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Abstract Background Tissue plasminogen activator (tPA) is recommended as the preferred thrombolytic therapy for acute myocardial infarction (AMI). This study aimed to explore tPA-related adverse events (AEs) reported in the United States Food and Drug Administration Adverse Event Reporting System (FAERS), assess the potential safety of three preferred tPA therapies for treating AMI, and provide guidance for selecting tPA for prehospital thrombolysis. Method Four algorithms, including ROR, PRR, BCPNN, and MGPS, were used to quantify the signals of Tenecteplase, Reteplase, and Alteplase related AEs and compare the differential degrees of the three tPA-associated AEs in the actual data. Result We detected 18 signals of Tenecteplase-induced AE, 29 signals of Reteplase-induced AE, and 22 signals of Alteplase-induced AE. Among the three drugs, Tenecteplase had the highest signal intensity for intracranial hemorrhage-related AE, followed by Alteplase. Besides, Reteplase had the highest signal intensity for procedure-related AE and Alteplase had the highest signal intensity for arrhythmia-related AE. The time-onset analysis indicates that we should be vigilant for AEs, especially within the first week and the first 1–2 days after medication. Conclusion This study identified and compared the signals of AE related to Tenecteplase, Reteplase, and Alteplase in AMI patients.

Abstract High-power terahertz (THz) quantum cascade laser, as an emerging THz solid-state radiation source, is attracting attention for numerous applications including medicine, sensing, and communication. However, due to the sub-wavelength confinement of the waveguide structure, direct beam brightness upscaling with device area remains elusive due to several mode competition and external optical lens is normally used to enhance the THz beam brightness. Here, we propose a metallic THz photonic crystal resonator with a phase-engineered design for single mode surface emission over a broad area. The quantum cascade surface-emitting laser is capable of delivering an output peak power over 185 mW with a narrow beam divergence of 4.4° × 4.4° at 3.88 THz. A high beam brightness of 1.6 × 107 W sr−1m−2 with near-diffraction-limited M2 factors of 1.4 in both vertical and lateral directions is achieved from a large device area of 1.6 × 1.6 mm2 without using any optical lenses. The adjustable phase shift between the lattices enables a stable and high-intensity surface emission over a broad device area, which makes it an ideal light extractor for large-scale THz emitters. Our research paves the way to high brightness solid-state THz lasers and facilitates new applications in standoff THz imaging, detection, and diagnosis.

Salmonella is one of the main foodborne pathogens causing foodborne diseases for human beings. How to effectively control the Salmonella contamination is an urgent question in the field of food safety. In this study, hydroxypropyl-β-cyclodextrin (HP-β-CD) and curcumin (CUR) were incubated to construct the inclusion complex, which was used as a photosensitizer. Then the CUR-HP-β-CD mediated photodynamic inactivation technology (PDI) on Salmonella typhimurium ATCC14028 in food samples was determined under light-activated, and the mechanisms of the antibacterial activities were studied. Using 40% of ethanol and 2:1 (n/n) of HP-β-CD, the highest CUR inclusion rate (60.08%) was observed at 45 ℃ for 4 h. The water solubility of the inclusion complex was significantly (P

Abstract Aims of this study This study aims to investigate the potential of Huangqin Tang (HQT), a traditional Chinese medicine formulation, in the treatment of breast cancer (BC) through a comprehensive approach integrating network pharmacology, molecular docking, and experimental validation. Methods Chemical composition and target information of HQT were collected using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease-related target genes were obtained from the GeneCards database. Network pharmacological analysis, including construction of compound-disease-target networks and protein-protein interaction networks, was performed. Molecular docking simulations were conducted to evaluate the binding affinity between HQT components and key targets. Experimental validation was carried out using cell viability assays, clone formation assays, flow cytometry, Western blotting, and pathway analysis. Results A total of 210 candidate targets were identified. Network analysis revealed STAT3, AKT1, MAPK3 etc. as central targets. Enrichment analysis suggested HQT may exert anti-tumor effects through regulating lipid metabolism and inflammation related pathways. Molecular docking showed that the key compounds baicalein, wogonin, kaempferol and quercetin all bound effectively to MAPK1. The binding of baicalein to IL6 and naringenin to TNF-α was also relatively stable. The experimental results demonstrated that HQT effectively inhibited the proliferation of breast cancer cells, with IC50 values of 2.334 mg/mL and 1.749 mg/mL in MCF-7 cells at 24 h and 48 h, and IC50 values of 1.286 mg/mL and 1.496 mg/mL in MDA-MB-231 cells at 24 h and 48 h, respectively. Furthermore, HQT induced cell cycle arrest at the G2/M phase in breast cancer cells and downregulated the expression of related proteins including CDK1, Cyclin B1, CDK2, and Cyclin E. Additionally, HQT promoted apoptosis in breast cancer cells by upregulating the expression of Bak and CC-3, while downregulating the expression of Bcl-2. Notably, HQT also exhibited regulatory effects on the HIF-1 signaling pathway. Conclusions This study provides insights into the potential multi-component and multi-target mechanisms of HQT against BC, suggesting it may achieve therapeutic effects through regulating inflammatory response and cancer-related pathways via the identified active compounds and targets. The findings highlight the importance of integrating traditional medicine with modern approaches for the development of novel cancer therapies.

Abstract Background Faced with the high cost and limited efficiency of classical randomized controlled trials, researchers are increasingly applying adaptive designs to speed up the development of new drugs. However, the application of adaptive design to drug randomized controlled trials (RCTs) and whether the reporting is adequate are unclear. Thus, this study aimed to summarize the epidemiological characteristics of the relevant trials and assess their reporting quality by the Adaptive designs CONSORT Extension (ACE) checklist. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to January 2020. We included drug RCTs that explicitly claimed to be adaptive trials or used any type of adaptative design. We extracted the epidemiological characteristics of included studies to summarize their adaptive design application. We assessed the reporting quality of the trials by Adaptive designs CONSORT Extension (ACE) checklist. Univariable and multivariable linear regression models were used to the association of four prespecified factors with the quality of reporting. Results Our survey included 108 adaptive trials. We found that adaptive design has been increasingly applied over the years, and was commonly used in phase II trials (n = 45, 41.7%). The primary reasons for using adaptive design were to speed the trial and facilitate decision-making (n = 24, 22.2%), maximize the benefit of participants (n = 21, 19.4%), and reduce the total sample size (n = 15, 13.9%). Group sequential design (n = 63, 58.3%) was the most frequently applied method, followed by adaptive randomization design (n = 26, 24.1%), and adaptive dose-finding design (n = 24, 22.2%). The proportion of adherence to the ACE checklist of 26 topics ranged from 7.4 to 99.1%, with eight topics being adequately reported (i.e., level of adherence ≥ 80%), and eight others being poorly reported (i.e., level of adherence ≤ 30%). In addition, among the seven items specific for adaptive trials, three were poorly reported: accessibility to statistical analysis plan (n = 8, 7.4%), measures for confidentiality (n = 14, 13.0%), and assessments of similarity between interim stages (n = 25, 23.1%). The mean score of the ACE checklist was 13.9 (standard deviation [SD], 3.5) out of 26. According to our multivariable regression analysis, later published trials (estimated β = 0.14, p

Abstract Background Over time, the amount of germs resistant to antibacterial medications has been steadily rising because of their prolonged and indiscriminate use. The increase in drug resistance significantly threatens to human health and has become a globally recognized issue of concern. Therefore, identifying new antibacterial drugs is urgently needed. Forward Polysaccharides are natural macromolecular substances that exist in plants, microorganisms, and animals, They have an immense amount of use in the food and medical industries. Polysaccharides can be categorized as plant, animal, or microbial based on the sources of the polysaccharides. Conclusion Polysaccharides are natural compounds with antibacterial properties that exerts antibacterial activity by disrupting bacterial cell walls and cell membranes. They show potential as candidates for the creation and application of novel antibiotics. This article reviews the classification of polysaccharides, their isolation and purification, mechanisms of action, and antibacterial activity. The primary objective of this study is to lay down an empirical groundwork for examining the antibacterial properties of polysaccharides.

Abstract Cancer immunotherapy has rapidly transformed cancer treatment, yet resistance remains a significant hurdle, limiting its efficacy in many patients. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have emerged as pivotal regulators of gene expression and cellular processes. Increasing evidence indicates their involvement in modulating resistance to cancer immunotherapy. Notably, certain circRNAs function as miRNA sponges or interact with proteins, influencing the expression of immune-related genes, including crucial immune checkpoint molecules. This, in turn, shapes the tumor microenvironment and significantly impacts the response to immunotherapy. In this comprehensive review, we explore the evolving role of circRNAs in orchestrating resistance to cancer immunotherapy, with a specific focus on their mechanisms in influencing immune checkpoint gene expression. Additionally, we underscore the potential of circRNAs as promising therapeutic targets to augment the effectiveness of cancer immunotherapy. Understanding the role of circRNAs in cancer immunotherapy resistance could contribute to the development of new therapeutic strategies to overcome resistance and improve patient outcomes.

IntroductionThe role of immune cells in the pathogenesis and advancement of diabetic nephropathy (DN) is crucial. The objective of this study was to identify immune-cell-related biomarkers that could potentially aid in the diagnosis and management of DN.MethodsThe GSE96804 dataset was obtained from the Gene Expression Omnibus (GEO) database. Then, screen for intersections between differentially expressed genes (DEGs) and immune-related genes (IRGs). Identify core genes through protein-protein interaction (PPI) networks and the Cytoscape plugin. Subsequently, functional enrichment analysis was conducted. In addition, ROC analysis is performed to accurately identify diagnostic biomarkers. Apply the CIBERSORT algorithm to evaluate the proportion of immune cell infiltration. Finally, the mRNA, protein, and immunofluorescence expression of the biomarker was validated in the DN rat model.ResultsThe study yielded 74 shared genes associated with DN. Enrichment analysis indicated significant enrichment of these genes in focal adhesion, the humoral immune response, activation of the immune response, Cytokine-cytokine receptor interaction, and IL-17 signaling pathway. The optimal candidate gene VCAM1 was identified. The presence of VCAM1 in DN was further validated using the ROC curve. Analysis of immune cell infiltration matrices revealed a high abundance of monocytes, naïve B cells, memory B cells, and Macrophages M1/M2 in DN tissues. Correlation analysis identified one hub biomarker associated with immune-infiltrated cells in DN. Furthermore, our findings were validated through in vivo RT qPCR, WB, and IF techniques.ConclusionsOur research indicates that VCAM1 is a signature gene associated with DN and is linked to the progression, treatment, and prognosis of DN. A comprehensive examination of immune infiltration signature genes may offer new perspectives on the clinical diagnosis and management of DN.

Lake ecosystems confront escalating challenges to their stability and resilience, most intuitively leading to biodiversity loss, necessitating effective preservation strategies to safeguard aquatic environments. However, the complexity of ecological processes governing lake biodiversity under multi-stressor interactions remains an ongoing concern, primarily due to insufficient long-term bioindicator data, particularly concerning macroinvertebrate biodiversity. Here we utilize a unique, continuous, and in situ biomonitoring dataset spanning from 2011 to 2019 to investigate the spatio-temporal variation of macroinvertebrate communities. We assess the impact of four crucial environmental parameters on Lake Dongting and Lake Taihu, i.e., water quality, hydrology, climate change, and land use. These two systems are representative of lakes with Yangtze-connected and disconnected subtropical floodplains in China. We find an alarming trend of declining taxonomic and functional diversities among macroinvertebrate communities despite improvements in water quality. Primary contributing factors to this decline include persistent anthropogenic pressures, particularly alterations in human land use around the lakes, including intensified nutrient loads and reduced habitat heterogeneity. Notably, river-lake connectivity is pivotal in shaping differential responses to multiple stressors. Our results highlight a strong correlation between biodiversity alterations and land use within a 2–5 km radius and 0.05–2.5 km from the shorelines of Lakes Dongting and Taihu, respectively. These findings highlight the importance of implementing land buffer zones with specific spatial scales to enhance taxonomic and functional diversity, securing essential ecosystem services and enhancing the resilience of crucial lake ecosystems.

A self-sustained burner was built for diesel oil without an atomizer using metal fiber felt as an evaporator. The effects of firing rate, excess air coefficient, and altitude on the temperature distribution, NOx emission, and CO emission were studied. The results indicated that fuel evaporation and combustion inside the burner are significantly influenced by the altitude. The overall temperature distribution inside the burner first decreased and then increased with the increase in altitude. The main reasons for the formation of NOx are the local high temperature during start-up and the high temperature after flame stabilization. The NOx emission initially decreased and then increased with the increase in altitude. The NOx emission is the lowest at an altitude of 1700 m and reaches its maximum value at an altitude of 4780 m. The main cause of CO generation is incomplete combustion during the start-up process. The CO emission decreased with the increase in the excess air coefficient at the same altitude. Less CO is produced with the increase in altitude at the same firing rate and excess air coefficient.

BackgroundAmidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored.ObjectiveThis study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education.MethodsA convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach’s alpha and test–retest reliability.ResultsThe C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale’s 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach’s α = 0.930) and test–retest reliability (0.794, p

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity.

The non-protein amino acid β-N-methylamino-L-alanine (BMAA), produced by cyanobacteria, has been recognized as a neurotoxin. L-serine as an antagonist of BMAA can effectively alleviate BMAA-induced neurotoxicity. Although BMAA has long been emphasized as a neurotoxin, with the emergence of BMAA detected in a variety of algae in freshwater around the world and its clear biological enrichment effect, it is particularly important to study the non-neurotoxic adverse effects of BMAA. However, there is only limited evidence to support the ability of BMAA to cause oxidative damage in the liver. The exact molecular mechanism of BMAA-induced liver injury is still unclear. The formation of neutrophil extracellular traps (NETs) is a ‘double-edged sword’ for the organism, excessive formation of NETs is associated with inflammatory diseases of the liver. Our results innovatively confirmed that BMAA was able to cause the formation of NETs in the liver during the liver injury. The possible mechanism may associated with the regulation of ERK/p38 and cGAS/STING signaling pathways. The massive formation of NETs was able to exacerbate the BMAA-induced oxidative stress and release of inflammatory factors in the mice liver. And the removal of NETs could alleviate this injury. This article will bring a new laboratory evidence for BMAA-induced non-neurotoxicity and immunotoxicity.

Background and aimsContrast-associated acute kidney injury (CA-AKI) may occur in patients undergoing medical procedures involving x-rays and radiocontrast media, potentially resulting in prolonged renal impairment. However, no effective treatments are available. Therefore, this study aimed to investigate the efficacy of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in reducing CA-AKI incidence among patients with atherosclerotic cardiovascular disease (ASCVD) undergoing percutaneous coronary intervention.MethodsThis retrospective cohort study included patients who underwent percutaneous coronary intervention between January 2020 and December 2021 at Tianjin Chest Hospital. The study endpoint was CA-AKI incidence, and the impact of selection bias and other potential confounding factors was mitigated using bias matching. Overall, 1,642 patients were included in this study: 821 patients received evolocumab treatment before contrast agent application, and 821 did not receive such treatment.ResultsCA-AKI incidence was 6.21% and 8.04% in the evolocumab and control groups, respectively. After propensity-score matching, the incidence rate was 5.09% and 14.16% in the evolocumab and control groups, respectively. Evolocumab treatment significantly reduced CA-AKI incidence (p

ObjectivePostoperative deep venous thrombosis (DVT) is commonly observed in patients undergoing craniotomy and is associated with a high incidence of pulmonary embolism and poor clinical outcomes. Herein, we investigated the prophylactic effect of DVT of intraoperative intermittent pneumatic compression (IPC) in patients undergoing craniotomy.MethodsA total of 516 patients who underwent elective craniotomy between December 2021 and December 2022 were enrolled in this study. Patients were randomly assigned to the intervention group (received intraoperative IPC) or control group (without IPC). Lower extremity ultrasound was performed on both legs before and after surgery (1 h, 24 h, and 7 days post-intervention). DVT was defined as the visualization of a thrombus within the vein lumen of the leg. Coagulation and platelet function were measured at the start and end of the craniotomy.ResultsA total of 504 patients (251 in the intervention group and 253 in the control group) completed the study. Among these patients, 20.4% (103/504) developed postoperative DVT within the first week after surgery, with 16.7% occurring within 24 h. The incidence of postoperative DVT in the intervention group (9.6%, 24/251) was significantly lower than that in the control group (22.9%, 58/253, p 0.05).ConclusionDVT may develop within 24 h after the craniotomy. Intraoperative application of IPC reduces the incidence of postoperative DVT.

Summary: Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3-mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We apply an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in humans and mice. We unexpectedly discover an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts are altered in Shank3-mutant mice and postmortem brain tissues from individuals with autism spectrum disorder. The enhanced SHANK3 transcriptome significantly improves the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest that both deterministic and stochastic transcription of the genome is associated with SHANK family genes.

The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4，GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.

The incidence of breast cancer is increasing annually, making it a major health threat for women. Chemoprevention using natural, dietary, or synthetic products has emerged as a promising approach to address this growing burden. Atractylenolide-III (AT-III), a sesquiterpenoid present in various medicinal herbs, has demonstrated potential therapeutic effects against several diseases, including tumors, nonalcoholic fatty liver disease, and cerebral ischemic injury. However, its impact on breast cancer chemoprevention remains unexplored. In this study, we used an N-methyl-N-nitrosourea (NMU)-induced rat breast cancer model and 17β-estradiol (E2)-treated MCF-10A cells to evaluate the chemopreventive potential of AT-III on mammary tumorigenesis. AT-III inhibited mammary tumor progression, evidenced by reduced tumor volume and multiplicity, prolonged tumor latency, and the reversal of NMU-induced weight loss. Furthermore, AT-III suppressed NMU-induced inflammation and oxidative stress through the Nrf2/ARE pathway in breast cancer tissues. In vitro, AT-III effectively suppressed E2-induced anchorage-independent growth and cell migration in MCF-10A cells. Nrf2 knockdown attenuated the protective effects of AT-III, highlighting the pivotal role of Nrf2 in AT-III-mediated suppression of tumorigenesis. The mechanism involves the induction of Nrf2 expression by AT-III through the autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Overall, the results of this study indicate that AT-III is a promising candidate for breast cancer chemoprevention and provide valuable insights into its molecular interactions and signaling pathways.

Abstract As the primary domain of ideological and political education in higher education institutions, ideological and political courses must align with principles rooted in human psychology and education. Integrating educational psychology into ideological and political teaching in universities enhances the scientific, targeted, and forward-thinking nature of such education. The burgeoning exploration of knowledge graph applications has extended to machine translation, semantic search, and intelligent question answering. Diverging from traditional text matching, the knowledge spectrum graph transforms information acquisition in search engines. This paper pioneers a predictive system for delineating the relationship between educational psychology and ideological and political education in universities. Initially, it extracts diverse psychological mapping relationships of students, constructing a knowledge graph. By employing the KNN algorithm, the system analyzes psychological characteristics to effectively forecast the relationship between educational psychology and ideological and political education in universities. The system's functionality is meticulously detailed in this paper, and its performance is rigorously tested. The results demonstrate high accuracy, recall rates, and F1 values. The F1 score can reach 0.95enabling precise sample classification. The apex of the average curve for system response time peaks at approximately 2.5 s, maintaining an average response time of less than 3 s. This aligns seamlessly with the demands of practical online teaching requirements. The system adeptly forecasts the relationship between educational psychology and ideological and political education in universities, meeting response time requirements and thereby fostering the scientific and predictive nature of ideological and political teaching in higher education institutions.

Abstract DNA damage response (DDR) pathways are responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cellular genome, including homologous recombination repair (HRR) pathway, mismatch repair (MMR) pathway, etc. In ovarian cancer, current studies are focused on HRR genes, especially BRCA1/2, and the results show regional and population differences. To characterize germline mutations in DDR genes in ovarian cancer in Southwest China, 432 unselected ovarian cancer patients underwent multi-gene panel testing from October 2016 to October 2020. Overall, deleterious germline mutations in DDR genes were detected in 346 patients (80.1%), and in BRCA1/2 were detected in 126 patients (29.2%). The prevalence of deleterious germline mutations in BRCA2 is higher than in other studies (patients are mainly from Eastern China), and so is the mismatch repair genes. We identified three novel BRCA1/2 mutations, two of which probably deleterious (BRCA1 p.K1622* and BRCA2 p.L2987P). Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. In conclusion, our study highlights the necessity of comprehensive germline mutation detection of DNA damage response genes in ovarian cancer patients, which is conducive to patient management and genetic counseling.

Abstract Background To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China. Methods An anonymous electronic survey was conducted by Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth. Results 722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master’s degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training. Conclusions EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master’s and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.

Abstract This paper addresses the resource allocation (RA) for ultra‐dense network (UDN), where base stations (BSs) are densely deployed to meet the demands of future wireless communications. However, the design of RA in UDN is challenging, as the RA problem is non‐convex and NP‐hard. Therefore, this paper considers and studies a semi‐distributed resource block (RB) allocation scheme, in order to achieve a well‐balanced trade‐off between performance and complexity. In the context of semi‐distributed RB allocation scheme, the problem can be decomposed into the subproblem of clustering and the subproblem of cluster‐based RB allocation. We first improve the K‐means clustering algorithm by employing the Gaussian modified method, which can significantly decrease the number of iterations for carrying out the K‐means algorithm as well as the failure possibility of clustering. Then, bat algorithm (BA) is introduced to attack the problem of cluster‐based RB allocation. In order to make the original BA applicable to the problem of RB allocation, chaotic sequences are adopted to discretize the initial position of the bats, and simultaneously increase the population diversity of the bats. Furthermore, in order to speed up the convergence of BA, the logarithmic decreasing inertia weight is employed for improving the original BA. Our studies and performance results show that the proposed approaches are capable of achieving a desirable trade‐off between the performance and the implementation complexity.

Freshwater biodiversity is increasingly threatened by dams and many other anthropogenic stressors, yet our understanding of the complex responses of different biotas and their multiple facets remains limited. Here, we present a multi-faceted and integrated-indices approach to assess the differential responses of freshwater biodiversity to multiple stressors in the Yangtze River, the third longest and most dam-densely river in the world. By combining individual biodiversity indices of phytoplankton, zooplankton, periphyton, macroinvertebrates, and fish with a novel integrated aquatic biodiversity index (IABI), we disentangled the effects of hydrology, water quality, land use, and natural factors on both α and β diversity facets in taxonomic, functional, and phylogenetic dimensions. Our results revealed that phytoplankton and fish species and functional richness increased longitudinally, while fish taxonomic and phylogenetic β diversity increased but phytoplankton and macroinvertebrate β diversity remained unchanged. Hydrology and water quality emerged as the key drivers of all individual biodiversity indices, followed by land use and natural factors, with fish and phytoplankton showed the strongest responses. Importantly, we found that natural, land use, and hydrological factors indirectly affected biodiversity by altering water quality, which in turn directly influenced taxonomic and phylogenetic IABIs. Our findings highlight the complex interplay of multiple stressors in shaping freshwater biodiversity and underscore the importance of considering both individual and integrated indices for effective conservation and management. We propose that our multi-faceted and integrated-indices approach can be applied to other large, dam-modified river basins globally.

ABSTRACT Acute ischemic stroke (AIS) patients with active COVID-19 infection often have more severe symptoms and worse recovery. COVID-19 infection can cause gut microbiota dysbiosis, which is also a risk factor for poor outcomes in AIS patients. However, the association between gut microbiota and functional outcomes among AIS patients with COVID-19 infection has not been fully clarified yet. In this study, we performed 16S rRNA gene sequencing to characterize the gut microbial community among AIS patients with acute COVID-19 infection, AIS patients with post-acute COVID-19 infection, and AIS patients without COVID-19 infection. We found that AIS patients with acute COVID-19 experienced poorer recovery and significant gut dysbiosis, characterized by higher levels of Enterobacteriaceae and lower levels of Ruminococcaceae and Lachnospiraceae. Furthermore, a shorter time window (less than 28 days) between COVID-19 infection and stroke was identified as a risk factor for poor functional outcomes in AIS patients with COVID-19, and the enrichment of Enterobacteriaceae was indicated as a mediator in the relationship between infection time window and poor stroke outcomes. Our findings highlight the importance of early intervention after COVID-19 infection, especially by regulating the gut microbiota, which plays a role in the prognosis of AIS patients with COVID-19 infection.IMPORTANCEThe gut microbiota plays an important role in the association between respiratory system and cerebrovascular system through the gut-lung axis and gut-brain axis. However, the specific connection between gut bacteria and the functional outcomes of acute ischemic stroke (AIS) patients with COVID-19 is not fully understood yet. In our study, we observed a significant decrease in bacterial diversity and shifts in the abundance of key bacterial families in AIS patients with acute COVID-19 infection. Furthermore, we identified that the time window was a critical influence factor for stroke outcomes, and the enrichment of Enterobacteriaceae acted as a mediator in the relationship between the infection time window and poor stroke outcomes. Our research provides a new perspective on the complex interplay among AIS, COVID-19 infection, and gut microbiota dysbiosis. Moreover, recognizing Enterobacteriaceae as a potential mediator of poor stroke prognosis offers a novel avenue for future exploration and therapeutic interventions.

ObjectivesDiquat poisoning is an important public health and social security agency. This study aimed to develop a prognostic model and evaluate the prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning, focusing on how its impact changes over time after poisoning.MethodsThis was a retrospective cohort study using electronic healthcare reports from the Second Hospital of Hebei Medical University. The study sample included 80 patients with acute oral Diquat poisoning who were admitted to the hospital between January 2019 and May 2022. Time-to-event analyses were performed to assess the risk of all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The prognostic value of plasma DQ concentration on admission was assessed by computing the area under a time-dependent receiver operating characteristic curve (ROC).ResultsAmong the 80 patients, 29 (36.25%) patients died, and 51 (63.75%) patients survived in the hospital. Non-survivors had a median survival time (IQR) of 1.3(1.0) days and the longest survival time of 4.5 days after DQ poisoning. Compared with non-survivors, survivors had significantly lower amounts of ingestion, plasma DQ concentration on admission, lungs injury within 24 h after admission, liver injury within 24 h after admission, kidney injury within 24 h after admission, and CNS injury within 36 h after admission, higher APACHE II score and PSS within 24 h after admission (all p

Detecting microwave signals over a wide frequency range is endowed with numerous advantages as it enables simultaneous transmission of a large amount of information and access to more spectrum resources. This capability is crucial for applications such as microwave communication, remote sensing and radar. However, conventional microwave receiving systems are limited by amplifiers and band-pass filters that can only operate efficiently in a specific frequency range. Typically, these systems can only process signals within a three-fold frequency range, which limits the data transfer bandwidth of the microwave communication systems. Developing novel atom-integrated microwave sensors, for example, radio-frequency (RF) chip–coupled Rydberg atomic receiver, provides opportunities for a large working bandwidth of microwave sensing at the atomic level. In the current work, an ultra-wide dual-band RF sensing scheme was demonstrated by space-division multiplexing two RF-chip-integrated atomic receiver modules. The system can simultaneously receive dual-band microwave signals that span a frequency range exceeding 6 octaves (300 MHz and 24 GHz). This work paves the way for multi-band microwave reception applications within an ultra-wide range by RF-chip-integrated Rydberg atomic sensor.

One of the fundamental objectives in ecology is to investigate the ecological processes and associated factors governing the abundance and spatial distribution patterns of biodiversity. However, the reaction of biological communities to environmental degradation remains relatively unknown, even for ecologically crucial communities like macroinvertebrates in aquatic ecosystems. Here, we sampled 117 locations to quantify relative contributions of geographical and environmental factors, including water quality, land use, climate, and hydrological factors, to determine the absolute and relative compositions of macroinvertebrate communities and their spatial distribution in the Yellow River Basin (YRB), the sixth-longest river system on Earth. We assessed relative roles of species sorting and dispersal in determining macroinvertebrate community structure along YRB. Our results demonstrated that alpha and beta diversity indices showed an increase from the up- to low-reaches of YRB. The middle and low-reaches exhibited elevated species diversity and both regions exhibited relatively stable community compositions. The biodiversity of macroinvertebrates was influenced by a combination of geographical factors and environmental variables, with environmental factors predominantly serving as the principal determinants. Results of multiple linear regression and variance decomposition showed that the effect of environmental factors was approximately three times greater than that of spatial factors. These findings provide support for the hypothesis that species sorting, driven by environmental gradients, plays a significant role in shaping the community structure of macroinvertebrates in running water ecosystems at the basin scales. Moreover, the factors contributing to substantial shifts in biodiversity across different segments of YRB indicate that distinct river sections have been influenced by varying stressors, with downstream areas being more susceptible to the impacts of water pollution and urbanization resulting from human activities.

BackgroundThe aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall physical activity (PA), and diabetic kidney disease.MethodsOur study encompassed 2,633 participants, drawn from the cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, and employed survey-weighted logistic regression, generalized linear regression, and restricted cubic spline (RCS) analyses to ascertain the relationship between different domains of physical activity and diabetic kidney disease.ResultsAfter controlling for all confounders, multivariate logistic regression analyses revealed a lack of correlation between the various domains of physical activity and the prevalence of diabetic kidney disease. Multiple generalized linear regression analyses showed that durations of PA (β = 0.05, 95% CI, 0.01–0.09, P = 0.012) and TPA (β = 0.32, 95% CI, 0.10–0.55, P = 0.006) were positively associated with eGFR levels; and LTPA durations were inversely associated with UACR levels (β = -5.97, 95% CI, -10.50 - -1.44, P = 0.011). The RCS curves demonstrated a nonlinear relationship between PA, OPA, and eGFR, as well as a nonlinear correlation between PA and ACR. Subgroup and sensitivity analyses largely aligned with the outcomes of the multivariate generalized linear regression, underscoring the robustness of our findings.ConclusionOur population-based study explored the association between different domains of physical activity and diabetic kidney disease. Contrary to our expectations, we found no significant association between the duration of physical activity across all domains and the prevalence of diabetic nephropathy. Nonetheless, renal function markers, including eGFR and UACR, exhibited significant correlations with the duration of total physical activity (TPA) and leisure-time physical activity (LTPA), respectively, among diabetic patients. Interestingly, our findings suggest that diabetic patients engage in physical activity to preserve renal function, ensuring moderate exercise durations not exceeding 35 hours per week.

The physical properties of shale oil reservoirs under overburden pressure are of great significance for reservoir prediction and evaluation during exploration and development. Based on core, thin section, and SEM observations, as well as test data such as XRD, TOC, and porosity and permeability under pressure conditions, this study systematically analyzes the variation of physical properties of different lithofacies shales in the Jiyang depression and the influence of rock fabric on the physical variation under pressure. The porosity and permeability of shale samples significantly decrease under pressure. According to the phased reduction in porosity and permeability, the pressurization process is divided into three pressure stages: low pressure (15 MPa). The reduction of porosity is fastest in the low-pressure stage and slowest in the medium-pressure stage. The reduction of permeability is fastest in the low-pressure stage and the slowest in the high-pressure stage. The rock fabric has a significant impact on porosity and permeability under pressure conditions. The permeability of laminated shale and bedded shale is higher than that of massive shale under pressure, and the permeability loss rate is lower than that of massive shales. Especially under lower pressure, the difference can be 10–20 times. In addition, the reduction rate of porosity and permeability under pressure is negatively correlated with felsic minerals content, which is positively correlated with carbonate minerals content and clay minerals content. The contribution of clay minerals to the porosity reduction rate is dominant, followed by carbonate minerals. The contribution of carbonate minerals to the permeability reduction rate is dominant, followed by clay minerals. The TOC content has no significant impact on the porosity and permeability of shales under pressure in the study due to the low maturity.

BackgroundAcute myocardial infarction (AMI) is one of the most severe cardiovascular diseases and is associated with a high risk of in-hospital mortality. However, the current deep learning models for in-hospital mortality prediction lack interpretability. ObjectiveThis study aims to establish an explainable deep learning model to provide individualized in-hospital mortality prediction and risk factor assessment for patients with AMI. MethodsIn this retrospective multicenter study, we used data for consecutive patients hospitalized with AMI from the Chongqing University Central Hospital between July 2016 and December 2022 and the Electronic Intensive Care Unit Collaborative Research Database. These patients were randomly divided into training (7668/10,955, 70%) and internal test (3287/10,955, 30%) data sets. In addition, data of patients with AMI from the Medical Information Mart for Intensive Care database were used for external validation. Deep learning models were used to predict in-hospital mortality in patients with AMI, and they were compared with linear and tree-based models. The Shapley Additive Explanations method was used to explain the model with the highest area under the receiver operating characteristic curve in both the internal test and external validation data sets to quantify and visualize the features that drive predictions. ResultsA total of 10,955 patients with AMI who were admitted to Chongqing University Central Hospital or included in the Electronic Intensive Care Unit Collaborative Research Database were randomly divided into a training data set of 7668 (70%) patients and an internal test data set of 3287 (30%) patients. A total of 9355 patients from the Medical Information Mart for Intensive Care database were included for independent external validation. In-hospital mortality occurred in 8.74% (670/7668), 8.73% (287/3287), and 9.12% (853/9355) of the patients in the training, internal test, and external validation cohorts, respectively. The Self-Attention and Intersample Attention Transformer model performed best in both the internal test data set and the external validation data set among the 9 prediction models, with the highest area under the receiver operating characteristic curve of 0.86 (95% CI 0.84-0.88) and 0.85 (95% CI 0.84-0.87), respectively. Older age, high heart rate, and low body temperature were the 3 most important predictors of increased mortality, according to the explanations of the Self-Attention and Intersample Attention Transformer model. ConclusionsThe explainable deep learning model that we developed could provide estimates of mortality and visual contribution of the features to the prediction for a patient with AMI. The explanations suggested that older age, unstable vital signs, and metabolic disorders may increase the risk of mortality in patients with AMI.

Perfluorooctane sulfonate (PFOS), an officially listed persistent organic pollutant, is a widely distributed perfluoroalkyl substance. Epidemiological studies have shown that PFOS is intimately linked to the occurrence of insulin resistance (IR). However, the detailed mechanism remains obscure. In previous studies, we found that mitochondrial calcium overload was concerned with hepatic IR induced by PFOS. In this study, we found that PFOS exposure noticeably raised lysosomal calcium in L-02 hepatocytes from 0.5 h. In the PFOS-cultured L-02 cells, inhibiting autophagy alleviated lysosomal calcium overload. Inhibition of mitochondrial calcium uptake aggravated the accumulation of lysosomal calcium, while inhibition of lysosomal calcium outflowing reversed PFOS-induced mitochondrial calcium overload and IR. Transient receptor potential mucolipin 1 (TRPML1), the calcium output channel of lysosomes, interacted with voltage-dependent anion channel 1 (VDAC1), the calcium intake channel of mitochondria, in the PFOS-cultured cells. Moreover, we found that ATP synthase F1 subunit beta (ATP5B) interacted with TRPML1 and VDAC1 in the L-02 cells and the liver of mice under PFOS exposure. Inhibiting ATP5B expression or restraining the ATP5B on the plasma membrane reduced the interplay between TRPML1 and VDAC1, reversed the mitochondrial calcium overload and deteriorated the lysosomal calcium accumulation in the PFOS-cultured cells. Our research unveils the molecular regulation of the calcium crosstalk between lysosomes and mitochondria, and explains PFOS-induced IR in the context of activated autophagy.

BackgroundsImproving quality of life (QOL) is one of the main aims of lung transplantation (LTx). There is a need to identify those who have poor quality of life early. However, research addressing inter individual quality of life variability among them is lacking. This study aims to identify group patterns in quality of life among lung transplant recipients and examine the predictors associated with quality of life subgroups.MethodsIn total, 173 lung transplant recipients were recruited from one hospital in Guangdong Province between September 2022 and August 2023. They were assessed using the Lung Transplant Quality of Life scale (LT-QOL), Mindful Attention Awareness Scale (MAAS), Life Orientation Test-Revised scale (LOT-R), and Positive and Negative Affect Scale (PANAS). Latent profile analysis was used to identify QOL subtypes, and logistic regression analysis was used to examine the associations between latent profiles and sociodemographic and psychosocial characteristics.ResultsTwo distinct QOL profiles were identified: “low HRQOL” profile [N = 53 (30.94%)] and “high HRQOL” profile [N = 120 (69.06%)]. Single lung transplant recipients, and patients who reported post-transplant infection, high levels of negative emotion or low levels of mindfulness and optimism were significantly correlated with the low QOL subgroup.ConclusionUsing the domains of the LT-QOL scale, two profiles were identified among the lung transplant recipients. Our findings highlighted that targeted intervention should be developed based on the characteristics of each latent class, and timely attention must be paid to patients who have undergone single lung transplantation, have had a hospital readmission due to infection, exhibit low levels of optimism, low levels of mindfulness or high negative emotions.

Background Allergic asthma is the most prevalent asthma phenotype and is associated with the disorders of immune cells and glycolysis. Macrophages are the most common type of immune cells in the lungs. Calprotectin (S100A8 and S100A9) are two pro-inflammatory molecules that target the Toll-like receptor 4 (TLR4) and are substantially increased in the serum of patients with severe asthma. This study aimed to determine the effects of S100A8/A9 on macrophage polarization and glycolysis associated with allergic asthma. Methods To better understand the roles of S100A8 and S100A9 in the pathogenesis of allergic asthma, we used ovalbumin (OVA)-induced MH-S cells, and OVA-sensitized and challenged mouse models (wild-type male BALB/c mice). Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, flow cytometry, hematoxylin-eosin staining, and western blotting were performed. The glycolysis inhibitor 3-bromopyruvate (3-BP) was used to observe changes in glycolysis in mice. Results We found knockdown of S100A8 or S100A9 in OVA-induced MH-S cells inhibited inflammatory cytokines, macrophage polarization biomarker expression, and pyroptosis cell proportion, but increased anti-inflammatory cytokine interleukin (IL)-10 mRNA; also, glycolysis was inhibited, as evidenced by decreased lactate and key enzyme expression; especially, knockdown of S100A8 or S100A9 inhibited the activity of TLR4/myeloid differentiation primary response gene 88 (MyD88)/Nuclear factor kappa-B (NF-κB) signaling pathway. Intervention with lipopolysaccharides (LPS) abolished the beneficial effects of S100A8 and S100A9 knockdown. The observation of OVA-sensitized and challenged mice showed that S100A8 or S100A9 knockdown promoted respiratory function, improved lung injury, and inhibited inflammation; knockdown of S100A8 or S100A9 also suppressed macrophage polarization, glycolysis levels, and activation of the TLR4/MyD88/NF-κB signaling pathway in the lung. Conversely, S100A9 overexpression exacerbated lung injury and inflammation, promoting macrophage polarization and glycolysis, which were antagonized by the glycolysis inhibitor 3-BP. Conclusion S100A8 and S100A9 play critical roles in allergic asthma pathogenesis by promoting macrophage perturbation and glycolysis through the TLR4/MyD88/NF-κB signaling pathway. Inhibition of S100A8 and S100A9 may be a potential therapeutic strategy for allergic asthma.

Introduction: Virtual Reality (VR) is revolutionizing healthcare research and practice by offering innovative methodologies across various clinical conditions. Advances in VR technology enable the creation of controllable, multisensory 3D environments, making it an appealing tool for capturing and quantifying behavior in realistic scenarios. This paper details the application of VR as a tool for neurocognitive evaluation, specifically in attention process assessment, an area of relevance for informing the diagnosis of childhood health conditions such as Attention Deficit Hyperactivity Disorder (ADHD).Methods: The data presented focuses on attention performance results from a large sample (n = 837) of neurotypical male and female children (ages 6–13) tested on a visual continuous performance task, administered within an immersive VR classroom environment. This data was collected to create a normative baseline database for use to inform comparisons with the performances of children with ADHD to support diagnostic decision-making in this area.Results: Results indicate systematic improvements on most metrics across the age span, and sex differences are noted on key variables thought to reflect differential measures of hyperactivity and inattention in children with ADHD. Results support VR technology as a safe and viable option for testing attention processes in children, under stimulus conditions that closely mimic ecologically relevant challenges found in everyday life.Discussion: In response to these stimulus conditions, VR can support advanced methods for capturing and quantifying users’ behavioral responses. VR offers a more systematic and objective approach for clinical assessment and intervention and provides conceptual support for its use in a wide variety of healthcare contexts.

Abstract Background Studies suggested that the immunophenotype of hyaline vascular type Castleman disease (HVCD) lacked characteristics, which was easy to be confused with other diseases. Methods From January 2010 to June 2022, 17 cases of HVCD were selected from the Department of Pathology of Shaanxi Provincial People’s Hospital and the Department of Pathology of Shaanxi Provincial Cancer Hospital. 13 cases of reactive hyperplastic lymph nodes (RHL) and 11 cases of follicular lymphoma (FL) were selected as the control group. All cases were performed CD3, CD20, CD21 and BCL2 immunohistochemical staining. Results (i) In 17 cases of HVCD, the negative area of BCL2 of germinal center was significantly smaller than the negative area of CD3 of germinal center. However, in 13 cases of RHL, the negative area of CD3 of germinal center was basically consistent with the negative area of germinal center of BCL2 of germinal center. In 11 cases of FL, in neoplastic follicles, the negative area of CD3 was basically consistent with the positive area of BCL2. The difference between HVCD group and other two groups of diseases was statistically significant (P

Abstract For shade-intolerant species, shade light indicates the close proximity of neighboring plants and triggers the shade avoidance syndrome (SAS), which causes exaggerated growth and reduced crop yield. Here, we report that non-secreted ROT FOUR LIKE (RTFL)/DEVIL (DVL) peptides negatively regulate SAS by interacting with BRASSINOSTEROID SIGNALING KINASEs (BSKs) and reducing the protein level of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in Arabidopsis. The transcription of at least five RTFLs (RTFL13/16/17/18/21) is induced by low R:FR light. The RTFL18 (DVL1) protein is stabilized under low R:FR conditions and localized to the plasma membrane. A phenotype analysis reveals that RTFL18 negatively regulates low R:FR-promoted petiole elongation. BSK3 and BSK6 are identified as partners of RTFL18 through binding assays and structural modeling. The overexpression of RTFL18 or knockdown of BSK3/6 reduces BRASSINOSTEROID signaling and reduces low R:FR-stabilized PIF4 levels. Genetically, the overexpression of BSK3/6 and PIF4 restores the petiole phenotype acquired by RTFL18-overexpressing lines. Collectively, our work characterizes a signaling cascade (the RTFLs-BSK3/6-PIF4 pathway) that prevents the excessive activation of the shade avoidance response in Arabidopsis.

Abstract Background Previous observational studies have indicated a correlation between the gut microbiota and influenza; however, the exact nature of the bidirectional causal connection remains uncertain. Method A two-way, two-sample Mendelian randomization (MR) study was conducted to evaluate the possible causal connection between the gut microbiota and the two outcomes of influenza (pneumonia without influenza and influenza pneumonia). The statistical analysis of gut microbiota is derived from the information of the most extensive meta-analysis (GWAS) conducted by the MiBioGen Alliance, encompassing a sample size of 18,340.The summary statistical data for influenza (not pneumonia, n = 291,090) and influenza pneumonia (n = 342,499) are from GWAS data published by FinnGen consortium R8.Estimate and summarize Single-nucleotide polymorphisms (SNPs) using Inverse variance weighted (IVW), MR Egger, and Weighted median (WM) in bidirectional MR analysis. To assess the heterogeneity, horizontal pleiotropy, and stability of SNPs, we employed Cochran’s Q test, MR Egger intercept test, and sensitivity analysis. Result The IVW analysis indicated that there was a significant association between influenza infection and five bacterial taxa. Additionally, the abundance changes of seven gut microbiota were found to be causally related to influenza infection. In addition, seven bacterial taxa showed a significant association with the occurrence of influenza pneumonia. The findings from the WM analysis largely support the outcomes of IVW, however, the results of MR egger analysis do not align with IVW. Furthermore, there is no proof to substantiate the cause-and-effect relationship between influenza pneumonia and the composition of gut microbiota. Conclusion This analysis demonstrates a possible bidirectional causal connection between the prevalence of particular gut microbiota and the occurrence of influenza infection. The presence of certain gut microbiota may potentially contribute to the development of pneumonia caused by influenza. Additional investigation into the interaction between particular bacterial communities and influenza can enhance efforts in preventing, monitoring, and treating influenza.

Abstract As a new algorithm to achieve sparse aperture inverse synthetic aperture radar (SA‐ISAR) imaging, the alternating direction method of multipliers (ADMM) suffers from selection of model parameters and the inability to discriminate the target and non‐target components. Therefore, an improved ADMM (I‐ADMM) algorithm is proposed to solve these problems. First, the particle swarm optimisation (PSO) algorithm is utilised to obtain the optimal model parameters. Aiming to adequately preserve the target's shape information in the ISAR image, a modified image entropy (IE) is proposed to be the objective function of the PSO. Then, a new regularisation function is obtained from the ADMM based ISAR image. The proposed algorithm can enhance the target components and suppress the non‐target components by utilising the regularisation function. Finally, results based on the simulated and measured data show that the proposed I‐ADMM algorithm not only achieves at least 9.4% improvement in IE but also greatly improves the image quality as visually compared with the traditional ADMM algorithm which validates the effectiveness and superiority of the proposed algorithm. [Correction added on 13/09/23, after first online publication: In the following sentence in abstract “Finally, results based on… the proposed algorithm.” 10% was changed as 9.4%.]

Abstract Background Lysine crotonylation (Kcr) is up-regulation in colorectal cancer (CRC) tissues, while its specific contribution remains uncertain. This study aimed to elucidate the role and mechanism of crotonylation on Lys27 of histone H3 (H3K27cr) in facilitating CRC metastasis. Methods Immunohistochemistry was employed to investigate the correlation between H3K27cr and CRC metastasis. Both in vitro and in vivo assays employing loss function or gain function approaches were conducted to elucidate the role of LINC00922 in promoting CRC metastasis. ScRNA-seq analysis and immunoprecipitation analyses were employed to explore the underlying mechanism by which LINC00922 facilitates CRC metastasis through H3K27cr. Results Clinically, H3K27cr was upregulated in metastatic CRC tissues and positively correlated with advanced clinical stages. Functionally, knockdown of LINC00922 inhibited migration of CRC cells both in vitro and in vivo. Furthermore, the supplementation of NaCr restored the migration and invasion levels of LINC00922 stable knockdown cells by restoring the H3K27cr level. Mechanistically, LINC00922 promoted invasion and migration through H3K27cr mediated cell adhesion molecules (CAMs) in epithelial cells. Notably, LINC00922 interacted with the protein sirtuin 3 (SIRT3) and obstructed its binding to the promoter region of ETS1, leading to an elevation in the level of H3K27cr in this promoter region and the subsequent activation of ETS1 transcription. Conclusions Our findings uncovered a novel regulatory function of H3K27cr, regulated by LINC00922, in facilitating CRC metastasis. This discovery contributed to a deeper comprehension of the involvement of histone crotonylation in the metastatic process of CRC.

The assessment of ecotourism suitability is crucial for sustainable regional development and is seen as an effective strategy to achieve both environmental protection and economic growth. One of the key challenges in land research is effectively identifying potential ecotourism resources while balancing regional protection and development. This study mapped the suitability of ecotourism in Zhangjiajie, China, using a combination of various geospatial data sources and four machine-learning techniques. Additionally, an indicator system was developed, covering the ecological environment, geological geomorphology, socioeconomics, and resource availability. The prediction results for suitability classified the area into four categories: highly suitable, moderately suitable, marginally suitable, and unsuitable; based on the ensemble results generated by the four algorithms, these categories accounted for 19.34%, 28.78%, 23.87%, and 28.01% of the total area, respectively. This study’s findings illustrate the spatial distribution of ecotourism suitability in Zhangjiajie, providing valuable insights for identifying potential ecotourism resources as well as informing regional planning and policy-making.

Abstract Aim To identify latent profiles of nurses’ subjective well‐being (SWB) and explore its association with social support and professional self‐concept. Design This study used an online survey and cross‐sectional latent profile analysis design. Methods A total of 1009 nurses from 30 hospitals in Guangdong Province, China, were selected using convenience sampling. An online questionnaire survey comprising the following scales was distributed: Index of Well‐Being, Nurses’ Professional Self‐concept Questionnaire and Multidimensional Scale of Perceived Social Support. Nurses’ SWB was examined and categorized into profiles using nine Index of Well‐being items as explicit variables and ordinal logistic regression analysis was performed to explore factors related to the distinct categories. Results Nurses’ SWB was divided into four latent profiles: extremely low, low, moderate and high. Regression analysis showed that social support and professional self‐concept influenced SWB. There were statistically significant differences in age, title, working years, social support and professional self‐concept among nurses in the different well‐being categories. Ordered logistic regression analysis showed that social support and professional self‐concept are associated with different SWB profiles.

BackgroundDiabetic peripheral neuropathy (DPN) contributes to disability and imposes heavy burdens, while subclinical DPN is lack of attention so far. We aimed to investigate the relationship between vitamin D and distinct subtypes of subclinical DPN in type 2 diabetes (T2DM) patients.MethodsThis cross-sectional study included 3629 T2DM inpatients who undertook nerve conduction study to detect subclinical DPN in Zhongshan Hospital between March 2012 and December 2019. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) level

Background: Pancreatic adenocarcinoma (PAAD) is a highly malignant gastrointestinal tumor and is associated with an unfavorable prognosis worldwide. Considering the effect of mitochondrial metabolism on the prognosis of pancreatic cancer has rarely been investigated, we aimed to establish prognostic gene markers associated with mitochondrial energy metabolism for the prediction of survival probability in patients with PAAD.Methods: Gene expression data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, and the mitochondrial energy metabolism–related genes were obtained from the GeneCards database. Based on mitochondrial energy metabolism score (MMs), differentially expressed MMRGs were established for MMs-high and MMs-low groups using ssGSEA. After the univariate Cox and least absolute and selection operator (LASSO) analyses, a prognostic MMRG signature was used in the multivariate Cox proportional regression model. Survival and immune cell infiltration analyses were performed. In addition, a nomogram based on the risk model was used to predict the survival probability of patients with PAAD. Finally, the expression of key genes was verified using quantitative polymerase chain reaction and immunohistochemical staining. Intro cell experiments were performed to evaluated the proliferation and invasion of pancreatic cancer cells.Results: A prognostic signature was constructed consisting of two mitochondrial energy metabolism–related genes (MMP11, COL10A1). Calibration and receiver operating characteristic (ROC) curves verified the good predictability performance of the risk model for the survival rate of patients with PAAD. Finally, immune-related analysis explained the differences in immune status between the two subgroups based on the risk model. The high-risk score group showed higher estimate, immune, and stromal scores, expression of eight checkpoint genes, and infiltration of M0 macrophages, which might indicate a beneficial response to immunotherapy. The qPCR results confirmed high expression of MMP11 in pancreatic cancer cell lines, and IHC also verified high expression of MMP11 in clinical pancreatic ductal adenocarcinoma tissues. In vitro cell experiments also demonstrated the role of MMP11 in cell proliferation and invasion.Conclusion: Our study provides a novel two-prognostic gene signature—based on MMRGs—that accurately predicted the survival of patients with PAAD and could be used for mitochondrial energy metabolism–related therapies in the future.

Dissolved organic matter (DOM) constitutes the most active fraction in global carbon pools, with estuarine sediments serving as significant repositories, where DOM is susceptible to dynamic transformations. Anthropogenic nitrogen (N) and sulfur (S) inputs further complicate DOM by creating N-bearing DOM (DON) and S-bearing DOM (DOS). This study delves into the spatial gradients and transformation mechanisms of DOM, DON, and DOS in Pearl River Estuary (PRE) sediments, China, using combined techniques of UV–visible spectroscopy, Excitation–emission matrix (EEM) fluorescence spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), and microbial high-throughput sequencing. Results uncovered a distinct spatial gradient in DOM concentration, aromaticity (SUVA254), hydrophobicity (SUVA260), the content of substituent groups including carboxyl, carbonyl, hydroxyl and ester groups (A253/A203) of chromophoric DOM (CDOM), and the abundances of tyrosine/tryptophan-like protein and humic-like substances in fluorophoric DOM (FDOM). These all decreased from upper to lower PRE, accompanied by a decrease in O3S and O5S components, indicating seaward reduction in the contribution of terrestrial OM, especially anthropogenic inputs. Additionally, sediments exhibited a reduction in molecular diversity (number of formulas) of DOM, DON, and DOS from upper to lower PRE, with molecules tending towards a lower nominal oxidation state of carbon (NOSC) and higher bio-reactivity (MLBL), molecular weight (m/z) and saturation (H/C). While molecular composition of DOM remained similar in PRE sediments, the relative abundance of lignin-like substances decreased, with a concurrent increase in protein-like and lipid-like substances in DON and DOS from upper to lower PRE. Mechanistic analysis identified the joint influence of terrestrial OM, anthropogenic N/S inputs, and microbial processes in shaping the spatial gradients of DOM, DON, and DOS in PRE estuarine sediments. This study contributes valuable insights into the intricate spatial gradients and transformations of DOM, DON, and DOS within human-impacted estuarine sediments.

Accurate estimation of desert vegetation transpiration is key to regulating desert water resources of desert ecosystems. Sap flow density (SFD) can indirectly reflect a tree’s transpiration consumption, and it has been affected by climate warming and groundwater depths in desert ecosystems. Sap flow responses to meteorological conditions and groundwater depths are further affected by tree of different sizes. However, how meteorological factors and groundwater depths affects tree sap flow among tree sizes remains poorly understand. In this study, a 50 × 50 m P. euphratica stand was selected as a sample plot in the hinterland of the Taklamakan Desert, and the SFD of P. euphratica of different sizes was measured continuously using the thermal diffusion technique from May to October of 2021 and 2022. The results showed that SFD of large P. euphratica was consistently higher than that of small P. euphratica in 2021 and 2022. and the SFD of P. euphratica was significantly and positively correlated with solar radiation (Rad) and vapor pressure deficit (VPD), and the correlation was higher than that of the air temperature (Ta) and relative humidity (RH), and also showed a strong non-linear relationship. Analysis of the hour-by-hour relationship between P. euphratica SFD and VPD and Rad showed a strong hysteresis. Throughout the growing season, there was no significant relationship between SFD of P. euphratica and groundwater depth, VPD and Rad were still the main controlling factors of SFD in different groundwater depths. However, during the period of relative groundwater deficit, the effect of groundwater depth on the SFD of P. euphratica increased, and the small P. euphratica was more sensitive, indicating that the small P. euphratica was more susceptible to groundwater changes. This study emphasized that Rad and VPD were the main drivers of SFD during the growing season, as well as differences in the response of different sizes of P. euphratica to groundwater changes. The results of the study provide a scientific basis for future modeling of transpiration consumption in P. euphratica forests in desert oases, as well as the regulation and allocation of water resources.