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Inducing and maintaining general anesthesia requires a diverse set of medications. Currently, heart surgery anesthetic management does not adhere to any one standard protocol or set of drugs. To ensure steady circulatory function while providing sufficient sedation, anesthetic medications are carefully selected for cardiovascular operations. Among the opioids used most often in cardiac surgery are fentanyl, sufentanil, and remifentanil. As a cardiac anesthesiologist, your key responsibilities will be to maintain your patient’s blood pressure (BP) and oxygen levels, reduce the frequency and intensity of ischemia events, and make it easy for them to get off of cardiopulmonary bypass (CPB) and supplemental oxygen fast. Additionally, new knowledge gaps have been identified as a result of developments in cardiac anesthetics, which must be addressed. The goal of the most recent developments in cardiac anesthesia has been to decrease risks and increase accuracy in patient outcomes during cardiac surgeries. Furthermore, new methods and tools are contributing to the evolution of cardiovascular anesthesia toward a more dynamic, patient-centered approach, with an eye on boosting safety, decreasing complications, and facilitating better recovery for patients. New medications and methods have emerged in the field of anesthetic pharmacology, aiming to improve anesthesia management, particularly for patients who have cardiovascular disease. Optimal cardiovascular stability, fewer side effects, and enhanced surgical recovery are achieved by use of these medications. We have reviewed all the different kinds of cardiac anesthetic techniques and medications in this research. We have also examined the many new anesthetic medicines that have been produced and used for individuals with cardiovascular issues. Next, we covered prospects in the realm of cardiovascular anesthesia and novel cardiac anesthetic drugs.

ObjectivesThis study investigates the impact of five distinct stance widths on static balance and limits of stability in healthy adults under varying visual conditions, specifically with eyes open and closed.MethodsThe Prokin Balance Instrument was used to evaluate static balance with both eyes open and closed, as well as limits of stability with eyes open, in 20 healthy adults (male, age = 21.55 ± 1.39). Participants were assessed at five stance widths (0 cm, 10 cm, 20 cm, 30 cm, and self-selected width) for each condition. Statistical analysis of the test indices was conducted using repeated measures ANOVA.ResultsIn static balance tests, index values were higher with eyes closed than with eyes open, with this difference being most pronounced at narrower stance widths. Notably, a significant main effect was observed for all indicators, in the static balance test under varying visual and stance width conditions (P < 0.001). Significant interactions between visual conditions and stance width were identified for all static balance indicators (P < 0.001), except for average speed of anteroposterior sway (P = 0.195). Across both visual conditions, static balance indicators displayed a U-shaped distribution (a decrease followed by an increase) with increasing stance width, reaching a minimum at the self-selected width (16.35 ± 4.20 cm) and 20 cm. Additionally, significant main effects were observed for limits of stability in both the anteroposterior and mediolateral directions (P < 0.001). The limits of stability in the anteroposterior and mediolateral directions increased monotonically with stance width, peaking at 30 cm. The influence of stance width on static balance and limits of stability was significantly greater in the mediolateral direction compared to the anteroposterior direction, regardless of visual condition.ConclusionAs stance width increases, the reliance on visual input for maintaining static balance decreases in healthy adults. We recommend using a self-selected stance width to optimize static balance and a 30 cm stance width to achieve maximum limits of stability during postural assessments.

BackgroundThe ventrolateral preoptic nucleus (VLPO) is a crucial regulator of sleep, and its neurons are implicated in both sleep-wake regulation and anesthesia-induced loss of consciousness. Propofol (PRO), a widely used intravenous anesthetic, modulates the activity of VLPO neurons, but the underlying mechanisms, particularly the role of dopaminergic receptors, remain unclear.ObjectiveThis study aimed to investigate the effects of PRO on NA (−) neurons in the VLPO and to determine the involvement of D1 and D2 dopaminergic receptors in mediating these effects.MethodsUsing in vitro patch-clamp techniques, we identified and characterized NA (−) and NA (+) neurons in the VLPO based on their morphological, pharmacological, and electrophysiological properties. We assessed the effects of PRO on spontaneous excitatory postsynaptic currents (sEPSCs) and inhibitory postsynaptic currents (sIPSCs) in NA (−) neurons, both in the presence and absence of dopaminergic receptor modulators.ResultsPRO significantly increased the firing frequency of NA (−) neurons while decreasing the firing frequency of NA (+) neurons. This activation of NA (−) neurons was mediated through GABA_A receptors, as evidenced by the increased frequency of sEPSCs and altered sIPSCs dynamics. Dopamine (DA) attenuated the PRO-induced increase in sEPSCs frequency and suppression of sIPSCs frequency in NA (−) neurons via D1 receptors, but not D2 receptors. Blocking D1 receptors with SCH23390 reversed the effects of DA on PRO-induced changes, while D2 receptor antagonist sulpiride had minimal impact.ConclusionOur findings demonstrate that PRO excites sleep-promoting NA (−) neurons in the VLPO, primarily through GABA_A receptors, with dopaminergic modulation occurring via D1 receptors. These results provide new insights into the neural mechanisms underlying general anesthesia and highlight the potential role of dopaminergic signaling in modulating anesthetic effects on sleep-related neural circuits.

Enhancing agricultural economic resilience is a critical component for ensuring sustainable agricultural development and promoting agricultural modernization. To explore the diverse influencing factors and effective pathways for enhancing agricultural economic resilience in the context of digital transformation in China, this study constructs a theoretical model of data elements empowering agricultural economic resilience based on the “Technology-Organization-Environment” framework. Using dynamic QCA methods, panel data from 30 provinces and municipalities in China from 2012 to 2022 are analyzed to configure the factors influencing agricultural economic resilience. The results indicate that no single variable constitutes a necessary condition for high agricultural economic resilience. With the introduction of time effects, it is found that digital inclusive finance and the necessity of agricultural industry digitalization have been increasing year by year. The patterns of enhancing agricultural economic resilience can be summarized as follows: the market-driven industrial technological innovation ecosystem optimization model, the TOE-enabled agricultural digital development model and the government-led cultural promotion of agricultural digital transformation model, all showing significant temporal and regional effects. Based on these findings, it is recommended that regions strengthen the synergistic interaction among elements in the technology, organization, and environment dimensions and formulate differentiated strategies for enhancing agricultural economic resilience tailored to local economic levels and the actual development of agricultural industries. These insights provide both theoretical and practical value for enhancing agricultural economic resilience in various regions worldwide.

AimThe diagnosis of sarcopenia in patients on peritoneal dialysis (PD) in clinics is limited owing to its relatively complicated process and the need for expensive assessment equipment. This study aimed to develop and validate sex-specific nomogram models based on body mass index (BMI), handgrip strength, and other routine follow-up examination indicators to predict sarcopenia in patients on PD.MethodsFrom March 2023 to February 2024, 699 eligible patients were recruited from the PD centers of two tertiary hospitals in southeastern China. Routine follow-up examination indicators such as age, BMI, biochemical indicators, dialysis adequacy, handgrip strength, and five-repetition sit-to-stand test, were used as potential predictive variables. Multivariate logistic regression analyses were used to separately determine the predictive factors for men and women. Nomogram models were constructed based on the results of the multivariate analyses, which were internally validated using a bootstrap re-sampling method (n = 2000). Predictive performance was validated using a receiver operating characteristic (ROC) curve.ResultsThe prevalence of sarcopenia in Chinese patients on PD was 13.92%. The nomogram models based on multivariate analyses revealed both handgrip strength and BMI as independent predictors of sarcopenia in men and women on PD. The bootstrap-corrected area under the ROC curves of the models was 0.924 (95% CI: 0.888–0.959) and 0.936 (95% CI, 0.906–0.966) for men and women, respectively. The calibration curves of both models demonstrated high consistency between the observed and anticipated values.ConclusionThe two nomogram models based on BMI and handgrip strength demonstrated good predictive ability for sarcopenia in male and female patients on PD. Subsequently, these may be used as convenient and inexpensive methods for the early detection and timely management of sarcopenia in patients on PD.

IntroductionThe detection efficiency of tea diseases and defects ensures the quality and yield of tea. However, in actual production, on the one hand, the tea plantation has high mountains and long roads, and the safety of inspection personnel cannot be guaranteed; on the other hand, the inspection personnel have factors such as lack of experience and fatigue, resulting in incomplete and slow testing results. Introducing visual inspection technology can avoid the above problems.MethodsFirstly, a dynamic sparse attention mechanism (Bi Former) is introduced into the model backbone. It filters out irrelevant key value pairs at the coarse region level, utilizing sparsity to save computation and memory; jointly apply fine region token to token attention in the remaining candidate regions. Secondly, Haar wavelets are introduced to improve the down sampling module. By processing the input information flow horizontally, vertically, and diagonally, the original image is reconstructed. Finally, a new feature fusion network is designed using a multi-head attention mechanism to decompose the main network into several cascaded stages, each stage comprising a sub-backbone for parallel processing of different features. Simultaneously, skip connections are performed on features from the same layer, and unbounded fusion weight normalization is introduced to constrain the range of each weight value.ResultsAfter the above improvements, the confidence level of the current mainstream models increased by 7.1%, mAP0.5 increased by 8%, and reached 94.5%. After conducting ablation experiments and comparing with mainstream models, the feature fusion network proposed in this paper reduced computational complexity by 10.6 GFlops, increased confidence by 2.7%, and increased mAP0.5 by 3.2%.DiscussionThis paper developed a new network based on YOLOv8 to overcome the difficulties of tea diseases and defects such as small target, multiple occlusion and complex background.

Pathogenesis of endometriosis (EN) is still unknown, but growing evidence suggests that immune regulation may be important, and the pattern of peripheral immune changes in reproductive women with EN has yet to be fully explored. In this study, we conducted a comprehensive and systematic analysis of immune cell subsets within T cells, B cells, NK cells, and γδ T cells in peripheral blood (PB) samples from women with EN, women with uterine fibroids (UF) but without EN (UF-alone), and healthy controls using multi-parameter flow cytometry. Our findings revealed that UF, a common comorbidity of EN, exhibited similar peripheral immune features to EN, particularly in T cell and B cell immunity. Compared to healthy controls, we constructed the peripheral immune profile of EN. This profile highlighted that the immunopathogenic factors in EN predominantly relate to the immune disorder of B cells and their subsets, as well as the functional abnormalities within immune cell subsets of CD4+ T cells, CD8+ T cells, and γδ T cells. Moreover, using the random forest (RF) machine-learning method, we developed a diagnostic model that can effectively identify the patients with EN from healthy controls. The immune factors identified within this model could be pivotal for unraveling the immune pathogenic mechanisms of EN. Our study is the first to present a comprehensive depiction of the circulating immune features in EN, although the detailed roles and underlying mechanisms of these immune factors in the context of EN require further investigation.

BackgroundThe role of vitamin C in osteoarthritis (OA) is still a subject of debate. Our aim was to combine the National Health and Nutrition Examination Survey (NHANES) and MR studies to explore the relationship between vitamin C intake and OA.MethodsClinical information on participants during NHANES 2003–2018 was collected and the relationship between vitamin C intake and OA risk was assessed using logistic regression modelling. In MR analyses, three methods were used to explore the causality of vitamin C intake with OA. Sensitivity analysis to verify the stability of the MR study.ResultsThe cross-sectional study included a total of 31,527 participants, categorizing them into low (93.0 mg) level groups based on their vitamin C intake levels. Logistic regression models showed that vitamin C intake was not associated with OA risk (p > 0.05). Inverse-variance weighted (IVW) method of MR study showed no causality between vitamin C intake and OA (OR = 0.993, 95% CI: 0.901 ~ 1.095, p = 0.882). Sensitivity analysis indicated that the MR study was reliable.ConclusionOur cross-sectional and MR studies showed that vitamin C intake was not associated with OA risk. More researches are needed in the future to investigate the link between vitamin C and OA.

ObjectiveTo investigate the epidemiological characteristics of hypothyroidism in Qinghai Province, analyze its related influencing factors, establish the normal reference range of thyroid function, and explore the relationship between thyroid hormone (THs), thyroid stimulating hormone (TSH) and metabolic syndrome (MS) in Qinghai population within the normal range, so as to provide some scientific basis for the prevention and treatment of hypothyroidism in Qinghai Province.MethodsA total of 2790 residents aged 18 and over from Qinghai were selected through stratified cluster random sampling. Data were collected via questionnaires, physical examinations, and laboratory tests.Results1. A total of 2628 eligible residents in Qinghai were included in this study, and the total prevalence of hypothyroidism was 30.25%, among which the prevalence of subclinical hypothyroidism was 29.22%, and the prevalence of clinical hypothyroidism was 1.03%. 2. The prevalence of hypothyroidism in women was significantly higher than that in men (36.69% vs 24.30%); smoking and drinking were risk factors for hypothyroidism. 3. In the excluded subjects, 1544 were abnormal thyroid ultrasound, abnormal thyroid function and/or positive thyroid autoantibodies, and the remaining 1084 were reference populations. According to the reference population data, the 95% reference ranges of TSH, FT4, FT3 were 0.43-5.51 mIU/L, 11.0-20.4 pmol/L, 3.63-5.73 pmol/L, respectively. 4. In the normal thyroid function population in Qinghai, MS and its related components were positively correlated with FT3 and FT4 levels, but not significantly correlated with TSH levels.Conclusion1. The prevalence of hypothyroidism in adults in Qinghai is relatively high, accounting for about one-thirtieth of the total population. Smoking and drinking have a certain impact on the incidence of hypothyroidism. 2. It provides a reference range for the diagnosis of thyroid diseases in Qinghai province, which is different from that of reagent suppliers, and has certain promotion significance in the western region. 3. MS and its related components are positively correlated with FT3 and FT4 levels, but not with TSH levels in people with normal thyroid function in Qinghai. Early thyroid function screening is of great significance for the prevention of MS.

The microbial communities inhabiting polar ecosystems, particularly in Maxwell Bay, Antarctica, play a pivotal role in nutrient cycling and ecosystem dynamics. However, the diversity of these microbial communities remains underexplored. In this study, we aim to address this gap by investigating the distribution, environmental drivers, and metabolic potential of microorganisms in Maxwell Bay. We analyzed the prokaryotic and eukaryotic microbiota at 11 stations, revealing distinctive community structures and diverse phylum dominance by using high-throughput sequencing. Spatial analysis revealed a significant impact of longitude on microbial communities, with microeukaryotes exhibiting greater sensitivity to spatial factors than microprokaryotes. We constructed co-occurrence networks to explore the stability of microbial communities, indicating the complexity and stability of microprokaryotic communities compared with those of microeukaryotes. Our findings suggest that the microeukaryotic communities in Maxwell Bay are more susceptible to disturbances. Additionally, this study revealed the spatial correlations between microbial communities, diversity, and environmental variables. Redundancy analysis highlighted the significance of pH and dissolved oxygen in shaping microprokaryotic and microeukaryotic communities, indicating the anthropogenic influence near the scientific research stations. Functional predictions using Tax4Fun2 and FUNGuild revealed the metabolic potential and trophic modes of the microprokaryotic and microeukaryotic communities, respectively. Finally, this study provides novel insights into the microbial ecology of Maxwell Bay, expanding the understanding of polar microbiomes and their responses to environmental factors.

ObjectiveTo comprehensively assess the global burden of syphilis and related risk factors over 1990–2021, forecast future disease trends, and understand the impact of syphilis on global health.MethodsGlobal Burden of Disease Study 2021 (GBD 2021) data were used for age-, sex-, and region-stratified analysis of the numbers and age-standardized rates (per 100,000 population) of syphilis incidence, prevalence, deaths, and disability-adjusted life years (DALYs). Next, a differential analysis of syphilis risk factors was performed. Finally, trends for years after 2021 were predicted using Bayesian age–period–cohort (BAPC) prediction models.ResultsIn 2021, the total number of syphilis prevalence globally was 70,541,482.80 (95% uncertainty interval: 54,910,897.66–88,207,651.97), with the highest numbers noted in Central Sub-Saharan Africa [4,622.60 (95% uncertainty interval: 3,591.97–5,753.45)]. Over 1990–2021, the global age-standardized prevalence and incidence rates increased, whereas the age-standardized death and DALY rates decreased. Among all groups, infants aged

ObjectiveTuberculosis (TB) is the leading cause of mortality worldwide. Previous studies have reported that TB susceptibility can be caused by vitamin D deficiency, which is affected by polymorphisms in the vitamin D receptor (VDR) gene. However, these results have been inconsistent. Therefore, we performed a meta-analysis to investigate the association between VDR polymorphisms and TB susceptibility.MethodsWe systematically searched for relevant literature in PubMed, Embase, and Medline databases through December 31st, 2022. Inclusion and exclusion criteria were made to ensure that HIV-negative population is the targeted subjects. The pooled odds ratio (OR) and 95% confidence interval (CI) were then used to assess the strength of the association, and the quality of the included articles was evaluated using the Newcastle–Ottawa Scale. Potential sources of heterogeneity were evaluated based on subgroup and meta-regression analyses.ResultsIn our meta-analysis, we found that the FokI polymorphism in the VDR gene was associated with increased TB susceptibility in the allele and recessive genotype models (OR f vs. F = 1.235, 95%CI: 1.035–1.475; OR ff vs. Ff + FF = 1.317, 95%CI: 1.005–1.727. Further subgroup analysis based on ethnicity demonstrated the association with the risk of TB in all genotype models of the FokI polymorphism for Han population. Meta-regression analysis also indicated that ethnicity could be a potential source of heterogeneity in the FokI and BsmI polymorphisms in the VDR gene. However, publication year was another source of heterogeneity for the TaqI polymorphism.ConclusionIn summary, the FokI polymorphism in the VDR gene was found to increase the risk of TB in the HIV-negative population, both overall and in Asian populations. The findings presented in this paper could provide clues for preventing TB from the perspective of vitamin D supplementation, which is a controversial topic in the field of medicine and health.

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are employed extensively in the management of type 2 diabetes and obesity. However, there is a paucity of real-world data on their safety and tolerability for metabolic and nutritional adverse events in large sample populations. This study aimed to analyse the metabolic and nutritional safety signatures of different GLP-1 RAs by exploring the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).Methods: AEs data were extracted from the FDA Adverse Event Reporting System database for each GLP-1 RA from the time of its launch until the second quarter of 2023. The reported odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayesian Geometric Mean and Bayesian Confidence Propagation Neural Network were employed to identify AE signals.Results: A system organ class of metabolism and nutrition disorders was employed to filter AE reports, resulting in the identification of 10,450 reports for exenatide, 2,860 reports for liraglutide, 240 reports for albiglutide, 4,847 reports for dulaglutide, 2,905 reports for semaglutide, 1,089 reports for tirzepatide, and 13 reports for lixisenatide. Semaglutide (ROR, 3.34; 95%CI, 3.22), liraglutide (ROR, 2.78; 95%CI, 2.69), and exenatide (ROR, 2.15; 95%CI, 2.11) were associated with metabolism and nutrition disorders. The number of AE signals detected were as follows: albiglutide (n = 1), lixisenatide (n = 2), tirzepatide (n = 11), exenatide (n = 12), liraglutide (n = 16), semaglutide (n = 20), dulaglutide (n = 22). Dehydration was the most frequent AE contributing to serious outcomes for liraglutide (n = 318, 23.93%), dulaglutide (n = 434, 20.90%), semaglutide (n = 370, 25.10%) and tirzepatide (n = 70, 32.86%). The time to onset (TTO) of AE was statistically different between exenatide and the other GLP-1 RAs (p < 0.001), and the Weibull parameters for dehydration for liraglutide, dulaglutide, and semaglutide analyses all showed an early failure-type profile.Conclusion: Our study suggests that exenatide, liraglutide, and semaglutide are more susceptible to metabolic and nutritional AEs than other GLP-1 RAs. Liraglutide, dulaglutide, semaglutide, and tirzepaptide’s potential to induce dehydration, necessitates special attention. Despite certain deficiencies, GLP-1 RAs have considerable potential for the treatment of eating disorders.

E11 causes acute fulminant hepatitis in newborns. We investigated the pathological changes of different tissues from premature male twins who died due to E11 infection. The E11 expression level was higher in the liver than in other tissues. IP10 was upregulated in liver tissue in the patient group, and might be regulated by IFNAR and IRF7, whereas IFNα was regulated by IFNAR or IRF5.

ObjectivesFibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins.MethodsGene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types.ResultsThe NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3.ConclusionFGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.

Storm surges, a significant coastal hazard, cause substantial damage to both property and lives. Precise and efficient storm surge models are crucial for long-term risk assessment and guiding emergency management decisions. While high-fidelity dynamic models offer accurate predictions, their computational costs are substantial. Hence, recent efforts focus on developing data-driven storm surge surrogate models. This study focuses on the Pearl River Estuary in Guangdong Province. Initially, the dynamic ADvanced CIRCulation (ADCIRC) model was utilized to construct storm surge data for 16 historical typhoons, serving as training, validation, and testing data for data-driven models. Subsequently, Long Short-Term Memory (LSTM), Convolutional Neural Networks (CNN), and Informer deep learning (DL) models were employed for forecasting of storm surge over the next 1h, 3h, 6h, 12h, and 18h. Finally, Shapley Additive exPlanations (SHAP) values were used for interpretability analysis of the input factors across different models. Results indicated that the proposed DL storm surge prediction model can effectively replicate the dynamic model’s simulation results in short-term forecasts, significantly reducing computational costs. This model offers valuable scientific assistance for future coastal storm surge forecasts in the Greater Bay Area.

BackgroundRadiomics, an emerging field, presents a promising avenue for the accurate prediction of biomarkers in different solid cancers. Lung cancer remains a significant global health challenge, contributing substantially to cancer-related mortality. Accurate assessment of Ki-67, a marker reflecting cellular proliferation, is crucial for evaluating tumor aggressiveness and treatment responsiveness, particularly in non-small cell lung cancer (NSCLC).MethodsA systematic review and meta-analysis conducted following the preferred reporting items for systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guidelines. Two authors independently conducted a literature search until September 23, 2023, in PubMed, Embase, and Web of Science. The focus was on identifying radiomics studies that predict Ki-67 expression in lung cancer. We evaluated quality using both Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Radiomics Quality Score (RQS) tools. For statistical analysis in the meta-analysis, we used STATA 14.2 to assess sensitivity, specificity, heterogeneity, and diagnostic values.ResultsTen retrospective studies were pooled in the meta-analysis. The findings demonstrated that the use of computed tomography (CT) scan-based radiomics for predicting Ki-67 expression in lung cancer exhibited encouraging diagnostic performance. Pooled sensitivity, specificity, and area under the curve (AUC) in training cohorts were 0.78, 0.81, and 0.85, respectively. In validation cohorts, these values were 0.78, 0.70, and 0.81. Quality assessment using QUADAS-2 and RQS indicated generally acceptable study quality. Heterogeneity in training cohorts, attributed to factors like contrast-enhanced CT scans and specific Ki-67 thresholds, was observed. Notably, publication bias was detected in the training cohort, indicating that positive results are more likely to be published than non-significant or negative results. Thus, journals are encouraged to publish negative results as well.ConclusionIn summary, CT-based radiomics exhibit promise in predicting Ki-67 expression in lung cancer. While the results suggest potential clinical utility, additional research efforts should concentrate on enhancing diagnostic accuracy. This could pave the way for the integration of radiomics methods as a less invasive alternative to current procedures like biopsy and surgery in the assessment of Ki-67 expression.

Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.

IntroductionPerceptual learning of facial expression is shown specific to the train expression, indicating separate encoding of the emotional contents in different expressions. However, little is known about the specificity of emotional recognition training with the visual search paradigm and the sensitivity of learning to near-threshold stimuli.MethodsIn the present study, we adopted a visual search paradigm to measure the recognition of facial expressions. In Experiment 1 (Exp1), Experiment 2 (Exp2), and Experiment 3 (Exp3), subjects were trained for 8 days to search for a target expression in an array of faces presented for 950 ms, 350 ms, and 50 ms, respectively. In Experiment 4 (Exp4), we trained subjects to search for a target of a triangle, and tested them with the task of facial expression search. Before and after the training, subjects were tested on the trained and untrained facial expressions which were presented for 950 ms, 650 ms, 350 ms, or 50 ms.ResultsThe results showed that training led to large improvements in the recognition of facial emotions only if the faces were presented long enough (Exp1: 85.89%; Exp2: 46.05%). Furthermore, the training effect could transfer to the untrained expression. However, when the faces were presented briefly (Exp3), the training effect was small (6.38%). In Exp4, the results indicated that the training effect could not transfer across categories.DiscussionOur findings revealed cross-emotion transfer for facial expression recognition training in a visual search task. In addition, learning hardly affects the recognition of near-threshold expressions.

Hepatocellular carcinoma is one of the leading cancers worldwide and is a potential consequence of fibrosis. Therefore, the identification of key cellular and molecular mechanisms involved in liver fibrosis is an important goal for the development of new strategies to control liver-related diseases. Here, single-cell RNA sequencing data (GSE136103 and GES181483) of clinical liver non-parenchymal cells were analyzed to identify cellular and molecular mechanisms of liver fibrosis. The proportion of endothelial subpopulations in cirrhotic livers was significantly higher than that in healthy livers. Gene ontology and gene set enrichment analysis of differentially expressed genes in the endothelial subgroups revealed that extracellular matrix (ECM)-related pathways were significantly enriched. Since anthrax toxin receptor 2 (ANTXR2) interacts with the ECM, the expression of ANTXR2 in the liver endothelium was analyzed. ANTXR2 expression in the liver endothelium of wild-type (WT) mice significantly decreased after a 4-time sequential injection of carbon tetrachloride (CCl4) to induce liver fibrosis. Next, conditional knockout mice selectively lacking Antxr2 in endothelial cells were generated. After endothelial-specific Antxr2 knockout mice were subjected to the CCl4 model, the degree of liver fibrosis in the knockout group was significantly more severe than that in the control group. In addition, ANTXR2 in human umbilical vein endothelial cells promoted matrix metalloproteinase 2 (MMP2) activation to degrade the ECM in vitro. Finally, endothelial-specific overexpression of Antxr2 alleviated the development of liver fibrosis following adeno-associated virus treatment. Collectively, these results suggested that endothelial ANTXR2 plays a protective role in liver fibrosis. This function of ANTXR2 may be achieved by promoting MMP2 activation to degrade the ECM.

Breast cancer (BC) is the most prevalent malignancy among women worldwide. Traditional research models such as primary cancer cell and patient-derived tumor xenografts (PDTXs) have limitations. Cancer cells lack a tumor microenvironment (TME) and genetic diversity, whereas PDTXs are expensive and have a time-consuming preparation protocol. Therefore, alternative research models are warranted. Patient-derived organoids (PDOs) are a promising in vitro model. They mimic the TME, gene expression, and cell types of original cancer tissues. PDOs have been successfully developed from various cancers, including BC. In this review, we focused on the value and limitations of PDOs in BC research, including their characteristics and potential in drug development, personalized therapy, immunotherapy, and the application prospects of PDOs in drug testing and prognosis.

Research on the interaction between depositional evolution process and marine transgression is critical to understanding the transform mechanism of sedimentary systems and guiding hydrocarbon exploration. The early Miocene witnessed the most significant sea-level rise since the Cenomanian, which resulted in extensive marine-influenced deposits worldwide. However, the relationship between the process of depositional evolution and long-term marine transgressions (>1 Ma) remains poorly understood. The Pearl River Mouth Basin in the South China Sea offers a comprehensive deposition record of the early Miocene marine transgression. This study employs high-quality 3D seismic, well-logging, and core data to investigate the impact of the early Miocene transgression on the evolutionary dynamics of the sedimentary system. The regional sea level exhibited a prolonged rise of at least 100 m during the deposition period of the Miocene Zhujiang Formation, corresponding to the long-term marine transgressive in the South China Sea. Throughout this marine transgression, depositional systems developed in the study area include tidal flats, fan deltas, meandering river deltas, and shallow marine shelf sand bodies. The marine transgression process resulted in a significant change in depositional system types, which can be divided into seven units from Unit 1 at the bottom to Unit 7 at the top. The predominant deposition environment transitioned from tidal flats in Units 1-3 to meandering river deltas in Units 4-5, and finally to shallow marine shelf systems in Units 6-7. In the early stage (Units 1-3), the regional uplifts hindered sea level transgression and caused erosion, leading to the development of small-scale proximal fan deltas. In the middle stage (Units 4-5), these regional uplifts submerged, and meandering river deltas dominated with sediments derived from distant extrabasinal sources. During the late stage (Units 6-7), regional sea levels reached their peak, transforming the entire basin into a shallow marine shelf system. Additionally, this marine transgression significantly influenced the distribution of hydrocarbon resources. Notably, the shallow marine shelf sand bodies in Units 6-7 warrant substantial attention for future exploration. This study outlines the complicated transitional processes within depositional systems during long-term marine transgression events, holding relevance for the global evolution of marginal sea basins.

Background: Single-cell RNA sequencing (scRNA-seq) enables specific analysis of cell populations at single-cell resolution; however, there is still a lack of single-cell-level studies to characterize the dynamic and complex interactions between osteoporotic vertebral compression fractures (OVCFs) and Kümmell’s disease (KD) in the osteoimmune microenvironment. In this study, we used scRNA-seq analysis to investigate the osteoimmune microenvironment and cellular composition in OVCFs and KD.Methods: ScRNA-seq was used to perform analysis of fractured vertebral bone tissues from one OVCF and one KD patients, and a total of 8,741 single cells were captured for single-cell transcriptomic analysis. The cellularity of human vertebral bone tissue was further analyzed using uniform manifold approximation and projection. Pseudo-time analysis and gene enrichment analysis revealed the biological function of cell fate and its counterparts. CellphoneDB was used to identify the interactions between bone cells and immune cells in the osteoimmune microenvironment of human vertebral bone tissue and their potential functions.Results: A cellular profile of the osteoimmune microenvironment of human vertebral bone tissue was established, including mesenchymal stem cells (MSCs), pericytes, myofibroblasts, fibroblasts, chondrocytes, endothelial cells (ECs), granulocytes, monocytes, T cells, B cells, plasma cells, mast cells, and early erythrocytes. MSCs play an immunoregulatory function and mediate osteogenic differentiation and cell proliferation. The differentiation trajectory of osteoclasts in human vertebral bone tissue was also revealed. In addition, ECs actively participate in inflammatory infiltration and coupling with bone cells. T and B cells actively participate in regulating bone homeostasis. Finally, by identifying the interaction of ligand–receptor pairs, we found that immune cells and osteoclasts have bidirectional regulatory characteristics, have the effects of regulating bone resorption by osteoclasts and promoting bone formation, and are essential for bone homeostasis. It is also highlighted that CD8-TEM cells and osteoclasts might crosstalk via CD160–TNFRSF14 ligand–receptor interaction.Conclusion: Our analysis reveals a differential landscape of molecular pathways, population composition, and cell–cell interactions during OVCF development into KD. OVCFs exhibit a higher osteogenic differentiation capacity, owing to abundant immune cells. Conversely, KD results in greater bone resorption than bone formation due to depletion of MSCs and a relatively suppressed immune system, and this immune imbalance eventually leads to vertebral avascular necrosis. The site of action between immune cells and osteoclasts is expected to be a new therapeutic target, and these results may accelerate mechanistic and functional studies of osteoimmune cell types and specific gene action in vertebral avascular necrosis and pathological bone loss diseases, paving the way for drug discovery.

Mechanical ventilation is a widely used short-term life support technique, but an accompanying adverse consequence can be pulmonary damage which is called ventilator-induced lung injury (VILI). Mechanical ventilation can potentially affect the central nervous system and lead to long-term cognitive impairment. In recent years, many studies revealed that VILI, as a common lung injury, may be involved in the central pathogenesis of cognitive impairment by inducing hypoxia, inflammation, and changes in neural pathways. In addition, VILI has received attention in affecting the treatment of cognitive impairment and provides new insights into individualized therapy. The combination of lung protective ventilation and drug therapy can overcome the inevitable problems of poor prognosis from a new perspective. In this review, we summarized VILI and non-VILI factors as risk factors for cognitive impairment and concluded the latest mechanisms. Moreover, we retrospectively explored the role of improving VILI in cognitive impairment treatment. This work contributes to a better understanding of the pathogenesis of VILI-induced cognitive impairment and may provide future direction for the treatment and prognosis of cognitive impairment.

BackgroundPatients with intraventricular hemorrhage (IVH) are at a higher risk of developing hydrocephalus and often require external ventricular drainage or long-term ventriculoperitoneal shunt surgery.ObjectiveTo investigate whether cerebrospinal fluid drainage in patients with IVH due to aneurysmal subarachnoid hemorrhage (aSAH) reduces the incidence of chronic hydrocephalus.MethodA retrospective analysis was conducted on patients with aSAH treated at our hospital between January 2020 and December 2022. The first analysis compared patients with and without IVH, while the second analysis compared IVH patients with and without chronic hydrocephalus. The third analysis compared IVH patients who underwent in different drainage methods which is lumbar drainage (LD) or external ventricular drainage (EVD). The primary outcome measure was the incidence of chronic hydrocephalus.ResultOf the 296 patients hospitalized with aSAH, 108 (36.5%) had IVH, which was associated with a significantly higher incidence of chronic hydrocephalus compared to patients without IVH (49.1% vs. 16.5%, p

ObjectiveThe Klotho protein is a well-documented anti-aging protein known for its diverse biological functions. Hyperlipidemia is an established independent risk factor for various chronic diseases. However, there is limited understanding of the connection between Klotho and hyperlipidemia. The aim was to assess the association between serum Klotho levels and hyperlipidemia among adults.MethodsThe study included 11,618 individuals from the NHANES database from 2006 to 2017. Hyperlipidemia was diagnosed following the National Cholesterol Education Program guidelines. Serum Klotho concentration was measured by an enzyme-linked immunosorbent assay kit, and the association between Klotho and hyperlipidemia was assessed by a multivariable logistic regression model. Fitted smoothing curves and threshold-effect analysis were employed to describe nonlinear relationships.ResultsIn our multiple logistic regression models, serum Klotho concentration was significantly associated with hyperlipidemia after adjusting for comprehensive confounders (per SD increment odds ratio (OR): 0.91; 95% confidence interval (CI): 0.86–0.97). Compared to individuals in the lowest Klotho quartile, those in the highest quartile exhibited a substantially decreased prevalence of hyperlipidemia (OR: 0.72; 95% CI: 0.58–0.90). Using a two-segment logistic regression model, we identified a U-shaped relationship between serum Klotho concentration and hyperlipidemia, with an inflection point at 1,365.5 pg/mL. Subgroup analysis did not reveal any potential moderating effects.ConclusionThis study revealed an inverse relationship between Klotho levels and hyperlipidemia. Further investigation is warranted to explore the underlying mechanism between serum Klotho and hyperlipidemia.

BackgroundSarcopenia, often observed in the elderly, is associated with declining skeletal muscle mass and impaired muscle function. This condition has been consistently linked to a less favorable prognosis in various malignancies. Computed tomography (CT) is a frequently employed modality for evaluating skeletal muscle mass, enabling the measurement of the skeletal muscle index (SMI) at the third lumbar vertebra (L3) level. This measurement serves as a defining criterion for sarcopenia. The meta-analysis dealt with evaluating the promise sarcopenia held as a prognostic indicator in individuals with colorectal cancer.MethodsResearch relevant to the subject was determined by systematically searching PubMed, Embase, Web of Science, WANFANG, and CNKI (up to June 11, 2023, published studies). In this meta-analysis, the incidence of sarcopenia in individuals with colorectal cancer was combined to analyze the disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) of these individuals with and without sarcopenia. The included research was evaluated for quality per the Newcastle-Ottawa Scale (NOS) score. In the multivariate analysis of each study, the direct extraction of hazard ratio (HR) with a 95% confidence interval (CI) was executed. STATA 11.0 was applied to integrate and statistically analyze the data.ResultsOverall 20 articles participated in this meta-analysis. A 34% incidence of sarcopenia was noted in colorectal cancer. The presence of sarcopenia denoted a decrease in OS (HR=1.72,95% CI=1.45-2.03), DFS (HR=1.42,95% CI=1.26-1.60) and CSS (HR=1.48,95% CI=1.26-1.75) in individuals with colorectal cancer. In addition, the subgroup analysis depicted a pattern consistent with the overall analysis results.ConclusionCT-defined sarcopenia exhibits promise as an indicator of survival prognosis in individuals with colorectal cancer. Future studies need a more rigorous definition of sarcopenia to further verify these findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431435.

Acute myocardial ischemia is a disease with high morbidity and mortality, and re-perfusion is currently the best intervention. However, re-perfusion may lead to further myocardial injury and increase the area of myocardial infarction. The mechanism of myocardial ischemia-re-perfusion injury is complex, but with more in-depth study, it has been proved that the immune system plays an important role in the process of MIRI. Among them, the γδT cell population has received increasing attention as the main early source of IL-17A in many immune response models. Because γδT cells have the characteristics of linking innate immunity and adaptive immunity,they can rapidly produce IL-17A and produce subsequent immune killing of cardiomyocytes. It can be seen that γδT cells play an important role in MIRI. Therefore, here we review the research progress of immune response in myocardial ischemia-re-perfusion injury, the key characteristics of γδT cells and the role of rapidly produced IL-17 in myocardial ischemia-re-perfusion injury, and propose relevant treatment strategies and prospects for myocardial repair, in order to provide new ideas and methods for clinical treatment of myocardial ischemia-re-perfusion injury.

Background: Osteosarcoma (OS), a primary malignant bone tumor, confronts therapeutic challenges rooted in multidrug resistance. Comprehensive understanding of disease occurrence and progression is imperative for advancing treatment strategies. m7G modification, an emerging post-transcriptional modification implicated in various diseases, may provide new insights to explore OS pathogenesis and progression.Methods: The m7G-related molecular landscape in OS was probed using diverse bioinformatics analyses, encompassing LASSO Cox regression, immune infiltration assessment, and drug sensitivity analysis. Furthermore, the therapeutic potential of AZD2014 for OS was investigated through cell apoptosis and cycle assays. Eventually, multivariate Cox analysis and experimental validations, were conducted to investigate the independent prognostic m7G-related genes.Results: A comprehensive m7G-related risk model incorporating eight signatures was established, with corresponding risk scores correlated with immune infiltration and drug sensitivity. Drug sensitivity analysis spotlighted AZD2014 as a potential therapeutic candidate for OS. Subsequent experiments corroborated AZD2014's capability to induce G1-phase cell cycle arrest and apoptosis in OS cells. Ultimately, multivariate Cox regression analysis unveiled the independent prognostic importance of CYFIP1 and EIF4A1, differential expressions of which were validated at histological and cytological levels.Conclusion: This study furnishes a profound understanding of the contribution of m7G-related genes to the pathogenesis of OS. The discerned therapeutic potential of AZD2014, in conjunction with the identification of CYFIP1 and EIF4A1 as independent risk factors, opens novel vistas for the treatment of OS.

IntroductionEts1 is a lymphoid-enriched transcription factor that regulates B- and Tcell functions in development and disease. Mice that lack Ets1 (Ets1 KO) develop spontaneous autoimmune disease with high levels of autoantibodies. Naïve CD4 + T cells isolated from Ets1 KO mice differentiate more readily to Th17 cells that secrete IL-17, a cytokine implicated in autoimmune disease pathogenesis. To determine if increased IL-17 production contributes to the development of autoimmunity in Ets1 KO mice, we crossed Ets1 KO mice to mice lacking the IL-17 receptor A subunit (IL17RA KO) to generate double knockout (DKO) mice.MethodsIn this study, the status of the immune system of DKO and control mice was assessed utilizing ELISA, ELISpot, immunofluorescent microscopy, and flow cytometric analysis of the spleen, lymph node, skin. The transcriptome of ventral neck skin was analyzed through RNA sequencing. S. aureus clearance kinetics in in exogenously infected mice was conducted using bioluminescent S. aureus and tracked using an IVIS imaging experimental scheme.ResultsWe found that the absence of IL17RA signaling did not prevent or ameliorate the autoimmune phenotype of Ets1 KO mice but rather that DKO animals exhibited worse symptoms with striking increases in activated B cells and secreted autoantibodies. This was correlated with a prominent increase in the numbers of T follicular helper (Tfh) cells. In addition to the autoimmune phenotype, DKO mice also showed signs of immunodeficiency and developed spontaneous skin lesions colonized by Staphylococcus xylosus. When DKO mice were experimentally infected with Staphylococcus aureus, they were unable to clear the bacteria, suggesting a general immunodeficiency to staphylococcal species. γδ T cells are important for the control of skin staphylococcal infections. We found that mice lacking Ets1 have a complete deficiency of the γδ T-cell subset dendritic epidermal T cells (DETCs), which are involved in skin woundhealing responses, but normal numbers of other skin γδ T cells. To determine if loss of DETC combined with impaired IL-17 signaling might promote susceptibility to staph infection, we depleted DETC from IL17RA KO mice and found that the combined loss of DETC and impaired IL-17 signaling leads to an impaired clearance of the infection.ConclusionsOur studies suggest that loss of IL-17 signaling can result in enhanced autoimmunity in Ets1 deficient autoimmune-prone mice. In addition, defects in wound healing, such as that caused by loss of DETC, can cooperate with impaired IL-17 responses to lead to increased susceptibility to skin staph infections.

Background: Inflammation and fibrosis are typical symptoms of non-alcoholic steatohepatitis (NASH), which is one of the most common chronic liver diseases. The cGAS-STING signaling pathway has been implicated in the progression of NASH, and targeting this pathway may represent a new therapeutic strategy. Licorice is a widely used herb with anti-inflammatory and liver-protective properties. In this study, we assessed the effect of licorice extract on the cGAS-STING pathway.Methods: Bone marrow-derived macrophages (BMDMs) were treated with licorice extract and then stimulated with HT-DNA, 2'3'-cGAMP, or other agonists to activate the cGAS-STING pathway. Quantitative real-time PCR and western blot were conducted to analyze whether licorice extract could affect the cGAS-STING pathway. Methionine and choline-deficient diet (MCD) was used to induce NASH in mice, which were treated with licorice extract (500 mg/kg) by gavage and/or c-176 (15 mg/kg) by intraperitoneal injection every 2 days. After 6 weeks of treatment, histological analysis of liver tissue was performed, along with measurements of plasma biochemical parameters.Results: Licorice extract inhibits cGAS-STING pathway activation. Mechanistically, it might function by inhibiting the oligomerization of STING. Treatment with licorice extract reduced inflammation and fibrosis in MCD diet-induced NASH mice models. Furthermore, we found that the therapeutic effect of combination treatment with licorice extract and C-176 (STING inhibitor) on the pathology and fibrosis of MCD diet-induced NASH models was similar to that of licorice extract or C-176 administered alone.Conclusion: Licorice extract can inhibit the cGAS-STING pathway and improve hepatic inflammation and fibrosis in NASH mice models. It strongly suggests that licorice extract may be a candidate therapeutic for NASH.

BackgroundTic disorders (TD) are a kind of neuropsychiatric disease that frequently occur among preschool and school-age children, mainly characterized by motor tics or sometimes accompanied by vocal tics, and its pathogenesis is still unclear. The clinical manifestations are mainly characterized by chronic multiple movements, rapid muscle twitching, involuntary occurrence, and language disorder. Acupuncture, tuina, traditional Chinese medicine, and other methods are commonly used in clinical treatments, which have unique therapeutic advantages but have not been recognized and accepted by the international community. This study conducted a quality evaluation and meta-analysis of the currently published randomized controlled trials (RCTs) of acupuncture for TD in children in order to provide reliable evidence-based medical evidence for acupuncture for TD.MethodsAll the randomized controlled trials (RCTs) using the intervention methods acupuncture + traditional Chinese medical herbs, acupuncture + tuina, and acupuncture, and the control group using Western medicine were included in the analysis. The main outcomes were obtained by using the Yale Global Tic Severity Scale (YGTSS), the Traditional Chinese medicine (TCM) syndrome score scale, and clinical treatment efficiency. Secondary outcomes included adverse events. The risk of bias in the included studies was assessed according to the tool recommended by Cochrane 5.3. The risk of bias assessment chart, risk of bias summary chart, and evidence chart in this study will be produced using R and Stata software.ResultsThere were 39 studies that met the inclusion criteria, including 3,038 patients. In terms of YGTSS, the TCM syndrome score scale changes and shows a clinically effective rate, and we found that acupuncture combined with Chinese medicine is the best treatment.ConclusionAcupuncture + traditional Chinese medical herbs may be the best therapy to improve TD in children. At the same time, compared with Western medicine commonly used in clinical practice, acupuncture and acupuncture combined with tuina therapy have better effects on improving TD in children.

BackgroundHepatocellular carcinoma (HCC) is a complex disease with a poor outlook for patients in advanced stages. Immune cells play an important role in the progression of HCC. The metabolism of sphingolipids functions in both tumor growth and immune infiltration. However, little research has focused on using sphingolipid factors to predict HCC prognosis. This study aimed to identify the key sphingolipids genes (SPGs) in HCC and develop a reliable prognostic model based on these genes.MethodsThe TCGA, GEO, and ICGC datasets were grouped using SPGs obtained from the InnateDB portal. A prognostic gene signature was created by applying LASSO-Cox analysis and evaluating it with Cox regression. The validity of the signature was verified using ICGC and GEO datasets. The tumor microenvironment (TME) was examined using ESTIMATE and CIBERSORT, and potential therapeutic targets were identified through machine learning. Single-cell sequencing was used to examine the distribution of signature genes in cells within the TME. Cell viability and migration were tested to confirm the role of the key SPGs.ResultsWe identified 28 SPGs that have an impact on survival. Using clinicopathological features and 6 genes, we developed a nomogram for HCC. The high- and low-risk groups were found to have distinct immune characteristics and response to drugs. Unlike CD8 T cells, M0 and M2 macrophages were found to be highly infiltrated in the TME of the high-risk subgroup. High levels of SPGs were found to be a good indicator of response to immunotherapy. In cell function experiments, SMPD2 and CSTA were found to enhance survival and migration of Huh7 cells, while silencing these genes increased the sensitivity of Huh7 cells to lapatinib.ConclusionThe study presents a six-gene signature and a nomogram that can aid clinicians in choosing personalized treatments for HCC patients. Furthermore, it uncovers the connection between sphingolipid-related genes and the immune microenvironment, offering a novel approach for immunotherapy. By focusing on crucial sphingolipid genes like SMPD2 and CSTA, the efficacy of anti-tumor therapy can be increased in HCC cells.

Background and objectivesTelangiectatic osteosarcoma (TOS) is a rare but highly malignant subtype of osteosarcoma. Although surgical treatment is the primary treatment modality for osteosarcoma, evidence on the benefits of different surgical methods in patients with TOS is lacking. This study aimed to compare the effects of different surgical and adjuvant treatments on overall survival of TOS, and the association of patient demographics, oncological characteristics, and socioeconomic status on treatment outcomes.MethodThis retrospective study selected the most common TOS cases of the extremities registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1989 to 2019. Univariate and multivariate Cox regression models were used to analyze all prognostic factors, and Kaplan-Meier analyses were performed for disease-specific treatment factors of survival.ResultA total of 127 patients were included in the analysis. The average age at initial diagnosis was 20.09 years. In univariate analyses, the absence of metastasis at initial diagnosis, limb-salvage surgery, adjuvant chemotherapy, and no regional lymph node dissection were associated with a lower risk of death. Multivariate analysis further showed that the presence or absence of distant metastasis and regional lymph node dissection, implementation of adjuvant chemotherapy, and choice of surgical method were independent predictors of prognosis.ConclusionDistant metastasis and regional lymph node dissection are associated with poorer outcomes in TOS, and amputation has no better prognosis than limb salvage surgery. Compared with conventional chemotherapy, neoadjuvant chemotherapy did not significantly improve the prognosis of TOS.

The Upper Cambrian Xixiangchi Formation in the Southern Sichuan Basin, China, has favorable hydrocarbon accumulation conditions. The accumulation factors and enrichment conditions of this formation were key considerations in this study. By analyzing core, thin section, seismic, and geochemical data, the research shows that there are many sets of granular and crystalline dolomite reservoirs in the Xixiangchi Formation vertically, with thin thickness of single-reservoir. During the transformation of karst and tectonism, dissolution pores and fractures developed to form an ideal reservoir space. The reservoir of the Xixiangchi Formation is connected to the Lower Cambrian source rock through a fault system. The high-energy shoal facies of the Xixiangchi Formation are located on the oil and gas migration path, providing an appropriate reservoir space for forming the source reservoir configuration relationship between the lower generation and upper reservoir. The key factors affecting hydrocarbon accumulation in the Xixiangchi Formation are sufficient oil and gas supply, development of inherited paleo-uplift, effective transportation system, and favorable reservoir-forming combination. The inherited paleo-uplift controls the distribution of gas reservoirs. Owing to the short migration distance of oil and gas, hydrocarbon is found near source hydrocarbon accumulation, and the paleo-uplift slope area should be targeted for exploration in future studies.

BackgroundAs a product of adipose tissue, resistin exceeds other adipokines in its role in regulating appetite, energy expenditure, insulin sensitivity, inflammation, and immunity, similar to thyroid hormones. This study aimed to evaluate the association between resistin levels and thyroid dysfunction and to explore variations in circulating resistin levels before and after treatment for thyroid dysfunction.MethodsThis study was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. A comprehensive search of PubMed, Embase, and Cochrane databases was conducted until June 15, 2022, with no start date restriction, according to the preregistered protocol (PROSPERO-CRD42022336617). RevMan version 5.4 and R software package version 4.2.0 were used for statistical analyses.ResultsFourteen studies with 1716 participants were included in this study. The findings of the meta-analysis confirmed that the resistin levels of patients with thyroid dysfunction were significantly higher than those of the euthyroid function control group (mean difference [MD] = 2.11, 95% confidence interval [CI] = 1.11–3.11, P < 0.00001). Furthermore, the resistin levels of patients with hyperthyroidism (MD = 3.23, 95% CI = 0.68–5.79, P = 0.01) and subclinical hypoidism (MD = 1.37, 95% CI = 0.31–2.42, P = 0.01) were significantly higher than those of euthyroid controls. The resistin levels of patients with thyroid dysfunction after treatment were significantly lower than those before treatment (MD = 1.00, 95% CI = 0.34–1.65, P = 0.003), especially in patients with hyperthyroidism (MD = 2.16, 95% CI = 1.00–3.32, P = 0.0003). Correlation analysis confirmed a positive correlation between resistin levels and free triiodothyronine (FT3) levels in patients with thyroid dysfunction (r = 0.27578, P = 0.001).ConclusionsOur meta-analysis demonstrates that resistin levels are significantly higher in patients with thyroid dysfunction, and the resistin levels after treatment in patients with thyroid dysfunction are significantly lower than those before treatment. Correlation analysis shows a positive correlation between resistin levels and FT3 levels in patients with thyroid dysfunction.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022336617.

The purpose of this paper is to reach the optimal active and reactive power operation of multiple dispersed resources consisting of mobile energy storage system (MESS), demand response (DR) and photovoltaic (PV), for flexibility improvement of distribution network with uncertain PV and DR, minimization of power loss and operation cost whilst satisfaction of both power factor and voltage variation requirement. Especially, the flexibility aspect of distribution network is focused due to its significance for supporting economic operation without voltage rise issue during high PVs integration. Firstly, the active and reactive power operation spaces of MESS and PV inverter are discussed under power factor constraint. Then, the stochastic characteristics of PV generation and DR of microgrids are investigated using probability distribution. After that, the optimization framework coordination with dispersed MESS, PV inverter and DR to ensure operational flexibility of distribution network is proposed. Finally, the total cost minimization based flexibility improvement approach is presented by optimizing power loss, uncertain risk, operation cost of distribution network and MESS, satisfying operation constraints of both distribution network and dispersed resources. Simulation results conducted on the IEEE 69-bus system demonstrate the effectiveness of the proposed approach for PV accommodation, voltage quality improvement as well as peak load shaving.

In this study, a two-compartment biofilm reactor was designed for iturin A production. The biofilm reactor consists of a stirred-tank fermentor containing exclusively suspended cells and a packing column where the biofilm is attached. Polyester fiber with sphere shape and rough surfaces was chosen as the carrier of biofilm in packing column. Batch, fed-batch, and repeated-batch fermentation using Bacillus velezensis ND in the biofilm reactor were studied. Compared to conventional suspended cell fermentations, the productivity of iturin A in batch and fed-batch biofilm fermentation were increased by 66.7% and 63.3%, respectively. Maximum itutin A concentration of 6.8 ± 0.1 g/L and productivity of 46.9 ± 0.2 mg/L/h were obtained in fed-batch biofilm fermentation. Repeated-batch fermentation showed high stability, with almost same profile as batch fermentation. After a step-wise temperature control strategy was introduced in the biofilm reactor, productivity of iturin A was increased by 131.9% compared to suspended cell reactor. This superior performance of biofilm reactor confirms that it has great potential in industrial production of iturin A.

Grade II and III gliomas are heterogeneous and aggressive diseases. More efficient prognosis models and treatment methods are needed. This study aims to construct a new risk model and propose a new strategy for grade II and III gliomas. The data were downloaded from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), gene set enrichment analysis (GSEA), and the EMTome website for analysis. The Human Cell Landscape website and the Genomics of Drug Sensitivity in Cancer website were used for single-cell analysis and drug susceptibility analysis. Gene set enrichment analysis, gene function enrichment analysis, univariate and multivariate Cox regression analyses, Pearson’s correlation analysis, log-rank test, Kaplan–Meier survival analysis, and ROC analysis were performed. We constructed an immune-related prognostic model associated with the isocitrate dehydrogenase 1 (IDH1) mutation status. By analyzing the immune microenvironment of patients with different risk scores, we found that high-risk patients were more likely to have an inflammatory immune microenvironment and a higher programmed death ligand-1 (PD-L1) expression level. Epithelial–mesenchymal transition (EMT)-related gene sets were significantly enriched in the high-risk group, and the epithelial–mesenchymal transition phenotype was associated with a decrease in CD8+ T cells and an increase in M2 macrophages. Transforming growth factor-β (TGF-β) signaling was the most important signaling in inducing epithelial–mesenchymal transition, and TGFB1/TGFBR1 was correlated with an increase in CD8+ T cytopenia and M2 macrophages. Survival analysis showed that simultaneous low expression of TGFBR1 and PD-L1 had better survival results. Through single-cell analysis, we found that TGFB1 is closely related to microglia and macrophages, especially M2 macrophages. Finally, we discussed the sensitivity of TGFB1 inhibitors in gliomas using cell line susceptibility data. These results demonstrated a potential immunotherapy strategy in combination with the TGFB1/TGFBR1 inhibitor and PD-1/PD-L1 inhibitor for grade II and III gliomas.

BackgroundThe purpose of this meta-analysis was to explore the effects of low-carbohydrate ketogenic diets on cardiovascular risk factors in overweight or obese patients. However, there are limited literature data about effects of low-carbohydrate ketogenic diets on cardiovascular risk factors in obese or overweight patients.MethodsWe systematically searched PubMed, EMBASE, Web of Science, OVID, and Cochrane Library databases (last updated in September 2022) for randomized controlled trials (RCTs) which recruited overweight or obesity patients on ketogenic diets in order to control cardiovascular risk factors (blood glucose, weight, and lipids). The overall effect size for continuous variables was expressed as a weighted standardized mean difference (SMD) with a confidence interval of 95%. Considering type 2 diabetes mellitus (T2DM) status at baseline, subgroup analyses were performed when appropriate, based on T2DM comorbidity among patients. The effect model was selected according to heterogeneity.ResultsWe finally selected 21 studies. Low carbohydrate ketogenic diets exerted a greater impact on cardiovascular risk factors in obese/ overweight patients with T2DM when compared with those on non-ketogenic diets, with lower fasting plasma glucose (FPG) (SMD, −0.75; P < 0.001) and hemoglobin A1c (HbA1c) (SMD, −0.53; P < 0.001) levels identified. Low-carbohydrate ketogenic diets significantly reduced body mass index (BMI) (SMD, −2.27; P = 0.032), weight (SMD, −6.72; P < 0.001), and waist circumference (SMD, −4.45; P = 0.003) in obese/ overweight patients with T2DM. Also, ketogenic diets improved lipid profiles in these patients; triglyceride (TG) (SMD, −0.32; P = 0.013) levels were lowered and high density lipoprotein (HDL) showed an upward trend with the P-value close to statistically significant level (SMD, −0.32; P = 0.052). In general, irrespective of diabetic status at baseline, ketogenic diets were more effective in reducing TG (SMD, −0.2; P = 0.02) and increasing HDL (SMD, 0.11; P = 0.03) levels when compared with non-ketogenic diets.ConclusionsLow-carbohydrate ketogenic diets effectively improved cardiovascular risk factors (blood glucose, weight, and lipids) in obese/ overweight patients, especially those with T2DM when compared with non-ketogenic diets.

IntroductionGiven the fact that flipped instruction especially with the aid of technology has gained momentum in second language (L2) instruction, numerous L2 researchers have explored the usefulness of flipped classroom for L2 learning.MethodsAs an attempt to further this research area, the current research examined the effect of flipped listening instruction on the Chinese English as a foreign language (EFL) students’ listening performance and listening anxiety using a quasi-experimental research design. To this end, a total number of 44 EFL learners from two intact classes in a Chinese language school were selected as the participants of the research and they were randomly assigned as the control group (N = 21) and an experimental group (N = 23). Within a course of one semester, the control group was instructed employing traditional listening instruction, while the experimental group were taught based on the flipped mode of instruction.ResultsThe data collection was carried out by administering the listening section of IELTS and Foreign Language Listening Anxiety Scale (FLLAS).DiscussionThe results of ANCOVA revealed that the flipped listening instruction significantly enhanced listening performance of the participants. Also, the flipped classroom substantially reduced listening anxiety of the EFL learners. The outcomes of this research might provide notable implications for EFL practitioners.

Avian coccidiosis is a common enzootic disease caused by infection of Eimeria species parasites. It causes huge economic losses in the global poultry industry. Current control using anticoccidial drugs or vaccination is limited due to drug resistance and the relatively high cost of vaccines. Improving host genetic resistance to Eimeria species is considered an effective strategy for improved control of coccidiosis. Circular RNAs (circRNAs) have been found to function as biomarkers or diagnoses of various kinds of diseases. The molecular biological functions of circRNAs, miRNAs, and mRNAs related to Sasso chicken have not yet been described during Eimeria species challenge. In this study, RNA-seq was used to profile the expression pattern of circRNAs, miRNAs, and mRNAs in spleens from Eimeria tenella-infected and non-infected commercial dual-purpose Sasso T445 breed chickens. Results showed a total of 40 differentially expressed circRNAs (DEcircRNAs), 31 differentially expressed miRNAs (DEmiRNAs), and 820 differentially expressed genes (DEmRNAs) between infected and non-infected chickens. Regulatory networks were constructed between differentially expressed circRNAs, miRNAs, and mRNAs to offer insights into the interaction mechanisms between chickens and Eimeria spp. Functional validation of a significantly differentially expressed circRNA, circMGAT5, revealed that circMGAT5 could sponge miR-132c-5p to promote the expression of the miR-132c-5p target gene monocyte to macrophage differentiation-associated (MMD) during the infection of E. tenella sporozoites or LPS stimulation. Pathologically, knockdown of circMGAT5 significantly upregulated the expression of macrophage surface markers and the macrophage activation marker, F4/80 and MHC-II, which indicated that circMGAT5 might inhibit the activation of macrophage. miR-132c-5p markedly facilitated the expression of F4/80 and MHC-II while circMGAT5 could attenuate the increase of F4/80 and MHC-II induced by miR-132c-5p, indicating that circMGAT5 exhibited function through the circMGAT5-miR-132c-5p-MMD axis. Together, our results indicate that circRNAs exhibit their resistance or susceptive roles during E. tenella infection. Among these, circMGAT5 may inhibit the activation of macrophages through the circMGAT5-miR-132c-5p-MMD axis to participate in the immune response induced by Eimeria infection.

IntroductionSkin cancer is one of the most common types of cancer. An accessible tool to the public can help screening for malign lesion. We aimed to develop a deep learning model to classify skin lesion using clinical images and meta information collected from smartphones.MethodsA deep neural network was developed with two encoders for extracting information from image data and metadata. A multimodal fusion module with intra-modality self-attention and inter-modality cross-attention was proposed to effectively combine image features and meta features. The model was trained on tested on a public dataset and compared with other state-of-the-art methods using five-fold cross-validation.ResultsIncluding metadata is shown to significantly improve a model's performance. Our model outperformed other metadata fusion methods in terms of accuracy, balanced accuracy and area under the receiver-operating characteristic curve, with an averaged value of 0.768±0.022, 0.775±0.022 and 0.947±0.007.ConclusionA deep learning model using smartphone collected images and metadata for skin lesion diagnosis was successfully developed. The proposed model showed promising performance and could be a potential tool for skin cancer screening.

Trichomes are differentiated epidermal cells and exist on above-ground organs of nearly all land plants with important roles in resistance to a wide range of biotic and abiotic stresses. We attempted to obtain candidate gene (s) for Hairy glume (Hg), responsible for the trichome on wheat glume, by using bulked segregant exome capture sequencing (BSE-Seq), while Hg was only mapped in 0.52–3.26 Mb of 1AS. To further fine map this gene and identify candidate genes in this region, a near isogenic line-derived population consisting of 2,050 F2 lines was generated in the present study. By analyzing this population, Hg was fine mapped into a 0.90 cM region covering a physical distance of ~825.03 Kb encompassing 6 high- and 23 low-confidence genes in the reference genome of Chinese Spring. A presence-absence variation was identified in the fine mapping region through analyses of sequence-tagged sites markers and genome sequences of the hairy glume parent of the near isogenic lines. The results presented here will be useful for further cloning Hg in wheat.

Currently, industrial production of l-threonine (Thr) is based on direct fermentation with microorganisms such as Escherichia coli, which has the characteristics of low cost and high productivity. In order to elucidate the key metabolic features of the synthesis pathway of Thr in E. coli to provide clues for metabolic regulation or engineering of the strain, this study was carried out on an l-threonine over-producing strain, in terms of analyses of metabolic flux, enzyme control and metabonomics. Since environmental disturbance and genetic modification are considered to be two important methods of metabolic analysis, addition of phosphate in the media and comparison of strains with different genotypes were selected as the two candidates due to their significant influence in the biosynthesis of Thr. Some important targets including key nodes, enzymes and biomarkers were identified, which may provide target sites for rational design through engineering the Thrproducing strain. Finally, metabolic regulation aimed at one biomarker identified in this study was set as an example, which confirms that combined metabolic analyses may guide to improve the production of threonine in E. coli.

Currently, traditional electricity consumers are now shifting to a new role of prosumers since more integration of renewable energy to demand side. Accurate short-term load demand forecasting is significant to safe, stable, and reliable operation of a renewable energy-dominated power system. In this paper, a short-term load forecasting model based on a bidirectional long short-term memory network (Bi-LSTM) using kernel transfer operator is proposed to achieve short-term load demand forecasting. To consider the influence of seasonality, holiday effects and weather on load demand forecasting, and simultaneously to improve the accuracy and performance of the forecasting model, this paper implements the dimensionality reduction of the input data by introducing an improved kernel transfer operator based on the Perron-Frobenius method. On this basis, a Bayesian Bi-LSTM for short-term load demand forecasting is formulated to obtain the probability prediction interval of load demand. To verify the validity of the proposed method, the actual historical load demand in a certain region in China was used for model training and verification. The forecasting results are compared with several conventional load demand methods using probability prediction technics. Simulation analysis shows that the proposed method can effectively reflect the short-term uncertainty of load demand, and is superior to the conventional methods in terms of forecasting accuracy and computational performance.

Giant pandas have developed a series of foraging strategies to adapt to their special bamboo diets. Although bamboo is an important food resource for giant pandas in Liziping National Nature Reserve (Liziping NR), China, there are relatively few studies on their phyllosphere fungal community and its influencing factors. Herein, we used ITS1 amplification and metagenomic sequencing to analyze the phyllosphere fungi diversity and functions (KEGG, CAZyme, and antibiotic resistance gene) and explore the influencing factors for the three giant pandas foraging bamboo species (Arundinaria spanostachya, AS; Yushania lineolate, YL; and Fargesia ferax, FF) over different seasons (spring vs. autumn) in Liziping NR, China. We found that Ascomycota and Basidiomycota were the most dominant phyla in the bamboo phyllosphere. The alpha diversity (e.g., the Sobs index and Shannon index) was relatively higher in autumn samples than in spring samples, and the community structure differed significantly between the three bamboo species in spring and autumn. Some biotic and abiotic variables (e.g., the elevation and mean base diameter of bamboo) significantly influenced the abundance, diversity, and community structure of the bamboo phyllosphere fungal community. Moreover, the functional analysis showed the differences in the glycoside hydrolase community and antibiotic resistance gene (ARG) profile between spring and autumn samples. Co–occurrence network modeling suggested that AS phyllosphere fungal communities in autumn employed a much more complex network than that in spring, and the abundance of multidrug, tetracycline, and glycopeptide resistance genes was high and closely correlated with other ARGs. These results indicate that fungal community’s abundance, diversity, and community structure are mainly affected by the season, host species, and elevation. The season and host species are major factors affecting the biological functions (KEGG and CAZyme), ARGs, and interactions between sympatric bacterial and fungal communities in bamboo phyllosphere. This integrated study can provide a reference basis for the seasonal management of bamboo resources foraged by wild giant pandas, and predict the risk of antibiotic resistance in bamboo phyllosphere fungal flora in Liziping NR (Xiaoxiangling mountains), China.