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IntroductionTetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro.MethodsThe diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats.ResultsTet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis.DiscussionThis study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.

Underwater image super-resolution is vital for enhancing the clarity and detail of underwater imagery, enabling improved analysis, navigation, and exploration in underwater environments where visual quality is typically degraded due to factors like water turbidity and light attenuation. In this paper, we propose an effective hybrid dynamic Transformer (called HDT-Net) for underwater image super-resolution, leveraging a collaborative exploration of both local and global information aggregation to help image restoration. Firstly, we introduce a dynamic local self-attention to adaptively capture important spatial details in degraded underwater images by employing dynamic weighting. Secondly, considering that visual transformers tend to introduce irrelevant information when modeling the global context, thereby interfering with the reconstruction of high-resolution images, we design a sparse non-local self-attention to more accurately compute self-similarity by setting a top-k threshold. Finally, we integrate these two self-attention mechanisms into the hybrid dynamic transformer module, constituting the primary feature extraction unit of our proposed method. Quantitative and qualitative analyses on benchmark datasets demonstrate that our approach achieves superior performance compared to previous CNN and Transformer models.

Adverse weather conditions such as rain and haze often lead to a degradation in the quality of maritime images, which is crucial for activities like navigation, fishing, and search and rescue. Therefore, it is of great interest to develop an effective algorithm to recover high-quality maritime images under adverse weather conditions. This paper proposes a prompt-based learning method with degradation perception for maritime image restoration, which contains two key components: a restoration module and a prompting module. The former is employed for image restoration, whereas the latter encodes weather-related degradation-specific information to modulate the restoration module, enhancing the recovery process for improved results. Inspired by the recent trend of prompt learning in artificial intelligence, this paper adopts soft-prompt technology to generate learnable visual prompt parameters for better perceiving the degradation-conditioned cues. Extensive experimental results on several benchmarks show that our approach achieves superior restoration performance in maritime image dehazing and deraining tasks.

Due to the inherent power output correlation and uncertainty, renewable energy stations normally incur the deviation penalty in the day-ahead and real-time electricity market. Meanwhile, shared energy storage operators have been appearing to provide energy storage leasing services for neighboring renewable energy stations. In this context, this paper presents a novel optimization strategy to provide leasing services for renewable energy station clusters while improving the utilization rate and revenue of shared energy storage simultaneously. Especially, the proposed strategy utilizes a two-stage optimization model to incorporate the overselling risk. In the first stage, a matching index is defined to select a cluster of wind and solar power stations in the geographically-close region, when a set of highly complementary stations are selected by matching the typical output curve of the shared energy storage. In the second stage, an optimization strategy is determined to explore the benefit and risk of overselling for shared energy storage with the goal of maximizing the total revenue, when the correlation of wind and solar power output is realized in the scenario generation and sampling process. The results of numerical experiments have demonstrated that employing a moderate overselling method can provide an economical and efficient operational solution to improving the utilization of shared energy storage.

The estrogen receptor (ER) is a classical receptor protein that plays a crucial role in mediating multiple signaling pathways in various target organs. It has been shown that ER-targeting therapies inhibit breast cancer cell proliferation, enhance neuronal protection, and promote osteoclast formation. Several drugs have been designed to specifically target ER in ER-positive (ER+) breast cancer, including selective estrogen receptor modulators (SERM) such as Tamoxifen. However, the emergence of drug resistance in ER+ breast cancer and the potential side effects on the endometrium which has high ER expression has posed significant challenges in clinical practice. Recently, novel ER-targeted drugs, namely, selective estrogen receptor degrader (SERD) and selective estrogen receptor covalent antagonist (SERCA) have shown promise in addressing these concerns. This paper provides a comprehensive review of the structural functions of ER and highlights recent advancements in SERD and SERCA-related small molecule drugs, especially focusing on their structural optimization strategies and future optimization directions. Additionally, the therapeutic potential and challenges of novel SERDs and SERCAs in breast cancer and other ER-related diseases have been discussed.

PurposeWith advancements in medical technology and the growth of an aging society, the number of immunocompromised patients has increased progressively. Klebsiella pneumoniae (K. pneumoniae) is one of the most common opportunistic pathogens, causing a severe disease burden. We aimed to further clarify the differences in respiratory tract K. pneumoniae infections between immunocompromised and immunocompetent populations.MethodsWe retrospectively compared cases of respiratory tract K. pneumoniae infection in immunocompromised and immunocompetent patients admitted to Ruijin Hospital in Shanghai between January 2019 and August 2020 to clarify the differences between the two groups.ResultsWe enrolled 400 immunocompromised patients and 386 immunocompetent patients. Compared to the immunocompetent group, immunocompromised patients were more likely to develop bacteremia and shock and to require mechanical ventilation support during hospitalization. Immunocompromised patients also had a greater probability of polymicrobial infection and a higher rate of antibacterial resistance to carbapenem, which resulted in a higher intensive care unit admission rate, 30-day case fatality rate (CFR), and 6-month CFR. Multivariate analysis indicated that immunocompromised patients with respiratory diseases (odds ratio [OR], 2.189; 95% confidence interval [CI], 1.103-4.344; P = 0.025) and cardiovascular diseases (OR, 2.008; 95% CI, 1.055-3.822; P = 0.034), using mechanical ventilation (OR, 3.982; 95% CI, 2.053-7.722; P = 0.000), or infected with multidrug-resistant K. pneumoniae (OR, 3.870; 95%, 1.577-9.498; P = 0.003) were more likely to have a higher 30-day CFR.ConclusionThe disease burden of K. pneumoniae infection in immunocompromised patients is high. Immunocompromised patients who presented with respiratory diseases and cardiovascular diseases, used mechanical ventilation, or were infected with multidrug-resistant K. pneumoniae experienced a higher 30-day mortality rate.

BackgroundEarly surgical closure is warranted to prevent aortic valve lesion and aortic regurgitation (AR) in intracristal ventricular septal defects (icVSDs). Experiences for transcatheter device closure of icVSDs are still limited. Our objectives are to investigate AR progression following transcatheter closure of icVSDs in children and to explore the risk factors for AR progression.Methods and resultsFrom January 2007 to December 2017, 50 children with icVSD who had successfully undergone transcatheter closure were enrolled. With 4.0 (interquartile range: 3.0–6.2) years of follow-up, AR progression was observed in 20% (10/50) of patients after icVSD occlusion, among which 16% (8/50) remained in mild level and 4% (2/50) evolved to moderate. None progressed to severe AR. Freedom from AR progression was 84.0%, 79.5%, and 79.5% at 1, 5, and 10 years of follow-up. A multivariate Cox proportional-hazards model revealed that x-ray exposure time [hazard ratio (HR): 1.11, 95% confidence interval (CI): 1.04–1.18, P = 0.001] and the ratio of pulmonary to systemic blood flows (HR: 3.38, 95% CI: 1.11–10.29, P = 0.032) were independent predictors for AR progression.ConclusionsOur study suggested that transcatheter closure of icVSD in children is safe and feasible in mid- to long-term follow-up. No serious AR progression occurred after icVSD device closure. Greater left-to-right shunting and longer x-ray exposure time were both risk factors for AR progression.

ObjectiveTo compare the therapeutic effects of wedge resection and liver segment IVb + V resection on patients with T2b gallbladder cancer.MethodsThe clinical and pathological data of 40 patients with gallbladder cancer admitted to the Second Affiliated Hospital of Nanchang University from January 2017 to November 2019 were retrospectively analyzed, and they were divided into two groups according to different surgical methods. The control group underwent liver wedge resection, while the experimental group underwent liver segment IVb + V resection. Preoperative age, bilirubin index, tumor markers, postoperative complications and survival were compared between the two groups. Log-rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Kaplan-Meier survival curves were drawn.ResultsUnivariate analysis showed that tumor markers and degree of differentiation were the risk factors for the prognosis of patients with gallbladder carcinoma after radical cholecystectomy (P

BackgroundSpontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare disease with abdominal pain as the main clinical manifestation, but its optimal treatment strategy has not yet been determined. Based on this, this study explored a safe and effective treatment method by analyzing and comparing the safety and efficacy of conservative treatment and endovascular treatment in SISMAD patients.MethodsThe clinical and imaging data and treatment effects of 85 patients with SISMAD who were admitted to the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to December 2020 were retrospectively analyzed. Two groups were treated, the data of patients in conservative treatment group and endovascular treatment group were analyzed, and a safe and effective treatment method for SISMAD was discussed.ResultsThe mean follow-up time was 36.58 ± 25.03 months. The success rate of interventional operation was 86.11% (31/36), and the operation failed because the guide wire could not enter the true lumen in four cases. One case was terminated due to poor physical condition of the patient who could not tolerate surgery. There were no significant differences in gender, body mass index, clinical manifestations, and past history between conservative treatment and endovascular treatment (P > 0.05), but in age, superior mesenteric artery-distal aorta angle, distance from the superior mesenteric artery opening to dissection, dissection length, and true lumen stenosis. There was a statistical difference between the two groups in the rate and Yun classification (P

IntroductionRepeated hepatic arterial delivery of therapeutic agents to the liver by percutaneously implanted port-catheter systems has been widely used to treat unresectable liver cancer. This approach is applied to assess the therapeutic efficacy of repeated low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticle treatments in a rat model of hepatocellular carcinoma.MethodsN1S1 hepatoma bearing rats underwent placement of a percutaneously implanted hepatic artery port-catheter system and were allocated to untreated, control LDL-triolein (LDL-TO) or LDL-DHA nanoparticle infusions groups. Treatments were performed every three days over a nine day study period. MRI was performed at baseline and throughout the study. At the end of the study tissue samples were collected for analyses.Results and DiscussionImplantation of the port catheters was successful in all rats. MRI showed that repeated infusions of LDL-DHA nanoparticles significantly impaired the growth of the rat hepatomas eventually leading to tumor regression. The tumors in the LDL-TO treated group showed delayed growth, while the untreated tumors grew steadily throughout the study. Histopathology and MRI support these findings demonstrating extensive tumor necrosis in LDL-DHA treated groups while the control groups displayed minor necrosis. Molecular and biochemical analyses also revealed that LDL-DHA treated tumors had increased levels of nuclear factor-kappa B and lipid peroxidation and depletion of glutathione peroxidase 4 relative to the control groups. Evidence of both ferroptosis and apoptosis tumor cell death was observed following LDL-DHA treatments. In conclusion repeated transarterial infusions of LDL-DHA nanoparticles provides sustained repression of tumor growth in a rat hepatoma model.

BackgroundWe aimed to explore the risk factors for hemorrhage of esophagogastric varices (EGVs) in patients with hepatitis B cirrhosis and to construct a novel nomogram model based on the spleen volume expansion rate to predict the risk of esophagogastric varices bleeding.MethodsUnivariate and multivariate logistic regression analysis was used to analyze the risk factors for EGVs bleeding. Nomograms were established based on the multivariate analysis results. The predictive accuracy of the nomograms was assessed using the area under the curve (AUC or C-index) of the receiver operating characteristic (ROC) and calibration curves. Decision curve analysis was used to determine the clinical benefit of the nomogram. We created a nomogram of the best predictive models.ResultsA total of 142 patients' hepatitis B cirrhosis with esophagogastric varices were included in this study, of whom 85 (59.9%) had a history of EGVs bleeding and 57 (40.1%) had no EGVs bleeding. The spleen volume expansion rate, serum sodium levels (mmol/L), hemoglobin levels (g/L), and prothrombin time (s) were independent predictors for EGVs bleeding in patients with hepatitis B liver cirrhosis (P

Iron accumulation is an independent risk factor for postmenopausal osteoporosis, but mechanistic studies of this phenomenon are still focusing on molecular and genetic researches in model animal. Osteoporosis with iron accumulation is a distinct endocrine disease with complicated pathogenesis regulated by several proteins. However, the comprehensive proteome-wide analysis of human bone is lacking. Using multiplex quantitative tandem mass tag-based proteomics, we detected 2900 and quantified 1150 proteins from bone of 10 postmenopausal patients undergoing hip replacement. Comparing with non-osteoporosis patients, a total of 75 differentially expressed proteins were identified, comprising 53 downregulated proteins and 22 upregulated proteins. These proteins primarily affect oxidoreductase activity, GTPase activity, GTP binding, and neural nucleus development, were mainly enriched in neural, angiogenesis and energy-related pathways, and formed complex regulatory networks with strong interconnections. We ultimately identified 4 core proteins (GSTP1, LAMP2, COPB1, RAB5B) that were significantly differentially expressed in the bone of osteoporosis patients with iron accumulation, and validated the changed protein level in the serum of the medical examination population. Our systemic analysis uncovers molecular insights for revealing underlying mechanism and clinical therapeutics in osteoporosis with iron accumulation.

Combining the core-shell structure with the optimization of surface composition and structure in the shell is a fantastic strategy to enhance the electrocatalytic performances. Here, we synthesized trimetallic Au@PtxSny core-shell nanoparticles (NPs) with tunable composition and structure of Pt-Sn alloyed shells. Impressively, the Au@PtSn core-shell NPs with hexagonal PtSn alloyed shells exhibited the highest mass activity and specific activity toward ethanol oxidation reaction (EOR) in alkaline electrolyte, which are 13.0 and 12.7 times higher than those of the commercial Pt/C. In addition, the Au@PtSn core-shell NPs displayed the best stability compared to commercial Pt/C, with only 44.8% loss vs. 86.8% loss in mass activity after 1,000 s due to the stronger anti-poisoning ability for reaction intermediates. The theory calculations reveal that the introduction of Au core and alloying Pt with Sn both endow Pt with an appropriate d-band center, and thus effectively boosting the EOR activity.

Ubiquitin modification is a common post-translational protein modification and an important mechanism whereby the body regulates protein levels and functions. As a common enzyme associated with ubiquitin modification, the ubiquitin-editing enzyme A20 may be closely associated with the development of numerous pathological processes through its different structural domains. The aim of this paper is to provide an overview of the following: advances in ubiquitination research, the structure and function of A20, and the relationships between A20 and immune inflammatory response, apoptosis, necroptosis, pyroptosis, and autophagy.

A successful student has been defined as one who not only performs well in academics but is also happy. Hence, how to promote adolescents’ academic success and wellbeing is an important issue with which researchers have been concerned. A few studies have explored the relationship of filial piety to the academic achievement or life satisfaction of Chinese adolescents. However, in view of the close relationship between the two outcomes, the unique effects of filial piety on academic achievement and subjective wellbeing and their underlying mechanisms need to be further clarified. Based on a sample of 677 students in Grade 6 (Mage = 12.24, SD = 0.36) and their parents in Beijing, China, this study examines how adolescents’ reciprocal filial piety (RFP) and authoritarian filial piety (AFP) are related to their academic achievement and subjective wellbeing. It also examines the mediating role of adolescents’ educational expectations in these relationships, and the moderating role of parents’ educational expectations in the relationships of adolescents’ filial piety to educational expectations and of adolescents’ educational expectations to academic achievement and subjective wellbeing. The results indicate that, when the two outcome factors are considered simultaneously, RFP is positively related to academic achievement and subjective wellbeing. In contrast, AFP is negatively related to academic achievement but not significantly related to subjective wellbeing. Moreover, adolescents’ educational expectations play a mediating role in the relationships of both RFP and AFP to academic achievement and subjective wellbeing. In addition, the positive effect of adolescents’ educational expectations on subjective wellbeing is stronger when mothers’ educational expectations are higher, supporting the moderating role of parents’ educational expectations. Our findings provide new insights into and implications for the moderated mediation mechanism underlying the links between filial piety and early adolescent development.

Heat shock proteins (HSPs) are a large class of highly conserved chaperons, which play important roles in response to elevated temperature and other environmental stressors. In the present study, 5 HSP90 genes and 17 HSP70 genes were systematically characterized in spotted seabass (Lateolabrax maculatus). The evolutionary footprint of HSP genes was revealed via the analysis of phylogeny, chromosome location, and gene copy numbers. In addition, the gene structure features and the putative distribution of heat shock elements (HSEs) and hypoxia response elements (HREs) in the promoter regions were analyzed. The protein-protein interaction (PPI) network analyses results indicated the potential transcriptional regulation between the heat shock factor 1 (HSF1) and HSPs and a wide range of interactions among HSPs. Furthermore, quantitative (q)PCR was performed to detect the expression profiles of HSP90 and HSP70 genes in gill, liver, and muscle tissues after heat stress, meanwhile, the expression patterns in gills under alkalinity and hypoxia stresses were determined by analyzing RNA-Seq datasets. Results showed that after heat stress, most of the examined HSP genes were significantly upregulated in a tissue-specific and time-dependent manners, and hsp90aa1.1, hsp90aa1.2, hsp70.1, and hsp70.2 were the most intense responsive genes in all three tissues. In response to alkalinity stress, 11 out of 13 significantly regulated HSP genes exhibited suppressed expression patterns. Alternatively, among the 12 hypoxia-responsive-expressed HSP genes, 7 genes showed induced expressions, while hsp90aa1.2, hsp70.1, and hsp70.2 had more significant upregulated changes after hypoxic challenge. Our findings provide the essential basis for further functional studies of HSP genes in response to abiotic stresses in spotted seabass.

Currently, stretchable hydrogel has attracted great attention in the field of wearable flexible sensors. However, fabricating flexible hydrogel sensor simultaneously with superstretchability, high mechanical strength, remarkable self-healing ability, excellent anti-freezing and sensing features via a facile method remains a huge challenge. Herein, a fully physically linked poly(hydroxyethyl acrylamide)-gelatin-glycerol-lithium chloride (PHEAA-GE-Gl-LiCl) double network organohydrogel is prepared via a simple one-pot heating-cooling-photopolymerization method. The prepared PHEAA-GE-Gl-LiCl organohydrogel exhibits favorable stretchability (970%) and remarkable self-healing property. Meanwhile, due to the presence of glycerol and LiCl, the PHEAA-GE-Gl-LiCl organohydrogel possesses outstanding anti-freezing capability, it can maintain excellent stretchability (608%) and conductivity (0.102 S/m) even at −40°C. In addition, the PHEAA-GE-Gl-LiCl organohydrogel-based strain sensor is capable of repeatedly and stably detecting and monitoring both large-scale human motions and subtle physiological signals in a wide temperature range (from −40°C to 25°C). More importantly, the PHEAA-GE-Gl-LiCl organohydrogel-based sensor displays excellent strain sensitivity (GF = 13.16 at 500% strain), fast response time (300 ms), and outstanding repeatability. Based on these super characteristics, it is envisioned that PHEAA-GE-Gl-LiCl organohydrogel holds promising potentials as wearable strain sensor.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancer types worldwide, with the lowest 5-year survival rate among all kinds of cancers. Histopathology image analysis is considered a gold standard for PDAC detection and diagnosis. However, the manual diagnosis used in current clinical practice is a tedious and time-consuming task and diagnosis concordance can be low. With the development of digital imaging and machine learning, several scholars have proposed PDAC analysis approaches based on feature extraction methods that rely on field knowledge. However, feature-based classification methods are applicable only to a specific problem and lack versatility, so that the deep-learning method is becoming a vital alternative to feature extraction. This paper proposes the first deep convolutional neural network architecture for classifying and segmenting pancreatic histopathological images on a relatively large WSI dataset. Our automatic patch-level approach achieved 95.3% classification accuracy and the WSI-level approach achieved 100%. Additionally, we visualized the classification and segmentation outcomes of histopathological images to determine which areas of an image are more important for PDAC identification. Experimental results demonstrate that our proposed model can effectively diagnose PDAC using histopathological images, which illustrates the potential of this practical application.

Maximum deviation global discrimination index (MDGDI) is a new item selection method for cognitive diagnostic computerized adaptive testing that allows for attribute coverage balance. We developed the maximum limitation global discrimination index (MLGDI) from MDGDI, which allows for both attribute coverage balance and item exposure control. MLGDI can realize the attribute coverage balance and exposure control of the item. Our simulation study aimed to evaluate the performance of our new method against maximum global discrimination index (GDI), modified maximum GDI (MMGDI), standardized weighted deviation GDI (SWDGDI), and constraint progressive with SWDGDI (CP_SWDGDI). The results indicated that (1a) under the condition of realizing the attribute coverage balance, MDGDI had the highest attribute classification accuracy; (1b) when the selection strategy accommodated the practical constraints of the attribute coverage balance and item exposure control, MLGDI had the highest attribute classification accuracy; (2) adding the item exposure control mechanism to the item selection method reduces the classification accuracy of the attributes of the item selection method; and (3) compared with GDI, MMGDI, SWDGDI, CP_SWDGDI, and MDGDI, MLGDI can better achieve the attribute-coverage requirement, control item exposure rate, and attribute correct classification rate.

Pt-based multimetallic nanorings with a hollow structure are attractive as advanced catalysts due to their fantastic structure feature. However, the general method for the synthesis of such unique nanostructures is still lack. Here we report the synthesis of Pd@PtM (M = Rh, Ni, Pd, Cu) multimetallic nanorings by selective epitaxial growth of Pt alloyed shells on the periphery of Pd nanoplates in combination with oxidative etching of partial Pd in the interior. In situ generation of CO and benzoic acid arising from interfacial catalytic reactions between Pd nanoplates and benzaldehyde are critical to achieve high-quality Pt-based multimetallic nanorings. Specifically, the in-situ generated CO promotes the formation of Pt alloyed shells and their epitaxial growth on Pd nanoplates. In addition, the as-formed benzoic acid and residual oxygen are responsible for selective oxidative etching of partial Pd in the interior. When evaluated as electrocatalysts, the Pd@PtRh nanorings exhibit remarkably enhanced activity and stability for ethanol oxidation reaction (EOR) compared to the Pd@PtRh nanoplates and commercial Pt/C due to their hollow nanostructures.

Background: Pancreatic cancer (PC) is a lethal malignancy with an extremely unfavorable 5-year survival rate and a high mortality rate. Glutathione S-transferase mu-3 (GSTM3) has been shown to exert different functions in the progression and development of various cancers, except for PC. This study aimed to explore the role of GSTM3 in the malignant behavior and metabolic aspects of PC, its clinical significance, and its possible molecular mechanism in pancreatic cancer.Methods: Tumor microarrays of pancreatic ductal adenocarcinoma (PDAC) were used to evaluate the clinicopathological variables and GSTM3 expression by immunohistochemical staining. Kaplan–Meier survival and Cox regression analyses were further performed to assess the prognosis. The effect of GSTM3 on PC aggressiveness was detected using overexpressing and silencing transfection methods. Western blot, RT-qPCR, CCK-8, and cell cycle assay were applied to evaluate the expression level and proliferation. A xenograft animal model was assessed. Reactive oxygen species (ROS) were measured using the laser confocal scanner and glycolysis was detected using an Agilent Seahorse kit. RNA sequencing was used to assess the underlying mechanism and the signaling pathway involved.Results: GSTM3 was relatively poorly expressed in PDAC tissues compared to para-tumoral tissues and a high level of GSTM3 indicated good overall survival. Functionally, overexpression of GSTM3 could significantly inhibit cell proliferation by delaying the G0/G1 transition, whereas the opposite results were found in the GSTM3 downregulation group. In addition, xenograft animal models further confirmed the effect on proliferation. Moreover, silencing of GSTM3 induced ROS accumulation and promoted glycolysis in PC, indicating its tumor suppressive effect, and vice versa when GSTM3 was upregulated. Finally, RNA sequencing results demonstrated that GSTM3 facilitates anti-tumorigenicity partly via the JAK-STAT signaling pathway in PC.Conclusion: GSTM3 inhibited tumor progression and altered the metabolic pattern in PC. This may be a potential predictive biomarker in PC and a prospective therapeutic target.

Extracellular vesicles (EVs) from adipose tissue-derived stem cells have been reported to attenuate lipopolysaccharide (LPS) induced inflammation and sepsis while the specific mechanism is unclear. This study explored the underlying molecular mechanisms of EVs from adipose tissue-derived stem cells in reducing inflammation. LPS- induced macrophage models and mice model were established to mimic inflammation in vitro and in vivo. EVs were extracted from adipose tissue-derived stem cells and identified. It was found that proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, substantially decreased after EVs were applied to LPS-stimulated macrophages and mice, and thus, LPS induced M1 polarization was inhibited and sepsis was strongly alleviated. In the LPS induced macrophages, the expression of Notch signaling molecules and the activation of the NF-κB pathway were substantially decreased after the administration of EVs. Then, RBP-J−/− mice and macrophages were used. It was found that the miR-148a-3p level was significantly lower in the RBP-J−/− macrophages than in the wildtype macrophages. In the LPS induced macrophages, the increasing of miR-148a-3p was milder in the RBP-J−/− macrophages than in the wild type macrophages. Then, miR-148a-3p was overexpressed in macrophages and mice, and we found that the expression of proinflammatory cytokines was increased both in vivo and in vitro. The protective effect of EVs in LPS induced sepsis was diminished by the overexpression of miR-148a-3p. In conclusion, we proved that EVs could attenuate inflammation and further protect organ function by regulating the Notch-miR148a-3p signaling axis and then decreasing macrophage polarization to M1.

Large-scale patterns of species richness is an important issue in biogeography and ecology. The Qinghai-Tibetan Plateau (QTP) is a biodiversity hotspot in the world, which has an important status in the zoogeographical realms. Here, we analyzed the diversity patterns of Hemipteran insects in the QTP, and tested whether the patterns can be jointly explained by modern environmental as well as historical factors. A comprehensive geographic distribution dataset consisting of 1,166 Hemipteran species, which belong to 510 genera and 53 families, was compiled and used in our analyses. Patterns of richness were mapped into a grid-based map with a spatial resolution of 0.5° × 0.5°. An unbalanced diversity pattern of the Hemipteran insects in the QTP was presented, with more species in the eastern and southern parts of the plateau, while few species in the northern and main surface of the plateau. The northwestern Sichuan, the southern Gansu, the southeastern Tibet, the northwestern Yunnan and the eastern Qinghai were identified as diversity hotspots of species richness. Further analyses based on General linear models and Random Forest indicated that the diversity patterns of Hemipteran insects were influenced by both contemporary environmental factors and historical factors (e.g., habitat heterogeneity, climate stability, energy availability). Specifically, the species richness patterns of all Hemipteran insects in the QTP have been mainly affected by elevation range, temperature annual range, min temperature of coldest month, mean temperature of coldest quarter and the temperature change since the Last Glacial Maximum. In contrast, the water-related variables have relatively small effects on species richness. In addition, although habitat heterogeneity was indicated the most important factor for different suborders of Hemiptera, the climate stability was another dominate factor for Heteroptera and Auchenorrhyncha, while Sternorrhyncha was more affected by historical climate change.

The water-soluble nido-carborane was prepared by alkali treatment of o-carborane. A polymer PInd containing a polyindole structure was synthesized and employed to label the modified o-carborane. Subsequently, four polymeric nanomaterials were synthesized with the objective of encapsulating them in order to enhance its bioavailability. The experimental results showed that the fluorescent complex encapsulated by the pH-sensitive polymer A had the best UV absorption and fluorescence intensity, and thus A-PInd-C was chosen for subsequent experiments. The Transmission electron microscopy images revealed that the compounds exhibited a rounded internal morphology, with the layers exhibiting a tightly stacked arrangement. The AFM imaging revealed that the surface of the sample exhibited a relatively uniform and smooth appearance. In vitro release experiments conducted under acidic conditions demonstrated that A-PInd-C was released in a predominantly linear manner, with a maximum release rate of 80% observed within 48 h. Cellular imaging experiments showed that the compound could enter HeLa and HCT-116 cells and was mainly distributed around the nucleus, especially in the acidic environment. The results of the cell proliferation toxicity experiments demonstrated that A-PInd-C exhibited inhibitory effects on HeLa, PC-3 and L02 cells. Among these, the inhibitory effect on PC-3 cells was the most pronounced, reaching up to 70%. In conclusion, this paper solves the problem of poor bioavailability of carborane by improving the boron containing compounds and also makes the system have potential for Boron neutron capture therapy. [ABSTRACT FROM AUTHOR]

ObjectiveThis research aimed to investigate the association between the blood urea nitrogen-to-creatinine (BUN/Cr) ratio and the rate of in-hospital mortality in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF), who are also receiving care in intensive care unit (ICU).MethodsA retrospective study was conducted using the MIMIC-IV database. We collected data on BUN/Cr levels at admission for patients with AIS and concurrent AF. To assess the association between BUN/Cr and in-hospital mortality rate, statistical analysis was conducted employing multivariable logistic regression models and restricted cubic spline models. These models were utilized to investigate the potential relationship and provide insights into the impact of BUN/Cr on the likelihood of in-hospital mortality. Interaction and subgroup analyses were performed to evaluate the consistency of the correlation.ResultsThere were a total of 856 patients (age ≥ 18 years) with a median age of 78.0 years, of which 466 (54.4%) were female. Out of 856 patients, 182 (21.26%) died in the hospital. Upon controlling for confounding factors, the multivariable logistic regression analysis elucidated that patients falling within the third trisection (Q3 > 22.41 mg/dL) exhibited a noticeably increased susceptibility to in-hospital mortality when contrasted with their counterparts positioned in the second trisection (Q2: 17.2–22.41 mg/dL) (OR = 2.02, 95% CI: 1.26–3.26, p = 0.004). A non-linear J-shaped relationship was observed between BUN/Cr at ICU admission and in-hospital mortality rate (p = 0.027), with a turning point at 19.63 mg/dL. In the threshold analysis, there was a 4% rise in in-hospital mortality for each 1 mg/dL increase in BUN/Cr (OR: 1.04, 95% CI: 1.01–1.06, p = 0.012).ConclusionIn patients with AIS complicated by AF, BUN/Cr at admission shows a J-shaped correlation with in-hospital mortality rate. When BUN/Cr exceeds 19.63 mg/dL, the in-hospital mortality rate increases.

BackgroundThis study aimed to construct a clinical prediction model and nomogram to differentiate invasive from non-invasive pulmonary adenocarcinoma in solitary pulmonary nodules (SPNs).MethodWe analyzed computed tomography and clinical features as well as preoperative biomarkers in 1,106 patients with SPN who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University between January 2020 and December 2021. Clinical parameters and imaging characteristics were analyzed using univariate and multivariate logistic regression analyses. Predictive models and nomograms were developed and their recognition abilities were evaluated using receiver operating characteristic (ROC) curves. The clinical utility of the nomogram was evaluated using decision curve analysis (DCA).ResultThe final regression analysis selected age, carcinoembryonic antigen, bronchus sign, lobulation, pleural adhesion, maximum diameter, and the consolidation-to-tumor ratio as associated factors. The areas under the ROC curves were 0.844 (95% confidence interval [CI], 0.817–0.871) and 0.812 (95% CI, 0.766–0.857) for patients in the training and validation cohorts, respectively. The predictive model calibration curve revealed good calibration for both cohorts. The DCA results confirmed that the clinical prediction model was useful in clinical practice. Bias-corrected C-indices for the training and validation cohorts were 0.844 and 0.814, respectively.ConclusionOur predictive model and nomogram might be useful for guiding clinical decisions regarding personalized surgical intervention and treatment options.

BackgroundStroke, prevalent globally, particularly impacts low- and middle-income countries. Decreased lung function is one of the risk factors for stroke, and there is a lack of sufficient research on the association between the two, especially based on evidence from representative large samples. We aimed to explore the association between lung function and stroke incidence.MethodsWe collected data from 13,371 participants from the 2007–2012 U.S. national cross-sectional study and 11,192 participants from the Chinese national cohort study during the 2011–2018 follow-up period. Multivariate logistic regression and Cox proportional hazards regression were used to assess cross-sectional and longitudinal associations of peak expiratory flow with stroke risks. Additionally, we used publicly available GWAS data from a European population to conduct Mendelian randomization analysis, further exploring the potential causal relationship.ResultsThe results of the cross-sectional study suggest that a decline in peak expiratory flow may be associated with an increased risk of stroke. The cohort study revealed that, compared to the first tertile group, the risk of stroke incidence in the second and third tertile groups of PEF decreased by 19% (hazard ratio (HR) = 0.810, 95%CI = 0.684–0.960) and 21.4% (HR = 0.786, 95%CI = 0.647–0.956), respectively. Mendelian randomization analysis clarified that higher PEF levels are significantly associated with a reduced risk of stroke (OR = 0.852, 95%CI = 0.727–0.997).ConclusionDecreased lung function is a risk factor for stroke. As a simple and accurate indicator of lung function, PEF can be used to monitor lung function in community populations and patients for primary stroke prevention.

Porcine epidemic diarrhea virus (PEDV) is a single-stranded RNA virus with a capsid membrane that causes acute infectious gastrointestinal disease characterized by vomiting, diarrhea, and dehydration in swine. Piglets are more susceptible to PEDV than adults, with an infection rate reaching 90% and a fatality rate as high as 100%. Moreover, PEDV has a rapid transmission rate and broad transmission range. Consequently, PEDV has caused considerable economic losses and negatively impacted the sustainability of the pig industry. The surface spike (S) glycoprotein is the largest structural protein in PEDV virions and is closely associated with host cell fusion and virus invasion. As such, the S protein is an important target for vaccine development. In this article, we review the genetic variation, immunity, apoptosis-induction function, virulence, vaccine potential, and other aspects of the PEDV S protein. This review provides a theoretical foundation for preventing and controlling PEDV infection and serves as a valuable resource for further research and development of PEDV vaccines.

IntroductionNucleic acid-sensing (NAS) pathways could induce innate and adaptive immune responses. However, rare evidence exhibited how the core genes of the NAS pathways affected the immune response and prognosis of small cell lung cancer (SCLC) patients.MethodsWe conducted a comprehensive bioinformatic analysis based on the RNA profiles of 114 SCLC patients, including 79 from cBioPortal, 21 from GSE30219, and 14 from our sequencing data. The multiplex immunohistochemistry (mIHC) was used to characterize the role of NAS related genes in the tumor microenvironment (TME) of SCLC.ResultsA prognostic model (7NAS risk model) was constructed based on 7 NAS-related genes which was demonstrated as an independent prognostic index. The low-risk group was identified to have a better prognosis and an immune-activated microenvironment in both the public datasets and our dataset. Intriguingly, mIHC data showed that CD45+ immune cells, CD8+ T lymphocytes, and CD68+ macrophages were prevalently enriched in low-risk SCLC patients and positively correlated with IRF1 expression. Additionally, Patients in the low-risk group might have superior responses to chemotherapy and immunotherapy.ConclusionConclusively, this study created a new risk model based on genes associated with NAS pathways which could predict the prognosis and response of treatment in patients with SCLC.

In educational measurement, exploring the method of generating multiple high-quality parallel tests has become a research hotspot. One purpose of this research is to construct parallel forms item by item according to a seed test, using two proposed item selection heuristic methods [minimum parameters–information–distance method (MPID) and minimum information–parameters–distance method (MIPD)]. Moreover, previous research addressing test assembly issues has been limited mainly to situations in which the information curve of the item pool or seed test has a normal or skewed distribution. However, in practice, the distributions of information curves for tests are diverse. These include multimodal distributions, the most common type of which is the bimodal distribution. Therefore, another main aim of this article is to extend the information curves of unimodal distributions to bimodal distributions. Thus, this study adopts simulation research to compare the results of two item, response, theory (IRT)-based item matching methods (MPID and MIPD) using different information curve distributions for item pools or seed tests. The results show that the MPID and MIPD methods yield rather good performance in terms of both two statistical targets when the information curve has a unimodal distribution, and two new methods yield better performance than two existing methods in terms of test information functions target when the information curve has a bimodal distribution. [ABSTRACT FROM AUTHOR]

Development of simple and reliable sensor for detecting vitamin content is of great significance for guiding human nutrition metabolism, overseeing the quality of food or drugs, and advancing the treatment of related diseases. In this work, a simple electrochemical sensor was conveniently fabricated by modification a carbon electrode with vertically-ordered mesoporous silica film (VMSF), enabling highly sensitive electrochemical detection of vitamin B2 (VB2) based on the dual enrichment of the analyte by the supporting electrode and nanochannels. The widely used glassy carbon electrode (GCE), was preactivated using simple electrochemical polarization, The resulting preactivated GCE (p-GCE) exhibited improved potential resolution ability and enhanced peak current of VB2. Stable modification of VMSF on p-GCE (VMSF/p-GCE) was achieved without introducing another binding layer. The dual enrichment effect of the supporting p-GCE and nanochannels facilitated sensitive detection of VB2, with a linear concentration ranged from 20 nM to 7 μM and from 7 μM to 20 μM. The limit of detection (LOD), determined based on a signal-to-noise ratio of three (S/N = 3), was found to be 11 nM. The modification of ultra-small nanochannels of VMSF endowed VMSF/p-GCE with excellent anti-interference and anti-fouling performance, along with high stability. The constructed sensor demonstrated the capability to achieve direct electrochemical detection of VB2 in turbid samples including milk and leachate of compound vitamin B tablet without the need for complex sample pretreatment. The fabricated electrochemical can be easily regenerated and has high reusability. The advantages of simple preparation, high detection performance, and good regeneration endow the constructed electrochemical sensor with great potential for direct detection of small molecule in complex samples.

ObjectiveThis study aimed to evaluate the SpO2 (transcutaneous oxygen saturation) -mortality link in elderly T2DM (diabetes mellitus type 2) patients with cerebral infarction and identify their optimal SpO2 range.MethodsIn this investigation, we employed a comprehensive approach. Initially, we screened the MIMIC-IV database, identifying elderly T2DM patients with cerebral infarction, utilizing specific ICD-9 and ICD-10 codes. We then harnessed the power of restricted cubic splines to craft a visual representation of the correlation between SpO2 and 1-year mortality. To enhance our analysis, we harnessed Cox multivariate regression, allowing us to compute adjusted hazard ratios (HR) accompanied by 95% confidence intervals (CIs). Additionally, we crafted Cumulative Mortality Curve analyses, augmenting our study by engaging in rigorous subgroup analyses, stratifying our observations based on pertinent covariates.ResultsIn this study, 448 elderly T2DM patients with cerebral infarction were included. Within 1-year post-discharge, 161 patients (35.94%) succumbed. Employing Restricted Cubic Spline analysis, a statistically significant U-shaped non-linear relationship between admission ICU SpO2 levels and 1-year mortality was observed (P-value < 0.05). Further analysis indicated that both low and high SpO2 levels increased the mortality risk. Cox multivariate regression analysis, adjusting for potential confounding factors, confirmed the association of low (≤94.5%) and high SpO2 levels (96.5–98.5%) with elevated 1-year mortality risk, particularly notably high SpO2 levels (>98.5%) [HR = 2.06, 95% CI: 1.29–3.29, P-value = 0.002]. The cumulative mortality curves revealed the following SpO2 subgroups from high to low cumulative mortality at the 365th day: normal levels (94.5% < SpO2 ≤ 96.5%), low levels (SpO2 ≤ 94.5%), high levels (96.5% < SpO2 ≤ 98.5%), and notably high levels (>98.5%). Subgroup analysis demonstrated no significant interaction between SpO2 and grouping variables, including Sex, Age, Congestive heart failure, Temperature, and ICU length of stay (LOS-ICU; P-values for interaction were >0.05).ConclusionsStriking an optimal balance is paramount, as fixating solely on lower SpO2 limits or neglecting high SpO2 levels may contribute to increased mortality rates. To mitigate mortality risk in elderly T2DM patients with cerebral infarction, we recommend maintaining SpO2 levels within the range of 94.5–96.5%.

In the context of the rising prevalence of renewable energy, the need for precise and synchronized measurements in urban distribution networks has become increasingly critical. Conventional synchronization techniques, which predominantly depend on Global Navigation Satellite System (GNSS) timing signals, are often plagued by significant sampling time errors. Addressing this challenge, this study introduces an innovative automatic synchronization measurement method employing proportional-integral (PI) control. This method is composed of three integral components: the monitoring of local clock phases via pulses per second (PPS) signals, modulation of the clock phase through a PI controller, and the estimation of grid phasors from the synchronized sampled data. The test results of this method on a hardware platform demonstrate its capability to significantly reduce the sampling error from 2 × 10−3 V to an impressive 1 × 10−5 V, while also meeting the requirements of the synchronized phasor measurement standards outlined in C37.118.1. These advancements underscore the significant potential of PI-controlled simultaneous sampling in enhancing the operational efficiency and reliability of urban distribution networks, particularly in environments with a high integration of renewable energy sources.

BackgroundEsophagectomy is the gold standard treatment for resectable esophageal cancer; however, there is insufficient evidence to indicate potential advantages over standard minimally invasive esophagectomy (MIE) in treating thoracic esophageal cancer. Robot-assisted minimally invasive esophagectomy (RAMIE) bridges the gap between open and minimally invasive surgery. In this single-center retrospective review, we compare the clinical outcomes of EC patients treated with MIE and RAMIE.MethodWe retrospectively reviewed the clinical data of patients with esophageal cancer who underwent surgery at Qilu Hospital between August 2020 and August 2022, including 159 patients who underwent MIE and 35 patients who received RAMIE. The intraoperative, postoperative, and preoperative patient characteristics in both groups were evaluated.ResultsExcept for height, the MIE and RAMIE groups showed no significant differences in preoperative features (P>0.05). Further, there were no significant differences in intraoperative indices, including TNM stage of the resected tumor, tumor tissue type, or ASA score, between the two groups. However, statistically significant differences were found in some factors; the RAMIE group had a shorter operative time, less intraoperative bleeding, and more lymph nodes removed compared to the MIE group. Patients in the RAMIE group reported less discomfort and greater chest drainage on the first postoperative day than patients in the MIE group; however, there were no differences in other features between the two datasets.ConclusionBy comparing the clinical characteristics and outcomes of RAMIE with MIE, this study verified the feasibility and safety of RAMIE for esophageal cancer. Overall, RAMIE resulted in more complete lymph node clearance, shorter operating time, reduced surgical hemorrhage, reduced postoperative discomfort, and chest drainage alleviation in patients. To investigate the function of RAMIE in esophageal cancer, we propose undertaking a future clinical trial with long-term follow-up to analyze tumor clearance, recurrence, and survival after RAMIE.

Several of our internal organs, including heart, lungs, stomach, and spleen, develop asymmetrically along the left-right (LR) body axis. Errors in establishing LR asymmetry, or laterality, of internal organs during early embryonic development can result in birth defects. In several vertebrates—including humans, mice, frogs, and fish—cilia play a central role in establishing organ laterality. Motile cilia in a transient embryonic structure called the “left-right organizer” (LRO) generate a directional fluid flow that has been proposed to be detected by mechanosensory cilia to trigger asymmetric signaling pathways that orient the LR axis. However, the mechanisms that control the form and function of the ciliated LRO remain poorly understood. In the zebrafish embryo, precursor cells called dorsal forerunner cells (DFCs) develop into a transient ciliated structure called Kupffer’s vesicle (KV) that functions as the LRO. DFCs can be visualized and tracked in the embryo, thereby providing an opportunity to investigate mechanisms that control LRO development. Previous work revealed that proliferation of DFCs via mitosis is a critical step for developing a functional KV. Here, we conducted a targeted pharmacological screen to identify mechanisms that control DFC proliferation. Small molecule inhibitors of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) were found to reduce DFC mitosis. The SERCA pump is involved in regulating intracellular calcium ion (Ca2+) concentration. To visualize Ca2+ in living embryos, we generated transgenic zebrafish using the fluorescent Ca2+ biosensor GCaMP6f. Live imaging identified dynamic cytoplasmic Ca2+ transients (“flux”) that occur unambiguously in DFCs. In addition, we report Ca2+ flux events that occur in the nucleus of DFCs. Nuclear Ca2+ flux occurred in DFCs that were about to undergo mitosis. We find that SERCA inhibitor treatments during DFC proliferation stages alters Ca2+ dynamics, reduces the number of ciliated cells in KV, and alters embryo laterality. Mechanistically, SERCA inhibitor treatments eliminated both cytoplasmic and nuclear Ca2+ flux events, and reduced progression of DFCs through the S/G2 phases of the cell cycle. These results identify SERCA-mediated Ca2+ signaling as a mitotic regulator of the precursor cells that give rise to the ciliated LRO.

BackgroundIn critically ill patients, transcutaneous oxygen saturation (SpO2) upon admission is typically associated with in-hospital mortality. Nevertheless, the available information for patients with non-traumatic subarachnoid hemorrhage (SAH) is limited. In our study, our objective was to assess the correlation between SpO2 levels and mortality among patients diagnosed with severe SAH.MethodsIn this study, we extracted data from the Medical Information Marketplace in Intensive Care (MIMIC-IV) database, which comprises information on critically ill patients. By employing matching ICD-9 and ICD-10 codes, we identified 3,328 patients diagnosed with SAH. Every individual who was admitted to the intensive care unit (ICU) had their SpO2 data and various covariates, including age, sex, diagnosis, and duration of stay, recorded upon admission. Subsequently, the patients were categorized into three distinct groups according to their SpO2 levels: low (≤95%), moderate (95–98%), and high (≥98%). To investigate the association between percutaneous oxygen saturation and mortality in patients with severe SAH, logistic regression, and cubic spline models were utilized. The main outcomes of interest were 28- and 90-day mortality rates. Additionally, subgroup analyses were conducted to evaluate these correlations and assess the consistency of interactions.ResultsA cohort of 864 patients diagnosed with non-traumatic SAH was included in this study. The correlation between SpO2 and mortality displayed a U-shaped curve when utilizing a finite cubic spline function (non-linearity

BackgroundAt present, how to identify the benign or malignant nature of small (≤ 2 cm) solitary pulmonary nodules (SPN) are an urgent clinical challenge. This retrospective study aimed to develop a clinical prediction model combining clinical and radiological characteristics for assessing the probability of malignancy in SPNs measuring ≤ 2 cm.MethodIn this study, we included patients with SPNs measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to December 2021. Clinical features, preoperative biomarker results, and computed tomography characteristics were collected. The enrolled patients were randomized at a ratio of 7:3 into a training cohort of 775 and a validation cohort of 331. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. The receiver operating characteristic (ROC) curve was used to evaluate the identification ability of the model. The calibration power was evaluated using the Hosmer–Lemeshow test and calibration curve. The clinical utility of the nomogram was also assessed by decision curve analysis (DCA).ResultA total of 1,106 patients were included in this study. Among them, the malignancy rate of SPNs was 85.08% (941/1,106). We finally identified the following six independent risk factors by logistic regression: age, carcinoembryonic antigen, nodule shape, calcification, maximum diameter, and consolidation-to-tumor ratio. The area under the ROC curve (AUC) for the training cohort was 0.764 (95% confidence interval [CI]: 0.714–0.814), and the AUC for the validation cohort was 0.729 (95% CI: 0.647–0.811), indicating that the prediction accuracy of nomogram was relatively good. The calibration curve of the predictive model also demonstrated a good calibration in both cohorts. DCA proved that the clinical prediction model was useful in clinical practice.ConclusionWe developed and validated a predictive model and nomogram for estimating the probability of malignancy in SPNs measuring ≤ 2 cm. With the application of predictive models, thoracic surgeons can make more rational clinical decisions while avoiding overtreatment and wasting medical resources.

Serratia marcescens is a gram-negative bacterium that is able to produce many secondary metabolites, such as the prominent red pigment prodigiosin (PG). In this work, a ptrA-disrupted mutant strain with reduced PG production was selected from Tn5 transposon mutants. RT–qPCR results indicated that ptrA promoted elevated transcription of the pig gene cluster in S. marcescens FZSF02. Furthermore, we found that ptrA also controls several other important biological functions of S. marcescens, including swimming and swarming motilities, biofilm formation, hemolytic activity, and stress tolerance. In conclusion, this study demonstrates that ptrA is a PG synthesis-promoting factor in S. marcescens and provides a brief understanding of the regulatory mechanism of ptrA in S. marcescens cell motility and hemolytic activity.

ObjectiveThe study aimed to evaluate the relationship between serum sodium and mortality in critically ill patients with non-traumatic subarachnoid hemorrhage.MethodsThis is a retrospective investigation of critically ill non-traumatic patients with subarachnoid hemorrhage (SAH) utilizing the MIMIC-IV database. We collected the serum sodium levels at admission and determined the all-cause death rates for the ICU and hospital. We employed a multivariate Cox proportional hazard regression model and Kaplan–Meier survival curve analysis to ascertain the relationship between serum sodium and all-cause mortality. In order to evaluate the consistency of correlations, interaction and subgroup analyses were also conducted.ResultsA total of 864 patients with non-traumatic SAH were included in this study. All-cause mortality in the ICU and hospital was 32.6% (282/864) and 19.2% (166/864), respectively. Sodium levels at ICU admission showed a statistically significant J-shaped non-linear relationship with ICU and hospital mortality (non-linear P-value < 0.05, total P-value < 0.001) with an inflection point of ~141 mmol/L, suggesting that mortality was higher than normal serum sodium levels in hypernatremic patients. Multivariate analysis after adjusting for potential confounders showed that high serum sodium levels (≥145 mmol/L) were associated with an increased risk of all-cause mortality in the ICU and hospital compared with normal serum sodium levels (135–145 mmol/L), [hazard ratio (HR) = 1.47, 95% CI: 1.07–2.01, P = 0.017] and (HR = 2.26, 95% CI:1.54–3.32, P < 0.001). Similarly, Kaplan–Meier (K-M) survival curves showed lower survival in patients with high serum sodium levels. Stratified analysis further showed that the association between higher serum sodium levels and hospital all-cause mortality was stronger in patients aged < 60 years with a hospital stay of

IntroductionSurgeons may experience physical and mental health problems because of their jobs, which may lead to chronic muscle damage, burnout, or even withdrawal. However, these are often ignored in camera-holder assistants during laparoscopic surgery. We aimed to analyze the differences between operating surgeons and camera-holder assistants.MethodsFrom January 1, 2022, to December 31, 2022, a cross-sectional survey was conducted to evaluate the muscle pain, fatigue, verbal scolding, and task load for operating surgeons and camera-holder assistants. The Nordic Musculoskeletal Questionnaire, the Space Administration Task Load Index, and the Surgical Task Load Index (SURG-TLX) were combined in the questionnaire.Results2,184 operations were performed by a total of 94 operating surgeons and 220 camera assistants. 81% of operating surgeons and 78% of camera-holder assistants reported muscle pain/discomfort during the procedure. The most affected anatomic region was the shoulders for operating surgeons, and the lower back for camera-holder assistants. Intraoperative fatigue was reported by 41.7% of operating surgeons and 51.7% of camera-holder assistants. 55.2% of camera-holder assistants reported verbal scolding from the operating surgeons, primarily attributed to lapses in laparoscope movement coordination. The SURG-TLX results showed that the distributions of mental, physical, and situational stress for operating surgeons and camera-holder assistants were comparable.ConclusionLike operating surgeons, camera-holder assistants also face similar physical and mental health impairments while performing laparoscopic surgery. Improvements to the working conditions of the camera-holder assistant should not be overlooked.

The promise of electrochemically reducing excess anthropogenic carbon dioxide into useful chemicals and fuels has gained significant interest. Recently, indium–copper (In–Cu) alloys have been recognized as prospective catalysts for the carbon dioxide reduction reaction (CO2RR), although they chiefly yield carbon monoxide. Generating further reduced C1 species such as methane remains elusive due to a limited understanding of how In–Cu alloying impacts electrocatalysis. In this work, we investigated the effect of alloying In with Cu for CO2RR to form methane through first-principles simulations. Compared with pure copper, In–Cu alloys suppress the hydrogen evolution reaction while demonstrating superior initial CO2RR selectivity. Among the alloys studied, In7Cu10 exhibited the most promising catalytic potential, with a limiting potential of −0.54 V versus the reversible hydrogen electrode. Analyses of adsorbed geometries and electronic structures suggest that this decreased overpotential arises primarily from electronic perturbations around copper and indium ions and carbon–oxygen bond stability. This study outlines a rational strategy to modulate metal alloy compositions and design synergistic CO2RR catalysts possessing appreciable activity and selectivity.

BackgroundAir pollution may impair male fertility, but it remains controversial whether air pollution affects semen quality until now.ObjectivesWe undertake a meta-analysis to explore potential impacts of six pollutants exposure during the entire window (0–90 days prior to ejaculation) and critical windows (0–9, 10–14, and 70–90 days prior to ejaculation) on semen quality.MethodsSeven databases were retrieved for original studies on the effects of six pollutants exposure for 90 days prior to ejaculation on semen quality. The search process does not limit the language and search date. We only included original studies that reported regression coefficients (β) with 95% confidence intervals (CIs). The β and 95% CIs were pooled using the DerSimonian-Laird random effect models.ResultsPM2.5 exposure was related with decreased total sperm number (10–14 lag days) and total motility (10–14, 70–90, and 0–90 lag days). PM10 exposure was related with reduced total sperm number (70–90 and 0–90 lag days) and total motility (0–90 lag days). NO2 exposure was related with reduced total sperm number (70–90 and 0–90 lag days). SO2 exposure was related with declined total motility (0–9, 10–14, 0–90 lag days) and total sperm number (0–90 lag days).ConclusionAir pollution affects semen quality making it necessary to limit exposure to air pollution for Chinese men. When implementing protective measures, it is necessary to consider the key period of sperm development.

The process of suspension polymerization was utilized to create acrylate resin microspheres with mesh numbers of 140–200 μm and particle sizes of 100 μm for implementation in mesh coating technology. The copolymer of methyl methacrylate (MMA) and methyl acrylate (MA) served as the primary polymer, with dibenzoyl peroxide (DBPO) functioning as the initiator, and a mixture of calcium carbonate and deionized water served as the dispersion medium. The surface morphology of the synthesized microspheres was analyzed through Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) to confirm successful synthesis. The optimal reaction conditions for the synthesis of these microspheres were determined to be a dispersant dosage of 30 g of calcium carbonate with a monomer ratio of 4:1, a reaction time of 1 h, an initiator dosage of 1.2 g of BPO, and a reaction temperature of approximately 75–80 C, resulting in microspheres with a regular spherical shape and smooth surface.