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In the context of global warming， the Qinghai-Xizang Plateau is altering atmospheric circulation through sensible heat absorption and latent heat release.This not only impacts the water and energy balance of the plateau's ecosystem but also plays a crucial role in regulating Asian and global climates.In order to explore the change characteristics and influencing factors of evapotranspiration in different regions of alpine grassland ecosystem on the Qinghai-Xizang Plateau， and deepen understanding of plateau climate change and hydrological-ecological processes， based on the observed eddy and meteorological data in 2022， the variation characteristics and environmental influencing factors of actual evapotranspiration of alpine grassland ecosystems at the same altitude in Sijinlacuo （seasonal permafrost） and Tuotuo River （permafrost） on the Qinghai-Xizang Plateau were compared and analyzed.The results show that： （1） Significant differences existed between environmental factors at these two sites， particularly in wind speed， air temperature， and precipitation.The wind speed at Tuotuo River station greatly exceeded that at Shijinlasuo station； annual average air temperature and precipitation were lower at Tuotuo River station.（2） The average hourly evapotranspiration of Sijinlacuo Station at night was higher than those recorded at Tuotuo River Station， however， this trend reverses during daytime hours.The variation characteristics of daily evapotranspiration at the two stations had a similar trend.The date of sharp increase and maximum of evapotranspiration at Sijinlacuo Station were earlier than those at Tuotuo River Station.The monthly evapotranspiration of the two stations were unimodal， with the maximum value appeared in July in summer and the smaller value appeared in December， January and February in winter.（3） Wind speed and ground radiation showed differing correlations with evaporation across both stations.Wind speed had a stronger correlation with evaporation at Tuotuo River Station due to higher wind speeds compared to weaker correlations observed for Sijinlasuo Station where winds were less intense.Conversely， ground radiation showed opposite correlations with evaporation between both locations.Air temperature， water vapor pressure， and atmospheric longwave radiation demonstrated strong correlations with evaporation across both locations while air humidity， saturated water vapor pressure difference， and precipitation displayed weaker associations.Precipitation exhibited the weakest correlation.（4） Although precipitation served as the primary source of evaporated water content， sources such as glacier melt water and thawing permafrost played significant roles as well on the Qinghai-Xizang Plateau， resulting in subdued influence of precipitation on the evaporative process at both locations.These results contribute valuable insights into understanding regional variations in high-altitude grassland ecosystems' response to changing climatic conditions on the Qinghai-Xizang Plateau.

Abstract In this paper, we establish the existence and stability of periodic solutions for neutral-type differential equations with piecewise impulses on time scales. We first obtain some sufficient conditions for the existence of a unique periodic solution by using the Banach contraction mapping principle. We also prove the existence of at least one periodic solution using the Schauder fixed point theorem. In addition, we establish the stability results based on the existence of periodic solutions. It is worth noting that the results of this paper are based on time scales, so that they are applicable to continuous, discrete, and other types of systems.

Aim: The aim of this study was to validate a Chinese version of the painDETECT questionnaire (PD-Q) for the screening and assessment of neuropathic pain (NeP) in a Hong Kong Chinese population. Methods: The PD-Q was translated and cross-culturally adapted from the original German PD-Q, with forward and backward translation according to standard guidelines followed by cognitive debriefing, and finalized by an expert panel. A multicenter (6-site) observational study was conducted to evaluate the validity of the PD-Q. Patients aged 18 or above with medical conditions giving rise to either neuropathic or nociceptive pain (NoP) provided informed consent to participate in this study. Each patient was evaluated by at least two healthcare professionals for causes of pain, the visual analogue scale (VAS), numeric rating scale (NRS) and the PD-Q. Results: Hong Kong Chinese adults (n = 151) were given the clinical description of NeP (n = 93), NoP (n = 41), or mixed pain (n = 17). The mean age of study subjects was 58.5 years (age range: 26–90 years); 94 subjects (62.3%) were female. The mixed pain group was only analysed qualitatively, with validation based on the remaining 134 patients. Mean PD-Q scores for patients diagnosed with NeP and NoP were 19.9 [standard deviation (SD) = 6.4] and 12.5 (SD = 6.2) respectively. Receiver operating characteristic (ROC) curves were plotted for the upper/lower boundaries. The upper boundary was calculated on the basis of a neuropathic diagnosis and a nociceptive diagnosis. The cut-off point was > 18 (80% sensitivity, 60% specificity), and area under the ROC curve (AUC) was 0.67 (P < 0.001). The lower boundary was calculated on the basis of a nociceptive and a neuropathic diagnosis. The cut-off point was < 13 (90% sensitivity, 50% specificity), and AUC was 0.79 (P < 0.001). Conclusions: The PD-Q is a reliable and valid scale to determine neuropathic components of chronic pain in the Hong Kong Chinese population. Validation in a larger Chinese-speaking population worldwide is necessary.

Plant epidemics are often associated with weather-related variables. It is difficult to identify weather-related predictors for models predicting plant epidemics. In the article by Shah et al., to predict Fusarium head blight (FHB) epidemics of wheat, they explored a functional approach using scalar-on-function regression to model a binary outcome (FHB epidemic or non-epidemic) with respect to weather time series spanning 140 days relative to anthesis. The scalar-on-function models fit the data better than previously described logistic regression models. In this work, given the same dataset and models, we attempt to reproduce the article by Shah et al. using a different approach, boosted regression trees. After fitting, the classification accuracy and model statistics are surprisingly good.

Abstract The evaluation of financial sharing centres in enterprises typically relies on outdated financial data, lacks comprehensive assessment, and presents risks such as employee misconduct. To address these challenges, we propose a risk prediction model for enterprise financial sharing operations based on the K-means clustering algorithm for performance evaluation and the C4.5 algorithm for managing employee risks. Our approach enhances the accuracy and objectivity of performance evaluation while improving the efficiency of personnel risk management. Results indicate that the K-means algorithm classifies employee performance into five levels, facilitating comprehensive performance evaluation. Furthermore, through risk management optimisation, accuracy and recall rates increase to 0.905 and 0.890, respectively. The proposed risk prediction model achieves high accuracy rates of 90.5% and 92.4% in the training and test sets, respectively. Practical application of our methodology and model in A Group's financial sharing centre demonstrates their effectiveness and potential for enhancing the operation and management of enterprise financial sharing centres.

Abstract Background While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute‐on‐chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short‐term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short‐ and long‐term mortality in patients with ACLF. Methods This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3‐SMI). Subsequently, the patients were divided into sarcopenia and non‐sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short‐term (28 days) and long‐term (1 year and overall) mortality rates. Results A total of 414 patients were included, with a mean age of 52.88 ± 13.41 years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28 days (37%) and 209 patients died within 1 year (50.5%). We found that the 28‐day, 1‐year and overall mortality rates in the sarcopenia group were significantly higher than those in the non‐sarcopenia group (37% vs. 22.3%, P

Abstract The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment. Graphical Abstract

Abstract Degenerated endplate appears with cheese-like morphology and sensory innervation, contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population.1 However, the origin and development mechanism of the cheese-like morphology remain unclear. Here in this study, we report lumbar instability induced cartilage endplate remodeling is responsible for this pathological change. Transcriptome sequencing of the endplate chondrocytes under abnormal stress revealed that the Hippo signaling was key for this process. Activation of Hippo signaling or knockout of the key gene Yap1 in the cartilage endplate severed the cheese-like morphological change and disc degeneration after lumbar spine instability (LSI) surgery, while blocking the Hippo signaling reversed this process. Meanwhile, transcriptome sequencing data also showed osteoclast differentiation related gene set expression was up regulated in the endplate chondrocytes under abnormal mechanical stress, which was activated after the Hippo signaling. Among the discovered osteoclast differentiation gene set, CCL3 was found to be largely released from the chondrocytes under abnormal stress, which functioned to recruit and promote osteoclasts formation for cartilage endplate remodeling. Over-expression of Yap1 inhibited CCL3 transcription by blocking its promoter, which then reversed the endplate from remodeling to the cheese-like morphology. Finally, LSI-induced cartilage endplate remodeling was successfully rescued by local injection of an AAV5 wrapped Yap1 over-expression plasmid at the site. These findings suggest that the Hippo signaling induced osteoclast gene set activation in the cartilage endplate is a potential new target for the management of instability induced low back pain and lumbar degeneration.

Carbon fibre dispersion exerts a critical influence on the characteristics of carbon fibre-reinforced cement mortars (CFRCMs). This study accordingly investigated the dispersion of chopped carbon fibres (CCFs) in mortar using physical experiments with a transparent simulated mortar system comprising colloidal silica and silica sand as replacements for cement and aggregate, respectively, and evaluated the microstructures and conductive performances of corresponding CFRCM specimens. In the simulated solutions, bundled CCFs in order were more prone to disperse into single fibres than clustered ones in disorder due to no physical fixation, colloidal silica prevented the formation of CCF clusters during stirring, and the shear force of moving sand dispersed but also broke CCFs. In the CFRCMs, sand aggregates reaggregated dispersed CCFs while larger sand particles increased CCF dispersion and improved specimen conductivity. Thus, decreasing the amount of CCFs clusters before dispersion, and a short stirring time in a single direction should be provided to prepare CFRCMs with well-dispersed CCFs. Meanwhile, a more dispersible aggregate and less formation of void should be also essential.

The potential of FinTech algorithms to decrease gender bias in credit decisions is limited by the impartiality of the data used to train them. If the data is partial or biased, the algorithmic decision-making process may also be discriminatory, exacerbating existing inequalities. In this study, the effect of FinTech Firms on reducing gender inequality in bank loans in the USA is examined using a loan application from 60 U.S. banks from 2012 to 2022. We use a two-step system GMM approach to estimate the effect of FinTech algorithms on gender bias in credit decisions, focusing on female loan approval rates. Our results show that by controlling the other factor, banks with credit algorithms significantly increased the loan approval rates and thus reduced gender inequality in bank loans. Specifically, the female loan approval rates increased by 8% after banks adopted FinTech algorithms. We also find that the effect is more substantial for banks with higher baseline gender bias in credit decisions. We also performed the Difference in Difference analysis to analyse the policy shocks and FinTech adoption on bank loans’ gender inequality. Results of the study show that FinTech adoption and policy implications have significantly increased the loans for female borrowers. Our findings suggest that FinTech algorithms can potentially mitigate gender bias in credit decisions and promote gender equality in financial services.

Despite advances in targeted therapies, primary and acquired resistance make the treatment of colorectal cancer (CRC) a pressing issue to be resolved. According to reports, the development of CRC is linked to miRNA dysregulation. Multiple studies have demonstrated that miR-135b-5p has an aberrant expression level between CRC tissues and adjacent tissues. However, it is unclear whether there is a correlation between miR-135b-5p and cetuximab (CTx) resistance in CRC. Use the GEO database to measure miR-135b-5p expression in CRC. Additionally, RT-qPCR was applied to ascertain the production level of miR-135b-5p in three human CRC cells and NCM460 cells. The capacity of cells to migrate and invade was examined utilizing the wound-healing and transwell assays, while the CCK-8 assay served for evaluating cell viability, as well as colony formation assays for proliferation. The expected target protein of miR-135b-5p in CRC cell cetuximab resistance has been investigated using western blot. Suppression of miR-135b-5p could increase the CTx sensitivity of CTx-resistant CRC cells, as manifested by the attenuation of proliferation, migration, and invasion ability. Mechanistic studies revealed miR-135b-5p regulates the epithelial-to-mesenchymal transition (EMT) process and Wnt/β-catenin signaling pathway through downgulating FOXN3. In short, knockdowning miR-135b-5p could increase FOXN3 expression in CRC cells, promote the EMT process, and simultaneously activate the Wnt/β-catenin signaling pathway to elevate CTx resistance in CRC cells.

The gut fungi play important roles in human health and are involved in energy metabolism. This study aimed to examine gut mycobiome composition in obese subjects in two geographically different regions in China and to identify specific gut fungi associated with obesity. A total of 217 subjects from two regions with different urbanization levels [Hong Kong (HK): obese, n = 59; lean, n = 59; Kunming (KM): obese, n = 50; lean, n = 49. Mean body mass index (BMI) for obesity = 33.7] were recruited. We performed deep shotgun metagenomic sequencing on fecal samples to compare gut mycobiome composition and trophic functions in lean and obese subjects across these two regions. The gut mycobiome of obese subjects in both HK and KM were altered compared to those of lean subjects, characterized by a decrease in the relative abundance of Nakaseomyces, Schizosaccharomyces pombe, Candida dubliniensis and an increase in the abundance of Lanchanceathermotolerans, Saccharomyces paradox, Parastagonospora nodorum and Myceliophthorathermophila. Reduced fungal – bacterial and fungal – fungal correlations as well as increased negative fungal-bacterial correlations were observed in the gut of obese subjects. Furthermore, the anti-obesity effect of fungus S. pombe was further validated using a mouse model. Supplementing high-fat diet-induced obese mice with the fungus for 12 weeks led to a significant reduction in body weight gain (p

Cancer treatment has long been fraught with challenges, including drug resistance, metastasis, and recurrence, making it one of the most difficult diseases to treat effectively. Traditional therapeutic approaches often fall short due to their inability to target cancer stem cells and the complex genetic and epigenetic landscape of tumors. In recent years, cancer immunotherapy has revolutionized the field, offering new hope and viable alternatives to conventional treatments. A particularly promising area of research focuses on non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), and their role in cancer resistance and the modulation of signaling pathways. To address these challenges, we performed a comprehensive review of recent studies on lncRNAs and their impact on cancer immunotherapy. Our review highlights the crucial roles that lncRNAs play in affecting both innate and adaptive immunity, thereby influencing the outcomes of cancer treatments. Key observations from our review indicate that lncRNAs can modify the tumor immune microenvironment, enhance immune cell infiltration, and regulate cytokine production, all of which contribute to tumor growth and resistance to therapies. These insights suggest that lncRNAs could serve as potential targets for precision medicine, opening up new avenues for developing more effective cancer immunotherapies. By compiling recent research on lncRNAs across various cancers, this review aims to shed light on their mechanisms within the tumor immune microenvironment.

The aim of this research is to analyze the impact of mental health on the academic performance of junior and senior students studying in a university setting during the 2022–2023 academic year, in the post-COVID period. The study was conducted in Beijing, China, with the participation of 600 students, including 300 first-year students and 300 fifth-year students. DASS (Depression, Anxiety, and Stress Scale) and PHQ-9 (Patient Health Questionnaire-9) questionnaires were employed to measure mental health. The DASS assesses symptoms of depression, anxiety, and stress, while the PHQ-9 specifically evaluates depression severity. Academic performance was evaluated using a 12-point scale, which incorporated various criteria such as exam scores, coursework performance, and participation in extracurricular activities. The research was conducted across five faculties of the university from 2022 to 2023. In the study, fifth-year students demonstrated a higher level of mental health compared to first-year students, with an average DASS score of 27.1 and 24.2, respectively. Interestingly, despite this, first-year students achieved higher academic performance indicators, with an average score of 8.2 compared to 9.8 in fifth-year students. Correlation analysis revealed significant associations between stress, depression, and anxiety levels with academic performance (stress: r = −0.25, p

This paper aims to study a class of enterprise cluster models with feedback controls and time-varying delays on time scales. Based on periodic time scales theory and the fixed point theorem of strict-set-contraction, some new sufficient conditions for the existence of positive periodic solutions are obtained. Finally, two examples are presented to verify the validity and applicability of the main results in this paper.

6G networks are envisioned to deliver a large diversity of applications and meet stringent Quality of Service (QoS) requirements. Hence, integrated Terrestrial and Non-Terrestrial Network (TN-NTNs,) are anticipated to be key enabling technologies. However, the integration of TN-NTNs, faces a number of challenges that could be addressed through network virtualization technologies, such as Software-Defined Networking (SDN), Network Function Virtualization (NFV), and Network Slicing (NS). In this survey, we provide a comprehensive review of the adaptation of these networking paradigms in 6G networks. We begin with a brief overview of Non-Terrestrial Network (NTN) and virtualization techniques. Then, we highlight the integral role of Artificial Intelligence (AI) in improving network virtualization by summarizing major research areas where AI models are applied. Building on this foundation, we identify the main issues arising from the use of SDN, NFV, and NS in integrated TN-NTNs,, and propose a taxonomy of integrated TN-NTNs, virtualization offering a thorough review of relevant contributions. The taxonomy is built on a four-level classification that indicates — for each study — the level of TN-NTNs, integration, the virtualization technology used, the problem addressed, the type of the study, and the proposed solution, which can be based on conventional or AI-enabled methods. Finally, we discuss open issues and give insights on future research directions for the advancement of integrated TN-NTNs, virtualization in the 6G era.

Abstract Background Integrative Chinese and Western medicine (ICWM) is commonly used for the treatment of ulcerative colitis (UC) in clinical practice. However, it is unclear whether the details of ICWM interventions, such as selection rationale, implementation design, and potential interactions, were adequately reported. Therefore, this study aimed to assess the quality of reporting in the ICWM interventional randomized controlled trials (RCTs) of UC and to identify the common problems if any. Methods Through a search of 10 international electronic databases, we identified RCTs of UC with ICWM interventions published in English or Chinese from the inception date of each database up to 16 June 2023. Literature screening was strictly conducted based on the inclusion and exclusion criteria of the Population, Concept, and Context (PCC) framework. The general characteristics of the included studies were described. The quality of reporting was assessed according to three checklists, including the CONSORT (Consolidated Standards of Reporting Trials) with 36 items (except for one item 1b about abstract), the CONSORT for Abstracts (17 items), and a self-designed ICWM-related checklist (27 items covering design rationale, intervention details, outcome assessments, and analysis). The reporting scores of RCTs published before and after 2010 were compared. Results A total of 1458 eligible RCTs were included. For the reporting compliance, the median score (interquartile ranges) of the CONSORT (72 score in total), the CONSORT for Abstract (34 score), and ICWM-related (54 score) items was 21 (18–25), 13 (12–15), and 18 (15–21), respectively. Although the time period comparisons showed that reporting quality of included publications improved significantly after the CONSORT 2010 issued (P

The gut microbiota is engaged in multiple interactions affecting host health, and gut dysbiosis can lead to many diseases. However, the effects of acetylcysteine (NAC) on the gut microbiome composition in pigs using metagenomic sequencing have not been reported. In this study, we used metagenome sequencing to study the effects of NAC on the pig gut microbiome. Sequencing results showed that microbial diversity was changed after NAC treatment. Antibiotic Resistance Genes Database (ARDB) analysis demonstrated that the main genes modified were macb, tsnr, norm, bl2be-per, vansb and pbp1b in the NAC group. Our data showed that NAC could affect microbial distribution at the phylum, gene and species levels. At the species level, NAC significantly increased the abundances of Megasphaera, Lactobacillus reuteri and Megasphaeraelsdenii and reduced the abundances of Phascolarctobacterium succinatutens, Prevotellacopri and Selenomonasbovis compared with the control group. In addition, Gene Ontology (GO) analysis revealed that in the NAC group, cellular process, metabolic process and single-organism process were the dominant terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that RNA transport, MAPK signaling pathway, cell cycle, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and VEGF signaling pathway were the dominant signaling pathways in the NAC group. In conclusion, our results suggest that NAC may modify the piglet gut microbiome composition and these findings might provide a new strategy for maintaining animal and human health in the future.

Early-stage infective endocarditis (IE) can lead to severe complications, including infarctions and metastatic infections caused by inflammatory embolus shedding. Common embolism sites include the brain, spleen, kidneys, lungs, and intestines. Additionally, acute heart failure (AHF) can occur in up to 40% of cases, and its presence can impact the clinical outcomes of patients with IE. Cardiogenic shock (CGS) is often more likely to occur after AHF has taken place. If bacteria invade the blood, infectious shock can occur. Patients with IE can experience simple CGS, septic shock, or a combination of the two. Extracorporeal membrane oxygenation (ECMO) typically serves as a Bridge for Heart failure and Cardiogenic shock. Previous research indicates that there are limited reports of ECMO support for patients with IE after CGS has occurred. Because CGS may occur at any time during IE treatment, it is important to understand the timing of ECMO auxiliary support and how to carry out comprehensive treatment after support. Timely treatment can help to reduce or avoid the occurrence of serious complications and improve the prognosis of patients with IE. Our work combines a case study to review the ECMO support of IE patients after CGS through a literature review. Overall, we suggest that when patients with IE have large bacterial thrombosis and a greater risk of shedding, it is recommended to carefully evaluate the indications and contraindications for ECMO after discussion by a multidisciplinary team (MDT). Still, active surgical treatment at an early stage is recommended.

Abstract The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P

Glaesserella parasuis can induce endothelial barrier damage in piglets, although the mechanism by which this pathogen triggers inflammatory damage remains unclear. Baicalin possesses anti-inflammatory and anti-oxidant activities. However, whether baicalin can relieve endothelial barrier damage caused by Glaesserella parasuis infection has not yet been studied. Hence, we evaluated the ability of baicalin to counteract the changes induced by Glaesserella parasuis in porcine aortic vascular endothelial cells. The results showed that Glaesserella parasuis could upregulate the expression of pannexin 1 channel protein and promote the release of adenosine triphosphate, adenosine diphosphate, adenosine 3′-monophosphate, uridine triphosphate, uridine diphosphate, and uridine monophosphate in porcine aortic vascular endothelial cells. The expression level of purinergic receptor P2Y6 was upregulated in porcine aortic vascular endothelial cells triggered by Glaesserella parasuis. In addition, Glaesserella parasuis could activate phospholipase C-protein kinase C and myosin light chain kinase-myosin light chain signaling pathways in porcine aortic vascular endothelial cells. Baicalin could inhibit pannexin 1 channel protein expression, reduce adenosine triphosphate, adenosine diphosphate, adenosine 3′-monophosphate, uridine triphosphate, uridine diphosphate, and uridine monophosphate release, and attenuate the expression level of P2Y6 in porcine aortic vascular endothelial cells induced by Glaesserella parasuis. Baicalin could also reduce the activation of phospholipase C-protein kinase C and myosin light chain kinase-myosin light chain signaling pathways in porcine aortic vascular endothelial cells triggered by Glaesserella parasuis. Our study report that Glaesserella parasuis could promote pannexin 1 channel protein expression, induce nucleosides substance release, and P2Y6 expression in porcine aortic vascular endothelial cells and baicalin could inhibit the expression levels of pannexin 1, nucleosides substance, and P2Y6 in the porcine aortic vascular endothelial cells induced by Glaesserella parasuis, which might be served as some targets for treatment of inflammation disease caused by Glaesserella parasuis.

To explore the application efficacy and significance of deep learning in anesthesia management for gastrointestinal tumors (GITs) surgery, 80 elderly patients with GITs who underwent surgical intervention at our institution between January and September 2021 were enrolled. According to the preoperative anesthesia management methodology, patients were rolled into a control (Ctrl) group (using 10 mg dexamethasone 1-2 hours before surgery) and an experimental (Exp) group (using a deep learning-based anesthesia monitoring system on the basis of the Ctrl group), with 40 cases in each group. A comprehensive comparative analysis was performed between the two cohorts, encompassing postoperative cognitive evaluations, Montreal Cognitive Assessment (MoCA) scores, gastrointestinal functionality, serum biomarkers (including interleukin (IL)-6, C-reactive protein (CRP), and cortisol levels), length of hospitalization, incidence of complications, and other pertinent metrics. The findings demonstrated that anesthesia monitoring facilitated by deep learning algorithms effectively assessed the anesthesia state of patients. Compared to the Ctrl group, patients in the Exp group showed significant differences in cognitive assessments (word recall, number connection, number coding) (P

Background. Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods. We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results. Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16− NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16− NK cells. Conclusion. In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.

Background Hypoxaemia plays an important role in the development of pulmonary artery hypertension (PAH). Patients with acute respiratory distress syndrome (ARDS) in a high-altitude area have different pathophysiological characteristics from those patients in the plains. The goal of our study was to explore the clinical characteristics of PAH secondary to ARDS in a high-altitude area.Methods This was a prospective study conducted in the affiliated Hospital of Qinghai University. Two investigators independently assessed pulmonary artery pressure (PAP) and right ventricular function by transthoracic echocardiography. Basic information and clinical data of the patients who were enrolled were collected. A multivariable logistic regression model was used to evaluate the risk factors for PAH secondary to ARDS in the high-altitude area.Results The incidence of PAH secondary to ARDS within 48 hours in the high-altitude area was 44.19%. Partial pressure of oxygen/fraction of inspired oxygen

Abstract Background Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table. Methods This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA). Discussion As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date. Trial registration ClinicalTrial.gov NCT05207202. First published on January 26, 2022.

Abstract Background The incidence of pediatric inflammatory bowel disease (PIBD) has been steadily increasing globally. Delayed diagnosis of PIBD increases the risk of complications and contributes to growth retardation. To improve long-term outcomes, there is a pressing need to identify novel markers for early diagnosis of PIBD. Methods The candidate biomarkers for PIBD were identified from the GSE117993 dataset by two machine learning algorithms, namely LASSO and mSVM-RFE, and externally validated in the GSE126124 dataset and our PIBD cohort. The role of ficolin-1 (FCN1) in PIBD and its association with macrophage infiltration was investigated using the CIBERSORT method and enrichment analysis of the single-cell dataset GSE121380, and further validated using immunoblotting, qRT-PCR, and immunostaining in colon biopsies from PIBD patients, a juvenile murine DSS-induced colitis model, and THP-1-derived macrophages. Results FCN1 showed great diagnostic performance for PIBD in an independent clinical cohort with the AUC of 0.986. FCN1 expression was upregulated in both colorectal biopsies and blood samples from PIBD patients. Functionally, FCN1 was associated with immune-related processes in the colonic mucosa of PIBD patients, and correlated with increased proinflammatory M1 macrophage infiltration. Furthermore, single-cell transcriptome analysis and immunostaining revealed that FCN1 was almost exclusively expressed in macrophages infiltrating the colonic mucosa of PIBD patients, and these FCN1+ macrophages were related to hyper-inflammation. Notably, proinflammatory M1 macrophages derived from THP-1 expressed high levels of FCN1 and IL-1β, and FCN1 overexpression in THP-1-derived macrophages strongly promoted LPS-induced activation of the proinflammatory cytokine IL-1β via the NLRP3-caspase-1 axis. Conclusions FCN1 is a novel and promising diagnostic biomarker for PIBD. FCN1+ macrophages enriched in the colonic mucosa of PIBD exhibit proinflammatory phenotypes, and FCN1 promotes IL-1β maturation in macrophages via the NLRP3-caspase-1 axis.

Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the DMD gene. The full mutation spectrum of the DMD gene in Indonesian patients is currently unknown. Mutation-specific therapies are currently being developed, such as exon skipping or stop codon read-through therapy. This study was conducted with the aim of identifying the mutation spectrum of the DMD gene in Indonesia to guide future development and application of feasible therapeutic strategies. Methods This study is a cross sectional study that enrolled 43 male patients with a clinical suspicion of DMD or BMD. Multiplex ligation-dependent probe amplification (MLPA) reaction was performed to screen for the common mutations in the DMD gene. Results Out of 43 subjects, deletions accounted for 69.77% (n=30) cases, while duplications were found in 11.63% (n=5) cases. One novel duplication spanning exons 2 to 62 was identified. Deletion mutations clustered around the distal (66.67%) and proximal (26.67%) hot spot regions of the DMD gene while duplication mutations were observed solely at the proximal region. Two false positive cases of single exon deletion detected through MLPA were attributed to sequence mutations affecting primer ligation sites, confirming the need to validate all single exon deletions when using this screening method. Analysis of available maternal DNA samples showed that the rate of de novo mutations (48.15%) appears higher than expected in this population. Out of 31 patients who were classified as DMD based on clinical and genotype characterizations, 60.47% (n=26) of cases were suitable for exon skipping therapy. Conclusion This is the first comprehensive study showing the feasibility of implementing the MLPA method for routine screening of DMD patients in Indonesia. This is also the first study showing the potential applicability of exon skipping therapy in the majority of DMD cases in the country.

Abstract Background Acute respiratory distress syndrome (ARDS) patients with different lung morphology have distinct pulmonary mechanical dysfunction and outcomes. Whether lung morphology impacts the association between ventilatory variables and mortality remains unclear. Moreover, the impact of a novel combined ventilator variable [(4×DP) + RR] on morality in ARDS patients needs external validation. Methods We obtained data from the Chinese Database in Intensive Care (CDIC), which included adult ARDS patients who received invasive mechanical ventilation for at least 24 h. Patients were further classified into two groups based on lung morphology (focal and non-focal). Ventilatory variables were collected longitudinally within the first four days of ventilation. The primary outcome was 28-day mortality. Extended Cox regression models were employed to explore the interaction between lung morphology and longitudinal ventilatory variables on mortality. Findings We included 396 ARDS patients with different lung morphology (64.1% non-focal). The overall 28-day mortality was 34.4%. Patients with non-focal lung morphology have more severe and persistent pulmonary mechanical dysfunction and higher mortality than those with focal lung morphology. Time-varying driving pressure (DP) was more significantly associated with 28-day mortality in patients with non-focal lung morphology compared to focal lung morphology patients (P for interaction = 0.0039). The impact of DP on mortality was more significant than that of respiratory rate (RR) only in patients with non-focal lung morphology. The hazard ratio (HR) of mortality for [(4×DP) + RR] was significant in patients with non-focal lung morphology (HR 1.036, 95% CI 1.027–1.045), not in patients with focal lung morphology (HR 1.019, 95% CI 0.999–1.039). Interpretation The association between ventilator variables and mortality varied among patients with different lung morphology. [(4×DP) + RR] was only associated with mortality in patients with non-focal lung morphology. Further validation is needed.

As delay-tolerant and large-size content, for example, software updates, TV series, and virtual reality related content, become more prevalent in mobile networks, the need for efficient content delivery mechanisms becomes increasingly important,the traffic that carries these contents is not suitable to be evaluated using traditional network performance metrics, e.g., delay, throughput, and jitter. Based on this insight, we propose the solution of content dissemination from opportunistic mobile social communications (CODOMOC)which utilizes energy cost as an alternative performance metric and exploits daily human activity mobility pattern to determine how, when, and where the contents should be disseminated. Then, we introduce two options in CODOMOC to achieve different network operators’ objectives. The two options are the Only Dense (OD) option which aims at minimizing energy consumption for network operators and the Broadcast Efficiency (BE) option to further reduce the total carbon footprint of network operators. CODOMOC is evaluated by comparing with a mobility-based broadcast method. The results show that CODOMOC reduces the average energy consumption by 51% and 60% in the OD and BE options respectively. The proposed solution equipped with the two modes is expected to provide a higher degree of flexibility and reduce energy consumption for mobile networks, while, admittedly, the application scope of the solution and the associated methodologies proposed in this paper is restricted to important but non-urgent traffic delivery.

Objective To investigate the prevalence and influencing factors of poor sleep quality in preschool children in Chizhou city, Anhui province, and to provide evidences for improving children′s sleep health．Methods An on-site self-administered questionnaire survey was conducted among parents of 1815 children aged 3 – 6 years recruited with stratified random cluster sampling from 14 kindergartens in districts/counties of Chizhou city during June – July 2020. The Children′s Sleep Habits Questionnaire (CSHQ) – Chinese Version and a self-designed questionnaire were used in the survey. ResultsOf the 1 758 children (96.9% of the all children) with valid information, 76.3% were assessed as having poor sleep quality; the detection rates were 85.6% for bad bedtime habit, 46.6% for prolonged sleep latency, 46.6% for irregular sleep duration, 84.7% for sleep anxiety, 19.4% for waking up at night, 45.1% for parasomnia, 11.0% for sleep-disordered breathing, and 71.0% for daytime sleepiness, respectively. The results of multivariate unconditional logistic regression analysis showed that sharing one bed with relatives, sleeping in a separate bed but the same room with relatives, with a primary caregiver having the bedtime of not earlier than 22 o'clock, and with a primary caregiver using electronic products before bedtime were the risk factors for poor sleep quality of the preschool children; while, with a quiet sleeping environment and having siestas habit were the protective factors against poor sleep quality; the results also demonstrated that the children′s various poor sleep behaviors were significantly affected by following factors: in terms of risk effect (1) mean time of ≥ 30 minutes for each time of using electronic products for bad sleeping habit, (2) sharing one bed with relatives and sleeping in separate bed but in the same room with relatives for bad sleeping habit/sleep anxiety, (3) with a primary caregiver having the bedtime of not earlier than 22 o'clock for prolonged sleep latency/daytime spleepiness, (4) being a boy and with a primary caregiver using electronic products before bedtime for parasomnia; and in terms of protective effect (1) with a quiet sleeping environment against bad sleeping habit/prolonged sleep latency/irregular sleep duration/waking up at night/parasomnia/daytime sleepiness, (2) having siestas habit against irregular sleep duration, and (3) aged 5 – 6 years against sleep anxiety. Conclusion Among preschool children in Chizhou city, the prevalence rate of poor sleep quality, mainly manifested as unhealthy sleeping habit, is relatively high and affected significantly by sleeping environment, siestas habit, primary caregiver′s bedtime and electronic product usage before bedtime.

The abnormal expansion of G-rich hexanucleotide repeat, GGGGCC (G4C2), in chromosome 9 open reading frame 72 (C9orf72) is known to be the prevailing genetic cause of two fatal degenerative neurological diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It is well known that the DNA G4C2 repeat expansion with different lengths can form G-quadruplexes which affect gene transcription related to ALS/FTD, therefore it is crucial to understand DNA G4C2 G-quadruplex structures. Herein, by utilizing nuclear magnetic resonance (NMR) spectroscopy, we examined DNA G-quadruplex structure adopted by two G4C2 hexanucleotide repeats with an inosine substitution at position 4, d(G4C2)2-I4. We show that d(G4C2)2-I4 folds into an eight-layer parallel tetrameric G-quadruplex containing two parallel dimeric G-quadruplexes stacking together through π-π interaction via 5′-to-5′ mode in solution. Each dimeric G-quadruplex unit involves two propeller loops composed of two cytosine bases. This result is consistent with the observation in the crystal structure of d(G4C2)2. Our work not only sheds light on the structural diversity of G-quadruplexes adopted by d(G4C2)n but also provides a structural basis for drug design in treatment of ALS and FTD.

Abstract Background Pseudogenes play an essential role in tumor occurrence and progression. However, the functions and mechanisms of pseudogenes in clear cell renal cell carcinoma (ccRCC) remain largely elusive. Methods We quantified PEBP1P2 expression in ccRCC tissues and cells using fluorescence in situ hybridization and real-time PCR. Besides, we evaluated the role of PEBP1P2 in ccRCC using a lung metastasis model and a transwell assay. Finally, we documented the interactions between PEBP1P2, PEBP1, and KLF13 by performing luciferase, RNA immunoprecipitation, RNA pulldown, and targeted RNA demethylation assays. Results Low PEBP1P2 expression correlates significantly with advanced stages and poor prognosis in ccRCC patients. Besides, PEBP1P2 overexpression inhibits ccRCC metastasis formation in vivo and in vitro. Interestingly, PEBP1P2 directly interacted with 5-methylcytosine (m5C)-containing PEBP1 mRNA and recruited the YBX1/ELAVL1 complex, stabilizing PEBP1 mRNA. In addition, PEBP1P2 increased KLF13 mRNA levels by acting as a sponge for miR-296, miR-616, and miR-3194. Conclusions PEBP1P2 inhibits ccRCC metastasis formation and regulates both PEBP1 and KLF13. Therefore, molecular therapies targeting PEBP1P2 might be an effective treatment strategy against ccRCC and other cancers with low PEBP1P2 levels.

Here, using fecal metagenomics data of 2,320 individuals, the authors develop a microbiome-based machine learning approach showing high accuracy for multi-class disease diagnosis, highlighting its potential application in improving noninvasive diagnostics and monitor responses to therapy.

Here, by performing an integrative multi-omics analysis coupled to clinical features of COVID-19 patients prospectively followed for up to 6 month, the authors identify specific gut microbiome patterns associated with disease severity and development of post-acute COVID-19 syndrome.

Abstract Background Previously identified phenotypes of acute respiratory distress syndrome (ARDS) have been limited by a disregard for temporal dynamics. We aimed to identify longitudinal phenotypes in ARDS to test the prognostic and predictive enrichment of longitudinal phenotypes, and to develop simplified models for phenotype identification. Methods We conducted a multi-database study based on the Chinese Database in Intensive Care (CDIC) and four ARDS randomized clinical trials (RCTs). We employed latent class analysis (LCA) to identify longitudinal phenotypes using 24-hourly data from the first four days of invasive ventilation. We used the Cox regression model to explore the association between time-varying respiratory parameters and 28-day mortality across phenotypes. Phenotypes were validated in four RCTs, and the heterogeneity of treatment effect (HTE) was investigated. We also constructed two multinomial logistical regression analyses to develop the probabilistic models. Findings A total of 605 ARDS patients in CDIC were enrolled. The three-class LCA model was identified and had the optimal fit, as follows: Class 1 (n = 400, 66.1% of the cohort) was the largest phenotype over all study days, and had fewer abnormal values, less organ dysfunction and the lowest 28-day mortality rate (30.5%). Class 2 (n = 102, 16.9% of the cohort) was characterized by pulmonary mechanical dysfunction and had the highest proportion of poorly aerated lung volume, the 28-day mortality rate was 47.1%. Class 3 (n = 103, 17% of the cohort) was correlated with extra-pulmonary dysfunction and had the highest 28-day mortality rate (56.3%). Time-varying mechanical power was more significantly associated with 28-day mortality in Class 2 patients compared to other phenotypes. Similar phenotypes were identified in four RCTs. A significant HTE between phenotypes and treatment strategies was observed in the ALVEOLI (high PEEP vs. low PEEP) and the FACTT trials (conservative vs. liberal fluid management). Two parsimonious probabilistic models were constructed to identify longitudinal phenotypes. Interpretation We identified and validated three novel longitudinal phenotypes for ARDS patients, with both prognostic and predictive enrichment. The phenotypes of ARDS can be accurately identified with simple classifier models, except for Class 3.

IntroductionThe incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteria Pediococcus pentosaceus (P. pentosaceus) can interfere with intestinal immunity, but it is still unknown whether it can alleviate PIBD and the concrete mechanism of immune regulation is unclear.MethodsFor this study, 3-week-old juvenile mice were selected for modeling the development of PIBD. The mice treated with 2% DSS were randomly divided into two groups, which were given P. pentosaceus CECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism exploration in vivo. THP-1 and NCM460 cells were used to investigate the effects of P. pentosaceus CECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalk in vitro.ResultsP. pentosaceus CECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically, P. pentosaceus CECT8330 could inhibit intestinal epithelial apoptosis by suppressing the NF-κB signaling pathway. Meanwhile, it reprogramed macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, leading to a decreased secretion of IL-1β which contributes to the reduction in ROS production and epithelial apoptosis. Additionally, the 16S rRNA sequence analysis revealed that P. pentosaceus CECT8330 could recover the balance of gut microbiota, and a significantly increased content of Akkermansia muciniphila was particularly observed.ConclusionP. pentosaceus CECT8330 shifts macrophage polarization toward an anti-inflammatory M2 phenotype. The decreased production of IL-1β leads to a reduction in ROS, NF-κB activation, and apoptosis in the intestinal epithelium, all of which help to repair the intestinal barrier and adjust gut microbiota in juvenile colitis mice.

Although the Berlin definition of acute respiratory distress syndrome (ARDS), 2012 has been widely used in clinical practice, issues have occasionally been raised regarding various criteria since it was proposed. High-flow nasal oxygen (HFNO) is widely used for effective respiratory support in acute respiratory failure. As patients who do not require ventilation but meet the Berlin criteria have similar characteristics to those with ARDS, the definition of ARDS may be broadened to include patients receiving HFNO. As the PaO2/FiO2 under-recognizes the diagnosis of ARDS, a SpO2/FiO2 value of ≤315 may be considered instead of a PaO2/FiO2 value of ≤300 for diagnosing the condition in resource-constrained settings. In this context, patients with severe COVID-19 always meet other criteria for ARDS except for 7-day acute onset. Therefore, the timeframe for the onset of ARDS may be extended to up to 14 days. An expanded definition of ARDS may allow early identification of patients with less severe diseases and facilitate testing and application of new therapies in patients with a high risk of poor outcomes. Here, we discuss the major controversies regarding the extension of the ARDS definition with a view to improving clinical implementation and patient outcomes.

ObjectivesCutaneous tuberculosis with various manifestations can be divided into several clinical types according to the host's immune status and infective route. However, the etiological factors of this disease remain unclear. The objective of this study is to investigate the pathogens associated with the occurrence and different types of cutaneous tuberculosis.Methods58 Mycobacterium tuberculosis strains isolated from cutaneous tuberculosis over the last 20 years were sequenced and analyzed for genomic characteristics including lineage distribution, drug-resistance mutations, and mutations potentially associated with different sites of infection.ResultsThe M. tuberculosis strains from four major types of cutaneous tuberculosis and pulmonary tuberculosis shared similar genotypes and genomic composition. The strains isolated from cutaneous tuberculosis had a lower rate of drug resistance. Phylogenic analysis showed cutaneous tuberculosis and pulmonary tuberculosis isolates scattered on the three. Several SNPs in metabolism related genes exhibited a strong correlation with different infection sites.ConclusionsThe different infection sites of TB may barely be affected by large genomic changes in M. tuberculosis isolates, but the significant difference in SNPs of drug resistance gene and metabolism-related genes still deserves more attention.

Abstract Background Granulomatosis with polyangiitis (GPA) vasculitis with pulmonary-renal syndrome rarely presents in children and is associated with high mortality rates. Case presentation We present the case of a 13-year-old male with newly diagnosed GPA vasculitis, treated with extracorporeal membrane oxygenation, continuous renal replacement therapy, plasmapheresis, rituximab, cyclophosphamide, and corticosteroids. Conclusion This case presentation demonstrates that ECMO can be used as a life supporting therapy in pediatric patients with pulmonary hemorrhage from ANCA vasculitis in conjunction with other therapies.

Abstract Background Microplastics (MPs), which are smaller in size and difficult to degrade, can be easily ingested by marine life and enter mammals through the food chain. Our previous study demonstrated that following acute exposure to MPs, the serum testosterone content reduced and sperm quality declined, resulting in male reproductive dysfunction in mice. However, the toxic effect of long-term exposure to MPs at environmental exposure levels on the reproductive system of mammals remains unclear. Results In vivo, mice were given drinking water containing 100 μg/L and 1000 μg/L polystyrene MPs (PS-MPs) with particle sizes of 0.5 μm, 4 μm, and 10 μm for 180 consecutive days. We observed alterations in testicular morphology and reductions in testosterone, LH and FSH contents in serum. In addition, the viability of sperm was declined and the rate of sperm abnormality was increased following exposure to PS-MPs. The expression of steroidogenic enzymes and StAR was downregulated in testis tissues. In vitro, we used primary Leydig cells to explore the underlying mechanism of the decrease in testosterone induced by PS-MPs. First, we discovered that PS-MPs attached to and became internalized by Leydig cells. And then we found that the contents of testosterone in the supernatant declined. Meanwhile, LHR, steroidogenic enzymes and StAR were downregulated with concentration-dependent on PS-MPs. We also confirmed that PS-MPs decreased StAR expression by inhibiting activation of the AC/cAMP/PKA pathway. Moreover, the overexpression of LHR alleviated the reduction in StAR and steroidogenic enzymes levels, and finally alleviated the reduction in testosterone induced by PS-MPs. Conclusions PS-MPs exposure resulted in alterations in testicular histology, abnormal spermatogenesis, and interference of serum hormone secretion in mice. PS-MPs induced a reduction in testosterone level through downregulation of the LH-mediated LHR/cAMP/PKA/StAR pathway. In summary, our study showed that chronic exposure to PS-MPs resulted in toxicity of male reproduction under environmental exposure levels, and these potential risks may ring alarm bells of public health. Graphical abstract

Abstract Circular RNAs (circRNAs) have been recognized as significant participants in the progression of different cancers; however, the detailed mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain unclear. In this study, hsa_circ_0001394 was identified by RNA-seq analysis, and hsa_circ_0001394 was determined to be highly expressed in HCC specimens and cell lines. Patients with high expression of hsa_circ_0001394 tended to exhibit poor survival. Increased hsa_circ_0001394 expression in plasma was closely correlated with clinicopathological features including elevated vascular invasion and an advanced TNM stage, as indicated by alpha-fetoprotein (AFP) analysis. Hsa_circ_0001394 promoted the proliferation, migration, and invasion of HCC cells, whereas knockdown of hsa_circ_0001394 inhibited HCC tumorigenesis in vivo. In addition, mechanistic studies showed that miR-527 negatively interacted with hsa_circ_0001394. Furthermore, UBE2A was revealed to serve as a target of miR-527. Overall, the present study suggested that hsa_circ_0001394 may function as a sponge to promote HCC progression by regulating the miR-527/UBE2A pathway. Thus, hsa_circ_0001394 may become a promising biomarker and potential therapeutic target in HCC treatment.

The former reports of coherent beam combining (CBC) in the ultra-intense ultra-short laser field focus on the phase control technology and two-beam CBC. To study the four-beam tiled-aperture CBC in the ultra-intense and ultra-short laser field, we demonstrate four-beam CBC of femtosecond laser pulses based on chirped pulse amplification (CPA) scheme. In this experiment, the four beams were compressed using two grating compressors to simulate the situation in ultra-intense and ultra-short laser CBC systems. To achieve real-time measurement of the phase error between the four beams, we introduced a continuous reference laser and the phases of beams 2, 3, and 4 were locked to beam 1.A combined efficiency of 57% was achieved. Although the coherent combining efficiency is not very high, the possibility of a four-beam CBC based on the CPA scheme was confirmed, especially with different grating compressors which can reduce the limitation of gratings in single beam petawatt lasers. Finally, the remaining difficulties in the implementation of CBC of four beams and the methods to improve its efficiency were analyzed. The use of CBC in ultra-intense and ultrashort laser systems is of considerable significance.

Targeted delivery of antitumor drugs has been recognized as a promising therapeutic modality to improve treatment efficacy, reduce the toxic side effects and inhibit tumor recurrence. In this study, based on the high biocompatibility, large specific surface area, and easy surface modification of small-sized hollow mesoporous silica nanoparticles β-cyclodextrin (β-CD)-benzimidazole (BM) supramolecular nanovalve, together with bone-targeted alendronate sodium (ALN) were constructed on the surface of small-sized HMSNs. The drug loading capacity and efficiency of apatinib (Apa) in HMSNs/BM-Apa-CD-PEG-ALN (HACA) were 65% and 25%, respectively. More importantly, HACA nanoparticles can release the antitumor drug Apa efficiently compared with non-targeted HMSNs nanoparticles in the acidic microenvironment of the tumor. In vitro studies showed that HACA nanoparticles exhibited the most potent cytotoxicity in osteosarcoma cells (143B cells) and significantly reduced cell proliferation, migration and invasion. Therefore, the drug-efficient release of antitumor effect of HACA nanoparticles is a promising way to treat osteosarcoma.

Cytometry of Reaction Rate Constant (CRRC) is a method for studying cell-population heterogeneity using time-lapse fluorescence microscopy, which allows one to follow reaction kinetics in individual cells. The current and only CRRC workflow utilizes a single fluorescence image to manually identify cell contours which are then used to determine fluorescence intensity of individual cells in the entire time-stack of images. This workflow is only reliable if cells maintain their positions during the time-lapse measurements. If the cells move, the original cell contours become unsuitable for evaluating intracellular fluorescence and the CRRC experiment will be inaccurate. The requirement of invariant cell positions during a prolonged imaging is impossible to satisfy for motile cells. Here we report a CRRC workflow developed to be applicable to motile cells. The new workflow combines fluorescence microscopy with transmitted-light microscopy and utilizes a new automated tool for cell identification and tracking. A transmitted-light image is taken right before every fluorescence image to determine cell contours, and cell contours are tracked through the time-stack of transmitted-light images to account for cell movement. Each unique contour is used to determine fluorescence intensity of cells in the associated fluorescence image. Next, time dependencies of the intracellular fluorescence intensities are used to determine each cell's rate constant and construct a kinetic histogram "number of cells vs rate constant." The new workflow's robustness to cell movement was confirmed experimentally by conducting a CRRC study of cross-membrane transport in motile cells. The new workflow makes CRRC applicable to a wide range of cell types and eliminates the influence of cell motility on the accuracy of results. Additionally, the workflow could potentially monitor kinetics of varying biological processes at the single-cell level for sizable cell populations. Although our workflow was designed ad hoc for CRRC, this cell-segmentation/cell-tracking strategy also represents an entry-level, user-friendly option for a variety of biological assays (i.e., migration, proliferation assays, etc.). Importantly, no prior knowledge of informatics (i.e., training a model for deep learning) is required.