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Background and objective: Stress urinary incontinence (SUI) in women is a common condition that affects middle-aged and elderly women. Currently, there are still many limitations in the epidemiological research on SUI. This study aims to address the gap in the prevalence of female SUI in mainland China and provide theoretical support for the prevention and treatment of SUI. Methods: A comprehensive literature search was conducted on the prevalence of female SUI in mainland China, systematically searching Chinese and English databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Weipu Database as of April 1, 2024. Detailed criteria for screening and exclusion were established. The prevalence of SUI in the selected studies was synthesized using Stata MP (version 15) software, and a multisubgroup analysis, a sensitivity analysis, and publication bias detection of the prevalence of SUI were also performed using the software. Additionally, ArcGIS software (version 10.8) and Geoda software (version 1.2) were utilized to explore the geographical distribution characteristics of the prevalence of female SUI in mainland China. Key findings and limitations: A total of 688 articles were screened, and finally 85 articles were included. The overall rate of female SUI in mainland China was 24.5% (95% confidence interval: 22.5–26.5%). The heterogeneity of the study is statistically significant (I2 = 99.0%, p

Abstract Bladder cancer (BC) represents a prevalent and formidable malignancy necessitating innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have emerged as crucial regulators in cancer biology. In this study, we comprehensively evaluated ferroptosis levels in BC cells utilizing techniques encompassing lipid peroxidation assessment, transmission electron microscopy, and malondialdehyde (MDA) measurement. Additionally, we probed into the mechanistic intricacies by which circRNAs govern BC, employing RNA pull-down, RNA immunoprecipitation (RIP), and immunoprecipitation (IP) assays. Our investigation unveiled circSIRT5, which displayed significant downregulation in BC. Notably, circSIRT5 emerged as a promising prognostic marker, with diminished expression correlating with unfavorable clinical outcomes. Functionally, circSIRT5 was identified as an inhibitor of BC progression both in vitro and in vivo. Mechanistically, circSIRT5 exerted its tumor-suppressive activities through the formation of a ternary complex involving circSIRT5, SYVN1, and PHGDH. This complex enhanced the ubiquitination and subsequent degradation of PHGDH, ultimately promoting ferroptosis in BC cells. This ferroptotic process contributed significantly to the inhibition of tumor growth and metastasis in BC. In addition, FUS was found to accelerate the biogenesis of circSIRT5 in BC. These findings provide valuable insights into the pivotal role of circSIRT5 in BC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target for this malignancy.

Abstract Background In 2022, our team launched the pioneering national proficiency testing (PT) scheme for the pathological diagnosis of breast cancer, rapidly establishing its credibility throughout China. Aiming to continuously monitor and improve the proficiency of Chinese pathologists in breast pathology, the second round of the PT scheme was initiated in 2023, which will expand the number of participating institutions, and will conduct a nationwide investigation into the interpretation of HER2 0, 1+, and 2+/FISH- categories in China. Methods The methodology employed in the current round of PT scheme closely mirrors that of the preceding cycle in 2022, which is designed and implemented according to the “Conformity assessment—General requirements for proficiency testing”(GB/T27043—2012/ISO/IEC 17043:2010). More importantly, we utilized a statistics-based method to generate assigned values to enhance their robustness and credibility. Results The final PT results, published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927 ), showed that all participants passed the testing. However, a few institutions demonstrated systemic biases in scoring HER2 0, 1+, and 2+/FISH- with accuracy levels below 59%, considered unsatisfactory. Especially, the concordance rate for HER2 0 cases was only 78.1%, indicating challenges in distinguishing HER2 0 from low HER2 expression. Meanwhile, areas for histologic type and grade interpretation improvement were also noted. Conclusions Our PT scheme demonstrated high proficiency in diagnosing breast cancer in China. But it also identified systemic biases in scoring HER2 0, 1+, and 2+/FISH- at some institutions. More importantly, our study highlighted challenges in the evaluation at the extreme lower end of the HER2 staining spectrum, a crucial area for further research. Meanwhile, it also revealed the need for improvements in interpreting histologic types and grades. These findings strengthened the importance of robust quality assurance mechanisms, like the nationwide PT scheme conducted in this study, to maintain high diagnostic standards and identify areas requiring further training and enhancement.

This paper is concerned with a class of viscoelastic plate equations with past history. We first transform the original initial-boundary value problem into an equivalent one by means of the history space framework. Then we use the perturbed energy method to establish a stabilizability estimate. By employing the gradient property and quasi-stability of the dynamical system, we obtain the existence of a global attractor with finite fractal dimension.

Abstract Background Few studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D. Methods In this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression. Results The baPWV was linked with VFA, waist circumference, and women’s SFA in a general linear correlation study (P 0.05). Conclusions Compared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.

Abstract Background Influenza is a highly contagious respiratory disease that presents a significant challenge to public health globally. Therefore, effective influenza prediction and prevention are crucial for the timely allocation of resources, the development of vaccine strategies, and the implementation of targeted public health interventions. Method In this study, we utilized historical influenza case data from January 2013 to December 2021 in Fuzhou to develop four regression prediction models: SARIMA, Prophet, Holt-Winters, and XGBoost models. Their predicted performance was assessed by using influenza data from the period from January 2022 to December 2022 in Fuzhou. These models were used for fitting and prediction analysis. The evaluation metrics, including Mean Squared Error (MSE), Root Mean Squared Error (RMSE), and Mean Absolute Error (MAE), were employed to compare the performance of these models. Results The results indicate that the epidemic of influenza in Fuzhou exhibits a distinct seasonal and cyclical pattern. The influenza cases data displayed a noticeable upward trend and significant fluctuations. In our study, we employed SARIMA, Prophet, Holt-Winters, and XGBoost models to predict influenza outbreaks in Fuzhou. Among these models, the XGBoost model demonstrated the best performance on both the training and test sets, yielding the lowest values for MSE, RMSE, and MAE among the four models. Conclusion The utilization of the XGBoost model significantly enhances the prediction accuracy of influenza in Fuzhou. This study makes a valuable contribution to the field of influenza prediction and provides substantial support for future influenza response efforts.

BackgroundInfluenza is a respiratory infection that poses a significant health burden worldwide. Environmental indicators, such as air pollutants and meteorological factors, play a role in the onset and propagation of influenza. Accurate predictions of influenza incidence and understanding the factors influencing it are crucial for public health interventions. Our study aims to investigate the impact of various environmental indicators on influenza incidence and apply the ARIMAX model to integrate these exogenous variables to enhance the accuracy of influenza incidence predictions.MethodDescriptive statistics and time series analysis were employed to illustrate changes in influenza incidence, air pollutants, and meteorological indicators. Cross correlation function (CCF) was used to evaluate the correlation between environmental indicators and the influenza incidence. We used ARIMA and ARIMAX models to perform predictive analysis of influenza incidence.ResultsFrom January 2014 to September 2023, a total of 21,573 cases of influenza were reported in Fuzhou, with a noticeable year-by-year increase in incidence. The peak of influenza typically occurred around January each year. The results of CCF analysis showed that all 10 environmental indicators had a significant impact on the incidence of influenza. The ARIMAX(0, 0, 1) (1, 0, 0)12 with PM10(lag5) model exhibited the best prediction performance, as indicated by the lowest AIC, AICc, and BIC values, which were 529.740, 530.360, and 542.910, respectively. The model achieved a fitting RMSE of 2.999 and a predicting RMSE of 12.033.ConclusionThis study provides insights into the impact of environmental indicators on influenza incidence in Fuzhou. The ARIMAX(0, 0, 1) (1, 0, 0)12 with PM10(lag5) model could provide a scientific basis for formulating influenza control policies and public health interventions. Timely prediction of influenza incidence is essential for effective epidemic control strategies and minimizing disease transmission risks.

Abstract Targeting NLRP3 inflammasome has been recognized as a promising therapeutic strategy for the treatment of numerous common diseases. UK5099, a long‐established inhibitor of mitochondrial pyruvate carrier (MPC), is previously found to inhibit macrophage inflammatory responses independent of MPC expression. However, the mechanisms by which UK5099 inhibit inflammatory responses remain unclear. Here, it is shown that UK5099 is a potent inhibitor of the NLRP3 inflammasome in both mouse and human primary macrophages. UK5099 selectively suppresses the activation of the NLRP3 but not the NLRC4 or AIM2 inflammasomes. Of note, UK5099 retains activities on NLRP3 in macrophages devoid of MPC expression, indicating this inhibitory effect is MPC‐independent. Mechanistically, UK5099 abrogates mitochondria‐NLRP3 interaction and in turn inhibits the assembly of the NLRP3 inflammasome. Further, a single dose of UK5099 persistently reduces IL‐1β production in an endotoxemia mouse model. Importantly, structure modification reveals that the inhibitory activities of UK5099 on NLRP3 are unrelated to the existence of the activated double bond within the UK5099 molecule. Thus, this study uncovers a previously unknown molecular target for UK5099, which not only offers a new candidate for the treatment of NLRP3‐driven diseases but also confounds its use as an MPC inhibitor in immunometabolism studies.

Abstract Glycosylation is the most common post‐translational modification of proteins and regulates a myriad of fundamental biological processes under normal, and pathological conditions. Altered protein glycosylation is linked to malignant transformation, showing distinct glycopatterns that are associated with cancer initiation and progression by regulating tumor proliferation, invasion, metastasis, and therapeutic resistance. The glycopatterns of small extracellular vesicles (sEVs) released by cancer cells are promising candidates for cancer monitoring since they exhibit glycopatterns similar to their cell‐of‐origin. However, the clinical application of sEV glycans is challenging due to the limitations of current analytical technologies in tracking the trace amounts of sEVs specifically derived from tumors in circulation. Herein, a sEV GLYcan PHenotype (EV‐GLYPH) assay that utilizes a microfluidic platform integrated with surface‐enhanced Raman scattering for multiplex profiling of sEV glycans in non‐small cell lung cancer is clinically validated. For the first time, the EV‐GLYPH assay effectively identifies distinct sEV glycan signatures between non‐transformed and malignantly transformed lung cells. In a clinical study evaluated on 40 patients, the EV‐GLYPH assay successfully differentiates patients with early‐stage malignant lung nodules from benign lung nodules. These results reveal the potential to profile sEV glycans for noninvasive diagnostics and prognostics, opening up promising avenues for clinical applications and understanding the role of sEV glycosylation in lung cancer.

The power consumption of urban power systems is increasing rapidly with two typical trends: the first one is that the daily peak-valley difference of loads is more significant, and the power supply is tight during peak hours, which threatens the system’s safe and stable operation; the second one is that the load energy efficiency in urban power systems is not high, which is the primary source of carbon emission in the power industry. Therefore, reducing the peak power and improving the system’s energy efficiency are urgent tasks for enhancing the system’s security and achieving the carbon emission goals. The rapid development of the Internet of Things (IoTs) ushers new opportunities for regulating demand-side loads. By analyzing the technical characteristics of load control based on IoTs, this paper investigates the modeling methods of load resources. On this basis, different control and optimization methods of load resources are analyzed and compared thoroughly. Besides, considering that load control is not only related to technical methods but also impacted by incentive strategies, the load control mechanisms under the mature and immature market environments are analyzed. Finally, the research gap and prospect of load regulation are proposed.

Insufficient flexibility is a major barrier to the development of new power systems. Leveraging the resource allocation function of the electricity market is a promising way to enhance the flexibility of power systems and promote the consumption of renewables. The reasonable allocation of ancillary service costs plays a pivotal role in this function. Towards the target of “who causes, who shares,” various research related to cost allocation has been conducted. However, there is a lack of quantitative analysis of the impact of different cost allocation mechanisms on the market participants’ revenues. Whether various cost allocation mechanisms can alleviate the insufficient flexibility problem of power systems needs to be validated. With this in mind, taking operating reserve ancillary services as an example, a long-term market operation simulation model with energy-reserve joint clearing is established in this paper based on the time series production simulation. According to this, the revenues of market participants under different reserve cost allocation mechanisms are quantified. Besides, a self-dispatch model for the energy storage (ES) equipped by renewables is established, based on which the impact of ES on the revenues of renewables under different cost allocation mechanisms is analyzed. Case studies based on practical data from a provincial power grid in China demonstrate that with the well-designed reserve cost allocation mechanism, the revenues of flexible resources can be ensured. Meanwhile, renewables are incentivized to reduce their fluctuations and uncertainties by equipping the ES. Hence, the insufficient flexibility problem of power systems can be alleviated from both supply and requirements perspectives.

Rationale and objectives: Preoperative differentiation of malignant tumors (MT), pleomorphic adenomas (PA), and other benign tumors of the parotid gland is critical to clinical strategy, this study aimed to develop and validate a T2-weighted image (T2WI) based radiomics model through machine learning approaches for the triple classification of parotid gland tumors. Materials and methods: We retrospectively enrolled 147 patients from January 2010 to July 2022. T2WIs were used to extract radiomics features. Max-Relevance and Min-Redundancy (mRMR) and Extreme Gradient Boosting (XGBoost) algorithms were used to select features. Using a 5-fold cross-validation strategy, radiomics models were constructed using a Support Vector Machine (SVM), Logistic Regression (LR), and k-Nearest Neighbor (KNN) for the triple classification of parotid tumors. The three models were evaluated and compared using the receiver operator characteristic (ROC) curve, sensitivity, specificity, and accuracy. Results: A total of 1057 radiomics features were extracted, and 8 features were selected to developed the radiomics model, including First-order Median, First-order Skewness, First-order Minimum, Original_shape_Flatness, Glcm Inverse Variance, Glcm Inverse Variance, Glszm Low Gray Level Zone Emphasis, and Glszm Small Area Low Gray Level Emphasis. The mean area under the curves (AUCs) for the radiomics models in training and validation sets through LR, SVM and KNN were 0.85 and 0.80, 0.85 and 0.80 and 0.83 and 0.79, respectively. Conclusion: The T2WI-based radiomics models through LR, SVM and KNN demonstrated good performance in the triple classification of parotid tumors.

Invasive Emerald Ash Borer (EAB) damage pose significant challenges for sustainable forest management, necessitating accurate mapping of damaged ash trees. Traditional change detection methods, using time-series imagery, are essential for monitoring forest disturbances but complicated by abnormal fluctuations in original time-series features. Tree phenology also complicates this process by masking the reflectance characteristics indicative of EAB infestation. To address these challenges, we propose an improved change detection method integrating patterns from host tree phenology and EAB life history. This improved method includes: (1) select the indices with time stability to enhance detection reliability by partial least squares method (PLS); (2) correction on negative change values before and positive change values after the phenological peak based on known patterns of tree phenology and EAB life history. Result confirms that this method effectively reflects the seasonal growth and decline dynamics of ash trees, revealing the impacts of phenology and EAB infestation. EAB-damaged trees exhibited slower growth in May and premature decline in July compared with healthy tree, with the damage severity influencing the rate of leaf decline. This proposed method achieved an overall accuracy of 53.4%-76.7% across different months for ash trees with health, light and severe damage. This study highlights the capabilities of integrating pest life history and phenology in change detection method and provide a new method to monitor individual tree health across large areas by high-resolution satellite imagery.

Herein, a comprehensive review of the evolution of intelligent communication anti‐jamming techniques is provided. First, a clear definition of the concept and elaboration on the inherent connotations and capability characteristics of intelligent communication anti‐jamming is provided. Additionally, the initial construction of an intelligent communication anti‐jamming system architecture is outlined. Subsequently, the development of intelligent communication anti‐jamming is delved, tracing its progression from early‐stage adaptive anti‐jamming techniques to the more recent advancements in intelligent anti‐jamming, which are primarily based on game theory and machine learning. Moreover, the latest research findings in this domain are thoroughly examined and the existing challenges and bottlenecks that hinder current research progress are highlighted. Finally, several viable research directions for future studies in the field of intelligent anti‐jamming are proposed. The objective is to facilitate readers in gaining a comprehensive understanding of the concept, characteristics, and system architecture of intelligent communication anti‐jamming. Additionally, it is aimed to provide a comprehensive overview of the developmental process and current state of research, thereby furnishing conceptual and theoretical support for the design of more effective and practical intelligent communication anti‐jamming systems.

Rivers worldwide are warming due to the impact of climate change and human interventions. This study investigated river heatwaves in the Vistula River Basin, one of the largest river systems in Europe using long-term observed daily river water temperatures from the past 30 years (1991–2020). The results showed that river heatwaves are increased in frequency and intensity in the Vistula River Basin. The total number of river heatwaves showed clear increasing trend with an average rate of 1.400 times/decade, the duration of river heatwaves increased at an average rate of 14.506 days/decade, and the cumulative intensity of river heatwaves increased at an average rate of 53.169 °C/decade. The Mann-Kendall (MK) test was also employed, showing statistically significant increasing trends in the total number, duration, and intensity of heatwaves for all rivers, including the main watercourse of the Vistula River and its tributaries, with few exceptions. Air temperature is the major controller of river heatwaves for each hydrological station, and with the increase of air temperatures, river heatwaves will increase in frequency and intensity. Another impacting factor is flow, and with the increase of flow, river heatwaves tend to decrease in number, duration and intensity. The results suggested that mitigation measures shall be taken to reduce the effect of climate change on river systems.

Background: Hyperuricemia elevates gut permeability; however, the risk of its influence on the compromised intestinal barrier is poorly understood. Aims: This study was carried out, aiming to elucidate the orchestrators and disruptors of intestinal barrier in hyperuricemia. Methods: A mouse model of hyperuricemia was induced by administering adenine and oteracil potassium to mice. Allopurinol was used to decrease uric acid level, and antibiotics were administered to mice to deplete gut microbiota. Intestinal permeability was assessed using FITC-labeled dextran. Changes in gut microbial community were analyzed through 16S rRNA sequencing. IL-1β and TNF-α levels were quantified using ELISA. The expression of tight junction protein genes, TLR4, p65 and IL-1β, was determined with Q-PCR and Western blotting. Results: Allopurinol treatment effectively reduced intestinal permeability and serum TNF-α levels. Antibiotic treatment alleviated but not abolished intestinal permeability. Uric acid alone was insufficient to increase Coca2 monolayer permeability. Allopurinol treatment altered microbial composition and suppressed opportunistic infections. Re-establishing hyperuricemia in a germfree mouse model protected mice from intestinal injury. Allopurinol and antibiotic treatments reduced TLR4 and IL-1β expressions, increased occludin and claudin-1 expressions but suppressed NF-ĸB p65 signaling. However, removing gut microbiota aggravated lipid metabolic dysfunction. Conclusion: Gut microbiota is a direct and specific cause for intestinal barrier dysfunction.

Highlights The innovation of this work mainly lies in the auto-regulation of reactive oxygen species (ROS) balance effective by combination of ROS antibacterial and ROS scavenging anti-inflammatory functions with a core–shell nanoplatform (CeO2@ZIF-8/Au), which can not only achieve high antibacterial efficiency, but also promote wound healing, and provide a new idea for the nano-catalytic system in the field of wound healing of bacterial infection.

Highlights A thermoelectric aerogel of highly elastic, flame-retardant and high-temperature-resistant PEDOT:PSS/SWCNT composite is fabricated. The assembled thermoelectric generator generates a maximum output power of 400 μW at a temperature difference of 300 K. The self-powered wearable sensing glove can achieve wide-range temperature detection, complex hand motion recognition and high-temperature warning. The intelligent fire warning system enables highly sensitive and repeatable monitoring and alarm capabilities for high-temperature fire sources.

Abstract Air pollution has become a significant concern for human health, and its impact on influenza, has been increasingly recognized. This study aims to explore the spatiotemporal heterogeneity of the impacts of air pollution on influenza and to confirm a better method for infectious disease surveillance. Spearman correlation coefficient was used to evaluate the correlation between air pollution and the influenza case counts. VIF was used to test for collinearity among selected air pollutants. OLS regression, GWR, and STWR models were fitted to explore the potential spatiotemporal relationship between air pollution and influenza. The R2, the RSS and the AICc were used to evaluate and compare the models. In addition, the DTW and K-medoids algorithms were applied to cluster the county-level time-series coefficients. Compared with the OLS regression and GWR models, STWR model exhibits superior fit especially when the influenza outbreak changes rapidly and is able to more accurately capture the changes in different regions and time periods. We discovered that identical air pollutant factors may yield contrasting impacts on influenza within the same period in different areas of Fuzhou. NO2 and PM10 showed opposite impacts on influenza in the eastern and western areas of Fuzhou during all periods. Additionally, our investigation revealed that the relationship between air pollutant factors and influenza may exhibit temporal variations in certain regions. From 2013 to 2019, the influence coefficient of O3 on influenza epidemic intensity changed from negative to positive in the western region and from positive to negative in the eastern region. STWR model could be a useful method to explore the spatiotemporal heterogeneity of the impacts of air pollution on influenza in geospatial processes. The research findings emphasize the importance of considering spatiotemporal heterogeneity when studying the relationship between air pollution and influenza.

Abstract The active-cooling elastomer concept, originating from vascular thermoregulation for soft biological tissue, is expected to develop an effective heat dissipation method for human skin, flexible electronics, and soft robots due to the desired interface mechanical compliance. However, its low thermal conduction and poor adaptation limit its cooling effects. Inspired by the bone structure, this work reports a simple yet versatile method of fabricating arbitrary-geometry liquid metal skeleton-based elastomer with bicontinuous Gyroid-shaped phases, exhibiting high thermal conductivity (up to 27.1 W/mK) and stretchability (strain limit >600%). Enlightened by the vasodilation principle for blood flow regulation, we also establish a hydraulic-driven conformal morphing strategy for better thermoregulation by modulating the hydraulic pressure of channels to adapt the complicated shape with large surface roughness (even a concave body). The liquid metal active-cooling elastomer, integrated with the flexible thermoelectric device, is demonstrated with various applications in the soft gripper, thermal-energy harvesting, and head thermoregulation.

Study region: Pannonian Ecoregion, Hungary. Study focus: Bridging the gap between atmospheric influences and aquatic environments, this study embarked on a comprehensive reconstruction of daily surface water temperatures across lakes and rivers within the Pannonian Ecoregion over an extensive period of 150 years (1870–2021). New hydrological insights for the region: The analysis revealed a clear warming trend in waters over the past 150 years, and majority of this warming occurred in recent three to four decades (average warming rate: 0.317 °C/decade). Seasonal patterns indicated that winter and spring exhibited faster warming rates, followed by autumn and summer. There has been a significant increase in the number, duration, and intensity of heatwaves in both lakes and rivers, particularly pronounced in the last 30–40 years, and with the rise of air temperatures, river and lake heatwaves tend to intensity. These findings underscore the escalating impact of climate change on freshwater systems in the Pannonian Ecoregion, emphasizing the urgent need for mitigation measures. As the first study on river and lake heatwaves in Hungary and one of the few studies on river heatwaves worldwide, this study will provide reference for analysing extreme thermal events in aquatic systems.

Background The impact of heat waves and atmospheric oxidising pollutants on residential mortality within the framework of global climate change has become increasingly important. Objective In this research, the interactive effects of heat waves and oxidising pollutants on the risk of residential mortality in Fuzhou were examined. Methods We collected environmental, meteorological, and residential mortality data in Fuzhou from 1 January 2016, to 31 December 2021. We then applied a generalised additive model, distributed lagged nonlinear model, and bivariate three-dimensional model to investigate the effects and interactions of various atmospheric oxidising pollutants and heat waves on the risk of residential mortality. Results Atmospheric oxidising pollutants increased the risk of residential mortality at lower concentrations, and O3 and Ox were positively associated with a maximum risk of 2.19% (95% CI: 0.74–3.66) and 1.29% (95% CI: 0.51–2.08). The risk of residential mortality increased with increasing temperature, with a strong and long-lasting effect and a maximum cumulative lagged effect of 1.11% (95% CI: 1.01, 1.23). Furthermore, an interaction between atmospheric oxidising pollutants and heat waves may have occurred: the larger effects in the longest cumulative lag time on residential mortality per 10 µg/m3 increase in O3, NO2 and Ox during heat waves compared to non-heat waves were [−3.81% (95% CI: −14.82, 8.63)]; [−0.45% (95% CI: −2.67, 1.81)]; [67.90% (95% CI: 11.55, 152.71)]; 16.37% (95% CI: 2.43, 32.20)]; [−3.00% (95% CI: −20.80, 18.79)]; [−0.30% (95% CI: −3.53, 3.04)]. The risk on heat wave days was significantly higher than that on non-heat wave days and higher than the separate effects of oxidising pollutants and heat waves. Conclusions Overall, we found some evidence suggesting that heat waves increase the impact of oxidising atmospheric pollutants on residential mortality to some extent.

The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer’s disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.

Background: This paper aims to analyse the active components of Semen cuscutae (SC) by network pharmacology and screen the most stable compounds with tumour necrosis factor-alpha (TNF-α) by molecular docking to explore the mechanisms of SC treatment of recurrent spontaneous abortion (RSA) and provide a theoretical basis for drug development.Methods: The active compounds of SC and the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systems Pharmacology database and GeneCards, respectively. The RSA-SC target gene interaction network was obtained and visualized using the STRING database and Cytoscape software. GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects of SC. Interactions between TNF-α and drugs were analysed by molecular docking. Treatment of human trophoblast cells with sesamin and TNF-α was carried out to detect their proliferative and apoptotic abilities, and WB assay was carried out to detect EGFR, PTGS2, and CASP3 protein expression.Results: Ten compounds and 128 target genes were screened from SC, of which 79 overlapped with RSA target inflammatory genes, which were considered potential therapeutic targets. Network pharmacological analysis showed that sesamin, matrine, matrol, and other SC compounds had a good correlation with the inflammatory target genes of RSA. Related genes included PGR, PTGS1, PTGS2, TGFB1, and CHRNA7. Several signalling pathways are involved in the pathogenesis of RSA, such as the TNF-α signalling pathway, HIF-1 signalling pathway, oestrogen signalling pathway, proteoglycans in cancer cells, and FoxO signalling pathway. Molecular docking results suggested that sesamin was the most suitable natural tumour necrosis factor inhibitor (TNFi). Sesamin can promote proliferation and inhibit apoptosis in human trophoblasts by downregulating EGFR and CASP3 expression and upregulating PTGS2 expression.Conclusion: Our findings play an important role and basis for further research into the molecular mechanism of SC treatment of RSA and drug development of TNFi.

Objectives This study aims to examine the prevalence of comorbidities in adult patients with psoriasis and compare them with those in control subjects without psoriasis in Tianjin, China.Design The study is a cross-sectionalanalysis.Participants The participants were established by identifying all patients (age ≥18 years) who visited hospitals and clinics in Tianjin between 1 January 2016 and 31 October 2019.Setting The study group consisted of 20 678 adult patients with psoriasis, and a comparison group was created after 1:1 propensity score matching. Logistic regression analyses were conducted to examine the risk of 22 comorbidities for these two groups.Results Patients with psoriasis had a significantly higher prevalence of 11 comorbidities and a lower prevalence of 2 comorbidities within 12 months of follow-up. Our results also showed that the proportion of psoriatic arthritis might account for approximately 2% of all patients with psoriasis. This psoriatic arthritis group had a higher average age and CCI (Charlson Comorbidity Index) index score (2.27 >1.62, p

Abstract Aim Pathologists are currently supposed to be aware of both domestic and international guidelines for breast cancer diagnosis, but it is unclear how successfully these guidelines have been integrated into routine clinical practice in China. Thus, this national proficiency testing (PT) scheme for breast pathology was set up to conduct a baseline assessment of the diagnostic capability of pathologists in China. Methods This national PT plan is designed and implemented according to the “Conformity assessment—General requirements for proficiency testing” (GB/T27043—2012/ISO/IEC 17043:2010). Five cases of breast cancer with six key items, including histologic type, grade, ER, PR, HER2, and Ki67, were selected for testing among 96 participants. The final PT results were published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927/cn/col22/362 ). Results Our study demonstrated that the median PT score was 89.5 (54–100). Two institutions with scores 86%). However, the histologic grade showed low accuracy (74.0%). The unacceptable results mainly included incorrect evaluation of histologic grade (36.7%), inaccurate evaluation of ER/PR/HER2/Ki67 (28.2%), incorrect identification of C-AD as IBC-NST (15.7%), inappropriate use of 1+/2+/3+ rather than staining percentage for ER/PR (6.1%), misclassification of ER/PR

To realize a liberalized peer-to-peer (P2P) electricity market in distribution systems with network security, this paper develops a general framework for P2P trading in distribution systems with the utility's operation. The model is formulated as a bi-level programming. The utility's operation is an upper level problem, where a calculation method of network usage charges for P2P trading is also proposed. Peers' P2P trading is a lower level problem. An iterative algorithm based on analytical target cascading (ATC) is proposed to solve the model, where the interactions between utility and peers are presented. Numerical results on the IEEE 33-bus system demonstrate that the proposed method realizes a liberalized P2P market and ensures network security in distribution systems.

Introduction Currently, there exists considerable debate surrounding the optimal treatment approaches for different subtypes of patients with spinal cord injury (SCI). The purpose of this study was to conduct a comparative analysis of the benefits associated with conservative treatment and treatments with different surgical periods for patients diagnosed with acute traumatic central cord syndrome (ATCCS) and multilevel cervical canal stenosis (CCS). Methods A retrospective cohort study was conducted, and 93 patients who met inclusion and exclusion criteria in our hospital between 2015 and 2020 were followed for a minimum duration of 2 years. Among them, 30 patients (Group A) received conservative treatment, 18 patients (Group B) received early surgery (≤7 days), and 45 patients (Group C) received late surgery (>7 days). The American Spinal Injury Association (ASIA) grade, Japanese Orthopedic Association (JOA) score, and recovery rate (RR) were evaluated. Multivariate linear regression was used to analyze prognostic determinants. Cost‐utility analysis was performed based on the EQ‐5D scale. Results The ASIA grade, JOA score, and RR of all three groups improved compared with the previous evaluation (P 0.05). The EQ‐5D scale in Group B was optimal at the last follow‐up. The incremental cost‐utility ratio (ICUR) of Group A was the lowest, while that of Group B compared to Group A was less than the threshold of patients’ willingness to pay. Age, initial ASIA grade, and treatment types significantly affected the outcomes. Conclusions Both conservative and surgical treatments yield good results. Compared with patients who received conservative treatment and late surgery, patients who received early surgery had better clinical function and living quality. Despite the higher cost, early surgery is cost‐effective when compared to conservative treatment. Younger age, initial better ASIA grade, and earlier surgery were associated with better prognosis.

Abstract Tumour segmentation in medical images (especially 3D tumour segmentation) is highly challenging due to the possible similarity between tumours and adjacent tissues, occurrence of multiple tumours and variable tumour shapes and sizes. The popular deep learning‐based segmentation algorithms generally rely on the convolutional neural network (CNN) and Transformer. The former cannot extract the global image features effectively while the latter lacks the inductive bias and involves the complicated computation for 3D volume data. The existing hybrid CNN‐Transformer network can only provide the limited performance improvement or even poorer segmentation performance than the pure CNN. To address these issues, a short‐term and long‐term memory self‐attention network is proposed. Firstly, a distinctive self‐attention block uses the Transformer to explore the correlation among the region features at different levels extracted by the CNN. Then, the memory structure filters and combines the above information to exclude the similar regions and detect the multiple tumours. Finally, the multi‐layer reconstruction blocks will predict the tumour boundaries. Experimental results demonstrate that our method outperforms other methods in terms of subjective visual and quantitative evaluation. Compared with the most competitive method, the proposed method provides Dice (82.4% vs. 76.6%) and Hausdorff distance 95% (HD95) (10.66 vs. 11.54 mm) on the KiTS19 as well as Dice (80.2% vs. 78.4%) and HD95 (9.632 vs. 12.17 mm) on the LiTS.

AbstractContext Poziotinib and vonoprazan are two drugs mainly metabolized by CYP3A4. However, the drug-drug interaction between them is unknown.Objective To study the interaction mechanism and pharmacokinetics of poziotinib on vonoprazan.Materials and methods In vitro experiments were performed with rat liver microsomes (RLMs) and the contents of vonoprazan and its metabolite were then determined with UPLC-MS/MS after incubation of RLMs with vonoprazan and gradient concentrations of poziotinib. For the in vivo experiment, rats in the poziotinib treated group were given 5 mg/kg poziotinib by gavage once daily for 7 days, and the control group was only given 0.5% CMC-Na. On Day 8, tail venous blood was collected at different time points after the gavage administration of 10 mg/kg vonoprazan, and used for the quantification of vonoprazan and its metabolite. DAS and SPSS software were used for the pharmacokinetic and statistical analyses.Results In vitro experimental data indicated that poziotinib inhibited the metabolism of vonoprazan (IC50 = 10.6 μM) in a mixed model of noncompetitive and uncompetitive inhibition. The inhibitory constant Ki was 0.574 μM and the binding constant αKi was 2.77 μM. In vivo experiments revealed that the AUC(0-T) (15.05 vs. 90.95 μg/mL·h) and AUC(0-∞) (15.05 vs. 91.99 μg/mL·h) of vonoprazan increased significantly with poziotinib pretreatment. The MRT(0-∞) of vonoprazan increased from 2.29 to 5.51 h, while the CLz/F value decreased from 162.67 to 25.84 L/kg·h after pretreatment with poziotinib.Conclusions Poziotinib could significantly inhibit the metabolism of vonoprazan and more care may be taken when co-administered in the clinic.

Abstract The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lies at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination. Autofluorescence from a 70 kDa flavoprotein, succinate dehydrogenase A (SDHA), was found to be responsible for changes in optical properties within the FAD spectral region, with lower levels of flavinated SDHA in OSCC cells. Since flavinated SDHA is required for functional complexation with succinate dehydrogenase B (SDHB), decreased SDHB levels were observed in human OSCC tissue relative to normal tissues. Accordingly, the metabolism of OSCC cells was found to be significantly altered relative to normal cells, revealing vulnerabilities for both diagnosis and targeted therapy. Optimizing non-invasive tools based on optical and metabolic signatures of cancers will enable more precise and early diagnosis leading to improved outcomes in patients.

Abstract Background Lenvatinib is a multitargeted tyrosine kinase inhibitor used in the treatment of a variety of solid tumors. This study aims to investigate the potential pharmacokinetic interactions between lenvatinib and various azoles (ketoconazole, voriconazole, isavuconazole and posaconazole) when orally administered to rats. Methods A total of 30 Sprague–Dawley rats were randomly allocated into five groups and administered 20 mg/kg of ketoconazole, voriconazole, isavuconazole and 30 mg/kg of posaconazole and 0.5% CMC‐Na, through gavage for a duration of 7 days prior to the commencement of the experiment. On the final day, the rats were given 10 mg/kg of lenvatinib. The blood concentration of lenvatinib was determined using UPLC‐MS–MS. In vitro lenvatinib were incubated with azoles and rat liver microsomes (RLMs) or human liver microsomes (HLMs). Molecular docking was lastly used to examine the binding strength of the enzymes and ligands with Autodock Vina. Results AUC and Cmax of lenvatinib significantly increased with each of the azoles (p

Background: Glioblastoma (GBM) is a highly aggressive and fast-growing brain tumor, characterized by rapid progression, a very poor prognosis, and a high likelihood of recurrence. Thus, effective new therapeutic targets are urgently needed. Transmembrane proteins (TMEMs) have pro-cancer effects on multiple cancer types, but the mechanisms underlying the effects of TMEM17, particularly its role in GBM, remain unclear. Methods: We conducted bioinformatics analyses and immunohistochemistry to evaluate the role of TMEM17 in a variety of cancer types. Functional assays were conducted included the Cell Counting Kit-8 assay, annexin V-FITC/PI double staining, 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, wound healing assay, transwell invasion assay, and dual luciferase assay. Results: We found that TMEM17 is associated with a poor prognosis in GBM. Prognostic analyses confirmed that high TMEM17 expression predicted poorer survival, establishing its significance as an independent prognostic factor. Functional assays demonstrated that silencing TMEM17 in GBM cell lines inhibited proliferation and invasion, and induced apoptosis, underscoring its role in tumor aggressiveness. From a mechanistic perspective, we discovered that the Ying Yang 1 (YY1) transcription factor can bind to the promoter of TMEM17, regulating its upregulation. Regarding downstream mechanisms, knocking down TMEM17 inhibited the phosphoinositide 3-kinase/AKT pathway. These findings suggest that TMEM17 plays a significant role in GBM and may be a potential therapeutic target for this cancer. Conclusion: These data prove that TMEM17 plays a key role in the regulation of GBM and has great potential as a clinical therapeutic target for GBM.

Nonuniform transmission lines (NTLs) are widely used in pulsed power accelerators because they provide an efficient way to achieve impedance matching and pulse shaping. Since designing and constructing these accelerators typically demands substantial effort, finding the optimal impedance profile to maximize the power transmission efficiencies of the NTLs is important. In this paper, a convenient numerical method to determine the optimal impedance profile is proposed. First, the output of the NTL with arbitrary parameters is theoretically analyzed under arbitrary input conditions. It was found that only four factors affect the power transmission efficiency: the ratio of output impedance to input impedance, the ratio of input pulse width to the NTL’s one-way transit time, the normalized impedance profile, and the normalized input pulse. Based on these findings, a method designed to minimize the reflected component within the working frequency range is proposed. Using this method, an impedance profile demonstrating superior power transmission efficiency compared to the traditional exponential profile is identified. This work can provide a rapid and effective method to determine the impedance profile of the NTL, undoubtedly benefiting the design process of pulsed power accelerators.

For fiber technology, new approaches such as biomimetic materials, such as silks, are being intensively explored, providing new solutions for a variety of industries, including textiles, composites, and biomedical engineering. New approaches for spinning or these materials are needed. Despite recent advances in enhancing fiber tensile properties, achieving significant improvement in tensile properties remains a tedious and challenging task, suffering from little to no controlled extrusion process and difficult optimization in high‐dimensional parameter spaces. Herein, a novel robotic biomimetic pulling method that can rapidly enhance fiber tensile properties surpassing current methods in both speed and resulting fiber properties is shown. Using a controlled fiber‐pulling device with in situ tensile measurements and adaptive optimization based on Bayesian Optimization, fiber strength exceeding 300% of the traditional full factorial design method within just a few experimental iterations is reached. The rapid experimental method presents a potential avenue for enhancing the performance of artificial fibers across diverse industries and applications.

IntroductionThis study aimed to assess the correlation between the blood urea nitrogen (BUN)-to-creatinine (BUN/Cr) ratio and adverse outcomes (AOs) at 3 months in patients with acute ischemic stroke (AIS) in the Korean population.MethodsThis cohort study encompassed 1906 cases of AIS at a South Korean hospital from January 2010 to December 2016. To determine the linear correlation between the BUN/Cr ratio and AOs in AIS, a binary logistic regression model (BLRM) was employed. Additionally, generalized additive models and techniques for smooth curve fitting were utilized to reveal the nonlinear dynamics between the BUN/Cr ratio and AOs in patients with AIS.ResultsThe prevalence of AOs was 28.65%, with a median BUN/Cr ratio of 18.96. Following adjustments for covariates, the BLRM disclosed that the association between the BUN/Cr ratio and the risk of AOs in patients with AIS did not attain statistical significance. Nevertheless, a nonlinear relationship surfaced, pinpointing an inflection point at 21.591. To the left of this inflection point, a 31.42% reduction in the risk of AOs was noted for every 1-unit surge in the Z score of the BUN/Cr ratio [odds ratio (OR) = 0.686, 95% confidence interval (CI): 0.519, 0.906, p = 0.008]. On the right side of the inflection point, the effect size (OR = 1.405, 95% CI: 1.018, 1.902, p = 0.039) was determined.ConclusionThe findings of this study underscore the intricate nature of the relationship between the BUN/Cr ratio and 3-month outcomes in patients with AIS, establishing a robust groundwork for future investigations.

This work aimed to explore the mechanisms underlying the interaction of the active furanocoumarins in P. corylifolia on tofacitinib both in vivo and in vitro. The concentration of tofacitinib and its metabolite M8 was determined using UPLC-MS/MS. The peak area ratio of M8 to tofacitinib was calculated to compare the inhibitory ability of furanocoumarin contained in the traditional Chinese medicine P. corylifolia in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP3A4 (rCYP3A4). We found that bergapten and isopsoralen exhibited more significant inhibitory activity in RLMs than other furanocoumarins. Bergapten and isopsoralen were selected to investigate tofacitinib drug interactions in vitro and in vivo. Thirty rats were randomly allocated into 5 groups (n = 6): control (0.5% CMC-Na), low-dose bergapten (20 mg/kg), high-dose bergapten (50 mg/kg), low-dose isopsoralen (20 mg/kg) and ketoconazole. 10 mg/kg of tofacitinib was orally intervented to each rat and the concentration level of tofacitinib in the rats were determined by UPLC-MS/MS. More imporrantly, the results showed that bergapten and isopsoralen significantly inhibited the metabolism of tofacitinib metabolism. The AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞) and Cmax of tofacitinib increased in varying degrees compared with the control group (all p < 0.05), but CLz/F decreased in varying degrees (p < 0.05) in the different dose bergapten group and isopsoralen group. Bergapten, isopsoralen and tofacitinib exhibit similar binding capacities with CYP3A4 by AutoDock 4.2 software, confirming that they compete for tofacitinib metabolism. P. corylifolia may considerably impact the metabolism of tofacitinib, which can provide essential information for the accurate therapeutic application of tofacitinib.

Objective The purpose of this study was to evaluate the inclination and determinants influencing the selection of hospice care service institutions among elderly individuals in China.Design The study conducted has a cross-sectional design.Setting The study was conducted at four urban community centres in Wuhu, Anhui Province, China.Participants The sample consisted of 642 older adults, with ages ranging from 60 to over (mean age=71.03 years, SD=7.18).Method This study, based on the Anderson model, developed a questionnaire after conducting a preliminary survey and engaging in several group discussions. The final questionnaire encompassed the basic information, health status, attitude towards hospice care, choice of hospice care institutions and reasons of the older people. A regional population study was conducted using the Logistic regression model to estimate the ORs (OR) of influencing factors selected by hospice services.Results 38.5% of respondents expressed their willingness to receive hospice care, while 22.3% were unwilling and 39.3% felt ambivalent towards it. The acceptance rate of older people in hospice care increases with higher levels of education and monthly income. 47.0% of older people opted for hospice care in a general hospital ward, indicating that demand for hospice services among older people in Wuhu City is primarily focused on such wards. The univariate analysis revealed significant differences in the willingness of older individuals to accept hospice care services based on gender, age, educational attainment and income levels. Regardless of the location of hospice care, older men had a lower likelihood of being willing to use hospice services compared with older women. The proportion of older women choosing a hospice ward or general hospital was 53.8%, which was higher than that of older men at 42.0%. The proportion of older men choosing a community health service institution was 31.6%, higher than 23.3% of women. The educational level differences significantly influence the older people’s inclination towards receiving hospice care.Conclusion With the ageing population of Wuhu City on the rise, there is an increasing demand for hospice services. In their final journey, older individuals require multilevel hospice care services, which necessitates equipping general hospitals with hospice wards and using community health service centres to meet their specific needs.

The repair of critical-sized bone defects poses a significant challenge due to the absence of periosteum, which plays a crucial role in coordinating the processes of osteogenesis and vascularization during bone healing. Herein, we hypothesized that melatonin-encapsuled silk Fibronin electrospun nanofibers (SF@MT) could provide intrinsic induction of both osteogenesis and angiogenesis, thereby promoting vascularized bone regeneration. The sustained release of melatonin from the SF@MT nanofibers resulted in favorable biocompatibility and superior osteogenic induction of bone marrow mesenchymal stem cells (BMMSCs). Interestingly, melatonin promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in a BMMSC-dependent manner, potentially through the upregulation of vascular endothelial growth factor (VEGFA) expression in SF@MT-cultured BMMSCs. SF@MT nanofibers enhanced the BMMSC-mediated angiogenesis by activating the PI3K/Akt signaling pathway. In vivo experiments indicated that the implantation of SF@MT nanofibers into rat critical-sized calvarial defects significantly enhances the production of bone matrix and the development of new blood vessels, leading to an accelerated process of vascularized bone regeneration. Consequently, the utilization of melatonin-encapsulated silk Fibronin electrospun nanofibers shows great promise as a potential solution for artificial periosteum, with the potential to regulate the coupling of osteogenesis and angiogenesis in critical-sized bone defect repair.

Abstract Changes in the habitats of species can provide insights into the impact of climate change on their habitats. Species in the genus Morina (Morinoideae) are perennial herbaceous plants that are mainly distributed in the South Asian Mountains and Eastern Mediterranean. In China, there are four species and two varieties of this genus distributed across the Yunnan, Sichuan, Qinghai, and Gansu provinces. This study used the optimal MaxEnt model to simulate past, current, and future potentially suitable habitats of Morina kokonorica and Morina chinensis. Seventy data of M. kokonorica occurrences and 3 of M. chinensis were used in the model to predict potentially suitable habitats. The model prediction results indicated that both M. kokonorica and M. chinensis exhibited trends of northward migration to higher latitudes and westward migration along the Himalayas to higher elevations, suggesting that the northern valleys of Hengduan Mountains and northern and eastern parts of the Himalayas were potential refugia for M. kokonorica, and the potential refugia for M. chinensis was located in the eastern part of Qinghai‐Tibet Plateau. The results of this niche analysis showed that the two species had higher levels of interspecific competition and that the environmental adaptability of M. chinensis was stronger. This research could help further understand the response pattern of Morina to environmental change, to understand the adaptability of species to the environment, and promote the protection of species.

Idiopathic pulmonary fibrosis (IPF) is caused by persistent micro-injuries and aberrant repair processes. Myofibroblast differentiation in lung is a key event for abnormal repair. Dihydroartemisinin(DHA), a well-known anti-malarial drug, have been shown to alleviate pulmonary fibrosis, but its mechanism is not clear. Ferroptosis is involved in the pathgenesis of many diseases, including IPF. Ferritinophagy is a form of cellular autophagy which regulates intracellular iron homeostasis. The function of DHA on myofibroblasts differentiation of pulmonary and whether related with ferroptosis and ferritinophagy are unknown now. Using human fetal lung fibroblast 1(HFL1) cell line and the qRT-PCR, immunofluorescent and Western blotting techniques, we found that after TGF-β1 treatment, the levels of ɑ-SMA expression and ROS increased; the mRNA and protein levels of FTH1 and NCOA4, the content of Fe2+ and 4-HNE increased significantly at 6h, then gradually reduced with time. After DHA treatment, FHL1 cells appeared ferroptosis; the levels of α-SMA mRNA and protein reduced and the levels of ROS and 4-HNE increased; the Fe2+ levels decreased sharply at 6h, then increased with time, and were higher than normal since 24h; the mRNA and protein levels of FTH1 and NCOA4 decreased, exhibited a downward trend. These results show that Fe2+, ROS and lipid peroxidation are involved in and ferritinophagy is inhibited during fibroblast-to-myofibroblast differentiation; The depletion of Fe2+ at early stage induced by DHA treatment triggers the ferritinophagy in HFL1 cells, leading to degradation of FTH1 and NCOA4 and following increase of Fe2+ levels. DHA may inhibit the fibroblast-to-myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy.

Hydrogels have found wide applications in various fields, but further advances in hydrogel-based applications hinge upon overcoming the challenge of generating complex structures. Although three-dimensional (3D) printing enables customized designs, it remains challenging to print hydrogel structures directly without using supporting materials or incorporating polymeric or solid thickeners due to the low printability of hydrogel precursor solutions. Here, we demonstrate that direct 3D printing of sodium alginate (SA) hydrogel structures can be achieved by introducing ethanol into the SA solution. On the one hand, ethanol enables a sol-to-gel transition to occur by lowering the temperature. Our molecular dynamics (MD) simulations reveal that the gelation occurs due to disrupted hydrogen bonding interaction among SA chains and water. On the other hand, the presence of ethanol notably increases the viscosity, yield stress, and shear-thinning feature of SA solution, making it an ideal 3D printing ink. An isotropic shrinkage of the printed structures is observed after further gelation with Ca2+ ions and the removal of ethanol. Our study provides an effective approach for direct printing of SA hydrogels with enhanced printing resolution (>10 %), paving the way for more advanced hydrogel-based applications in various fields.

ABSTRACT: Objectives: The aim of this study was to characterise the whole genome sequence of multidrug-resistant Streptococcus pluranimalium strain SP21–2 of swine origin in China. Methods: Illumina Miseq (200X coverage) and Nanopore PromethION platform (100X coverage) were used for genome sequencing. Rapid Annotation using Subsystem Technology (RAST) was used to annotate the genome of SP21–2. The antimicrobial resistance genes (ARGs) were identified using ResFinder-4.1. Results: The assembled circular genome of S. pluranimalium SP21–2 was 1,987,058 bp in length with a GC content of 39.54%, and no plasmid sequence was detected. A total of 2086 coding sequences were predicted by RAST. Oxazolidinone-phenicol resistance gene, optrA, and pleuromutilin-lincosamide-streptogramin A resistance gene, lsa(E), are both located on chromosomes, associated with IS1216 and ISS1S, respectively. In addition, SP21–2 harbours lnu(B) (lincosamide), ant (6)-Ia and aac(6’)-aph(2”) (aminoglycoside), erm(B) (macrolide), and tet(O) (tetracycline). Conclusion: We firstly report the oxazolidinone-phenicol gene, optrA, and pleuromutilin-lincosamide-streptogramin A resistance gene, lsa(E), in S. pluranimalium. In this strain, we firstly identified ISS1S and IS1216 carrying ARGs in S. pluranimalium, which will provide a valuable reference to understanding potential transfer mechanisms of ARGs in S. pluranimalium.

Abstract Background The development and maintenance of normal bone tissue is maintained by balanced communication between osteoblasts and osteoclasts. The invasion of cancer cells disrupts this balance, leading to osteolysis. As the only bone resorbing cells in vivo, osteoclasts play important roles in cancer-induced osteolysis. However, the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in osteoclast resorption remains unclear. Methods In our study, we used a receptor activator of nuclear factor-kappa B (RANK) promoter‐driven Cre‐LoxP system to conditionally delete the PDK1 gene in osteoclasts in mice. We observed the effect of osteoclast‐specific knockout of PDK1 on prostate cancer-induced osteolysis. Bone marrow-derived macrophage cells (BMMs) were extracted and induced to differentiate osteoclasts in vitro to explore the role of PDK1 in osteoclasts. Results In this study, we found that PDK1 conditional knockout (cKO) mice exhibited smaller body sizes when compared to the wild-type (WT) mice. Moreover, deletion of PDK1 in osteoclasts ameliorated osteolysis and rPDK1educed bone resorption markers in the murine model of prostate cancer-induced osteolysis. In vivo, we discovered that osteoclast‐specific knockout of suppressed RANKL-induced osteoclastogenesis, bone resorption function, and osteoclast-specific gene expression (Ctsk, TRAP, MMP-9, NFATc1). Western blot analyses of RANKL-induced signaling pathways showed that conditional knockout of PDK1 in osteoclasts inhibited the early nuclear factor κB (NF-κB) activation, which consequently suppressed the downstream induction of NFATc1. Conclusion These findings demonstrated that PDK1 performs an important role in osteoclastogenesis and prostate cancer-induced osteolysis by modulating the PDK1/AKT/NF-κB signaling pathway.

Abstract Background In this study, a cross-sectional survey was used to understand and analyze the health status and health needs of the elderly in the community. The cluster analysis method was used to explore the relationship between health needs items and investigate the commonness among health demand items, to provide a reference for the development of health management of the elderly with chronic diseases. Methods We used convenience sampling to recruit the participants (aged 60 and above) from four urban community centers in Jinzhou City, Liaoning Province, China, in this study. This study uses the Medical Outcomes Study(MOS)36-Item Short-Form Health Survey. The self-designed questionnaire includes sociodemographic characteristics, chronic diseases, physical examination conditions, illness in the past two weeks, and a health needs questionnaire. SPSS 18.0 was used for data entry and analysis. Data analysis methods included descriptive statistical analysis, t-test, one-way analysis, cluster analysis, and linear multiple regression analysis. Results The rate of health needs among the elderly in the community for various health services is 1.3–69.7%, of which the top three are: regular physical examination (69.7%), day Care Center (67.7%), the establishment of a Medical Alert Systems (66.1%). The health needs of the elderly in the community are divided into three categories: basic needs (24 items), health education (13 items), and first aid (2 items). The regression analysis found that the influencing factors of health status were age, revenue and expenditure, medical expenses, health education, basic needs, and first aid. Conclusions The community should strengthen the management of chronic diseases of the elderly and the publicity and education of related knowledge, and provide complementary health care services according to the health needs of the elderly, improve the health of the elderly, and improve the quality of life of the elderly.