5 could inhibit Drp1(S616) phosphorylation, leading to a partial reduction of mitochondrial fission. In addition, Mdivi-1 could inhibit mitochondrial fission, decrease hepatocyte death, and attenuate liver I/R injury in mice. In conclusion, our data reveal the molecular mechanism of PGAM5 in driving hepatocyte death through activating mitochondrial fission in liver I/R injury., (© 2024. The Author(s).)

Radix Fici Simplicissimae (RFS) is widely studied, and is in demand for its value in medicines and food products, with increased scientific focus on its cultivation and breeding. We used ultra-high-performance liquid chromatography quadrupole-orbitrap mass spectrometry-based metabolomics to elucidate the similarities and differences in phytochemical compositions of wild Radix Fici Simplicissimae (WRFS) and cultivated Radix Fici Simplicissimae (CRFS). Untargeted metabolomic analysis was performed with multivariate statistical analysis and heat maps to identify the differences. Eighty one compounds were identified from WRFS and CRFS samples. Principal component analysis and orthogonal partial least squares discrimination analysis indicated that mass spectrometry could effectively distinguish WRFS from CRFS. Among these, 17 potential biomarkers with high metabolic contents could distinguish between the two varieties, including seven phenylpropanoids, three flavonoids, one flavonol, one alkaloid, one glycoside, and four organic acids. Notably, psoralen, apigenin, and bergapten, essential metabolites that play a substantial pharmacological role in RFS, are upregulated in WRFS. WRFS and CRFS are rich in phytochemicals and are similar in terms of the compounds they contain. These findings highlight the effects of different growth environments and drug varieties on secondary metabolite compositions and provide support for targeted breeding for improved CRFS varieties., (© 2024. The Author(s).)