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Abstract Background Although stem cell transplantation is a promising approach for the treatment of myocardial infarction (MI), there are still some problems faced such as the low survival rate of stem cells. Here, we investigated the role of Notoginsenoside R1 (NGR1) pretreatment in improving the effects of neonatal rat bone marrow mesenchymal stem cell (MSC) transplantation for treatment of MI. Methods Cardiac functions were detected by echocardiography and the myocardial infarct size was determined by Masson’s trichrome staining in a rat model of MI. The cardioprotective effects of NGR1/LY294002 co-pretreated MSCs was evaluated to explore the underlying mechanism. The angiogenesis was determined by vWF and α-SMA immunofluorescence staining and cell apoptosis was detected by TUNEL. In vitro, the effects of NGR1 on stem cell proliferation was examined by CCK-8 and levels of P-Akt, P-CREB, P-FoxO1 were detected by western blot. Apoptosis, ROS content, and cytokine levels were examined by DAPI and TUNEL staining, a ROS assay kit, and ELISA, respectively. Results NGR1 elevated the therapeutic effect of MSC transplantation on infarction by preserving cardiac function, increasing angiogenesis and expressions of IGF-1, VEGF, and SDF-1, and reducing cell apoptosis, whereas the addition of LY294002 prior to NGR1 treatment significantly counteracted the foregoing effects of NGR1. NGR1 pretreatment and SC79 pretreatment were similar in that both significantly increased P-Akt and P-FoxO1 levels in MSC and did not affect P-CREB levels. Besides, both NGR1 and SC79 promoted VEGF, SCF and bFGF levels in MSC cultures, and significantly reduced ROS accumulation and the attenuated cell apoptosis in MSC triggered by H2O2. Similarly, addition of LY294002 before NGR1 treatment significantly counteracted the aforementioned effects of NGR1 in vitro. Conclusions NGR1 pretreatment enhances the effect of MSC transplantation for treatment of MI through paracrine signaling, and the mechanism underlying this effect may be associated with PI3K/Akt/FoxO1 signaling pathways.

Abstract Background Salmonella Typhimurium (S. Typhimurium) is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms. As signaling molecules regulating the interaction between the host and gut microbiota, bile acids (BAs) play a protective role in maintaining gut homeostasis. However, the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored. Therefore, the aim of this study was to investigate the potential role of feeding BAs in protecting against S. Typhimurium infection in broilers. Methods A total of 144 1-day-old Arbor Acres male broilers were randomly assigned to 4 groups, including non-challenged birds fed a basal diet (CON), S. Typhimurium-challenged birds (ST), S. Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection (ST-ANT), and S. Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs (ST-BA). Results BAs supplementation ameliorated weight loss induced by S. Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers (P

Abstract Background Fetal growth restriction (FGR) is associated with various perinatal complications. Limited research has focused on the fetal heart in the context of FGR. This study aimed to investigate the application value of fetal heart quantification (HQ) technology in evaluating the size, morphology, and function of the heart in FGR. Methods A total of 31 fetuses diagnosed with FGR in our hospital from April 2022 to May 2024 were included, alongside another 31 normal fetuses matched for gestational age as the control group. Ultrasound Doppler parameters of the middle cerebral artery (MCA), umbilical artery (UA), venous catheter, and fetal HQ parameters were collected for comparative analysis, and perinatal data were followed up. Results Fetuses with FGR exhibited significant differences in various parameters of the MCA and UA compared to the control group (P

Abstract Background Previous investigations identified a connection between air pollution and kidney diseases. Nevertheless, there is a lack of comprehensive evidence on the long-term risks posed by air pollution with respect to acute kidney injury (AKI) and AKI-related death. Methods This prospective cohort analysis included 414,885 UK Biobank (UKB) participants who did not exhibit AKI at the study’s outset. AKI was defined based on ICD-10 codes recorded for hospitalized patients. Cox proportional hazards models were used to assess the association between prolonged exposure to air pollutants (particulate matter with diameters of 2.5 micrometers or less (PM2.5), between 2.5 and 10 micrometers (PM2.5−10), and 10 micrometers or less (PM10), along with nitrogen dioxide (NO2) and nitrogen oxides (NOx)) and the risk of AKI and AKI-related death, adjusting for potential confounders including sex, age, ethnicity, education, income, lifestyle factors, and relevant clinical covariates. Restricted cubic splines were applied to evaluate non-linear dose-response relationships, and stratified analyses were performed to explore potential effect modification across subgroups. Results Over an average follow-up duration of 11.7 years, 14,983 cases of AKI and 326 cases of AKI-related death were diagnosed. Quartile analysis showed individuals exposed to higher levels of these air pollutants had a significantly higher risk of developing AKI and AKI-related death compared to those in the lowest quartile (all P 0.05). Sensitivity analyses confirmed the robustness of our findings. Conclusion Our study reveals a direct association between prolonged air pollution exposure and elevated risks of both AKI and AKI-related death. These findings offer scientific validation for the adoption of environmental and public health measures directed towards the reduction of air pollution. Such initiatives could potentially ease the impact associated with AKI and AKI-related death.

Abstract We recorded dopamine release signals in centromedial and centrolateral sectors of the striatum as mice learned consecutive versions of visual cue-outcome conditioning tasks. Dopamine release responses differed for the centromedial and centrolateral sites. In neither sector could these be accounted for by classic reinforcement learning alone as classically applied to the activity of nigral dopamine-containing neurons. Medially, cue responses ranged from initial sharp peaks to modulated plateau responses; outcome (reward) responses during cue conditioning were minimal or, initially, negative. At centrolateral sites, by contrast, strong, transient dopamine release responses occurred at both cue and outcome. Prolonged, plateau release responses to cues emerged in both regions when discriminative behavioral responses became required. At most sites, we found no evidence for a transition from outcome signaling to cue signaling, a hallmark of temporal difference reinforcement learning as applied to midbrain dopaminergic neuronal activity. These findings delineate a reshaping of striatal dopamine release activity during learning and suggest that current views of reward prediction error encoding need review to accommodate distinct learning-related spatial and temporal patterns of striatal dopamine release in the dorsal striatum.

Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignancy with a favorable prognosis if detected early. However, there is a lack of accurate and reliable early detection tests for UCEC. This study aims to develop a precise and non-invasive diagnostic method for UCEC using circulating cell-free DNA (cfDNA) fragmentomics. Methods Peripheral blood samples were collected from all participants, and cfDNA was extracted for analysis. Low-coverage whole-genome sequencing was performed to obtain cfDNA fragmentomics data. A robust machine learning model was developed using these features to differentiate between UCEC and healthy conditions. Results The cfDNA fragmentomics-based model showed high predictive power for UCEC detection in training (n = 133; AUC 0.991) and validation cohorts (n = 89; AUC 0.994). The model manifested a specificity of 95.5% and a sensitivity of 98.5% in the training cohort, and a specificity of 95.5% and a sensitivity of 97.8% in the validation cohort. Physiological variables and preanalytical procedures had no significant impact on the classifier’s outcomes. In terms of clinical benefit, our model would identify 99% of Chinese UCEC patients at stage I, compared to 21% under standard care, potentially raising the 5-year survival rate from 84 to 95%. Conclusion This study presents a novel approach for the early detection of UCEC using cfDNA fragmentomics and machine learning showing promising sensitivity and specificity. Using this model in clinical practice could significantly improve UCEC management and control, enabling early intervention and better patient outcomes. Further optimization and validation of this approach are warranted to establish its clinical utility.

Abstract Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving the progressive degradation of the cartilage extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological and pathological processes, particularly in protein degradation. Excess cathepsins levels are reported to contribute to the development of OA. However, the causal relationship between the cathepsin family and knee and hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses to explore this causal association. Our results indicated that elevated serum levels of cathepsin O increase the overall risk of knee OA, while increased serum levels of cathepsin H enhance the risk of hip OA. Conversely, the reverse MR analyses did not reveal a reverse causal relationship between them. In summary, OA in different anatomical locations may genetically result from pathological elevations in different serum cathepsin isoforms, which could be utilized as diagnostic and therapeutic targets in clinical practice.

Abstract Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from clinical and fundamental researches to identify its antiarrhythmic effects, reviewing the evidences and mechanism for the SGLT2i antiarrhythmic effects and establishing a novel paradigm involving intracellular sodium, metabolism and autophagy to investigate the potential mechanisms of SGLT2i in mitigating arrhythmias. Graphical abstract

IntroductionAdamantinomatous craniopharyngioma (ACP) is difficult to cure completely and prone to recurrence after surgery. Ferroptosis as an iron-dependent programmed cell death, may be a critical process in ACP. The study aimed to screen diagnostic markers related to ferroptosis in ACP to improve diagnostic accuracy.MethodsGene expression profiles of ACP were obtained from the gene expression omnibus (GEO) database. Limma package was used to analyze the differently expressed genes (DEGs). The intersection of DEGs and ferroptosis-related factors was obtained as differently expressed ferroptosis-related genes (DEFRGs). Enrichment analysis was processed, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), disease ontology (DO), gene set enrichment analysis (GSEA), and Gene Set Variation Analysis (GSVA) analysis. Machine learning algorithms were undertaken for screening diagnostic markers associated with ferroptosis in ACP. The levels of DEFRGs were verified in ACP patients. A nomogram was drawn to predict the relationship between key DEFRG expression and risk of disease. The disease groups were then clustered by consensus clustering analysis.ResultsDEGs were screened between ACP and normal samples. Ferroptosis-related factors were obtained from the FerrDb V2 and GeneCard databases. The correlation between DEFRGs and ferroptosis markers was also confirmed. A total of 6 overlapped DEFRGs were obtained. Based on the results of the nomogram, CASP8, KRT16, KRT19, and TP63 were the protective factors of the risk of disease, while GOT1 and TFAP2C were the risk factors. According to screened DEFRGs, the consensus clustering matrix was differentiated, and the number of clusters was stable. CASP8, KRT16, KRT19, and TP63, were upregulated in ACP patients, while GOT1 was downregulated. CASP8, KRT16, KRT19, TP63, CASP8, and GOT1 affect multiple ferroptosis marker genes. The combination of these genes might be the biomarker for ACP diagnosis via participating ferroptosis process.DiscussionFerroptosis-related genes, including CASP8, KRT16, KRT19, TP63, and GOT1 were the potential markers for ACP, which lays the theoretical foundation for ACP diagnosis.

Abstract BackgroundBenign prostatic hyperplasia (BPH) is a global age-related disease. It has been reported that over half of the Chinese male population aged 70 years or older are experiencing BPH. Solid fuel, which is the major source of household air pollution, has been reportedly associated with several adverse events, including sex hormone disorders. Due to the certain relationship between sex hormone levels and prostate disease, the relationship between solid fuel use and lower urinary tract symptoms (LUTSs) suggestive of BPH (LUTS/BPH) deserves further exploration. ObjectiveThis study mainly aimed to investigate the association between solid fuel use and LUTS/BPH. MethodsThe data used in this study were obtained from the West China Natural Population Cohort Study. Household energy sources were assessed using questionnaires. LUTS/BPH was evaluated based on participant self-reports. We performed propensity score matching (PSM) to reduce the influence of bias and unmeasured confounders. The odds ratio (OR) and 95% CI of LUTS/BPH for the solid fuel group compared with the clean fuel group were calculated. We also conducted stratified analyses based on BMI, metabolic syndrome, waist to hip ratio, drinking status, smoking status, and age. ResultsA total of 5463 participants were included in this study, including 399 solid fuel users and 5064 clean fuel users. After PSM, the solid fuel group included 354 participants, while the clean fuel group included 701 participants. Solid fuel use was positively correlated with LUTS/BPH before and after PSM (OR 1.68, 95% CI 1.31‐2.15 and OR 1.81, 95% CI 1.35‐2.44, respectively). In stratified analyses, the OR of the nonsmoking group was higher than that of the smoking group (OR 2.56, 95% CI 1.56‐4.20 and OR 1.47, 95% CI 0.99‐2.18, respectively). Similarly, the OR of the nondrinking group was higher than that of the drinking group (OR 2.70, 95% CI 1.46‐4.99 and OR 1.48, 95% CI 1.01‐2.17, respectively). ConclusionsA positive correlation between solid fuel use and LUTS/BPH was observed. The results suggest that improving fuel structure for household cooking and other household needs can possibly help reduce the risk of LUTS/BPH.

BackgroundRecent studies have underscored the biological significance of RNA modifications in tumorigenicity and progression. However, the potential roles of RNA modifications in immune regulation and the formation of the tumor microenvironment (TME) in head and neck squamous carcinoma (HNSC) remain unclear.MethodsWe collected 199 untreated HNSC samples and clinicopathological data from Fujian Provincial Cancer Hospital. MeRIP-seq and RNA-seq were performed to generate methylation and gene expression profiles, respectively. Consensus molecular subtyping was employed to identify prognosis-related genes and RNA modification patterns in HNSC. Experiments confirmed the potential oncogenic behavior influenced by key genes. Molecular subtypes were identified through consensus clustering and validated using external cohort validation sets.ResultsAmong the RNA modification-related genes, IGF2BP1 emerged as the most prognostic. HNSC patients were categorized into high and low IGF2BP1 expression groups. High-expressing patients exhibited poorer survival and reduced chemosensitivity, coupled with increased tumor mutational burden, low PD-L1 expression, and limited immune cell infiltration, indicative of aggressive disease. Analysis revealed two distinct RNA modification patterns associated with IGF2BP1 expression: biosynthetically intense type (BIT) and oncogenically active type (OAT), each characterized by distinct clinical features, outcomes, and biological pathways. In an independent immunotherapy cohort, BIT patients displayed enhanced immune responses and sustained clinical benefits.ConclusionsThis study highlights the crucial link between RNA modification and TME diversity. Evaluating RNA modification in tumors improves our understanding of TME features and supports the development of effective immunotherapy strategies.

As aero-engines operate under extreme conditions such as high temperatures and speeds, the effectiveness of the engine tends to decrease. Therefore, real-time vibration monitoring of such structures is essential to ensure flight safety. However, the sensors used in the control system are prone to interference, thus leading to ineffective monitoring and eventually reducing the service life of the equipment. Therefore, in this study, a shear vibration sensor for real-time structural monitoring at 750 °C is designed and produced using a Langasite (LGS) crystal. Further, the high-temperature performance of the sensor is examined in the frequency, acceleration, and temperature ranges of 80–1000 Hz, 0.5–5g, and 30–750 °C, respectively. Its linearity is less than 1 %, which meets the application requirements of high-temperature piezoelectric vibration sensors. The average sensitivity of the sensor over the entire temperature range is 0.074 V/g. The sensor has good viability and can be used for testing in high-temperature environment applications as the sensitivity fluctuates by less than 2 % at different temperature points when applied to the same frequency. Furthermore, a temperature–vibration cross-decoupling approach is proposed to determine the acceleration value following temperature demodulation. The highest inaccuracy with respect to the reference acceleration is 4.54 %. Sensors also have a small size, are easy to install, and can maintain high reliability in harsh environments, playing an essential role in health assessment, fault prediction, and diagnosis of engines and other components. Therefore, the developed LGS acceleration sensor offers a promising alternative for real-time monitoring of structures in high-temperature environments, including aero-engines.

Abstract Lycibarbarspermidines are unusual phenolamide glycosides characterized by a dicaffeoylspermidine core with multiple glycosyl substitutions, and serve as a major class of bioactive ingredients in the wolfberry. So far, little is known about the enzymatic basis of the glycosylation of phenolamides including dicaffeoylspermidine. Here, we identify five lycibarbarspermidine glycosyltransferases, LbUGT1-5, which are the first phenolamide-type glycosyltransferases and catalyze regioselective glycosylation of dicaffeoylspermidines to form structurally diverse lycibarbarspermidines in wolfberry. Notably, LbUGT3 acts as a distinctive enzyme that catalyzes a tandem sugar transfer to the ortho-dihydroxy group on the caffeoyl moiety to form the unusual ortho-diglucosylated product, while LbUGT1 accurately discriminates caffeoyl and dihydrocaffeoyl groups to catalyze a site-selective sugar transfer. Crystal structure analysis of the complexes of LbUGT1 and LbUGT3 with UDP, combined with molecular dynamics simulations, revealed the structural basis of the difference in glycosylation selectivity between LbUGT1 and LbUGT3. Site-directed mutagenesis illuminates a conserved tyrosine residue (Y389 in LbUGT1 and Y390 in LbUGT3) in PSPG box that plays a crucial role in regulating the regioselectivity of LbUGT1 and LbUGT3. Our study thus sheds light on the enzymatic underpinnings of the chemical diversity of lycibarbarspermidines in wolfberry, and expands the repertoire of glycosyltransferases in nature.

Abstract Raman spectroscopy is a nondestructive and highly effective technique for analyzing biological tissues and diagnosing diseases by providing detailed spectral information about the specific molecular structures of substances. Its efficacy in these applications has been widely recognized, making it a powerful tool in the field. This article presents a comprehensive overview of the latest developments in Raman spectroscopy and its wide‐ranging applications in the diagnosis of critical diseases, such as cancer, infections, neurodegenerative diseases, and predicting surgical outcomes. It highlights the significant contributions of Raman spectroscopy in these areas, shedding light on its potential as a valuable diagnostic tool. This article delves into the advancements of Raman spectroscopy in biomedical sciences, with a specific focus on state‐of‐the‐art techniques such as surface‐enhanced Raman spectroscopy, resonance Raman spectroscopy, and tip‐enhanced Raman spectroscopy. These techniques have shown great potential in various applications within the field. The article explores their use in ex vivo and in vivo medical diagnosis, covering topics such as sample collection, data processing, and the successful establishment of correlations between Raman spectra and biochemical information in specific diseases. Furthermore, the article discusses the limitations of the current research and offers insights into potential future directions for further exploration in the field of Raman spectroscopy in biomedical sciences.

Introduction:Gan–jiang–ling–zhu (GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating yang, activating qi and dissipating dampness, GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated.Methods: NASH was induced in mice, followed by treatment with GJLZ decoction. Various methods including hematoxylin-eosin, oil red O staining, and triglyceride analysis were employed to evaluate the treatment effects of GJLZ decoction on NASH. Gut microbiota, metabolomics, cell viability assays, immunofluorescence and Western blotting were performed to unveil the mechanism behind GJLZ decoction.Results: GJLZ decoction treatment significantly improved hepatic steatosis in mice with NASH. It led to remodeling of gut flora and metabolite structures, including the 12-tridecenoic acid level. 12-Tridecenoic acid aggravated hepatic steatosis by promoting acetyl-coenzyme A carboxylase alpha (ACC) expression and inhibiting carnitine palmitoyltransferase 1A (CPT1A) expression. GJLZ decoction treatment reduced the 12-tridecenoic acid level, inhibited ACC activity and promoted CPT1A expression.Conclusion: Our results demonstrated that 12-tridecenoic acid aggravated hepatic steatosis by affecting the ACC–CPT1A axis and GJLZ decoction treatment effectively reduced the 12-tridecenoic acid level and improved steatosis.

Summary: We used a step-wheel system to examine the activity of striatal projection neurons as mice practiced stepping on complexly arranged foothold pegs in this Ferris-wheel-like device to receive reward. Sets of dorsolateral striatal projection neurons were sensitive to specific parameters of repetitive motor coordination during the runs. They responded to combinations of the parameters of continuous movements (interval, phase, and repetition), forming “chunking responses”—some for combinations of these parameters across multiple body parts. Recordings in sensorimotor cortical areas exhibited notably fewer such responses but were documented for smaller neuron sets whose heterogeneity was significant. Striatal movement encoding via chunking responsivity could provide insight into neural strategies governing effective motor control by the striatum. It is possible that the striking need for external rhythmic cuing to allow movement sequences by Parkinson’s patients could, at least in part, reflect dysfunction in such striatal coding.

Chinese Baijiu has always been preferred by the majority of alcoholic drink lovers with its rich aroma. With the popularity of drinking culture and mental health, low-alcohol Baijiu has achieved increasing attention. This paper innovatively adopts the coalescence method of separating emulsion to solve the turbidity problem in the process of degrading Baijiu. Firstly, the characteristics of feasible materials for turbidity removal via coalescence were explored. Three materials with different pore size, chemical composition, and wetting behavior, namely polyether sulfone (PES), glass fiber (GF) and polyvinylidene fluoride (PVDF), were characterized. Secondly, the emulsion structure and composition of the diluted Chinese Baijiu were analyzed. Finally, the selected porous materials were conducted to separate the precipitates in the degraded Baijiu for a clear Baijiu. The results found that both PVDF with excellent affinity to esters under alcohol solution and PES with small pore size exhibited efficient turbidity removal efficiency. Furthermore, the effect of pore size ranging from 0.1 to 5 μm of the PVDF coalescing material on the turbidity removal was investigated. However, the small pore size resulted in great pressure drop and followed the screening mechanism which contributed to high energy consumption and membrane fouling issue. The large pore size PVDF materials with average pore size of 1.6–4.0 μm achieved high flux of 5.30 × 104 L/(m2·h) with 90∼100% turbidity removal for 39% alcohol content-Baijiu via coalescence. The quality after coalescence removal of turbid was good indicating the coalescence removal method is a Chinese Baijiu turbidity removal potential technology.

In offshore pile engineering, the installation of jacked piles generates compaction effects within soil, thus further affecting previously installed adjacent piles. This study proposes a three-dimensional numerical model for pile group installation, soil consolidation, and loading analysis. Subsequently, the effect of pile spacing and pile length-to-diameter ratio on the deformation, internal forces, and vertical bearing capacity of adjacent piles are investigated. The results indicate that with an increase in pile center distance, the peak lateral displacement of the adjacent piles decreases, whereas the peak vertical displacement increases. As the pile length-to-diameter ratio increases, the peak vertical and lateral displacements of the adjacent piles are enhanced. In addition, the peak axial force of the adjacent piles initially decreases and then increases with the penetration depth of the subsequent pile, whereas the peak bending moment initially increases and then decreases. The vertical bearing capacity of the subsequent pile is significantly superior to that of the adjacent piles. Therefore, the effects of pile installation on adjacent piles should be included in pile engineering. The impact of the subsequent pile installation on the bearing capacity of adjacent piles can be significantly reduced by increasing the pile center distance and pile length-to-diameter ratio. The findings provide useful guidance for pile group engineering.

ObjectiveThe established link between posttranslational modifications of histone and non-histone lysine (K) residues in cell metabolism, and their role in cancer progression, is well-documented. However, the lactylation expression signature in triple-negative breast cancer (TNBC) remains underexplored.MethodsWe conducted a comprehensive lactylproteome profiling of eight pairs of TNBC samples and their matched adjacent tissues. This was achieved through 4-Dimensional label-free quantitative proteomics combined with lactylation analysis (4D-LFQP-LA). The expression of identified lactylated proteins in TNBC was detected using immunoblotting and immunohistochemistry (IHC) with specific primary antibodies, and their clinicopathological and prognostic significance was evaluated.ResultsOur analysis identified 58 lactylation sites on 48 proteins, delineating the protein lactylation alteration signature in TNBC. Bioinformatic and functional analyses indicated that these lactylated proteins play crucial roles in regulating key biological processes in TNBC. Notably, lactylation of lysine at position 12 (H4K12lac) in the histone H4 domain was found to be upregulated in TNBC. Further investigations showed a high prevalence of H4K12lac upregulation in TNBC, with positive rates of 93.19% (137/147) and 92.93% (92/99) in TNBC tissue chip and validation cohorts, respectively. H4K12lac expression correlated positively with Ki-67 and inversely with overall survival (OS) in TNBC (HR [hazard ratio] =2.813, 95%CI [credibility interval]: 1.242-6.371, P=0.0164), suggesting its potential as an independent prognostic marker (HR=3.477, 95%CI: 1.324-9.130, P=0.011).ConclusionsLactylation is a significant post-translational modification in TNBC proteins. H4K12lac emerges as a promising biomarker for TNBC, offering insights into the lactylation profiles of TNBC proteins and linking histone modifications to clinical implications in TNBC.

As a crucial regulator influencing tumor progression, nicotinamide adenine dinucleotide (NAD+) is widely acknowledged. However, its role in endometrial cancer (EC) is not completely understood. In this study, we aimed to develop an NAD+metabolic-related genes (NMRGs) risk signature that could reflect the prognosis of EC patients and their responsiveness to immunotherapy and chemotherapy. Data from The Cancer Genome Atlas (TCGA) databases and the Molecular Signatures Database (MSigDB) confirmed two distinct NMRG subtypes in EC patients using consensus clustering, and a risk score was constructed utilizing an NAD+-related prognostic signature depending on the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Receiver operating characteristic (ROC) curves were employed to assess the model’s precision. Additionally, we used Gene Set Enrichment Analysis (GSEA) to predict the biological signaling pathways that might be involved. We also explored the role of the risk score in immune cell infiltration, tumor mutation burden (TMB), immunotherapy, and chemotherapy. Our study established a prognostic risk signature based on six NMRGs, and we observed that the high-risk group was associated with a poorer prognosis. Furthermore, we identified a strong correlation between the high-risk group and several pathways, including DNA replication, cell cycle, and mismatch repair. Lastly, our findings highlighted the influence of NMRGs on the regulation of immune infiltration in EC. Therefore, this signature holds potential value in predicting the prognosis of EC patients and guiding their management, including decisions regarding immunotherapy and chemotherapy, ultimately improving the accuracy of EC patient care.

Abstract Background There is a substantially increasing need for general practitioners (GPs) for future unpredictable pandemic crises, especially at the community-based health services (CBHS) level to protect the vast and varied grassroot-level population in China. Thus, it is crucial to understand the factors that affect Chinese medical students’ GP career choices and commitments to CBHS. Methods Leveraging the self-administered data collected across the country, this study conducted logistic regressions with 3,438 medical students. First, descriptive statistics of outcome variables and independent variables were provided. Then, stepwise logistic regression models were built, starting from adding individual characteristics, and then familial and institutional characteristics. Last, post-estimation was conducted to further assess whether there were significant marginal effects. Results Results showed that women students were 24% less likely to choose GP careers but were 1.25 times more likely to commit to CBHS than their men peers, holding other individual, familial, and institutional characteristics constant. In addition, students who major in GP-orientated were more likely to choose GP careers and commit to CBHS, respectively, than those who major in clinical medicine. Furthermore, familial characteristics like annual income and mother’s educational level only significantly predicted commitments to CBHS. Notably, sex-related differences in GP career choices and commitments to CBHS – by different regions – were observed. Conclusions Understanding the factors that affect medical students’ GP career choices sheds light on how medical education stakeholders can make informed decisions on attracting more medical students to GP-orientated majors, which in turn cultivates more GP professionals to meet the nation’s demand for GPs. In addition, by understanding the factors that influence medical students’ commitment to CBHS, policymakers could make beneficial policies to increase medical students’ motivations to the grassroot-level health institutions, and devote to CBHS as gatekeepers for a large population of residents’ health.

Abstract Background The increasing number of pertussis cases worldwide over the past two decades has challenged healthcare workers, and the role of environmental factors and climate change cannot be ignored. The incidence of pertussis has increased dramatically in mainland China since 2015, developing into a serious public health problem. The association of meteorological factors on pertussis has attracted attention, but few studies have examined the impact of air pollutants on this respiratory disease. Methods In this study, we analyzed the relationship between outdoor air pollution and the pertussis incidence. The study period was from January 2013 to December 2018, and monthly air pollutant data and the monthly incidence of patients in 31 provinces of China were collected. Distributed lag nonlinear model (DLNM) analysis was used to estimate the associations between six air pollutants and monthly pertussis incidence in China. Results We found a correlation between elevated pertussis incidence and short-term high monthly CO2 and O3 exposure, with a 10 μg/m3 increase in NO2 and O3 being significantly associated with increased pertussis incidence, with RR values of 1.78 (95% CI: 1.29-2.46) and 1.51 (95% CI: 1.16-1.97) at a lag of 0 months, respectively. Moreover, PM2.5 and SO2 also played key roles in the risk of pertussis surged. These associations remain significant after adjusting for long-term trend, seasonality and collinearity. Conclusions Overall, these data reinforce the evidence of a link between incidence and climate identified in regional and local studies. These findings also further support the hypothesis that air pollution is responsible for the global resurgence of pertussis. Based on this we suggest that public health workers should be encouraged to consider the risks of the environment when focusing on pertussis prevention and control.

Abstract Endometrial receptivity has been widely understood as the capacity of the endometrium to receive implantable embryos. The establishment of endometrial receptivity involves multiple biological processes including decidualization, tissue remodeling, angiogenesis, immune regulation, and oxidative metabolism. Extracellular vesicles (EVs) are lipid-bilayer-membrane nanosized vesicles mediating cell-to-cell communication. Recently, EVs and their cargo have been proven as functional factors in the establishment of endometrial receptivity. In this review, we comprehensively summarized the alteration of endometrium/embryo-derived EVs during the receptive phase and retrospected the current findings which revealed the pivotal role and potential mechanism of EVs to promote successful implantation. Furthermore, we highlight the potentiality and limitations of EVs being translated into clinical applications such as biomarkers of endometrial receptivity or reproductive therapeutic mediators, and point out the direction for further research.

Abstract Behçet’s disease (BD) is a systemic vasculitis that can affect multiple systems, including the skin, mucous membranes, joints, eyes, gastrointestinal and nervous. However, the pathogenesis of BD remains unclear, and it is believed that immune-inflammatory reactions play a crucial role in its development. Immune cells are a critical component of this process and contribute to the onset and progression of BD. By regulating the function of these immune cells, effective control over the occurrence and development of BD can be achieved, particularly with regards to monocyte activation and aggregation, macrophage differentiation and polarization, as well as T cell subset differentiation. This review provides a brief overview of immune cells and their role in regulating BD progression, which may serve as a theoretical foundation for preventing and treating this disease.

Abstract This paper presents a surface acoustic wave (SAW) sensor based on coplanar integrated Langasite (LGS) that is fabricated using wet etching, high-temperature bonding, and ion beam etching (IBE) processes. The miniaturized multiparameter temperature‒pressure-humidity (TPH) sensor used the MXene@MoS2@Go (MMG) composite to widen the humidity detection range and improve the humidity sensitivity, including a fast response time (3.18 s) and recovery time (0.94 s). The TPH sensor was shown to operate steadily between 25–700 °C, 0–700 kPa, and 10–98% RH. Coupling issues among multiple parameters in complex environments were addressed by decoupling the Δf-temperature coupling factor to improve the accuracy. Therefore, this work can be applied to simultaneous measurements of several environmental parameters in challenging conditions.

Background: Cervical cancer is the most common gynecological malignancy in the world and seriously threatens to women’s lives and health. Polypyrimidine tract binding protein 1 (PTBP1), as an important splicing factor, has been identified as a proto-oncogene in several cancers, but its role and mechanism in cervical cancer remain poorly understood. Thus, our aim is to explore the impact of PTBP1 on proliferation, migration, apoptosis of cervical cancer cells, and its underlying mechanisms. Methods: The biological functions in cervical cancer cells were determined using small interfering RNA (siRNA), agonist, Cell Counting Kit-8 (CCK-8), transwell, migration test, western blot, real-time-PCR, immunohistochemistry and immunofluorescence, respectively. Results: The results indicated that PTBP1 was highly expressed in cervical cancer patients and cervical cancer cell lines compared to the normal group. Moreover, PTBP1 silencing significantly inhibited cell proliferation, and migration in both HeLa and SiHa cells. The PTBP1 silencing also induced mitochondrial apoptosis through upregulating Bax and mitochondrial apoptotic protein Cytochrome C, and downregulating B-Cell Leukemia/Lymphoma 2 (Bcl2) protein. Additionally, PTBP1 silencing induced autophagy by downregulating Sequestosome I (p62) and upregulating the ratio of Light chain 3-Ⅱ/Light chain 3-Ⅰ (LC3-Ⅱ/LC3-Ⅰ). Mechanistically, we found that the Phosphoinositide 3-kinase (PI3K) agonist reversed the changes induced by PTBP1 silencing. Conclusions: Overall, PTBP1 silencing can induce cervical cancer cells apoptosis mainly through PI3K/AKT pathway and protective autophagy. This study provides preliminary evidence for PTBP1 as a therapeutic target or prognostic marker for cervical cancer.

Abstract Background Night-time light pollution (NLP), which breaks the natural cycle of day and night, has become a new threat to urban ecosystems. Plants are the main component of urban ecosystems and play an irreplaceable role in maintaining urban ecological balance. The effects of NLP with various radiation sources, including green, white, blue and red light provided by light-emitting diodes, on urban plants, Euonymus japonicus and Rosa hybrida, were examined in a block field experiment. Results NLP caused photoinhibition and oxidative stress in plants, and the extent of the deleterious effects varied with the spectral distribution of artificial light sources and species. Both E. japonicus and R. hybrida were more sensitive to blue and red light, which reduced the pigment concentration, net photosynthetic rate, stomatal limit value, effective quantum yield, apparent electron transfer rate and photochemical quenching coefficient, and markedly increased the malondialdehyde content and total antioxidant capacity. However, those negative effects under white light were only present in E. japonicus and not in R. hybrida. Furthermore, blue and red light significantly decreased the stomatal conductance of E. japonicus. In contrast, green light had no significant effect on the above indices for both species. All spectra did not significantly change the sugars and starch contents for either species. Conclusions Considering that the spectral distribution of artificial light at night in cities has great heterogeneity and that its effect varies with plant species, it is important to arrange tree species with NLP tolerance and install appropriate light sources in urban areas based on the corresponding physiological responses and adaptation of urban trees.

Abstract Background We aimed to evaluate the optimal management for elderly patients with nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT). Methods A total of 283 elderly patients with NPC diagnosed from 2015 to 2019 were enrolled in the study. Overall survival (OS) was the primary endpoint. Univariate and multivariate Cox regression analyses were preformed to identify potential prognostic factors. The recursive partitioning analysis (RPA) was used for risk stratification. Kaplan-Meier survival curves were applied to evaluate the survival endpoints, and log-rank test was utilized to assess differences between groups. The prognostic index (PI) was constructed to further predict patients’ prognosis displayed by nomogram model. The area under the receiver operating characteristic (ROC) curves (AUC) and the calibration curves were applied to assess the effectiveness of the model. Results Based on RPA-based risk stratification, we demonstrated that elderly NPC patients who were treated with IC followed by RT had similar OS as those with induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) in the middle- (stage I-III and pre-treatment EBV > 1840 copies/ml) and high-risk groups (stage IVA). IMRT alone may be the optimal treatment option for the low-risk group (stage I-III with pre-treatment EBV ≤ 1840 copies/ml). We established an integrated PI which was indicted with stronger prognostic power than each of the factors alone for elderly NPC patients (The AUC of PI was 0.75, 0.80, and 0.82 for 1-, 3-, 5-year prediction of OS, respectively). Conclusion We present a robust model for clinical stratification which could guide individual therapy for elderly NPC patients.

Abstract Graphium sarpedon is a significant foliar pest of Laurel plants in China. In this study, the MaxEnt model was used to investigate the distribution of G. sarpedon and predict its potential distribution areas in China in the future (2050s and 2090s) based on three Shared Socioeconomic Pathways (SSP1‐2.6, SSP2‐4.5, and SSP5‐8.5), and key environmental variables affecting its distribution were identified. The results showed that under the current climatic conditions, the suitable distribution areas of G. sarpedon were 92.17°–134.96° E and 18.04°–33.61° N, including Yangtze Plain (Middle and Lower), Pearl River Delta, Yangtze River Delta, and Lingnan areas. Under the future climate conditions, the total suitable distribution area of G. sarpedon decreased, but the area of medium suitable area increased. The study identified 11 key environmental variables affecting the distribution of G. sarpedon, the most critical of which was Precipitation of Warmest Quarter (bio18) and precipitation in April, May, June, and September (prec4, prec5, prec6, and prec9). This study is beneficial for monitoring and preventing the possible changes of G. sarpedon and provides theoretical references for its prevention and control.

ABSTRACT: This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3–7 d), middle stage (17–21 d), and late stage (31–35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers.

Birds exhibit a high degree of migratory diversity, which is influenced by various ecological factors and life history strategies. Conducting studies on tropical bird migration, of which research is scarce, and comparing it with temperate birds can enhance our understanding of bird migration behaviour and its underlying mechanisms. In this study, we explored the migration behaviour of a breeding population of the Barn Swallow (Hirundo rustica) in Zhanjiang, southern China, a region located in the northern tropics, using light-level geolocators. From 2021 to 2023, we deployed geolocators on 92 breeding swallows and retrieved geolocators successfully from 23 individuals. These swallows all exhibited migratory behaviour, and wintering on various islands in Southeast Asia. They displayed sex differences in their wintering locations. All males concentrated in Borneo, while females primarily chose Borneo but also dispersed to the Philippines, South China Sea, and Vietnam for wintering. The studied swallow population adopted a seasonal migration pattern of “indirect in autumn, direct in spring”, bypassing the ecological barrier of the South China Sea in autumn and tending to directly cross it in spring migration. Moreover, the distance and duration of autumn migration was significantly longer than those of the spring migration. Compared to temperate Barn Swallows, the Barn Swallow population breeding in Zhanjiang adopts a pattern of “intra-tropical migration” and initiates autumn migration earlier. The formation of their migration pattern may be limited by ecological and physiological factors.

ObjectiveBempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for hypercholesterolemia. Nonetheless, the outcomes of the initial investigations might have been more definitive and coherent. Our objective was to perform a quantitative meta-analysis in order to evaluate bempedoic acid's safety and effectiveness.MethodsA search was conducted on ClinicalTrials.gov, and PubMed from the time of inception until September 28, 2023. Randomized controlled trials comparing the safety and efficacy of bempedoic acid among patients with statin intolerance and those without were included in our analysis. The trial outcomes were summarized using a random effects model and were provided as mean differences or odds ratios (ORs) with a confidence interval of 95%. Additionally, trial heterogeneity and the possibility of bias were evaluated and investigated.ResultsBempedoic acid treatment reduced low-density lipoprotein cholesterol levels more than placebo (mean difference -2.97%, 95% CI -5.89% to -0.05%), according to a pooled analysis of 16 eligible trials. The risk of death (OR 1.18, 95% CI 0.70 to 1.98) and muscle-associated occurrences (OR 1.00, 95% CI 0.77 to 1.31) was not impacted by bempedoic acid. In contrast, discontinuation of treatment was more frequently caused by adverse events in the bempedoic acid group (OR 1.13, 95% CI 1.01 to 1.27).ConclusionsIn patients with statin intolerance as well as those without, bempedoic acid is a safe and efficacious lipid-lowering agent, according to findings from randomized controlled trials.

The tetraspanin CD81 is one of the main entry receptors for Hepatitis C virus, which is a major causative agent to develop liver cirrhosis and hepatocellular carcinoma (HCC). Here, we identify CD81 as one of few surface proteins that are downregulated in HCV expressing hepatoma cells, discovering a functional role of CD81 beyond mediating HCV entry. CD81 was downregulated at the mRNA level in hepatoma cells that replicate HCV. Kinetics of HCV expression were increased in CD81-knockout cells and accompanied by enhanced cellular growth. Furthermore, loss of CD81 compensated for inhibition of pro-survival TBK1-signaling in HCV expressing cells. Analysis of functional phenotypes that could be associated with pro-survival signaling revealed that CD81 is a negative regulator of NF-κB. Interaction of the NF-κB subunits p50 and p65 was increased in cells lacking CD81. Similarly, we witnessed an overall increase in the total levels of phosphorylated and cellular p65 upon CD81-knockout in hepatoma cells. Finally, translocation of p65 in CD81-negative hepatoma cells was markedly induced upon stimulation with TNFα or PMA. Altogether, CD81 emerges as a regulator of pro-survival NF-κB signaling. Considering the important and established role of NF-κB for HCV replication and tumorigenesis, the downregulation of CD81 by HCV and the associated increase in NF-κB signaling might be relevant for viral persistence and chronic infection.

Abstract Background Transtendon repair and repair after completion of the tear have been widely used to treat partial-thickness rotator cuff tears (PT-RCTs). The present study was aimed to compare the clinical outcomes and tendon integrity following arthroscopic repair of articular PT-RCTs using transtendon repair or repair after completion of the tear. Methods We performed a systematic electronic database search on Cochrane Central Register of Controlled Trials, PubMed and Embase to identify articles equating articular-sided PT-RCTs repair. The randomized controlled clinical trials that met our criteria were evaluated for quality of methodology. The results obtained were further analyzed and correlated to present the benefits and drawbacks comparing the two surgical procedures. Result According to our inclusion and exclusion criteria, six articles were included in the present study. A total of 501 patients were analyzed as part of this study. The results indicated that both the surgical treatments provided excellent functional improvements and tendon integrity. However, no significant differences for the visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, constant score, range of motion, postoperative adhesive capsulitis, tendon integrity and patient satisfaction were found between the two cohorts (p > 0.05). Conclusions Both transtendon technique and repair after completion of the tear for articular-sided partial rotator cuff tear provide improvements in clinical outcome with a low complication rate and a high rate of healing.

Abstract Gastric cancer (GC) is one of the major causes of cancer deaths with 5-year survival ratio of 20%. RNU12 is one of long noncoding RNAs (lncRNAs) regulating the tumor progression. However, how RNU12 affecting GC is not clear. qRT-PCR was utilized for determining the RNU12 expression in cell lines, 113 cases of paired gastric cancer (GC) and their adjacent normal gastric tissues. The biofunction alterations of RNU12 were assessed by its overexpression or knockdown in GC cells. MTT and cloning assay were assayed for the cell proliferation, the flow cytometry for the detection of cell cycle and the wound healing assay (WHA) and transwell invasion assay (TIA) for examining the migration and invasion of cells. The expressions of a set of genes related proliferation and migration were investigated with the Western Blotting (WB). RNA immunoprecipitation (RIP), biotinylated RNA pull-down and dual luciferase reporter tests were used to detect the interactions of RNU12 with miR-575/BLID. The in vivo proliferation and migration ability of RNU12 infected cells were determined in zebrafish system. This study revealed that RNU12 inhibited proliferation, invasion and metastasis by sponging of miR-575 and regulating the downstream BLID and modulated EMT of GC cells. The RNU12/miR-575/BLID axis is likely to be the prognosis biomarkers and drug targets of GC.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a new infectious disease first discovered in Ta-pieh Mountains in central China in 2009. It is caused by a novel bunyavirus infection (SFTSV). Since the first discovery of SFTSV, there have been case reports and epidemiological studies on SFTS in several East Asian countries, such as South Korea, Japan, Vietnam and so on. With the rising incidence of SFTS and the rapid spread of the novel bunyavirus around the world, it is clear that the virus has a pandemic potential and may pose a threat to global public health in the future. Early studies have suggested that ticks are an important medium for the transmission of SFTSV to humans; in recent years, it has been reported that there is also human-to-human transmission. In endemic areas, potential hosts include a variety of livestock and wildlife. When people are infected with SFTV, the main clinical manifestations are high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, liver and kidney function damage, and even MODS, with a mortality rate of about 10–30%. This article reviews the latest progress of novel bunyavirus, including virus transmission vector, virus genotypic diversity and epidemiology, pathogenesis, clinical manifestation and treatment.

The widespread use of artificial light at night (ALAN) due to urbanization and infrastructure development has raised concerns about its potential impacts on plant physiology. To explore the effects of ALAN with different light intensities on the photosynthesis and respiration of two urban vascular plants, Euonymus japonicus Thunb and Rosa hybrida E.H.L.Krause, under continuous and non-continuous-light conditions, respectively, a field experiment was conducted. Our findings indicate that continuous ALAN significantly inhibited the photosynthesis and respiration of the two plants, disrupting the carbon-balance pattern of their leaves during the day, but this effect is influenced by the intensity of ALAN and plant species. Euonymus japonicus Thunb is more susceptible to continuous ALAN than Rosa hybrida E.H.L.Kraus. Non-continuous ALAN did not significantly affect the photosynthesis and respiration of two species during the day. Furthermore, we observed that high light intensity at night could also impact the value of the net photosynthetic rate (Pn) of Euonymus japonicus Thunb during the night. Turning off light sources at night, reducing the light intensity, and cultivating ALAN-tolerant plants are effective measures to reduce the negative effects of ALAN on plants and maintain plants’ normal carbon-balance mode. Future studies should explore the effects of different types of artificial-light sources combined with other environmental conditions on the photosynthesis and respiration of plants at the canopy scale.

BackgroundThe continuous exploration of oligometastatic disease has led to the remarkable achievements of local consolidative therapy (LCT) and favorable outcomes for this disease. Thus, this study investigated the potential benefits of LCT in patients with single-organ metastatic pancreatic ductal adenocarcinoma (PDAC).MethodsPatients with single-organ metastatic PDAC diagnosed between 2010 - 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to minimize selection bias. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates.ResultsA total of 12900 patients were identified from the database, including 635 patients who received chemotherapy combined with LCT with a 1:1 PSM with patients who received only chemotherapy. Patients with single-organ metastatic PDAC who received chemotherapy in combination with LCT demonstrated extended median overall survival (OS) by approximately 57%, more than those who underwent chemotherapy alone (11 vs. 7 months, p < 0.001). Furthermore, the multivariate Cox regression analysis revealed that patients that received LCT, younger age (< 65 years), smaller tumor size (< 50 mm), and lung metastasis (reference: liver) were favorable prognostic factors for patients with single-organ metastatic PDAC.ConclusionThe OS of patients with single-organ metastatic pancreatic cancer who received LCT may be prolonged compared to those who received only chemotherapy. Nevertheless, additional prospective randomized clinical trials are required to support these findings.

An efficient and rapid immunochromatographic assay (ICA) has been engineered for the detection of Streptococcus suis (S. suis). The underpinning principle of this ICA test lies in the use of polyclonal antibodies (pAbs) decorated with colloidal gold, which are specific to S. suis. These pAbs were derived from rabbits immunized with type II histidine triad protein (HtpsC) and HtpsC-N of S. suis. The sensitivity of the ICA was noteworthy, identifying S. suis at bacterial concentrations as diminutive as 1.0 × 103 CFU/mL. Moreover, the assay demonstrated respectable specificity and did not indicate false positives for other bacterial species (Escherichia coli, Salmonella, Staphylococcus aureus, Listeria monocytogenes, Streptococcus pyogenes, Streptococcus lactis, or Enterococcus faecalis). The assay was also capable of detecting multiple S. suis serotypes containing the htpsC gene, including serotypes 1–9, 12, 14, 16 and 23. Nonetheless, the detection of S. suis that lacks the htpsC gene remained beyond the capabilities of this assay. A simultaneous analysis of 16 samples utilizing PCR substantiated the reliability of the ICA test. The assay’s results can be procured within a 15-min window, making it a suitable option for field application. Broadly, this study underscores the potential of the HtpsC protein as a target antigen for the detection of S. suis, and proposes that the HtpsC protein be evaluated further in other detection assays specific for S. suis.

Objective Assess whether local health facilities can adequately support the performance of general practitioners (GPs) trained by China’s national compulsory services programme (CSP).Design Prospective cohort study.Setting Health facilities in middle and western rural areas in China, 2015–2022.Participants Cohorts of CSP graduates from 2015 to 2019 in four major medical universities.Main outcomes Job performance measured by a 12-item Job Performance Scale; productivity measured by outpatient volume per day; turnover measured by ever changing jobs within the past year.Results 91.2%, 92.0% and 90.5% GPs working in township health centres reported inadequate medication, equipment and external assistance from higher level hospitals, while CSP graduates working in secondary or tertiary hospitals reported a lower rate of less than 60%. The top three tests reported as lacking were blood gases (67.7%), microbiology (61.6%) and cancer biomarkers (49.7%); the top three lacked procedures were CT scan (64.8%), MRI scan (58.1%) and ambulatory BP monitoring (55.8%); and the top three lacked drugs were drugs for cardiovascular diseases (23.3%), systematic hormonal preparations (17.7%) and traditional Chinese medicines (13.0%). Multivariable analysis showed that facility support was positively associated with job performance—adequate medication increased job performance by 2.2 points (95% CI 0.7 to 3.8), and adequate external assistance increased job performance by 3.3 points (95% CI 1.8 to 4.8). Facility support was also positively associated with productivity—adequate medication increased outpatients seen per day by 20% (95% CI 0.1 to 0.3), and adequate equipment increased outpatients seen per day by 12% (95% CI 0.0 to 0.2). Facility support did not have significant impact on turnover, but GPs who changed jobs in the past year were 1.9–2.3 times more likely to report adequate facility support.Conclusion GPs in township health centres experienced a high prevalence of shortage in facility support. The identification of a positive association between facility support and performance and productivity has implications for future research and resources deployment in primary healthcare.

Urban plants are currently confronted with the stresses posed by artificial light at night (ALAN) and drought. A field block experiment was designed to explore the potential effects of ALAN and drought on the photosynthesis and physiological characters of two common urban plants, Euonymus japonicus (E. japonicus) and Rosa hybrida (R. hybrida). Each plant species was subjected to four distinct treatments: neither ALAN nor drought, ALAN, drought, and both ALAN and drought. The result showed the following: (1) ALAN significantly reduced the effective quantum yield (ΦPSII), apparent electron transfer rate (ETR), photochemical quenching parameter (qp), net photosynthetic (Pn), stomatal conductance (Gs), stomatal limit value (Ls), and the pigment concentrations and remarkably increased the content of malondialdehyde (MDA), total antioxidant capacity (TAC), and starch in both E. japonicus and R. hybrida. Furthermore, ALAN increased the soluble saccharides of E. japonicus, and this effect of ALAN also occurred on R. hybrida under drought. (2) Drought significantly decreased the ΦPSII, ETR, qp, Pn, Gs, Ls, and the pigment concentrations and remarkably increased the content of MDA and TAC for both E. japonicus and R. hybrida. Moreover, drought did not significantly change the starch content of both species, and it significantly increased the content of soluble saccharides for E. japonicus. (3) The interaction between ALAN and drought occurred on the ΦPSII, ETR, Pn, MDA, and TAC of E. japonicus, but had no effect on R. hybrida. For urban areas affected by ALAN and drought, it is advisable to select plant species with strong stress resistance for gardening purposes, and plants directly exposed to ALAN should receive sufficient water during hot and dry weather conditions to maintain their normal growth.

Prolonged half-life of protein-based therapeutics can improve drug efficacy. However, the impact of drug half-life on gene therapy, which inherently provides long-lasting production of the desired therapeutic protein, remains unclear. In this study, several proteins with extended half-lives were engineered by fusion with the soluble monomeric immunoglobulin G 1 (IgG1) fragment crystallizable (sFc) or Fc region of IgG in adeno-associated virus (AAV)-delivered gene therapy. It was demonstrated that extending the half-life of a small-sized bifunctional protein and fibroblast growth factor 21 (FGF21) significantly increased their concentrations in the bloodstream circulation. Moreover, the half-life extension of AAV-delivered FGF21 resulted in a remarkable reduction in liver injury and blood glucose, and improved glucose tolerance and insulin sensitivity in type 2 diabetes mellitus animal models. These results demonstrate the therapeutic potential of gene therapy with prolonged drug half-life in the treatment of human diseases.

Abstract Backgrounds We aimed to test whether the prediction of presurgical metabolic syndrome for postsurgical survival outcomes of gastric cancer hinges upon cigarette smoking status. Methods This study is a part of the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients with gastric cancer received radical resection of primary gastric cancer between January 2000 and December 2010, with the latest follow‐up ended in December 2015. The 1:1 propensity score matching analysis was adopted to balance confounders between smokers and never‐smokers. Effect‐size estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). Model performance was evaluated using the Hosmer and Lemeshow test and 10‐fold cross‐validated area under the receiver operating characteristic curve (AUROC). Statistical analyses were completed with SAS software (v9.4). Results Total 2779 patients with gastric cancer were analyzed, including 2223 smokers and 556 never‐smokers. Median follow‐up time was 45.6 months. Cigarette smoking was not associated with postsurgical survival differences. Presurgical metabolic syndrome complication was significantly associated with increased gastric cancer‐specific mortality in smokers (HR [95% CI]: 2.73 [1.53–4.89], p

The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury. Valproate is a histone deacetylase inhibitor and multitarget drug, which has been demonstrated to protect retinal neurons. In this study, we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling. We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope. Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein, phosphorylated eukaryotic translation initiation factor 2α, and caspase-12 in the endoplasmic reticulum of retinal ganglion cells. These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress. These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

Abstract Background Bisphenol A (BPA) exposure and its structural analogs (BPS and BPF) might cause endocrine alterations and adverse physiological effects. Few studies to date have directly explored the association between its structural analogs (BPS, BPF) and sex hormones in adult male participants. Therefore, we aimed to assess the associations between BPA, BPS, BPF, and sex hormones in American adult men. Methods We used data from the U.S. National Health and Nutrition Examination Survey 2011–2016. We excluded participants without data available on sex hormones and urinary bisphenols. Furthermore, participants consuming sex hormone medications were excluded. Multivariable regression models were performed to assess the association between bisphenols and sex hormones. Results In this study, 2367 participants were included. Of 2367, in 1575 participants, the data on BPS and BPF were available. We found that a per unit increase in BPF was associated with 0.575 ng/dL higher total testosterone (TT) (Model 2: 95% CI: 0.047, 1.103, P = 0.033). However, there was no significant association between BPA or BPS and TT. Furthermore, increased BPA and BPS levels were associated with higher levels of sex hormone-binding globulin (SHBG) (Model 2: β = 0.364, 95% CI: 0.158, 0.571; β = 0.25, 95% CI: 0.071, 0.429, respectively). Additionally, participants in the highest BPA exposure quartile (quartile 4) had 4.072 nmol/L higher levels of SHBG than those in quartile 1 (Model 2: 95% CI: 0.746, 7.397, P = 0.017; P for trend =0.005). Both BPA and BPS were negatively associated with free testosterone (FT, nmol/L) after full adjustment (Model 2, β = − 0.01%, P = 0.0211, P = 0.0211; Model 2, β = − 0.01%, P = 0.0258, respectively). However, BPF was positively associated with FT (Model 2, β = 0.0029%, P = 0.0028). Conclusion Our study indicated that exposure to both BPA and its substitutions could alter sex hormone levels. This finding supports the possibility that human exposure to bisphenols at environmental levels might affect the endogenous hormone balance.

Background China started a national program in 2010 to train qualified general practitioners with compulsory services program (CSP) in rural and remote areas. While the program has shown positive effects on staffing primary healthcare (PHC) in rural areas, very little is known about how well they perform. This study aims to evaluate the job performance of medical graduates from this program and the influence of program design on job performance.Methods A cohort study was conducted with graduates from CSP and non-CSP (NCSP) from four medical universities in central and western China. Baseline and three waves of follow-up surveys were conducted from 2015-2020. The pass rate of China National Medical Licensing Examinations (NMLE) and self-reported job performance were used as measurements. Multivariable regressions were used to identify factors affecting job performance.Results 2154 medical graduates were included, with 1586 CSP and 568 NCSP graduates. CSP (90.6%) and NCSP (87.5%) graduates showed no difference in passing the NMLE (P = .153). CSP graduates reported similar job performance with NCSP graduates (CSP, 63.7; NCSP, 64.2); in the multivariable regression, CSP graduates scored 0.32 and 1.36 points lower in the total sample and graduates of 2015-2017, respectively, but not significantly. Having formally funded positions improved the job performance of CSP (β coefficient = 4.87, P < .05). After controlling for Qinghai which adopted a different contracting strategy, “working in hometown” showed significant influence on job performance (β coefficient = 1.48, P < .05).Conclusion CSP graduates have demonstrated as good job performance as NCSP, proving the competency to provide high-quality care for remote and rural areas. The contracted township health centers (THCs) should provide guidance for CSP graduates, especially in the first few years after graduation. The local government should provide formally funded positions on time and prioritize signing contracts with hometowns or places nearby.

Abstract This study evaluated the impact of elevated body mass index (BMI) on short- and long-term outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. A total of 7229 patients undergoing IVF/ICSI fresh cycles and subsequent frozen embryo transfer cycles from 2014 to 2020 were divided into normal (18.5–24.9 kg/m2) and high BMI (≥ 25 kg/m2) groups. Ovarian response, pregnancy outcomes, and safety of both mother and fetus were the main outcome measures. Furthermore, multivariate analysis was used to determine whether BMI was associated with cumulative live birth rate (CLBR). Results showed that for younger women (

Abstract Purpose This study aimed to analyse the genomic alteration profiles and immune characteristics of a cohort of Chinese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and immunotherapy as well as their prognostic significance. Methods PD-L1 expression and clinicopathological information were obtained from 98 cervical cancer patients. Differences in PD-L1 expression and gene mutations between squamous cell carcinoma (SCC) and adenocarcinoma (AC) were analysed by the chi-square test or Fisher's exact test. Differences in gene mutations between our cohort and The Cancer Genome Atlas (TCGA) cohort were tested by Fisher's exact test. Logistic regression was used to analyse factors influencing TMB-high. Results Positive PD-L1 expression was significantly higher in cervical SCC than in cervical AC (87% vs. 39%, p