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Abstract Background The existing drugs for ovarian cancer (OC) are unsatisfactory and thus new drug targets are urgently required. We conducted proteome-wide Mendelian randomization (MR) and colocalization analysis to pinpoint potential targets for OC. Methods Data on protein quantitative trait loci (pQTL) for 734 plasma proteins were obtained from large genome-proteome-wide association studies. Genetic associations with OC were derived from the Ovarian Cancer Association Consortium, which included 25,509 cases and 40,941 controls. MR analysis was performed to evaluate the association between the proteins and the OC risk. Colocalization analysis was conducted to check whether the identified proteins and OC shared causal variants. In addition, the phenome-wide MR analysis was performed to clarify protein associations across the phenotype, and drug target databases were examined for target validation. Results Genetically predicted circulating levels of 44 proteins were associated with OC risk at Benjamini-Hochberg correction. Genetically predicted 17 proteins had evidence of the increased risk of OC (CLEC11A, MFAP2, TYMP, PDIA3, IL1R1, SPINK1, PLAU, DKK2, IL6ST, DLK1, LRRC15, CDON, ANGPTL1, SEMA4D, AKR1A1, TNFAIP6, and FCGR2B); 27 proteins decreased the risk of OC(SIGLEC9, RARRES1, SPINT3, TMEM132A, HAVCR2, CNTN2, TGFBI, GSTA1, HGFAC, TREML2, GRAMD1C, ASAH2, CPNE1, CCL25, MAPKAPK2, POFUT1, PREP, NTNG1, CA10, CACNA2D3, CA8, MAN1C1, MRC2, IL10RB, RBP4, GP5 and CALCOCO2). Bayesian colocalization demonstrated that GRAMD1C, RBP4, PLAU, PDIA3, MFAP2, POFUT1, MAN1C1 and DKK2 shared the same variant with OC. The phe-MR analyses assessed the side effects of these 44 identified proteins, and the drug target database offered information on both approved and investigational indications. Conclusion This study provides proof of a causal relationship between genetically predicted 44 proteins associated with OC risk, which could serve as promising drug targets for OC.

Abstract Tension-adhesion interplay is a crucial mechanism in multicellular organisms that determines the tension differential among internal and external interfaces, which in turn, mediates tissue surface tension and cell sorting, morphogenesis and remodeling, and cancer progression. Cadherins are widely believed to be involved, yet key aspects of the process are neither well characterized nor quantified. This study demonstrates the critical role of N-cadherin in driving tension polarization throughout the actin cortical network. N-cadherin regulates both tension increase at the cell-medium (external) interface and decrease at the cell-cell (internal) interface, and their quantitative magnitudes, both absolute and relative, strongly depend on the surface density of N-cadherin. Furthermore, the strength of tension polarization also increases with respect to the number of cell-cell interfaces for cells within a multicellular cluster. The cadherin-actin contractility linkage is mediated by Rac1, which serves as a molecular switch to trigger cortex remodeling and contraction via myosin II. Inhibition of Rac1 activity decreases tension polarization and leads to reduced coherence in both small clusters and spheroids. These results provide a pathway to reconcile opposing theories for tissue surface tension generation and perspectives in cancer treatment.

Abstract Background Muscle quality index (MQI), an emerging health index, is calculated by dividing handgrip strength by skeletal muscle mass. Current evidence on the correlation between MQI and type 2 diabetes mellitus (T2DM), insulin resistance (IR) is limited. This work aims to study that correlation. Methods This study involves a cross-sectional analysis on data from the National Health and Nutrition Examination Survey (NHANES) during the period from 2011 to 2014. To explore the correlation between MQI, IR and T2DM, multivariate logistic regression, receiver operating characteristic (ROC) curve, subgroup analysis, and restricted cubic spline regression were employed. Results A total of 2816 American adults were enrolled in this study, among whom 1264 (44.9%) had IR, and 300 (10.7%) had T2DM. Logistic regression and RCS regression analyses showed a significant negative linearly correlation between MQI and the prevalence of IR (OR = 0.708, 95%=0.514, 0.976) and T2DM (OR = 0.676, 95%CI = 0.472, 0.969). Subgroup analysis further revealed a stronger correlation between MQI and IR among individuals with obesity. ROC analysis showed that compared with skeletal muscle and grip strength, MQI (AUC = 0.679 for IR and 0.688 for T2DM) can serve as a more reliable identification factor for IR and T2DM. Conclusion This study provides evidence that decreased levels of MQI are correlated with an increased risk of IR and T2DM, indicating the potential utility as a marker for identifying IR and T2DM.

Abstract Background Based on triglyceride, body mass index (BMI), alanine aminotransferase/ aspartate aminotransferase ratio, fasting blood glucose, the ZJU index is proven to be a novel and effective parameter for screening NAFLD in Chinese. This study aims to evaluate the correlation between ZJU values and the risk of developing gallstones. Methods The data from the National Health and Nutrition Examination Survey (NHANES) database during the period from 2017 to 2020 were analyzed in this cross-sectional study. And 6155 participants were included to assess the correlation between the ZJU index and the formation of gallstones through multivariate logistic regression, receiver operating characteristic (ROC) curve, subgroup analysis, and restricted cubic spline regression (RCS) analyses. Results In this population-based study, 6155 participants aged 18 years and older were included, among which, 671 had gallstones. Logistic regression and RCS regression analyses indicated a significant positive non-linearly correlation between the ZJU index and the prevalence of gallstones (OR = 1.044, 95% CI: 1.032, 1.056), with an inflection point of 40.6. Subgroup analysis further revealed a stronger correlation between the risk of developing gallstones and the ZJU index in females. ROC analysis indicated that the ZJU index (AUC = 0.653) can serve as a more robust predictor for developing gallstones compared to traditional indices, with a sensitivity of 55.9%, a specificity of 67.1% and a cutoff of 43.4. Conclusion This study provides evidence that elevated the ZJU index is correlated with an increased risk of developing gallstones.

Abstract Pancreatic ductal adenocarcinoma (PDAC) accounts for 95% of all pancreatic cancer cases, posing grave challenges to its diagnosis and treatment. Timely diagnosis is pivotal for improving patient survival, necessitating the discovery of precise biomarkers. An innovative approach was introduced to identify gene markers for precision PDAC detection. The core idea of our method is to discover gene pairs that display consistent opposite relative expression and differential co‐expression patterns between PDAC and normal samples. Reversal gene pair analysis and differential partial correlation analysis were performed to determine reversal differential partial correlation (RDC) gene pairs. Using incremental feature selection, the authors refined the selected gene set and constructed a machine‐learning model for PDAC recognition. As a result, the approach identified 10 RDC gene pairs. And the model could achieve a remarkable accuracy of 96.1% during cross‐validation, surpassing gene expression‐based models. The experiment on independent validation data confirmed the model's performance. Enrichment analysis revealed the involvement of these genes in essential biological processes and shed light on their potential roles in PDAC pathogenesis. Overall, the findings highlight the potential of these 10 RDC gene pairs as effective diagnostic markers for early PDAC detection, bringing hope for improving patient prognosis and survival.

Abstract Background Frailty is an emerging global burden of disease, characterized as an age-related clinical syndrome. Recent studies have suggested a potential link of circulating protein levels with the onset of frailty. This study aims to analyze the potential causal relationships of plasma proteins with frailty using a Mendelian Randomization (MR) study design. Methods Associations of plasma proteins with frailty were assessed using inverse variance weighted (IVW), MR-Egger regression, weighted median, maximum-likelihood method, and MR-PRESSO test. Protein-protein interaction network construction and gene ontology functional enrichment analysis were conducted based on MR-identified target proteins. Results After false discovery rate (FDR) correction, MR analysis identified five plasma proteins, including BIRC2 [OR = 0.978, 95%CI (0.967–0.990)] and PSME1 [OR = 0.936, 95%CI (0.909–0.965)], as protective factors against frailty, and 49 proteins, including APOB [OR = 1.053, 95%CI (1.037–1.069)] and CYP3A4 [OR = 1.098, 95%CI (1.068–1.128)], as risk factors. Network analysis suggested BIRC2, PSME1, APOE, and CTNNB1 as key intervention targets. Conclusion This study employed MR design to investigate the association of circulating plasma proteins with frailty, identified five proteins negatively associated with frailty risk and 49 proteins positively associated with frailty.

Abstract To analyze the trend changes in the disease burden of depressive disorder (DD) among youth and adolescents aged 10 to 29 years globally from 1990 to 2021 to provide a theoretical basis for the prevention and treatment of DD in young populations. Utilizing data from the Global Burden of Disease Study 2021, prevalence rates and disability-adjusted life years (DALYs) were employed as indicators. Trends in the disease burden of DD among global youth aged 10 to 29 years from 1990 to 2021 were analyzed with joinpoint regression models. The analysis incorporated major risk factors. Concurrently, an age-period-cohort model was used to provide a more comprehensive assessment of the prevalence and burden of DD. Over the past 30 years, the prevalence rates of DD and DALYs rate among the 10–29-year-old age group generally showed an increasing trend, with values for females being consistently higher than values for males. Notably, compared with the other age groups, the 10- to 14- year-old age group presented more significant increases in both prevalence and DALYs. Regional disparity analysis revealed that while high-sociodemographic index (SDI) regions showed an increasing trend in DD prevalence and DALYs, middle- to low-SDI regions showed some decline. This study highlights the global disease burden of depressive disorder among young populations. The significant increase in both prevalence and DALYs in the 10- to 14-year-old age group emphasizes the trend toward an earlier onset of depressive disorder, also underlining the disparities in depressive disorder management between high-SDI and low-SDI regions. Clinical trial number: not applicable.

The aim of this experiment was to investigate the effect of Lycium barbarum polysaccharides (LBP) on alleviating soybean meal-induced enteritis (SBMIE) in spotted sea bass Lateolabrax maculatus. The diet with 44% fishmeal (FM) content was used as a blank control, and soybean meal (SM) was used to replace 50% FM as an experimental control to induce enteritis. Then, on the basis of experimental control, 0.10%, 0.15%, and 0.20% LBP were added as experimental diets. A total of 225 spotted sea bass (44.52 ± 0.24 g) were randomly divided into 5 groups and fed the corresponding diets for 52 d. The results showed that 0.15% LBP decreased serum D-lactic acid (D-LA) content and diamine oxidase (DAO) activity (P

Abstract The spectrum of synucleinopathies, including Parkinson’s disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), is characterized by α-synuclein (αSyn) pathology, which serves as the definitive diagnostic marker. However, current diagnostic methods primarily rely on motor symptoms that manifest years after the initial neuropathological changes, thereby delaying potential treatment. The symptomatic overlap between PD and MSA further complicates the diagnosis, highlighting the need for precise and differential diagnostic methods for these overlapping neurodegenerative diseases. αSyn misfolding and aggregation occur before clinical symptoms appear, suggesting that detection of pathological αSyn could enable early molecular diagnosis of synucleinopathies. Recent advances in seed amplification assay (SAA) offer a tool for detecting neurodegenerative diseases by identifying αSyn misfolding in fluid and tissue samples, even at preclinical stages. Extensive research has validated the effectiveness and reproducibility of SAAs for diagnosing synucleinopathies, with ongoing efforts focusing on optimizing conditions for detecting pathological αSyn in more accessible samples and identifying specific αSyn species to differentiate between various synucleinopathies. This review offers a thorough overview of SAA technology, exploring its applications for diagnosing synucleinopathies, addressing the current challenges, and outlining future directions for its clinical use.

Abstract Background Ovarian clear cell carcinoma (OCCC) has a disproportionately high incidence among women in East Asia. Patients diagnosed with OCCC tend to experience worse clinical outcomes than those with high-grade serous carcinoma (HGSC) at advanced stages. The unfavorable prognosis of OCCC can be partly attributed to its frequent resistance to conventional chemotherapy. Within a precision medicine framework, we sought to provide a comprehensive molecular characterization of OCCC using whole-exome sequencing to uncover potential molecular targets that may inform novel therapeutic strategies. Methods We performed whole-exome sequencing analysis on tumor-normal paired samples from 102 OCCC patients. This comprehensive genomic characterization of a substantial cohort of OCCC specimens was coupled with an analysis of clonal progression. Results On analyzing 102 OCCC samples, ARID1A (67%) and PIK3CA (49%) emerged as the most frequently mutated driver genes. We identified tier 1 or 2 clinically actionable molecular targets in 40% of cases. This included DNA mismatch repair deficiency (n = 1), as well as BRCA2 (n = 1), PIK3CA (n = 36), KRAS G12C (n = 1), and ATM (n = 4) mutations. Furthermore, 45% of OCCC samples displayed ARID1A biallelic loss. Interestingly, we identified previously unreported mutations in the 5’ untranslated region of the TERT gene that harbored an adverse prognostic significance. Clock-like mutational processes and activated APOBECs were major drivers of somatic point mutations. Mutations arising from DNA mismatch repair deficiency were uncommon. Reconstruction of clonal evolution revealed that early genetic events likely driving tumorigenesis included mutations in the ARID1A, PIK3CA, TERT, KRAS, and TP53 genes. Conclusions Our study provides a comprehensive characterization of the genomic landscape and clonal evolution in OCCC within a substantial cohort. These findings unveil potentially actionable molecular alterations that could be leveraged to develop targeted therapies.

Abstract Background Predicting chemorefractory disease in advanced epithelial ovarian cancer (EOC) remains challenging. This study aimed to identify clinicopathological factors and hemogram data as predictive markers for chemorefractory EOC and to explore potential therapeutic approaches that may mitigate these unfavorable conditions. Methods We conducted a retrospective analysis of patients with advanced EOC treated with chemotherapy. Hemogram data and clinicopathological variables were collected. We employed logistic regression to assess factors associated with chemorefractory EOC and used the Kaplan–Meier method for survival analysis. Results Among the 191 patients analyzed, suboptimal surgery, lymphocyte count

Abstract Background Recent studies have identified a correlation between insulin resistance (IR) and depression. This study aims to explore the correlation between estimated glucose disposal rate (eGDR), a practical and noninvasive measure for assessing IR, and depression in the general population. Methods In this population-based cross-sectional study, data from 28,444 adults aged 18 years old or older in the NHANES during the period from 1999 to 2018 were analyzed. The correlation between eGDR and depression was examined through multivariate logistic regression analyses, subgroup analyses, restricted cubic spline, and interaction tests. Furthermore, a mediation analysis was conducted to elucidate the role of the atherogenic index of plasma (AIP) in mediating the effect of eGDR on depression. Results Multivariate logistic regression analysis and restricted cubic splines analysis indicated that eGDR can exhibit a linearly correlation with depression (OR = 0.913; 95% CI: 0.875, 0.953). Subjects in eGDR6-8 and eGDR > 8 groups had a decrease risk of depression as 25.4% and 41.5% than those in the eGDR

Abstract Circadian rhythm regulates a variety of biological processes in almost all living organisms. Modern lifestyles, e.g. transmeridian travel, night shift, light at night, etc., frequently disrupt people’s regular sleep-wake cycles and create a misalignment (circadian desynchrony) between the natural environment and the endogenous body clock, and between different circadian oscillators within the body. The long-term consequences of circadian desynchrony on neurodevelopment and adult behavior remain elusive. Increasing clinical evidence supports a correlation between the disruption of the circadian system and neurodevelopmental disorders, such as autism spectrum disorders. Despite clinical correlations, experimental evidence is yet to establish a link between circadian disturbance in early life and adult behavioral changes. Here, using a “short day” (SD) mouse model, in which mice were exposed to an 8 h/8 h light/dark (LD) cycle mimicking a “shift work” schedule from gestation day 1 to postnatal day 21, we performed a battery of behavioral tests to assess changes in adult behaviors, including sociability, affective behaviors, stereotypy, cognition and locomotor functions. In contrast to the control mice kept in a 12 h/12 h LD cycle, the adult SD mice entrained to the 8 h/8 h LD cycle, but their free running rhythms remained normal in constant darkness. Interestingly, however, the SD mice displayed diminished sociability, a reduced preference for social novelty, excessive repetitive behaviors, and compromised cognitive functions, all of which resemble characteristics of autism-like behavioral alterations. In addition, the SD mice exhibited significant anxiety- and depressive-like behaviors and impaired motor functions. By western blotting and immunostaining analyses, hyperactivation of the mTORC1/S6K1 pathway was detected in multiple forebrain regions of SD mice. These findings underscore the enduring impact of early-life circadian disruption on neurochemical signaling and behavioral patterns into adulthood, highlighting a pivotal role for circadian regulation in neurodevelopment.

Abstract Crystalline-silicon heterojunction back contact solar cells represent the forefront of photovoltaic technology, but encounter significant challenges in managing charge carrier recombination and transport to achieve high efficiency. In this study, we produced highly efficient heterojunction back contact solar cells with a certified efficiency of 27.09% using a laser patterning technique. Our findings indicate that recombination losses primarily arise from the hole-selective contact region and polarity boundaries. We propose solutions to these issues and establish a clear relationship between contact resistivity, series resistance, and the design of the rear-side pattern. Furthermore, we demonstrate that the wafer edge becomes the main channel for current density loss caused by carrier recombination once electrical shading around the electron-selective contact region is mitigated. With the advanced nanocrystalline passivating contact, wafer edge passivation technologies and meticulous optimization of front anti-reflection coating and rear reflector, achieving efficiencies as high as 27.7% is feasible.

Abstract Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents to address these defects. In this review, we provide an overview and prospect of the new antibacterial agents that can be used or have the potential to be applied in bone cement, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides and enzymes. Additionally, we have conducted a preliminary assessment of the feasibility of bone cement containing N-halamine, which has demonstrated good antibacterial activities. The conclusion of this review is that the research and utilization of bone cement containing novel antibacterial agents contribute to addressing the limitations of ALBCs. Therefore, it is necessary to continue expanding the research and use of bone cement incorporating novel antibacterial agents. This review offers a novel perspectives for designing ABCs and treating bone infections. Graphical abstract

Terahertz (THz) wireless communication has been recognized as a powerful technology to meet the ever-increasing demand of ultra-high rate services. In order to achieve efficient and reliable wireless communications over THz bands, it is extremely necessary to find an appropriate waveform for THz communications. In this paper, performance comparison of various single-carrier and multi-carrier waveforms over THz channels will be provided. Specifically, first, a system model for terahertz communication is briefly described, which includes amplifier nonlinearity, propagation characteristic, phase noise, etc. Then, the transceiver architectures related to both single-carrier and multi-carrier waveforms are presented, as well as their corresponding signal processing techniques. To evaluate the suitability of the waveforms, key performance metrics concerning power efficiency, transmission performance, and computational complexity are provided. Simulation results are provided to compare and validate the performance of different waveforms, which demonstrate the outstanding performance of Discrete-Fourier-Transform spread Orthogonal Frequency Division Multiplexing (DFT-s-OFDM) to THz communications when compared to Cyclic Prefix-OFDM (CP-OFDM) and other single-carrier waveforms.

Introduction: Cytochrome P450 enzymes (P450s) are recognized as the most versatile catalysts worldwide, playing vital roles in numerous biological metabolism and biosynthesis processes across all kingdoms of life. Despite the vast number of P450 genes available in databases (over 300,000), only a small fraction of them (less than 0.2 %) have undergone functional characterization. Objectives: To provide a convenient platform with abundant information on P450s and their corresponding reactions, we introduce the P450Rdb database, a manually curated resource compiles literature-supported reactions catalyzed by P450s. Methods: All the P450s and Reactions were manually curated from the literature and known databases. Subsequently, the P450 reactions organized and categorized according to their chemical reaction type and site. The website was developed using HTML and PHP languages, with the MySQL server utilized for data storage. Results: The current version of P450Rdb catalogs over 1,600 reactions, involving more than 590 P450s across a diverse range of over 200 species. Additionally, it offers a user-friendly interface with comprehensive information, enabling easy querying, browsing, and analysis of P450s and their corresponding reactions. P450Rdb is free available at http://www.cellknowledge.com.cn/p450rdb/. Conclusions: We believe that this database will significantly promote structural and functional research on P450s, thereby fostering advancements in the fields of natural product synthesis, pharmaceutical engineering, biotechnological applications, agricultural and crop improvement, and the chemical industry.

Objective: This study presents the development and validation of a nomogram aimed at predicting platinum-sensitivity and survival outcomes in women with advanced epithelial ovarian cancer (EOC). Materials and methods: Data from a retrospective cohort of women diagnosed with stage III/IV EOC between Jan 2011 and Dec 2021 treated at our institute were collected. Clinical and pathological characteristics were analyzed using logistic regression analysis to identify independent predictors of platinum-sensitivity. Impact on progression-free (PFS) and overall survival (OS) was determined by Kaplan–Meier and Cox regression analysis. A nomogram was constructed based on the significant predictors, and its performance was evaluated using calibration, discrimination, and validation analyses. Results: Of the 210 patients, 139 (66.19%) had platinum-sensitive and 71 (33.81%) were platinum-resistant disease. On multivariate analysis, platinum-resistance correlated with neoadjuvant chemotherapy (OR 2.15; 95% CI 1.10–4.21), clear cell/mucinous histology (OR 5.04; 95% CI 2.20–11.54), and sub-optimal debulking status (OR 3.37; 95% CI 1.44–7.91). Median PFS and OS were also significantly shorter for patients with neoadjuvant chemotherapy (23 vs. 10 months and 69 vs. 29 months, respectively), clear cell/mucinous histology (15 vs. 3 months and 63 vs. 11 months, respectively), and suboptimal debulking (26 vs. 5 months and 78 vs. 24 months, respectively). The nomogram demonstrated good predictive accuracy for platinum-sensitivity in the cohort as indicated by high concordance index of 0.745. Calibration plots showed excellent agreement and internal validation further confirmed the reliability of the nomogram's performance. Conclusion: A novel predictive nomogram based on type of initial treatment, histology, and debulking status was developed, which provides a friendly and reliable tool for predicting platinum-sensitivity and survival outcomes in women with advanced EOC. Its application may assist clinicians in individualizing treatment decisions.

Abstract Microbes are important components of the tumor microenvironment and have a close relationship with tumors. However, there is still a lack of research on the intratumoral microbiota in bladder cancer and its impact on the tumor immune microenvironment. In this study, we used fluorescence in situ hybridization (FISH) and observed a substantial presence of microbiota in bladder cancer tissues, with greater abundance compared to that in normal bladder tissues. Based on the BIC database, we found that the microbiome of bladder cancer is highly diverse and its structure is significantly different from that of other tumors. To investigate the relationships among the intratumoral microbiota, tumor immunity, and prognosis in bladder cancer patients, we analyzed bladder cancer-specific differentially expressed immune- and antimicrobial-related genes from the ImmPort, TISIDB, and TCGA databases. We identified 11 hub genes and constructed a prognostic risk model. Further analysis revealed differences at the family and genus levels between distinct groups. Using LEfSe analysis, we identified six hub biomarkers and developed a novel microbial-based scoring system. The scoring system allows subgrouping of bladder cancer patients, with significant differences in prognosis, immune cell infiltration, tumor mutation burden, and immune checkpoints among different groups. Further FISH and immunofluorescence co-staining experiments initially verified that the specific distribution of microorganisms and M2 macrophages in bladder cancer may be closely related to the poor prognosis of patients. In conclusion, this study revealed the characteristics of the intratumoral microbiota in bladder cancer and identified potential prognostic targets for clinical application.

Heat waves are a significant environmental issue threatening global human health. Extreme temperatures can lead to various heat-related illnesses, with heatstroke being among the most severe. Currently, there are no effective treatments to mitigate the multi-organ damage caused by heatstroke. We found that heat stress activated autophagy. Knockdown of the autophagy-related gene 7 (ATG7) or knockout of the autophagy initiation regulatory genes UNC-51-like autophagy activating kinase 1/2 (ULK1/ULK2) increased cell death. PF-06409577, an allosteric activator of AMP-activated protein kinase β (AMPKβ), reduced heat stress-induced cell death by promoting autophagy. Inhibition of ATG7 or ULK1 weakened PF-06409577′s protective effect on cells. Treatment of heatstroke mouse models with PF-06409577 suppressed high temperature-induced damage to multiple organs, including the liver, kidneys, lungs, and small intestine. PF-06409577 protected liver and kidney functions, lowered the expression of kidney injury markers neutrophil gelatinase associated lipocalin (Ngal), secreted phosphoprotein 1 (Spp1), and clusterin (Clu), and reduced levels of the inflammatory factor IL-6. Additionally, it decreased heat stress-induced macrophage infiltration and IL-6 production in the liver. The results indicate that activation of autophagy serves a protective function during heat stress, and the AMPK activator PF-06409577 exhibits potential in mitigating heatstroke-induced multi-organ damage through its ability to promote autophagy.

BackgroundRecent studies have identified a correlation between inflammation and depression. This study aims to explore the correlation between the red blood cell distribution width (RDW) to albumin ratio (RAR), a practical measure for assessing inflammation, and depression in the general population.MethodsIn this population-based cross-sectional study, data from 28932 adults aged≥18 years old in the NHANES during the period of 1999–2018 were analyzed. To examine the correlation between RAR and depression, multivariate logistic regression analyses, subgroup analyses, restricted cubic spline analyses, and interaction tests were conducted. Furthermore, a mediation analysis was performed to elucidate the role of atherogenic index of plasma (AIP) in mediating the effect of RAR on depression.ResultsMultivariate logistic regression analyses and restricted cubic splines analysis indicated that RAR can exhibit a linearly correlation with depression (OR = 1.335; 95% CI: 1.222, 1.458). Subjects in RAR Q2, Q3, Q4 groups had an increased risk on depression as 22.8%, 22.9% and 51.9% than those in the Q1 group. This positive correlation was more pronounced in those with history of cancers. The ROC analysis indicated that the area under the curve (AUC) for RAR (AUC=0.593) was significantly greater than that for RDW and albumin individually. Mediation analysis indicated that AIP mediated 7.8% of the correlation of RAR with depression.ConclusionsThe findings of this study indicated a significant linear positive correlation between RAR and the prevalence of depression, with AIP serving as a mediator.

BackgroundThe prospective application of plasma Epstein-Barr virus (EBV) DNA load as a noninvasive measure of intestinal EBV infection remains unexplored. This study aims to identify ideal threshold levels for plasma EBV DNA loads in the diagnosis and outcome prediction of intestinal EBV infection, particularly in cases of primary intestinal lymphoproliferative diseases and inflammatory bowel disease (IBD).MethodsReceiver operating characteristic (ROC) curves were examined to determine suitable thresholds for plasma EBV DNA load in diagnosing intestinal EBV infection and predicting its prognosis.Results108 patients were retrospectively assigned to the test group, while 56 patients were included in the validation group. Plasma EBV DNA loads were significantly higher in the intestinal EBV infection group compared to the non-intestinal EBV infection group (Median: 2.02 × 102 copies/mL, interquartile range [IQR]: 5.49 × 101-6.34×103 copies/mL versus 4.2×101 copies/mL, IQR: 1.07 ×101-6.08×101 copies/mL; P < 0.0001). Plasma EBV DNA levels at 9.21×101 and 6.77×101 copies/mL proved beneficial for the identification and prognostication in intestinal EBV infection, respectively. Values of 0.82 and 0.71 were yielded by the area under the ROC curve (AUC) in the test cohort, corresponding to sensitivities of 84.38% (95% confidence interval [95%CI]: 68.25%-93.14%) and 87.5% (95%CI: 69%-95.66%), specificities of 83.33% (95%CI: 64.15%-93.32%) and 68.09% (95%CI: 53.83%-79.6%), positive predictive values (PPV) of 87.1% (95%CI: 71.15%-94.87%) and 58.33% (95%CI: 42.2%-72.86%), and positive likelihood ratios (LR+) of 5.06 and 2.74 in the validation cohort, respectively. Furthermore, a plasma EBV DNA load of 5.4×102 copies/mL helped differentiate IBD with intestinal EBV infection from primary intestinal EBV-positive lymphoproliferative disorders (PIEBV+LPDs), achieving an AUC of 0.85 within the test cohort, as well as 85% sensitivity (95%CI: 63.96%-94.76%), 91.67% specificity (95%CI: 64.61%-99.57%), 94.44% PPV (95%CI: 74.24%-99.72%), and an LR+ of 10.2 in the validation cohort.ConclusionsPlasma EBV DNA load demonstrates notable potential in distinguishing between different patient cohorts with intestinal EBV infection, although its sensitivity requires further optimization for clinical application.

Cold-spray processing is a promising technique for the metallization of carbon fiber-reinforced plastics (CFRPs). However, the adhesion between the cold-sprayed metal deposits and CFRP substrate needs to be improved. In this study, a novel two-step strategy was developed to significantly enhance the adhesion strength of cold-sprayed Sn/epoxy-based CFRP interfaces. The first step involved eroding the CFRP substrate at a high gas temperature (623 K) to artificially expose the carbon fibers at the surface. In the second step, Sn particles were deposited on the eroded CFRP substate at 523 K, forming a uniform coating. The exposed carbon fibers (CFs) serve as linkages and anchors at the Sn/CFRP interfaces, significantly enhancing the adhesion strength of the single-step Sn coating (∼2 MPa) to ∼ 6.25 MPa after three or more passes. A surface roughness of Sa ≈ 40 μm after the first step was optimal for enhancing the mechanical interlocking at the interfaces. These findings emphasize the importance of interfacial modification in enhancing the mechanical interlocking between the materials, which is crucial for the dominant adhesion mechanism, and suggest an effective strategy that can be applied in continuous cold-spray processing.

The design and synthesis of drug molecules is a pivotal stage in drug development that traditionally requires significant investment in time and finances. However, the integration of artificial intelligence (AI) in drug design accelerates the identification of potential drug candidates, optimizes the drug development process, and contributes to more informed decision-making. The application of AI in molecular generation is changing the way researchers explore the chemical space and design novel compounds. It accelerates the process of drug discovery and materials science, enabling rapid exploration of the vast chemical landscapes for the identification of promising candidates for further experimental validation. The application of AI in predicting reaction products accelerates the synthesis planning process, contributes to the automation of synthetic chemistry tasks, and supports chemists in making informed decisions during drug discovery. This paper reviewed the recent advances in two interrelated areas: the application of AI in molecular generation and synthesis routes. It will provide insights into the innovative ways in which AI is transforming traditional approaches in drug development and predict its future progress in these key fields.

This study aimed to examine the effect of quercetin (QUE) on the antioxidant capacity of spotted sea bass that were fed a high soybean meal diet. 44 % fish meal was used as a healthy control, and soybean meal instead of 50 % fish meal induced a negative reaction. On this basis, 0.25, 0.50, 0.75, and 1.00 g/kg QUE were added, respectively. A total of 540 spotted sea bass were randomly allocated into 6 groups and provided with diets that corresponded to their respective groups for a duration of 56 days. The results showed a significant decrease in the antioxidant capacity of spotted sea bass fed a high soybean meal diet. The inclusion of QUE considerably improved the antioxidant capacity of spotted sea bass. This was evidenced by the notable rise in glutathione (GSH) levels in the intestine and liver, as well as the elevated levels of catalase (CAT) and total antioxidant capacity (T-AOC) in the liver. Furthermore, transcriptome results showed that the S-transferase (GST) gene in the glutathione metabolism pathway was significantly down-regulated by high soybean meal, while with the addition of QUE, noteworthy alterations in genes associated with the PI3K-Akt signaling pathway, Foxo signaling pathway, and AMPK signaling pathway. These signaling pathways are involved in signal transduction, apoptosis, and oxidative stress. On the other hand, genes related to energy metabolism, such as phosphoenolpyruvate carboxykinase (PEPCK), were observed to be upregulated. These pathways could potentially contribute to the antioxidant properties of QUE.

Abstract Helwingia, a shrub of the monotypic cosmopolitan family Helwingiaceae, is distinguished by its inflorescence, in which flowers are borne on the midrib of the leaf—a trait not commonly observed in related plant families. Previous studies have investigated the development of this unusual structure using comparative anatomical methods. However, the scarcity of genomic data has hindered our understanding of the origins and evolutionary history of this uncommon trait at the molecular level. Here, we report the first high-quality genome of the family Helwingiaceae. Assembled using HiFi sequencing and Hi-C technologies, the genome of H. omeiensis is anchored to 19 chromosomes, with a total length of 2.75 Gb and a contig N50 length of 6.78 Mb. The BUSCO completeness score of the assembled genome was 98.2%. 53,951 genes were identified, of which 99.7% were annotated in at least one protein database. The high-quality reference genome of H. omeiensis provides an essential genetic resource and sheds light on the phylogeny and evolution of specific traits in the family Helwingiaceae.

Platinum-resistant ovarian cancer (PROC) refers to disease progression within 6 months after the completion of platinum-based chemotherapy. Historically, treatment options for PROC were limited with a poor prognosis and non-platinum single agent plus bevacizumab has been the mainstay of treatment. Fortunately, there have been notable advancements in recent years, leading to an advance in treatment paradigms for this challenging disease. Various combinations of chemotherapy, targeted agents such as poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy are being explored for an improved treatment outcome. Antibody-drug conjugates targeting folate receptor alpha, which deliver a cytotoxic payload directly to cancer cells, have emerged as a promising therapeutic approach for PROC. WEE1 inhibitors, such as adavosertib, function by inhibiting the WEE1 kinase activity, leading to premature entry of a cell into mitosis phase and thus increased DNA damage. It has been observed that cancer cells with TP53 mutations may be more sensitive to WEE1 inhibitors. Biomarker testing such as analysis of the expression level of folate receptor alpha or mutation in TP53 may be applicable for identifying patients who are more likely to respond to the specific therapy, enabling a more personalized treatment approach. This overview summarizes key clinical findings on the efficacy and safety of theses novel biomarker-driven therapeutic approaches.

Abstract Background Lung cancer stands as the second most prevalent malignant neoplasm worldwide. Addressing the underlying mechanisms propelling the progression of non-small cell lung cancer is of paramount importance. In this study, we have elucidated the pivotal role of PHF12 in this context. Materials and methods We harnessed clinical lung cancer tissue samples and non-small cell lung cancer cell lines to discern the expression pattern of PHF12. In vitro assays probing cell proliferation were conducted to substantiate the functional impact of PHF12. Furthermore, an in vivo Xenograft model was employed to dissect the role of PHF12. Employing ChIP assays and qRT-PCR, we delved into the intricate binding dynamics between PHF12 and HDAC1. Mechanistic insights into the PHF12-HDAC1 axis in lung cancer progression were pursued via RNA-seq and GSEA analyses. Results Notably, PHF12 exhibited a substantial upregulation within tumor tissue, concomitant with its correlation to HDAC1. The trilogy of cell proliferation assays, transwell assays, and the Xenograft model collectively underscored the promoting influence of PHF12 on lung cancer proliferation, both in vitro and in vivo. The ChIP assay unveiled the transcriptional regulatory role of PHF12 in governing HDAC1 expression. This correlation extended to both mRNA and protein levels. PHF12 promotes NSCLC progression through regulating HDCA1 expression. Intriguingly, the rescue of function within NSCLC cell lines post PHF12 knockdown was achievable through HDAC1 overexpression. Additionally, our findings unveiled the capacity of the PHF12-HDAC1 axis to activate the EGFR/AKT signaling pathway, thereby further corroborating its significance in lung cancer progression. Conclusion Our study identified PHF12 as an oncogenic role in lung cancer proliferation and migration for the first time. PHF12 transcriptionally regulate HDAC1 and activate EGFR/AKT signaling pathway in NSCLC progression. PHF12 may serve as an important target in lung cancer therapy.

Abstract Veratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both target natural products by utilizing a biomimetic rearrangement to form the C-nor-D-homo steroid core and a stereoselective reductive coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.

Alfalfa (Medicago sativa. L.) is a globally significant autotetraploid legume forage crop. However, despite its importance, establishing efficient gene editing systems for cultivated alfalfa remains a formidable challenge. In this study, we pioneered the development of a highly effective ultrasonic-assisted leaf disc transformation system for Gongnong 1 alfalfa, a variety widely cultivated in Northeast China. Subsequently, we created a single transcript CRISPR/Cas9 (CRISPR_2.0) toolkit, incorporating multiplex gRNAs, designed for gene editing in Gongnong 1. Both Cas9 and gRNA scaffolds were under the control of the Arabidopsis ubiquitin-10 promoter, a widely employed polymerase II constitutive promoter known for strong transgene expression in dicots. To assess the toolkit’s efficiency, we targeted PALM1, a gene associated with a recognizable multifoliate phenotype. Utilizing the CRISPR_2.0 toolkit, we directed PALM1 editing at two sites in the wild-type Gongnong 1. Results indicated a 35.1% occurrence of editing events all in target 2 alleles, while no mutations were detected at target 1 in the transgenic-positive lines. To explore more efficient sgRNAs, we developed a rapid, reliable screening system based on Agrobacterium rhizogenes-mediated hairy root transformation, incorporating the visible reporter MtLAP1. This screening system demonstrated that most purple visible hairy roots underwent gene editing. Notably, sgRNA3, with an 83.0% editing efficiency, was selected using the visible hairy root system. As anticipated, tetra-allelic homozygous palm1 mutations exhibited a clear multifoliate phenotype. These palm1 lines demonstrated an average crude protein yield increase of 21.5% compared to trifoliolate alfalfa. Our findings highlight the modified CRISPR_2.0 system as a highly efficient and robust gene editing tool for autotetraploid alfalfa.

Introduction In this study, we investigated the effect of depression on the interaction between lung disease and cardiovascular health (CVH). Methods Utilising data from the National Health and Nutrition Examination Survey (2013–2018), we employed multivariate regression and bootstrap mediation analysis to explore the relationships among lung diseases, depression, and CVH scores. Results Complex and significant associations were identified among lung diseases, depression, and CVH scores, with depression mediating 9.42% of the effect on CVH, especially for chronic bronchitis patients. Conclusions Depression significantly mediated the relationship between lung disease and reduced CVH scores, highlighting the importance of mental health management in lung disease patients.

Unmanned aerial-undersea vehicles(UAUVs), with broad application prospects in both military and civilian fields, have gradually become a research hotspot in the field of robotics in recent years. UAUVs were taken as the research object in this study, and the development status of the bionic, multirotor, fixed-wing, and hybrid UAUV prototypes were discussed. In addition, the water-entry/exit strategies of the prototypes were reviewed. The important issues faced in the research on UAUVs were summarized, including the optimal design of bionic configuration, stability control during the trans-medium process, and propulsion selection, providing a reference for the subsequent research and development of trans-medium vehicles.

Enteromorpha prolifera polysaccharide (EPP) is a kind of seaweed polysaccharide with outstanding biological activity. In this study, a 49-day culture trial was conducted to explore the effects of dietary EPP on intestinal health in spotted sea bass. Six experimental diets containing 0, 3, 6, 9, 12, and 15 g/kg EPP were formulated. A total of 540 similarly sized and healthy spotted sea bass were randomly assigned to 6 groups and fed the respective diet. The results showed that dietary EPP supplementation significantly improved the activity of digestive enzymes, including amylase, lipase, and trypsin, and reduced the permeability of the intestinal mucosa, which was shown to significantly reduce the content of D-lactic acid and the activity of diamine oxidase in serum. On the other hand, intestinal villi length and muscle thickness increased significantly, and intestinal tissue morphology improved. Dietary EPP also changed intestinal microbial composition, increased Firmicutes abundance, and increased intestinal microbial diversity. Transcriptome results suggest that EPP may improve intestinal tissue morphology and intestinal barrier function by up-regulating tight junction protein 1 (TJP1) and zona occludens 1 (ZO-1) genes, thereby improving intestinal health. In addition, significant changes in several inflammatory factor genes were observed. EPP may have enormous potential for regulating immune and inflammatory responses. In conclusion, dietary EPP can significantly improve the intestinal health of spotted sea bass.

As a prebiotic, laminarin has functions such as antioxidant and improving the body's immunity. This study explores the antioxidant capacity and nonspecific immune effects of laminarin by adding different concentration gradients (0 %, 0.4 %, 0.8 %, 1.2 %, 1.6 %, and 2 %) to the diet of spotted sea bass, Lateolabrax maculatus. 450 spotted sea bass (initial weight: 7.14 ± 0.10 g) were randomly divided into 6 groups, each group was repeated 3 times, 25 fish per experimental tank, and fed with different concentrations of laminarin. After 56 days of feeding, samples were collected and measured for antioxidant capacity and non-specific immune indicators. The results show that, in terms of antioxidant capacity, the dietary addition of 0.8 % laminarin significantly increased the serum total antioxidant capacity, glutathione content, and superoxide dismutase activity in spotted sea bass (P

Abstract The diversity of secondary metabolites is an important means for plants to cope with the complex and ever‐changing terrestrial environment. Plant biosynthetic gene clusters (BGCs) are crucial for the biosynthesis of secondary metabolites. The domestication and evolution of BGCs and how they affect plant secondary metabolites biosynthesis and environmental adaptation are still not fully understood. Buckwheat exhibits strong resistance and abundant secondary metabolites, especially flavonoids, allowing it to thrive in harsh environments. A non‐canonical BGC named UFGT3 cluster is identified, which comprises a phosphorylase kinase (PAK), two transcription factors (MADS1/2), and a glycosyltransferase (UFGT3), forming a complete molecular regulatory module involved in flavonoid biosynthesis. This cluster is selected during Tartary buckwheat domestication and is widely present in species of the Fagopyrum genus. In wild relatives of cultivated buckwheat, a gene encoding anthocyanin glycosyltransferase (AGT), which glycosylates pelargonidin into pelargonidin‐3‐O‐glucoside, is found inserted into this cluster. The pelargonidin‐3‐O‐glucoside can help plants resist UV stress, endowing wild relatives with stronger high‐altitude adaptability. This study provides a new research paradigm for the evolutionary dynamics of plant BGCs, and offers new perspectives for exploring the mechanism of plant ecological adaptability driven by environmental stress through the synthesis of secondary metabolites.

Abstract The spherulitic morphology of isotactic polypropylene can be transformed into the oriented fibrillar morphology through hot stretching processes with varying temperature (Ts) or altering strain (εt). The effects of Ts and εt on the structural characteristics of fibrillar crystals are comprehensively investigated with respect to crystal orientation, long periodic spacing, lamellar thickness (Lc), crystallinity (Xc), melting point, and chain relaxation behavior. Small‐angle X‐ray scattering patterns illustrate that the fibrillar crystals consist of alternated stacks of crystalline lamellae and amorphous layers. High Ts leads to a low orientation degree of lamellae, whereas large εt facilitates a high orientation level. The Xc and mean Lc are improved continuously with the increasing of Ts or εt, indicating a stretching‐enhanced crystallization behavior driven by the two factors. The endothermic profiles reveal that new chain‐folded lamellae with relatively thinner thickness form during the hot stretching process. The formation of thinner lamellae is dominated by the melting–recrystallization mechanism. This work would provide guidance for optimizing process conditions to manipulate the microstructure of hot‐stretched semicrystalline polymers.

Deep convolutional neural networks (CNNs) have achieved remarkable success in various computer vision tasks. However, the lack of interpretability in these models has raised concerns and hindered their widespread adoption in critical domains. Generating activation maps that highlight the regions contributing to the CNN's decision has emerged as a popular approach to visualize and interpret these models. Nevertheless, existing methods often produce activation maps contaminated with irrelevant background noise or incomplete object activation, limiting their effectiveness in providing meaningful explanations. To address this challenge, we propose Union Class Activation Mapping (UnionCAM), an innovative visual interpretation framework that generates high-quality class activation maps (CAMs) through a novel three-step approach. UnionCAM introduces a weighted fusion strategy that adaptively combines multiple CAMs to create more informative and comprehensive activation maps. First, the denoising module removes background noise from CAMs by using adaptive thresholding. Subsequently, the union module fuses the denoised CAMs with region-based CAMs using a weighted combination scheme to obtain more comprehensive and informative maps, which we refer to as fused CAMs. Lastly, the activation map selection module automatically selects the optimal CAM that offers the best interpretation from the pool of fused CAMs. Extensive experiments on ILSVRC2012 and VOC2007 datasets demonstrate UnionCAM's superior performance over state-of-the-art methods. It effectively suppresses background noise, captures complete object regions, and provides intuitive visual explanations. UnionCAM achieves significant improvements in insertion and deletion scores, outperforming the best baseline. UnionCAM makes notable contributions by introducing a novel denoising strategy, adaptive fusion of CAMs, and an automatic selection mechanism. It bridges the gap between CNN performance and interpretability, providing a valuable tool for understanding and trusting CNN-based systems. UnionCAM has the potential to foster responsible deployment of CNNs in real-world applications.

BackgroundMetabolic Visceral Fat Score (METS-VF) recently introduced is posited to be a superior metric for assessing visceral adipose tissues (VAT) compared to traditional obesity indexes. This study aims to elucidate the correlation between METS-VF and the incidence of gallstones.MethodsIn this cross-sectional study, the data from the National Health and Nutrition Examination Survey (NHANES) during the period from 2013 to 2020 were analyzed. And the correlation between METS-VF and the incidence of gallstones was explored through multivariate logistic regression analysis, receiver operating characteristic (ROC) curve, subgroup analysis and restricted cubic spline (RCS) regression.ResultsThis study included 5,975 participants, of whom 645 (10.8%) were gallstone formers. As the quartile range of METS-VF increased, a notable rise in the prevalence of gallstones was observed (3.2% vs. 7.4% vs. 12.1% vs. 20.6%, p

BackgroundWhile the correlation between physical activity (PA) and mental health is well known, the mediating mechanism of resilience between the two variables remains unclear.ObjectivesTo systematically evaluate the relationship between PA and mental health, and explore the mediating role of resilience between them.MethodsA systematic search of electronic databases (PubMed, Web of Science, ProQuest, Ebsco, China Knowledge, and China Biomedical Database) was conducted to identify relevant studies, and meta-analytic procedures were used to assess the strength of the relationships between PA and mental health. Furthermore, a meta-analytic structural equation model (MASEM) was used to assess the mediating effects of resilience, ensuring the reliability of our findings.ResultsThe findings of 15 studies (17,043 subjects) were subjected to meta-analysis and route analysis. The findings of the meta-analysis revealed a statistically significant positive correlation of 0.288 (95% CI, 0.166–0.402) between PA and positive indicators of mental health, as well as a statistically significant negative correlation (95% CI, −0.342 to −0.171) with negative indicators of mental health. Furthermore, the results of MASEM path analysis indicated that PA may indirectly impact both positive and negative indicators of mental health through the mediating factor of resilience. The indirect effect values were 0.108 (95% CI, 0.080–0.141) and −0.074 (95% CI, −0.100 to −0.051), respectively, accounting for 40.15% of the total effect value and 28.91%.ConclusionPhysical activity is positively correlated with positive indicators of mental health and negatively correlated with negative indicators of mental health. Moreover, PA can positively influence mental health through the mediating role of resilience.

A novel acrylic monomer containing a nitrofuran motif, referred to as long-chain nitrofuran methacrylate (LNFMA), is reported. In comparison to the previously reported nitrofuran methacrylate (NFMA), LNFMA has a longer side chain, and when incorporated into bone cement, the resulting LNFMA bone cement exhibits improved mechanical strength. At the same concentration, NFMA-5% cement has only 21.6 ± 1.3 MPa, while LNFMA-5% cement has a compressive strength of 42.64 ± 0.94 MPa. LNFMA bone cements exhibit antimicrobial activity against Staphylococcus aureus, with LNFMA-30% cement reaching 57.38% ± 5.53%. Moreover, LNFMA cement demonstrates excellent biocompatibility both in vitro and in vivo. The results showed that LNFMA monomer had optimized mechanical strength compared with previously reported NFMA monomers, and LNFMA bone cement had good antibacterial activity and biocompatibility.

ABSTRACT: High-laying ducks are often fed high-energy, nutritious feeds to maintain high productivity, which predisposes them to lipid metabolism disorders and the development of fatty liver syndrome (FLS), which seriously affects production performance and has a substantial economic impact on the poultry industry. Therefore, it is necessary to elucidate the mechanisms underlying the development of fatty liver syndrome. In this study, seven Shan Partridge ducks, each with fatty liver syndrome and normal laying ducks, were selected, and Hematoxylin Eosin staining (HE staining), Masson staining, and transcriptome sequencing were performed on liver tissue. In addition to exploring key genes and pathways using conventional analysis methods, we constructed the first Kyoto Encyclopedia of Genes and Genomes (KEGG) database-based predefined gene set containing 12,764 pathways and 16,836 genes and further performed gene set enrichment analysis (GSEA) on the liver transcriptome data. Finally, key nodes and biological processes were identified via the protein-protein interaction (PPI) network. The results showed that the liver in the FL group exhibited steatosis and fibrosis, and a total of 3,663 genes with upregulated expression versus 2,296 downregulated genes were screened by conventional analysis. GSEA analysis and PPI network analysis revealed that the liver in the FL group exhibited disruption of the mitochondrial electron transport chain, leading to decreased oxidative phosphorylation and the secretion of excessive proinflammatory factors amid the continuous accumulation of lipids. Under continuous chronic inflammation, cell cycle arrest triggers apoptosis, while fibrosis becomes more severe, and procarcinogenic genes are activated, leading to the continuous development and deterioration of the liver. In conclusion, the predefined gene set constructed in this study can be used for GSEA, and the identified hub genes provide useful reference data and a solid foundation for the study of the genetic regulatory mechanism of fatty liver syndrome in ducks.

Targeting nucleotide enzymes emerges as a promising avenue for impeding tumor proliferation and fortifying anti-tumor immunogenicity. The non-canonical role of nucleotide enzymes remains poorly understood. In this study, we have identified that Phosphoglucomutase 2 (PGM2) rapidly accumulates at the DNA damage site to govern the DNA damage response mediated by the phosphorylation at Serine 165 and by forming a complex with Rho-associated coiled-coil-containing protein kinase 2 (ROCK2). Silencing PGM2 in Glioblastoma Multiforme (GBM) cells heightens DNA damage in vitro and enhances the sensitivity of temozolomide (TMZ) treatment by activating anti-tumor immunity in vivo. Furthermore, we demonstrate that pharmacological inhibition of ROCK2 synergistically complements TMZ treatment and pembrolizumab (PD-L1) checkpoint immunotherapy, augmenting anti-tumor immunity. This study reveals the non-canonical role of the nucleotide enzyme PGM2 in the regulation of DNA damage response and anti-tumor immunity, with implications for the development of therapeutic approaches in cancer treatment.

Background: Endothelial dysfunction is a complication of diabetes mellitus (DM), characterized by impaired endothelial function in both microvessels and macrovessels, closely linked to atherosclerosis (AS). Endothelial dysfunction, characterized by impaired endothelial cell (EC) function, is a pivotal factor in AS and DM. Circular RNAs (circRNAs) are endogenous non-coding RNAs that can act as competing endogenous RNAs (ceRNAs) and regulate gene expression. However, the role of circRNAs in ECs dysfunction and AS under high glucose (HG) condition remains elusive. Methods: We performed high-throughput sequencing to identify differentially expressed (DE) circRNAs in human umbilical vein endothelial cells (HUVEC) exposed to HG, one risk factors of endothelial dysfunction and AS. We then validated eight candidate circRNAs by qRT-PCR and functional analysis, directing our attention to hsa_circ_0122319. Moreover, microarray analysis identified the differential expression profiles of miRNAs and mRNAs regulated by hsa_circ_0122319. Subsequently, the construction of the ceRNAs network employed bioinformatic analysis and Cytoscape software. Furthermore, the role of the PI3K-Akt signaling pathway in regulating ceRNAs was evaluated. Results: We detected 917 DE circRNAs in HG treated HUVEC. The parental genes of these circRNAs were enriched in cell cycle, cellular senescence and endocytosis related pathways. The differential expression of hsa_circ_0122319 was confirmed to be most obvious at the cellular level and in clinical samples by qPCR experiments. After overexpression of hsa_circ_0122319, 49 DE miRNAs and 459 DE mRNAs were identified using microarray analysis. Subsequently, a ceRNAs network was constructed, comprising hsa_circ_0122319, 8 miRNAs, and 41 mRNAs. Conclusion: In summary, our study delves into the role of circRNAs in endothelial dysfunction associated with DM and AS. Through high-throughput sequencing and validation, we identified hsa_circ_0122319 as a pivotal regulator of ECs function under HG conditions. It also showed that hsa_circ_0123319 has the potential to serve as a biomarker for DM and its vascular complications, and provides new evidence for future exploration of the intricate molecular mechanisms of endothelial dysfunction in the progression of DM and AS.

Abstract Pulmonary tuberculosis (TB) can result in irreversible damage and lead to tuberculous destructive lung (TDL), a severe chronic lung disease that is associated with a high mortality rate. Additionally, pulmonary hypertension (PH) is a hemodynamic disorder that can be caused by lung diseases. The objective of this study is to investigate the risk factors associated with PH in active TB patients diagnosed with TDL. We conducted a retrospective review of the medical records of 237 patients who were diagnosed with TDL, active pulmonary tuberculosis, and underwent echocardiography at the Third People’ Hospital of Shenzhen from January 1, 2016, to June 30, 2023. Univariate and multivariate logistic regression analyses were performed to identify factors that correlated with the development of pulmonary hypertension. Univariate and multivariate logistic regression analyses revealed that several factors were associated with an increased risk of pulmonary hypertension (PH) in individuals with tuberculosis destroyed lung (TDL). These factors included age (OR = 1.055), dyspnea (OR = 10.728), D-dimer (OR = 1.27), PaCO2 (OR = 1.040), number of destroyed lung lobes (OR = 5.584), bronchiectasis (OR = 3.205), and chronic pleuritis (OR = 2.841). When age, D-dimer, PaCO2, and number of destroyed lung lobes were combined, the predictive value for PH in patients with TDL was found to be 80.6% (95% CI 0.739–0.873),with a sensitivity of 76.6% and specificity of 73.2%. Advanced age, elevated D-dimer levels, hypercapnia, and severe lung damage were strongly correlated with the onset of PH in individuals with active pulmonary tuberculosis (PTB) and TDL. Furthermore, a model incorporating age, D-dimer, PaCO2, and the number of destroyed lung lobes might be valuable in predicting the occurrence of PH in patients with active PTB and TDL.

Abstract Crystalline silicon solar cells with regular rigidity characteristics dominate the photovoltaic market, while lightweight and flexible thin crystalline silicon solar cells with significant market potential have not yet been widely developed. This is mainly caused by the brittleness of silicon wafers and the lack of a solution that can well address the high breakage rate during thin solar cells fabrication. Here, we present a thin silicon with reinforced ring (TSRR) structure, which is successfully used to prepare free-standing 4.7-μm 4-inch silicon wafers. Experiments and simulations of mechanical properties for both TSRR and conventional thin silicon structures confirm the supporting role of reinforced ring, which can share stress throughout the solar cell preparation and thus suppressing breakage rate. Furthermore, with the help of TSRR structure, an efficiency of 20.33% (certified 20.05%) is achieved on 28-μm silicon solar cell with a breakage rate of ~0%. Combining the simulations of optoelectrical properties for TSRR solar cell, the results indicate high efficiency can be realized by TSRR structure with a suitable width of the ring. Finally, we prepare 50 ~ 60-μm textured 182 × 182 mm2 TSRR wafers and perform key manufacturing processes, confirming the industrial compatibility of the TSRR method.

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4–8%) of CD45+ cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.

Abstract Background Colorectal cancer (CRC) is a prevalent malignancy with high mortality and morbidity rates. Although the significant efficacy of immunotherapy is well established, it is only beneficial for a limited number of individuals with CRC. Methods Differentially expressed immune-related genes (DE-IRGs) were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ImmPort databases. A prognostic signature comprising DE-IRGs was developed using univariate, LASSO, and multivariate Cox regression analyses. A nomogram integrating the independent prognostic factors was also developed. CIBERSORT was used to assess immune cell infiltration (ICI). Furthermore, wound-healing, colony formation, migration, and invasion assays were performed to study the involvement of ACTG1 in CRC. Results A signature including six DE-IRGs was developed. The overall survival (OS) rate was accurately estimated for TCGA and GSE38832 cohorts. The risk score (RS) of the signature was an independent factor for OS. Moreover, a nomogram encompassing age, RS, and pathological T stage accurately predicted the long-term OS probability of individuals with CRC. The high-risk group had an elevated proportion of patients treated with ICIs, including native B cells, relative to the low-risk group. Additionally, ACTG1 expression was upregulated, which supported the proliferation, migration, and invasion abilities of CRC cells. Conclusions An immune-related prognostic signature was developed for predicting OS and for determining the immune status of individuals with CRC. The present study provides new insights into accurate immunotherapy for individuals with CRC. Moreover, ACTG1 may serve as a new immune biomarker.

The aim of this paper is to investigate the grinding characteristics and mechanism of 2D- SiC/SiC composites with 0°/90° orthogonal anisotropic structured surfaces under different scratching fiber angles (angle between scratch direction and fiber orientation, SFA). A series of surface single abrasive scratching tests were conducted. The effects of the scratch fiber angle on the grinding force, surface morphology and roughness were investigated. The results show that the scratch force and surface roughness at different scratch fiber angles are in the order of 0° > 30°> 45°; SFA also has an important effect on the surface microstructure. The grinding mechanism of 2D-SiCf/SiC composites was analyzed by single-particle scratching test. The results of the scratch force and surface morphology provide strong evidence of the differences produced during the grinding process. The advantages of ultrasonic vibration over conventional machining were further identified by comparing specific scratch energies. This study elucidates the damage behavior of 2D-Sicf/sic composites in correlation with the influence of angle, and these results provide a new guideline for ultrasonic vibratory grinding of woven fiber-reinforced ceramic matrix composites for machining quality.