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Abstract This study developed and validated a deep learning network using baseline magnetic resonance imaging (MRI) to predict Ki-67 status in meningioma patients. A total of 1239 patients were retrospectively recruited from three hospitals between January 2010 and December 2023, forming training, internal validation, and two external validation cohorts. A representation learning framework was utilized for modeling, and performance was assessed against existing methods. Furthermore, Kaplan–Meier survival analysis was conducted to investigate whether the model could be used for tumor growth prediction. The model achieved superior results, with areas under the curve (AUCs) of 0.797 for internal testing and 0.808 for generalization, alongside 0.756 and 0.727 for 3- and 5-year tumor growth predictions, respectively. The prediction was significantly associated with the growth of asymptomatic small meningiomas. Overall, the model provides an effective tool for early prediction of Ki-67 and tumor volume growth, aiding in individualized patient management.

Summary: Background: Preoperative prediction of visual outcomes following pituitary adenoma surgery is challenging yet crucial for clinical decision-making. We aimed to develop models using radiomics from multiparametric MRI to predict postoperative visual outcomes. Methods: A cohort of 152 patients with pituitary adenoma was retrospectively enrolled and divided into recovery and non-recovery groups based on visual examinations performed six months after surgery. Radiomic features of the optic chiasm were extracted from preoperative T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced T1-weighted imaging (T1CE). Predictive models were constructed using the least absolute shrinkage and selection operator wrapped with a support vector machine through five-fold cross-validation in the development cohort and evaluated in an independent test cohort. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity. Results: Four models were established based on radiomic features selected from individual or combined sequences. The AUC values of the models based on T1WI, T2WI and T1CE were 0.784, 0.724, 0.822 in the development cohort, and 0.767, 0.763, 0.794 in the independent test cohort. The multiparametric model demonstrated superior performance among the four models, with AUC of 0.851, accuracy of 0.832. sensitivity of 0.700, specificity of 0.910 in the development cohort, and AUC of 0.847, accuracy of 0.800, sensitivity of 0.882 and specificity of 0.750 in the independent test cohort. Conclusion: The multiparametric model utilizing radiomics of optic chiasm outperformed single-sequence models in predicting postoperative visual recovery in patients with pituitary adenoma, serving as a novel approach for enhancing personalized treatment strategies.

Abstract Background The association between ABO blood types and outcome of aneurysm subarachnoid hemorrhage (aSAH) has not reached a conclusion. This study was performed to testify the difference of outcome between ABO blood types. Methods 663 aSAH patients hospitalized in the West China hospital were enrolled. The association between ABO blood types and outcomes including mortality and delayed cerebral ischemia (DCI) was verified by the univariate and multivariate logistic regression. Glasgow Outcome Score (GOS) at discharge, length of ICU stay, length of hospital stay were also compared between different ABO blood types. Results 663 aSAH patients were divided into four groups according to their ABO blood types: AB type (46, 6.9%), A type (211, 31.8%), B type (169, 25.4%),O type (237, 35.7%). The GCS, WFNS, Hunt Hess, modified Fisher, aneurysm location and incidence of intraventricular hemorrhage did not show different distribution among ABO blood types. Among four coagulation indexes, only the activated partial thromboplastin time (APTT) showed different distribution among ABO blood types (p

Abstract To address the fatigue damage issues in continuous beam bridges under vehicle loads, a method using vibration-mixed steel fiber-reinforced concrete to improve critical vulnerable areas of the bridge is proposed, thereby enhancing the bridge’s fatigue resistance. Fatigue performance and micro electron microscopy tests were designed for vibration-mixed steel fiber-reinforced concrete, analyzing its damage conditions and microstructural changes under 0 to 2 million cyclic loads, and the key mechanical parameters of the concrete were determined. Based on this, a numerical analysis model was established to simulate the fatigue damage of continuous beam bridges under moving vehicle loads. The results show that piers made with vibration-mixed steel fiber-reinforced concrete exhibit a 56.86% reduction in compressive damage compared to conventional piers, a reduction in stiffness damage range, and a 29.35% increase in fatigue life.

As a pivotal component within water diversion engineering, the aqueduct has experienced substantial growth in recent years. Scholars have extensively explored the interaction between water and solid structures within aqueducts. Notably, the question of whether the presence of water in the aqueduct can either enhance seismic absorption or exacerbate seismic responses has emerged as a crucial concern in aqueduct structural seismic resistance. To address this quandary, a refined two-way fluid-structure interaction methodology has been employed. This method accounts for variations in water pressure, water inertia forces, excitation frequencies, and aqueduct aspect ratios. It meticulously monitors liquid level changes using the Volume of Fluid (VOF) method, while FLUENT tracks wall pressure. Consequently, it calculates the aqueduct displacement under different influencing factors. The outcomes reveal that the water within the aqueduct exhibits Tuned Liquid Damping (TLD) effects, with the shock absorption effectiveness being directly related to water quality rather than differences in moving water pressure. Higher excitation frequencies result in increased peak aqueduct displacements but reduced water body oscillations. Under consistent water quality conditions, greater aspect ratios yield higher moving water pressures and, consequently, improved shock absorption capabilities.

Abstract Aiming to address the shortcomings of existing semi-active control algorithms with poor robustness and the limited generalization ability of current evaluation methods based on deterministic analysis, a novel approach based on probability density evolution is proposed. This method is designed to assess the seismic reliability, enabling a more comprehensive evaluation of the control effectiveness of aqueduct structures. Building upon this, an intelligent semi-active control algorithm leveraging machine learning is introduced. The algorithm is further validated through engineering case studies to investigate semi-active control strategies in response to random seismic events. The results show that the seismic reliability of the machine learning-based semi-active control algorithm is significantly higher than that of the uncontrolled state for the same failure threshold under random seismic effects.

COVID-19 vaccination is the most effective strategy for preventing severe disease and death. Inactivated vaccines are the most accessible type of COVID-19 vaccines in developing countries. Several studies, including work from our group, have demonstrated that the third dose (booster vaccination) of inactivated COVID-19 vaccine induces robust humoral and cellular immune responses. The present study aimed to examine miRNA expression profile in participants who received a homologous third dose of the CoronaVac vaccine. Samples of peripheral blood mononuclear cells (PBMCs) were collected from healthcare volunteers both before and 1–2 weeks after the booster dose. miRNA microarray analysis in a discovery cohort of six volunteers identified 67 miRNAs with differential expression. Subsequently, the expression of six miRNAs related to immune responses was examined in a validation cohort of 31 participants via qRT-PCR. Our results validated the differential expression of miR-25-5p, miR-34c-3p, and miR-206 post-booster, with a significant correlation to the receptor binding domain (RBD)-specific antibody. Bioinformatic analysis suggested that miR-25-5p, miR-34c-3p, and miR-206 may target multiple pathways involved in immune regulation and inflammation. Therefore, our study highlights miR-25-5p, miR-34c-3p, and miR-206 in PBMCs as promising biomarkers for assessing the immune response induced by the booster dose of the CoronaVac vaccine.

High-pressure swirling injection and combustion are important phenomena in a modern gas turbine engine as its compression ratio has been significantly increased to improve thermodynamic efficiency. Large eddy simulations are conducted to analyze turbulent flow and combustion of kerosene-air in a dual-air-swirler gas turbine model combustor at a supercritical pressure of 4 MPa, above the critical pressure of kerosene. The present work focuses particularly on effects of the two air swirler angles on flow and combustion dynamics. Numerical results indicate that the inner air swirler exerts strong impact on fuel-air mixing and chemical reactions inside the inner injector, leading to a Y shaped recirculating flow and a V shaped flame at an inner swirler angle of 40°. The precessing vortex core (PVC) is generated by the inner air swirling injection, and detailed analyses reveal that the PVC frequency is controlled mainly by the inner swirl number and the maximum axial velocity from the inner injector. The outer air swirler makes significant impact on the central recirculation structure and turbulent combustion inside the combustion chamber and weakly influences the PVC frequency. For the present supercritical-pressure turbulent combustion in a dual-air-swirler system, it appears that proper combination of the two air swirler angles could avoid chemical reactions deep inside the injector while enhancing fuel-air mixing and combustion in the combustion chamber.

BackgroundLeukocytes play an important role in inflammatory response after a traumatic brain injury (TBI). We designed this study to identify TBI phenotypes by clustering blood levels of various leukocytes.MethodsTBI patients from the Medical Information Mart for Intensive Care-III (MIMIC-III) database were included. Blood levels of neutrophils, lymphocytes, monocytes, basophils, and eosinophils were collected by analyzing the first blood sample within 24 h since admission. Overall, TBI patients were divided into clusters following the K-means clustering method using blood levels of five types of leukocytes. The correlation between identified clusters and mortality was tested by univariate and multivariate logistic regression analyses. The Kaplan–Meier method was used to verify the survival difference between identified TBI clusters.ResultsA total of 172 (cluster 1), 791 (cluster 2), and 636 (cluster 3) TBI patients were divided into three clusters with the following percentages, 10.8%, 49.5%, and 39.8%, respectively. Cluster 1 had the lowest Glasgow Coma Scale (GCS) and the highest Injury Severity Score (ISS) while cluster 2 had the highest GCS and the lowest ISS. The mortality rates of the three clusters were 25.6%, 13.3%, and 18.1%, respectively. The multivariate logistic regression indicated that cluster 1 had a higher mortality risk (OR = 2.211, p = 0.003) than cluster 2, while cluster 3 did not show a significantly higher mortality risk than cluster 2 (OR = 1.285, p = 0.163). Kapan–Meier analysis showed that cluster 1 had shorter survival than cluster 2 and cluster 3.ConclusionThree TBI phenotypes with different inflammatory statuses and mortality rates were identified based on blood levels of leukocytes. This classification is helpful for physicians to evaluate the prognosis of TBI patients.

Clear cell meningioma (CCM) is an exceedingly rare subtype of meningioma, with spinal occurrences being even more uncommon. It predominantly affects children and is characterized by a high recurrence rate and poor prognosis, posing significant challenges for clinical treatment. Currently, gross total resection (GTR) is the best approach to reduce recurrence and improve prognosis in these patients. However, detailed descriptions of intraoperative findings, particularly for intraspinal cervical CCM, are scarce in the literature. Here, we report a rare case in which the upper cervical spinal CCM mimicked a schwannoma, detailing the surgical treatment strategy and prognosis. Additionally, we analyzed all previously reported cases of spinal CCM to investigate the clinical characteristics, optimal treatment strategies, and prognostic factors, which may be of particular interest to neurosurgeons.

Summary: Background: Surgical interventions for spontaneous supratentorial intracerebral haemorrhage (ICH) include conventional craniotomy (CC), decompressive craniectomy (DC), and minimally invasive surgery (MIS), with the latter encompassing endoscopic surgery (ES) and minimally invasive puncture surgery (MIPS). However, the superiority of surgery over conservative medical treatment (CMT) and the comparative benefits of different surgical procedures remain unclear. We aimed to evaluate the efficacy and safety of various surgical interventions for treating ICH. Methods: In this systematic review and network meta-analysis, we searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov from inception to June 16, 2024. Eligible studies were randomised controlled trials (RCTs) comparing surgery (i.e., CC, ES, MIPS, or DC) with CMT or comparing different types of surgeries in patients with spontaneous supratentorial ICH. Paired reviewers independently screened citations, assessed the risk of bias of included trials, and extracted data. Primary outcomes were good functional outcome and mortality at 6 months. Secondary outcomes were good functional outcome and mortality at different follow-up times, complications (rebleeding, brain infection, pulmonary infection), and hematoma evacuation rate. The frequentist pairwise and network meta-analysis (NMA) were performed. The GRADE approach was used to evaluate the certainty of evidence. This study is registered with PROSPERO, CRD42024518961. Findings: Of the 8573 total records identified by our searches, 31 studies (6448 patients) were eligible for the systematic review and network analysis. Compared with CMT, moderate certainty evidence showed that surgery improved good functional outcome (risk ratio [RR] 1.31, 95% CI 1.13–1.52; risk difference [RD] 9.1%, 95% CI 3.8 to 15.3; I2 = 36%) and reduced mortality (RR 0.82, 95% CI 0.71–0.95; RD −5.1%, 95% CI −8.2 to −1.4; I2 = 14%). Moderate certainty evidence from NMA suggested that compared with CMT, both ES (RR 1.51, 95% CI 1.18–1.93; RD 9.4%, 95% CI 3.3–17.1) and MIPS (RR 1.48, 95% CI 1.24–1.76; RD 15.7%, 95% CI 7.9–24.9) improved good functional outcome at 6 months, and both ES (RR 0.66, 95% CI 0.52–0.85; RD −17.0%, 95% CI −24.0 to −7.5) and CC (RR 0.75, 95% CI 0.60–0.94; RD −6.3%, 95% CI −10.1 to −1.5) reduced mortality at 6 months, whereas MIPS and DC showed a trend, although not statistically significant, towards a reduction in mortality. ES and MIPS also reduced pulmonary infection risk (ES RR 0.39, 95% CI 0.23–0.69; MIPS RR 0.35, 95% CI 0.20–0.60; RD −5.3%, 95% CI −6.6 to −3.3). ES showed higher hematoma evacuation than CC (MD: 7.03, 95% CI: 3.42–10.65; I2 = 94%). No difference in rebleeding or brain infection was found between CC and MIS. Interpretation: Current moderate certainty evidence suggested that surgical intervention of spontaneous supratentorial ICH, may be associated with improved functional outcomes and a reduced risk of death at 6 months. The advantages of surgical haematoma removal are particularly pronounced when MIS including ES and MIPS are employed. ES could improve functional outcomes, reduce the risk of mortality and pulmonary infection, and have a high hematoma evacuation rate, suggesting that it might be an optimal surgical treatment. Funding: National Natural Science Foundation of China, National Science Fund for Distinguished Young Scholars, Fundamental Research Funds for the Central Public Welfare Research Institutes, and 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University.

Liquid-liquid phase separation (LLPS) drives the formation of membraneless intracellular compartments within both cytoplasm and nucleus. These compartments can form distinct physicochemical environments, and in particular display different concentrations of proteins, RNA, and macromolecules compared to the surrounding cytosol. Recent studies have highlighted the significant role of aberrant LLPS in cancer development and progression, impacting many core processes such as oncogenic signalling pathways, transcriptional dysregulation, and genome instability. In hepatocellular carcinoma (HCC), aberrant formation of biomolecular condensates has been observed in a number of preclinical models, highlighting their significance as an emerging factor in understanding cancer biology and its molecular underpinnings. In this review, we summarize emerging evidence and recent advances in understanding the role of LLPS in HCC, with a particular focus on the regulation and dysregulation of cytoplasmic and nuclear condensates in cancer cells. We finally discuss how an emerging understanding of phase separation processes in HCC opens up new potential treatment avenues.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets epithelial cells in the respiratory tract, triggering an acute proinflammatory response and chronic lung inflammation. Probiotic supplementation has shown promise in reducing the nasopharyngeal SARS-CoV-2 viral load, diminishing symptom frequency and duration, and mitigating inflammation; thus, it is a potential strategy for treating coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. In this study, we evaluated the effects of the oral administration of the Lactobacillus plantarum GUANKE strain, a gram-positive bacterium originally isolated from a healthy individual, on SARS-CoV-2 infection in a human ACE2 transgenic mouse model. We found that GUANKE significantly reduced inflammatory cell infiltration and pulmonary interstitial exudation in mice. The transcription of CCL2, TNFA, IL1B, IL6, and IL17C in the lungs was reduced. The protein levels of TNF-α, IL-1β, IL-6, and IL-17 in the lungs were significantly lower in GUANKE-treated mice than in control mice. The viral load in GUANKE-treated mice was lower than that in saline-treated mice, although this difference did not reach statistical significance. L. plantarum GUANKE can decrease SARS-CoV-2-induced lung inflammation in mice, suggesting its potential for use as an agent for treating SARS-CoV-2 infection.IMPORTANCEMost otherwise healthy individuals develop only mild or moderate symptoms of coronavirus disease 2019 (COVID-19) caused by current strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and virus replication is mainly confined to the upper respiratory tract; however, the virus can infect the lower respiratory tract and promote inflammation. Probiotic supplementation has been shown to reduce nasopharyngeal SARS-CoV-2 viral load, reduce the overall number and duration of symptoms, and attenuate inflammation in clinical trials. We showed that a novel L. plantarum GUANKE strain alleviated SARS-CoV-2-induced pneumonia in mice. The transcription and production of inflammatory cytokines were suppressed, and GUANKE moderately reduced the viral load. L. plantarum GUANKE has the potential to become a candidate drug for the treatment of COVID-19 or other viral respiratory infections.

BackgroundTrastuzumab therapy for HER2-positive cancers is associated with cardiotoxicity. This umbrella review synthesizes evidence from systematic reviews and meta-analyses on cardioprotective interventions during trastuzumab treatment.MethodsA comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Systematic reviews and meta-analyses examining cardioprotective interventions in patients receiving trastuzumab were included. The methodological quality was assessed using the AMSTAR-2 tool. Data on cardiac events, treatment interruptions, left ventricular ejection fraction (LVEF) changes, and exercise interventions were synthesized.ResultsTen systematic reviews met the inclusion criteria. Statins demonstrated the strongest cardioprotective effect (RR = 0.47, 95% CI: 0.26–0.84), potentially preventing more than half of cardiac events during trastuzumab therapy, followed by beta-blockers (RR = 0.61, 95% CI: 0.39–0.93). Beta-blockers and ACEIs effectively reduced treatment interruptions, enabling approximately 40% more patients to maintain treatment continuity (RR = 0.63, 95% CI: 0.47–0.86). Among non-pharmacological interventions, structured exercise programs showed significant benefits in preserving cardiac function, demonstrating meaningful improvements in resting LVEF (WMD = −3.27%, 95% CI: −5.86 to −0.68).DiscussionThis review demonstrates that cardioprotective interventions, particularly statins and beta-blockers, significantly reduce the risk of cardiac complications during trastuzumab therapy. The positive impact on cardiac events and treatment interruptions suggests these interventions may enhance overall treatment efficacy by allowing more patients to complete their prescribed course.ConclusionEvidence strongly supports the systematic implementation of cardioprotective strategies in clinical practice, particularly statins and beta-blockers, as part of routine care protocols for patients receiving trastuzumab therapy. These interventions demonstrate significant potential in preventing cardiac complications and maintaining treatment continuity. Further research should focus on optimizing personalized approaches and evaluating long-term outcomes.

Streptococcus suis is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for S. suis human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of S. suis ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 S. suis ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of S. suis strains.

Heat moisture treatment (HMT) is a widely used method for starch modification due to its safe, green, environmentally friendly, and efficient characteristics. In this study, quinoa starch was modified by HMT with varying moisture contents (20%, 25%, and 30%) at a temperature of 120 °C for 10 hours, and its rheological properties, in vitro digestive properties, and structure were further evaluated. The steady rheology results indicated that all the samples were shear-thinning non-Newtonian fluids. After undergoing HMT, the apparent viscosity of quinoa starch decreased significantly. Additionally, the samples' apparent viscosity decreased as the moisture content of HMT increased. The results of frequency sweep showed that the storage modulus G' of quinoa starch decreased with the increase of moisture content of HMT, while the loss modulus G'', and loss factor increased with the increase of moisture content of HMT. The thixotropic results showed that the thixotropic ring area of quinoa starch decreased with the increase of the moisture content of HMT. Additionally, the results of in vitro digestion showed that the content of rapidly digestible starch in quinoa starch decreased significantly after HMT (P

Abstract Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer.

ABSTRACT Circulating extracellular vesicles (EVs) have been associated with the development of COVID-19 due to their roles in viral infection, inflammatory response, and thrombosis. However, the direct induction of lung inflammation by circulating EVs from severe COVID-19 patients remains unknown. EVs were extracted from the plasma of severe COVID-19 patients admitted to intensive care and healthy controls. To study the effect of COVID-19 EVs on lung inflammation, mice were intratracheally instilled with EVs. To examine the proinflammatory effects of EVs in vitro, bone marrow-derived macrophages were treated with EVs. COVID-19 but not control EVs triggered lung inflammation, as assessed by total protein level, total cell count, neutrophil count, and levels of proinflammatory cytokines in the bronchoalveolar lavage. COVID-19 EVs also promoted M1 polarization of alveolar macrophages in vivo. Treatment of bone marrow-derived macrophages with COVID-19 EVs enhanced the M1 phenotype and augmented the production of IL-1β, IL-6, and TNF-α. In summary, circulating EVs from severe COVID-19 patients induce lung inflammation in mice. EVs could become a potential therapeutic target for alleviating lung injury in COVID-19.IMPORTANCEExtracellular vesicles (EVs) have been reported to facilitate cytokine storm, coagulation, vascular dysfunction, and the spread of the virus in COVID-19. The direct role of circulating EVs from severe COVID-19 patients in lung injury remains unrecognized. Our study demonstrated that plasma EVs obtained from severe COVID-19 patients induced lung inflammation and polarization of alveolar macrophages in vivo. In vitro experiments also revealed the proinflammatory effects of COVID-19 EVs. The present study sheds fresh insight into the mechanisms of COVID-19-induced lung injury, highlighting EVs as a potential therapeutic target in combating the disease.

From January 2022 to November 2022, sporadic psittacosis occurred in Lishui city, China. The patients were presented with fever, cough, and pulmonary infiltration. Their clinical symptoms were not relieved after receiving cephalosporin, penicillin, beta-lactamase inhibitors, and quinolones. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid samples from the patients revealed Chlamydia psittaci infection. Then, three C. psittaci strains were isolated from the patients. Their whole genome sequences (WGSs) were obtained, and a core genome multilocus sequence typing (cgMLST) method was developed to study the population structure of C. psittaci. Using the constructed cgMLST method, 72 WGSs were divided into four related groups and ten sub-clusters. The Lishui strains formed a unique population of C. psittaci, which might represent a new variant of C. psittaci. In vitro antimicrobial susceptibility testing suggested that the Lishui strains were sensitive to tetracycline, macrolides, quinolones, and no drug-resistance was observed.

BackgroundFundus vessel segmentation is vital for diagnosing ophthalmic diseases like central serous chorioretinopathy (CSC), diabetic retinopathy, and glaucoma. Accurate segmentation provides crucial vessel morphology details, aiding the early detection and intervention of ophthalmic diseases. However, current algorithms struggle with fine vessel segmentation and maintaining sensitivity in complex regions. Challenges also stem from imaging variability and poor generalization across multimodal datasets, highlighting the need for more advanced algorithms in clinical practice.MethodsThis paper aims to explore a new vessel segmentation method to alleviate the above problems. We propose a fundus vessel segmentation model based on a combination of double skip connections, deep supervision, and TransUNet, namely DS2TUNet. Initially, the original fundus images are improved through grayscale conversion, normalization, histogram equalization, gamma correction, and other preprocessing techniques. Subsequently, by utilizing the U-Net architecture, the preprocessed fundus images are segmented to obtain the final vessel information. Specifically, the encoder firstly incorporates the ResNetV1 downsampling, dilated convolution downsampling, and Transformer to capture both local and global features, which upgrades its vessel feature extraction ability. Then, the decoder introduces the double skip connections to facilitate upsampling and refine segmentation outcomes. Finally, the deep supervision module introduces multiple upsampling vessel features from the decoder into the loss function, so that the model can learn vessel feature representations more effectively and alleviate gradient vanishing during the training phase.ResultsExtensive experiments on publicly available multimodal fundus datasets such as DRIVE, CHASE_DB1, and ROSE-1 demonstrate that the DS2TUNet model attains F1-scores of 0.8195, 0.8362, and 0.8425, with Accuracy of 0.9664, 0.9741, and 0.9557, Sensitivity of 0.8071, 0.8101, and 0.8586, and Specificity of 0.9823, 0.9869, and 0.9713, respectively. Additionally, the model also exhibits excellent test performance on the clinical fundus dataset CSC, with F1-score of 0.7757, Accuracy of 0.9688, Sensitivity of 0.8141, and Specificity of 0.9801 based on the weight trained on the CHASE_DB1 dataset. These results comprehensively validate that the proposed method obtains good performance in fundus vessel segmentation, thereby aiding clinicians in the further diagnosis and treatment of fundus diseases in terms of effectiveness and feasibility.

Drought poses a significant challenge to global crop productivity, necessitating innovative approaches to bolster plant resilience. Leveraging transgenic technology to bolster drought tolerance in crops emerges as a promising strategy for addressing the demands of a rapidly growing global populace. AtZAT10/STZ1, a C2H2-type zinc finger protein transcription factor has shown to significantly improve Arabidopsis’ tolerance to various abiotic stresses. In this study, we reports that AtSTZ1 confers notable drought resistance in upland cotton (Gossypium hirsutum), amplifying cotton fiber yield under varying conditions, including irrigated and water-limited environments, in field trials. Notably, AtSTZ1-overexpressing transgenic cotton showcases enhanced drought resilience across critical growth stages, including seed germination, seedling establishment, and reproductive phases. Morphological analysis reveals an expanded root system characterized by an elongated taproot system, increased lateral roots, augmented root biomass, and enlarged cell dimensions from transgenic cotton plants. Additionally, higher contents of proline, chlorophyll, soluble sugars, and enhanced ROS-scavenging enzyme activities are observed in leaves of transgenic plants subjected to drought, underscoring improved physiological adaptations. Furthermore, transgenic lines exhibit heightened photosynthetic rate, increased water use efficiency, and larger stomatal and epidermal cell sizes, coupled with a decline in leaf stomatal conductance and density, as well as diminished transpiration rates compared to the wild type counterparts. Transcriptome profiling unveils 106 differentially expressed genes in transgenic cotton leaves post-drought treatment, including protein kinases, transcription factors, aquaporins, and heat shock proteins, indicative of an orchestrated stress response. Collectively, these findings underscore the capacity of AtSTZ1 to augment the expression of abiotic stress-related genes in cotton following drought conditions, thus presenting a compelling candidate for genetic manipulation aimed at enhancing crop resilience.

BackgroundFibroblast growth factor receptor 1 (FGFR1) is known to play a crucial role in the pathogenesis of asthma, although the precise mechanism remains unclear. This study aims to investigate how DNA methylation-mediated silencing of FGFR1 contributes to the enhancement of NF-κB signaling, thereby influencing the progression of asthma.MethodsRT-qPCR was utilized to assess FGFR1 mRNA levels in the serum of asthma patients and BEAS-2B, HBEpiC, and PCS-301-011 cells. CCK8 assays were conducted to evaluate the impact of FGFR1 overexpression on the proliferation of BEAS-2B, PCS-301-011, and HBEpiC cells. Dual-luciferase and DNA methylation inhibition assays were performed to elucidate the underlying mechanism of FGFR1 gene in asthma. The MassARRAY technique was employed to measure the methylation levels of the FGFR1 DNA.ResultsElevated FGFR1 mRNA levels were observed in the serum of asthma patients compared to healthy controls. Overexpression of FGFR1 in BEAS-2B cells significantly enhanced cell proliferation and stimulated NF-ĸB transcriptional activity in HERK-293T cells. Furthermore, treatment with 5-Aza-CdR, a DNA demethylating agent, markedly increased the expression of FGFR1 mRNA in BEAS-2B, PCS-301-011, and HBEpiC cells. Luciferase activity analysis confirmed heightened NF-ĸB transcriptional activity in FGFR1-overexpressing BEAS-2B cells and BEAS-2B cells treated with 5-Aza-CdR. Additionally, a decrease in methylation levels in the FGFR1 DNA promoter was detected in the serum of asthma patients using the MassARRAY technique.ConclusionOur findings reveal a potential mechanism involving FGFR1 in the progression of asthma. DNA methylation of FGFR1 inactivates the NF-ĸB signaling pathway, suggesting a promising avenue for developing effective therapeutic strategies for asthma.

Background Coagulopathy is associated with poor prognosis of traumatic brain injury (TBI) patients. This study is performed to explore the association between serum magnesium level and the risk of coagulopathy in TBI. Methods TBI patients from the Medical Information Mart for Intensive Care-III database were included for this study. Logistic regression analysis was performed to explore risk factors and develop a predictive model for coagulopathy in TBI. The restricted cubic spline (RCS) was utilized to analyze the association between serum magnesium level and the development of coagulopathy. Receiver operating characteristic curve was drawn to evaluate the performance of the predictive model for coagulopathy. Results The incidence of coagulopathy in TBI was 32.6%. The RCS indicated the association between magnesium and coagulopathy was U-shaped. Multivariate logistic regression confirmed age, coronary heart disease, cerebral vascular disease, chronic liver disease, GCS, ISS, epidural hematoma, hemoglobin, shock index and magnesium level were independently associated with the coagulopathy in TBI. Compared with patients of magnesium level between 1.7 and 2.3 mg/dL, those with magnesium level below 1.7 mg/dL or above 2.2 mg/dL had a higher risk of coagulopathy. Conclusion Both hypermagnesemia and hypomagnesemia are associated with higher risk of coagulopathy in TBI patients. Physicians should pay more attention on preventing coagulopathy in TBI patients with hypomagnesemia or hypermagnesemia.

Abstract Background The Endothelial Activation and Stress Index (EASIX) is a novel marker of endothelial injury and correlates with survival of various patients. The endothelial dysfunction plays an important role on the pathophysiological process of traumatic brain injury (TBI). This study was designed to explore the prognostic value of EASIX on TBI patients. Methods 358 TBI patients hospitalized in the West China hospital between October 2018 and October 2022 were enrolled for this study. The EASIX was calculated based on the formula: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelets (109 cells/L). The univariate and multivariate logistic regression with forward method was performed to explore the association between EASIX and mortality. A prognostic model was developed combining significant risk factors in the multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to compare the predictive accuracy of the EASIX and the developed model. Results The 30-day mortality of enrolled 358 TBI patients was 51.1%. Non-survivors had higher EASIX than survivors (p

A sensitive and reliable method was developed and validated for the simultaneous determination of 6 carbamate pesticides and relevant metabolites based on the modified fast QuEChERS (quick, easy, cheap, effective, rugged and safe) method combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was also applied in the analysis of 23 commonly consumed oilseeds and oil samples. The sample was extracted with acetonitrile for three times and then the extracted solution was filtered directly through 250 mg precipitated silica adsorbent (PSA) and 250 mg C18. The mobile phase was water (containing 0.1% formic acid) and acetonitrile. The external standard protocols were adopted to validate the method in terms of recovery, linearity, precision, sensitivity, and relative standard deviation (RSD) under the optimized conditions. The linear calibration curves with different ranges were established with R2 > 0.997 3, limit of detections (LODs) ranged from 0.100 µg/kg to 2.000 µg/kg and limit of quantitations (LOQs) ranged from 0.300 µg/kg to 6.000 µg/kg. The limit of detection meets the detection requirement for the maximum residue limits in practical samples. Meanwhile, the recoveries ranged from 60.2% to 116.6% with associated RSDs ranged from 0.33% to 5.35% in 10 oilseeds matrices and ranged from 61.9% to 116.9% with RSDs ranged from 0.30% to 5.02% in 13 oil matrices. These features do make the UPLC-MS/MS an ideal analytical platform for accurate and high throughput analysis of carbamates residues in the complex matrix.

Objectives: We conducted a systematic analysis of the notifiable rickettsial diseases in humans in China during 1950-2022. Methods: We utilized descriptive statistics to analyze the epidemiological characteristics, clinical manifestations, and diagnostic characteristics of typhus group rickettsiosis (TGR) and scrub typhus (ST) cases. Results: Since the 1950s, there have been variations in the incidence rate of TGR and ST in China, with a downtrend for TGR and an uptrend for ST. The South became a high-incidence area of TGR, whereas the North was previously the high-incidence area. ST cases were concentrated in the South and the geographic area of ST spread northward and westward. The seasonality of TGR and ST were similar in the South but distinct in the North. Most TGR and ST cases were reported by county-level medical institutions, whereas primary institutions reported the least. Delayed diagnosis was associated with fatal outcomes of TGR and ST. Cases in low-incidence provinces, confirmed by laboratory tests and reported from county/municipal-level institutions had higher odds of delayed diagnoses. Conclusions: Our study revealed significant changes in the epidemiological characteristics of TGR and ST in China, which can provide useful information to enhance the control and prevention strategies of rickettsial diseases in China.

Objectives: The purpose of this research was to summarize the clinical and prognostic features of cavernous sinus meningiomas (CSM), evaluate the treatment strategies and long-term prognosis of CSM, and improve the management of CSM and the treatment effect for patients. Methods: We retrospectively studied the data of 54 patients who received initial surgical resection and 45 patients who received initial gamma knife radiosurgery (GKRS) for CSM at West China Hospital of Sichuan University from 2009 to 2021. Progression-free survival (PFS), Karnofsky Performance Scale (KPS) scores and neurological function recovery were adopted to assess a comprehensive management strategy for CSM. Results: Gross total resection (GTR) was performed in 51.9 % of cases with 3.7 % surgical mortality. The average follow-up time was 48.7 months, with a progression rate of 29.3 %. The overall improvement rate for cranial nerve function deficits was 50.0 %. By survival analysis, the extent of resection and the histological grade were significantly related to the prognosis. The role of postoperative GKRS is uncertain. For patients who received initial GKRS, the progression rate was 17.8 %, and the overall improvement rate for cranial nerve function deficits was 61.1 %. Primary treatment with GKRS showed better long-term tumor control in patients with CSM (P = 0.046). Conclusions: Maximum safe resection of CSM can improve the neurological function and quality of life of patients, but aggressive resection will cause high perioperative mortality and complication rates. For CSM patients who are suitable for initial gamma knife treatment, choosing GKRS can achieve better long-term tumor control and neurological outcomes.

Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ. Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met–GOx/Fe@LE NPs) was constructed. The coordination between iron ions (Fe3+) and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction. Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability. Moreover, this pH-responsive nanoplatform presents controllable drug release behavior. An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug. The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation. This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Lactic acid Bacteria (LAB) convert tryptophan to indole derivatives and induce protective IL-22 production in vivo. However, differences in metabolizing capabilities among LAB species have not been widely investigated. In the present study, we compared the capabilities of 186 LAB strains to produce four kinds of indole derivatives, including indole-3-carboxaldehyde (IAId), indole-3-lactic acid (ILA), indole-3-propanoic acid (IPA), and indole-3-acetic acid (IAA). These strains were isolated from fermented foods, dairy products, and the feces of healthy individuals, as well as from fish and shrimp from Shanxi and Jiangsu provinces. They represent 15 genera, including Bifidobacterium, Enterococcus, Lacticaseibacillus, Lactiplantibacillus, Lactobacillus, Lactococcus, Limosilactobacillus, Pediococcus, Streptococcus, Weissella, Latilactobacillus, Levilactobacillus, Ligilactobacillus, and Loigolactobacillus. The results indicate widespread IAId-producing capabilities in LAB strains, with positive rates of approximately 90% (106/117) and 100% (69/69) among strains from Shanxi and Jiangsu provinces, respectively. The concentrations of IAId ranged from 72.42 ng/mL to 423.14 ng/mL in all positive strains from Shanxi Province and from 169.39 ng/mL to 503.51 ng/mL in strains from Jiangsu Province. Intriguingly, we also observed specific ILA-producing capabilities in Lactiplantibacillus strains, with positive rates of 55.17% (16/29) and 80.95% (17/21) among strains isolated from Shanxi and Jiangsu provinces, respectively. The overall detection rates of ILA among all tested strains (including both Lactiplantibacillus and other genus strains) were 17.9% (21/117) and 26.1% (18/69). The concentrations of ILA in positive strains ranged from 12.22 ng/mL to 101.86 ng/mL and from 5.75 ng/mL to 62.96 ng/mL from Shanxi and Jiangsu provinces, respectively. IPA and IAA were not detected in any strains. Finally, these indole derivative-producing capabilities were not related to their geographical origins or isolation sources. The current study provides insights into the species- or genus-dependent capabilities for metabolizing indole derivatives. Defining the specific roles of LAB in indole derivative metabolism will uncover the exact physiological mechanisms and be helpful for functional strain screening.

BackgroundTraumatic brain injury (TBI) is a global health concern that often leads to poor prognosis. We designed this study to explore whether thiamine use is associated with a better prognosis of TBI.MethodsTBI patients selected from the Medical Information Mart for Intensive Care-III database were included in the study. Univariate and multivariate Cox regression analyses were performed to examine the relationship between thiamine use and mortality in TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-thiamine use group and the thiamine use group. Subgroup analysis was performed in the cohort after PSM to verify the association between thiamine use and mortality in TBI patients across different stratifications.ResultsThe incidence of thiamine use in TBI was 18.3%. The thiamine use group had a lower 30-day mortality rate (p < 0.001), a longer length of ICU stay (p < 0.001), and a longer length of hospital stay (p < 0.001) than the non-thiamine use group, both in the primary cohort before PSM and the cohort after PSM. A multivariate Cox regression analysis confirmed that thiamine use was independently associated with mortality (OR = 0.454, p < 0.001) after adjusting for confounding effects. In the cohort after PSM, the subgroup analysis showed that thiamine use is associated with lower mortality in TBI patients with a Glasgow Coma Scale (GCS) score of < 13, but it is not associated with mortality in TBI patients whose GCS score is ≥13.ConclusionThiamine supplementation is effective in improving the outcome of TBI, except in cases of mild TBI. The optimal thiamine supplementation strategy for TBI is worthwhile to be explored in future studies.

BackgroundThere are limited data available on the development of arrhythmias in patients at risk of high-degree atrioventricular block (HAVB) or complete heart block (CHB) following transcatheter aortic valve replacement (TAVR). ObjectiveThis study aimed to explore the incidence and evolution of arrhythmias by monitoring patients at risk of HAVB or CHB after TAVR using smartwatches. MethodsWe analyzed 188 consecutive patients in the prospective SMART TAVR (smartwatch-facilitated early discharge in patients undergoing TAVR) trial. Patients were divided into 2 groups according to the risk of HAVB or CHB. Patients were required to trigger a single-lead electrocardiogram (ECG) recording and send it to the Heart Health App via their smartphone. Physicians in the central ECG core lab would then analyze the ECG. The incidence and timing of arrhythmias and pacemaker implantation within a 30-day follow-up were compared. All arrhythmic events were adjudicated in a central ECG core lab. ResultsThe mean age of the patients was 73.1 (SD 7.3) years, of whom 105 (55.9%) were men. The mean discharge day after TAVR was 2.0 (SD 1.8) days. There were no statistically significant changes in the evolution of atrial fibrillation or atrial flutter, Mobitz I, Mobitz II, and third-degree atrial ventricular block over time in the first month after TAVR. The incidence of the left bundle branch block (LBBB) increased in the first week and decreased in the subsequent 3 weeks significantly (P

ABSTRACT Prevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia.IMPORTANCEAs a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients.MethodsSignificant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC).ResultsAmong 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt–Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt–Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality.ConclusionThe ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies.

Abstract The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.

To study the molecular mechanism of baicalein interrupting the programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway, molecular docking, molecular dynamics simulation, binding free energy calculation and principal component analysis were first performed to predict the inhibition effect of baicalein on this pathway, which was verified by enzyme-linked immunosorbent assay (ELISA) subsequently. Binding free energy calculations showed that the affinity of baicalein to the PD-L1 dimer was −32.41±0.31 kcal/mol. Free energy decomposition, contact numbers and nonbonded interaction results revealed that baicalein mainly interacted with the C-, C'-, F- and G-sheet domains of the PD-L1 dimer. Importantly, nonpolar interactions between the key residues Tyr56, Met115, Ala121, Asp122 and baicalein were dominant factors during the binding process. Cross-correlation matrixes and secondary structure results further demonstrated that baicalein could stably interact with the sheet domains of the PD-L1 dimer. The result of ELISA showed that the IC50 value of baicalein for inhibiting the PD-1/PD-L1 interaction was 79.47 µg/L. In conclusion, this study revealed that baicalein could directly bind to the PD-L1 dimer, thus blocking the PD-1/PD-L1 interaction, would provide basis for discovering natural small-molecule inhibitors of this pathway.

Based on imbibition replacement of shut-in well in tight oil reservoirs, this paper expounds the principle of saturation rebalancing during the shut-in process after fracturing, establishes an optimization method for shut-in time after horizontal well volume fracturing with the goal of shortening oil breakthrough time and achieving rapid oil breakthrough, and analyzes the influences of permeability, porosity, fracture half-length and fracturing fluid volume on the shut-in time. The oil and water imbibition displacement in the matrix and fractures occurs during the shut-in process of wells after fracturing. If the shut-in time is too short, the oil-water displacement is not sufficient, and the oil breakthrough time is long after the well is put into production. If the shut-in time is too long, the oil and water displacement is sufficient, but the energy dissipation in the formation near the bottom of the well is severe, and the flowing period is short and the production is low after the well is put into production. A rational shut-in time can help shorten the oil breakthrough time, extend the flowing period and increase the production of the well. The rational shut-in time is influenced by factors such as permeability, porosity, fracture half-length and fracturing fluid volume. The shortest and longest shut-in times are negatively correlated with porosity, permeability, and fracture half-length, and positively correlated with fracturing fluid volume. The pilot test in tight oil horizontal wells in the Songliao Basin, NE China, has confirmed that the proposed optimization method can effectively improve the development effect of horizontal well volume fracturing.

Background: A COVID-19 outbreak in the rural areas of Shijiazhuang City was attributed to the complex interactions among vaccination, host, and non-pharmaceutical interventions (NPIs). Herein, we investigated the epidemiological characteristics of all reported symptomatic cases by picking Shijiazhuang City, Hebei Province in Northern China as research objective. In addition, we established an age-group mathematical model to perform the optimal fitting and to investigate the dynamical profiles under three scenarios. Methods: All reported symptomatic cases of Shijiazhuang epidemic (January 2-February 3, 2021) were investigated in our study. The cases were classified by gender, age group and location, the distributions were analyzed by epidemiological characteristics. Furthermore, the reported data from Health Commission of Hebei Province was also analyzed by using an age-group mathematical model by two phases and three scenarios. Results: Shijiazhuang epidemic caused by SARS-CoV-2 wild strain was recorded with the peak 84 cases out of 868 reported symptomatic cases on January 11, 2021, which was implemented with strong NPIs by local government and referred as baseline situation in this study. The research results showed that R0 under baseline situation ranged from 4.47 to 7.72, and Rt of Gaocheng Distinct took 3.72 with 95% confidence interval from 3.23 to 4.35 on January 9, the declining tendencies of Rt under baseline situation were kept till February 3, the value of Rt reached below 1 on January 19 and remained low value up to February 3 for Gaocheng District and Shijiazhuang City during Shijiazhuang epidemic. This indicated Shijiazhuang epidemic was under control on January 19. However, if the strong NPIs were kept, but remote isolation operated on January 11 was not implemented as of February 9, then the scale of Shijiazhuang epidemic reached 9,482 cases from age group who were 60 years old and over out of 31,017 symptomatic cases. The investigation also revealed that Shijiazhuang epidemic reached 132,648 symptomatic cases for age group who were 60 years old and over (short for G2) under risk-based strategies (Scenario A), 58,048 symptomatic cases for G2 under late quarantine strategies (Scenario B) and 207,124 symptomatic cases for G2 under late quarantine double risk strategies (Scenario C), and that the corresponding transmission tendencies of Rt for three scenarios were consistently controlled on Jan 29, 2021. Compared with baseline situation, the dates for controlling Rt below 1 under three scenarios were delayed 10 days. Conclusions: Shijiazhuang epidemic was the first COVID-19 outbreak in the rural areas in Hebei Province of Northern China. The targeted interventions adopted in early 2021 were effective to halt the transmission due to the implementation of a strict and village-wide closure. However we found that age group profile and NPIs played critical rules to successfully contain Shijiazhuang epidemic, which should be considered by public health policies in rural areas of mainland China during the dynamic zero-COVID policy.

In this paper, an experimental study of steel fiber concrete using vibration mixing technology and the probability density evolution theory is applied to establish a nonlinear stochastic seismic response model for multistory concrete frame structures considering the randomness of structural parameters. The random evolution characteristics of the structural response are studied and analyzed, and a reliability analysis method for concrete frame structures based on PDEM theory is proposed. The equations are solved by the finite difference method in the TVD format, and the probability distribution of the deformation index of the concrete frame structure is obtained by summation, where the reliability is given according to the limit value of the index. The results confirm that the PDEM theory can accurately assess the functional reliability of the structure, and it is also found that the randomness of the structural parameters has a significant effect on its nonlinear dynamic response law, and that consideration of the randomness of the structural parameters at the early stage of the design can be of great help to the seismic resistance of the structure. This study not only provides a scientific basis for the optimization of the performance of steel fiber concrete but also provides a new perspective and tool for the analysis of probability density evolution in the field of structural earthquake engineering.

To validate the prevalence and biodiversity of ticks and tick-borne pathogens in Chongqing, a total of 601 ticks were collected from dogs, cattle, and goats within the Ta-pa Mountain range in Chongqing, China. Five distinct tick species were identified, including Ixodes ovatus (1.66%, 10/601), I. acutitarsus (0.50%, 3/601), Haemaphysalis flava (10.32%, 62/601), Ha. hystricis (9.82%, 59/601), and Ha. longicornis (77.70%, 467/601). A suit of semi-nest PCR and nest PCR primers were custom-synthesized for the detection of tick-borne pathogens. The analysis yielded positive results for 7.15% Rickettsia (Candidatus R. principis, R. japonica, and R. raoultii), 3.49% Anaplasma (A. bovis and A. capra), 1.16% Ehrlichia, 1.83% Coxiella burnetii, and 3.49% protozoa (Theileria. capreoli, T. orientalis, T. luwenshuni, and Babesia sp.) in ticks. Notably, Ca. R. principis was identified for the first time in I. ovatus and Ha. longicornis. These findings underscore the significant prevalence and diversity of ticks and their associated pathogens within the Chongqing Ta-pa Mountain region. This study accordingly provides an extensive dataset that contributes to the epidemiological understanding and disease prevention strategies for tick-borne illnesses in the local area.

Although various hypergolic propellants like MMH/N2O4 (monomethylhydrazine/dinitrogen tetroxide) are widely used in small rocket engines, there remains a lack of in-depth study conducted on their chemical reactions and spray combustion behaviors. To fill this research gap, a simplified chemical kinetic model that is suitable for three-dimensional simulation was proposed in this paper for MMH/N2O4. Then, numerical investigation was conducted using the Volume of Fluid (VOF) model to explore the transient injection and atomization of MMH/N2O4 impinging jets in a small bipropellant thruster. Also, the instantaneous formation and evolution of the fan-shaped liquid film were analyzed. With the spray distribution determined, the proposed kinetic model and two existing mechanisms were applied to simulate spray combustion and heat transfer within the thruster, respectively, under the Euler–Lagrange framework. According to the research results, the liquid film covered nearly the entire chamber wall with a sawtooth pattern, which protected against the high temperatures of the engine wall. Notably, the two existing mechanisms showed significant errors in predicting temperature changes around the wall due to the excessively simplified reaction pathways. In contrast, the proposed model enabled the accurate prediction of the chamber pressure, wall temperature, and thrust with an error of less than 10%. Given the high accuracy achieved by the proposed numerical method, it provides a valuable reference for the development of advanced space engines.

Since its emergence, SARS-CoV-2 virus, the causative agent of COVID-19, has undergone over three years of evolutionary changes. Throughout this evolutionary process, multiple variants, such as Alpha, Beta, Gamma, Delta, and Omicron, have emerged, leading to widespread outbreaks and pandemics. A comprehensive analysis of the evolution of SARS-CoV-2 over the past three years reveals its progression through three distinct stages.

Abstract Aims This study aims to explore the role of exosomes from cancer-associated fibroblasts (CAFs) induced by PDGF-BB in promoting the malignancy of oral squamous cell carcinoma (OSCC) and provide new insight into the mechanism of OSCC progression and its treatment. Main methods Exosomes were extracted from human oral mucosa fibroblasts (hOMFs) and CAFs. Differentially expressed miRNAs of exosomes between hOMFs and CAFs were analysed using high-throughput sequencing and self-programmed R software. Cal-27, a human tongue squamous carcinoma cell line, was treated with exosomes. Differentially expressed miRNAs between clinical cancer tissues and adjacent tissues and between hOMF and CAF exosomes were verified by qRT‒PCR. The effect of miR-3529-3p on Cal-27 cells was clarified by overexpressing or knocking down miR-3529-3p in Cal-27 cells. Sample expression and differentially expressed miRNA expression were compared between cancer and paracarcinoma tissues. Key findings We found that exosomes from CAFs (CAF-Exos) were internalized by tongue squamous carcinoma cells and promoted their proliferation, migration, invasion, and antiapoptotic effects. MiR-3529-3p was a significant differentially expressed miRNA between CAF-Exos and exosomes from hOMFs (hOMF-Exos). The overexpression of miR-3529-3p promoted proliferation, migration, and invasion and inhibited apoptosis of Cal-27 cells. Significance This study explores the role of PDGF-BB-induced CAFs in promoting malignancy in OSCC. This study will provide new insight into the mechanism of OSCC progression and its treatment.

Background:Traumatic brain injury (TBI) patients suffer high risks of mortality. Ondansetron has been verified to be effective in improving the prognosis of some kinds of critically ill patients. We design this study to explore whether ondansetron use is associated with lower risks of mortality among TBI patients.Methods:TBI patients from the Medical Information Mart for Intensive Care-III were collected. The usage of ondansetron, including intravenous injection and oral tablet, since admission to the Beth Israel Deaconess Medical Center between 2001 and 2012 was identified. Univariate and multivariate logistic regression were performed to analyze the relationship between the ondansetron use and mortality of TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-ondansetron use group and ondansetron use group. Sub-group analysis was performed to verify the association between the ondansetron use and mortality of TBI patients in different TBI severity levels after PSM.Results:In TBI cohorts before PSM, the usage incidence of ondansetron was 37.2%. The 30-day mortality was significantly lower in the ondansetron group (p < 0.001). The multivariate logistic regression showed that ondansetron was associated with the lower mortality of TBI patients (p = 0.008). In TBI cohorts after PSM, the 30-day mortality of the ondansetron group was lower than that of the non-ondansetron group, although without statistical significance (p = 0.079). Logistic regression indicated ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.051). In addition, Cox regression also presented that ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.052).Conclusion:Ondansetron usage is associated with a lower mortality risk of moderate-to-severe TBI but not mild TBI patients. Ondansetron may be a novel adjunctive therapeutic strategy to improve the prognosis of moderate-to-severe TBI patients.

BackgroundBiomarkers that reflect brain damage or predict functional outcomes may aid in guiding personalized stroke treatments. Serum neurofilament light chain (sNfL) emerges as a promising candidate for fulfilling this role.MethodsThis prospective, observational cohort investigation included 319 acute ischemic stroke (IS) patients. The endpoints were the incidence of early neurological deterioration (END, an elevation of two or more points in the National Institute of Health stroke scale score within a week of hospitalization compared with the baseline) and functional outcome at 3 months (an mRS score of >2 at 3 months was categorized as an unfavorable/poor functional outcome). The association of sNfL, which was assessed within 24 h of admission, with END and unfavorable functional outcomes at follow-up was assessed via multivariate logistic regression, whereas the predictive value of sNfL for unfavorable functional outcomes and END was elucidated by the receiver operating characteristic curve (ROC).ResultsOf 319 IS individuals, 89 (27.90%) suffered from END. sNfL not only reflects the severity of stroke measured by NIHSS score (p

Pituitary adenomas and intracranial aneurysms are prevalent neurosurgical conditions, but their simultaneous presence is uncommon, affecting only 0.5%-7.4% of those with pituitary adenomas. The strategy of treating aneurysms endovascularly before removing pituitary adenomas is widely adopted, yet reports on addressing both conditions at once through an endoscopic endonasal approach (EEA) are scarce. We present a case involving a pituitary adenoma coupled with an anterior communicating artery aneurysm. Utilizing the EEA, we excised the adenoma and clipped the aneurysm concurrently. The patient recovered well post-surgery, with follow-up assessments confirming the successful resolution of both the adenoma and aneurysm. We proved the feasibility of the EEA in the treatment of pituitary adenomas with anterior communicating artery aneurysms under specific anatomical relationships and close intraoperative monitoring.

Purpose: The large resection area of perianal tumor makes the skin defect hard to reconstruct. The keystone flap has demonstrated a growing application in skin defects. Herein, we aimed to explore the efficacy of keystone flap in the repair of skin defect after perianal tumor resection. Methods: This study is a retrospective review of patients diagnosed with perianal tumor from January 2010 to November 2021. A standardized data collection template was used to collect variables. The detailed process of the reconstructive surgery is carefully described in this article. After surgery, the healing process was closely observed. Results: Twenty patients underwent keystone flap repair. The average wound size before closure measured 3.5 × 4.9 cm2. Primary wound healing was achieved, and the flap survived during the follow up period, which ranged from 6 to 24 months. No severe complications occurred; slight edema was noticed in one patient. Conclusion: The application of keystone flap is a promising way to repair skin defect after tumor removal, and the complications rate was low after surgery. It can be concluded that this method is an effective and reliable way to repair perianal skin defect.

Abstract High-grade glioma is one of the deadliest primary tumors of the central nervous system. Despite the many novel immunotherapies currently in development, it has been difficult to achieve breakthrough results in clinical studies. The reason may be due to the suppressive tumor microenvironment of gliomas that limits the function of specific immune cells (e.g., T cells) which are currently the primary targets of immunotherapy. However, tumor-associated macrophage, which are enriched in tumors, plays an important role in the development of GBM and is becoming a research hotspot for immunotherapy. This review focuses on current research advances in the use of macrophages as therapeutic targets or therapeutic tools for gliomas, and provides some potential research directions.

Rapid detection of target foodborne pathogens plays more and more significant roles in food safety, which requires the efficiency, sensitivity, and accuracy. In this research, we proposed a new strategy of isothermal-molecular-amplification integrated with lateral-flow-strip for rapid detection of Salmonella without traditional enrichment-culture. The designed syringe-assisted-filtration can contribute to simultaneous collection and concentration of target bacterium from vegetable samples in just 3 min, resolving the drawbacks of traditional random sampling protocols. After simple and convenient ultrasonication, samples can be directly amplified at 39 °C in 25 min and the amplicons are qualitatively and quantitatively analyzed with the designed lateral-flow-strip in 5 min. Finally, satisfied results have been achieved within 40 min, which greatly improve the efficiency while the accuracy is also guaranteed. Furthermore, all detection steps can be completed under instrument-free conditions. This method will hold great promise for target pathogen detection in the resource-limited district, or for emergency on-site identification.