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Abstract Psychological help-seeking for suicidal ideation is a critical aspect of effective suicide prevention. Past research has documented low help-seeking amongst rural residents in China. This study investigates the patterns and predictors of help-seeking intentions for suicidal ideation versus mental (depression) and physical (heart disease) health conditions among Chinese rural residents using General Help-Seeking Questionnaire Vignette version. A total of 143 rural participants from sixteen villages in Hubei province of China completed the survey via home-visiting interviews. Results revealed a general trend that the help-seeking intentions decreased as the helping sources shifted from close others (spouses, family, etc.) to professional helpers and online sources. Additionally, rural residents with higher educational levels, high self-efficacy, and more severe suicide ideations were more willing to seek help; and suicide literacy was found to be negatively associated with help-seeking intentions. The implications of the research findings are discussed.

Background: The long-term effects of extracorporeal shockwave therapy (ESWT) on rotator cuff repair are unknown. Objectives: To investigate the functional outcomes and structural changes of ESWT at 3-year follow-up after rotator cuff repair. Methods: A randomized clinical trial was conducted, including patients who underwent rotator cuff repair. The patients were assigned to two groups based on whether they underwent radial ESWT 3 months postoperatively. The ESWT Group received 5 weeks of rehabilitation and ESWT weekly, whereas the CONTROL Group received only rehabilitation. Visual analog scale (VAS) pain score and functional scores were analyzed at 3 months (baseline), 6 months, and 3 years follow-up. In addition, MRI and ultrasonography were used to assess tendon maturation, integrity, tendon quality, acromiohumeral distance (AHD), and muscle fatty infiltration. Results: Finally, 32 participants completed all the assessments. At the final follow-up, 2 patients in the ESWT Group (16.5 %) versus one patient in the CONTROL Group (6.25 %) had rotator cuff failure (P = 0.176). The ESWT treatment showed similar clinical outcomes in VAS-pain score, functional scores, tendon quality, AHD, and muscle fatty infiltration versus the CONTROL Group (Ps > 0.05). MRI analysis indicated improved tendon healing after ESWT treatment at both 6-month (P = 0.036) and 3-year follow-up (P = 0.028). Conclusion: Early intervention with radial ESWT sustained long-term effects on the healing of the repaired rotator cuff and similar functional outcomes at long-term follow-up compared with standard rehabilitation.

Objective:. Comparative studies of median sternotomy and partial upper sternotomy in total arch replacement for type A aortic dissection are rare, and the safety and benefits of partial upper sternotomy need further evaluation. This study aimed to explore the effectiveness and prognosis of partial upper sternotomy in total arch replacement among patients with type A aortic dissection. Methods:. This is a retrospective study of patients who underwent total arch replacement for type A aortic dissection at the First Medical Center of Chinese People’s Liberation Army General Hospital between January 2016 and December 2019. They were grouped into the median sternotomy and partial upper sternotomy groups according to the different treatment methodologies. The intra-operative and prognostic indicators were compared between both groups. Results:. Forty-nine patients were included: 31 in the median sternotomy group and 18 in the partial upper sternotomy group. The partial upper sternotomy group had a shorter incision ((9.0 ± 0.8) cm vs. (25.5 ± 1.3) cm, P = 0.02) and smaller postoperative total drainage volume (885 mL vs. 1,820 mL, P = 0.03) than the median sternotomy group. The differences between the 2 groups with respect to other intra-operative indicators such as operation duration, cardiopulmonary bypass duration, aortic occlusion duration, hypothermic circulatory arrest duration, and intra-operative blood loss, and prognostic indicators such as red blood cell infusion, ventilator aid duration, cardiac intensive care unit stay, postoperative hospital stay, and postoperative complications were not significantly different (all P > 0.05). Conclusions:. The utilization of partial upper sternotomy in patients with type A aortic dissection resulted in a smaller incision and more aesthetically pleasing scar, along with reduced drainage volume compared to median sternotomy.

Abstract Background Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration. Methods We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT). Additionally, we assessed the accuracy of single-cell data from the perspective of driving factors, cell typing, anti-fibrosis performance of left ventricular assist device (LVAD). Candidate drugs were screened using L1000FWD. Results All four heart diseases exhibit myocardial fibrosis, with only MI showing an increase in macrophage proportions. Macrophages participate in myocardial fibrosis through various fibrogenic molecules, especially evident in DCM and MI. Abnormal RNA metabolism and dysregulated transcription are significant drivers of macrophage-mediated fibrosis. Furthermore, profibrotic macrophages exhibit M1 polarization and increased MMT. In HF patients, those responding to LVAD therapy showed a significant decrease in driver gene expression, M1 polarization, and MMT. Drug repurposing identified cinobufagin as a potential therapeutic agent. Conclusion Using integrated single-cell transcriptomics, we identified the drivers of macrophage-mediated myocardial fibrosis in four heart diseases and confirmed the therapeutic effect of LVAD on improving HF with single-cell accuracy, providing novel insights into the diagnosis and treatment of myocardial fibrosis.

Abstract Background Hemorrhagic fever with renal syndrome (HFRS), a life-threatening zoonosis caused by hantavirus, poses significant mortality risks and lacks specific treatments. This study aimed to delineate the transcriptomic alterations during the recovery phases of HFRS. Methods RNA sequencing was employed to analyze the transcriptomic alterations in peripheral blood mononuclear cells from HFRS patients across the oliguric phase (OP), diuretic phase (DP), and convalescent phase (CP). Twelve differentially expressed genes (DEGs) were validated using quantitative real-time PCR in larger sample sets. Results Our analysis revealed pronounced transcriptomic differences between DP and OP, with 38 DEGs showing consistent expression changes across all three phases. Notably, immune checkpoint genes like CD83 and NR4A1 demonstrated a monotonic increase, in contrast to a monotonic decrease observed in antiviral and immunomodulatory genes, including IFI27 and RNASE2. Furthermore, this research elucidates a sustained attenuation of immune responses across three phases, alongside an upregulation of pathways related to tissue repair and regeneration. Conclusion Our research reveals the transcriptomic shifts during the recovery phases of HFRS, illuminating key genes and pathways that may serve as biomarkers for disease progression and recovery.

ObjectiveTo explore the independent risk factors that affect the overall survival (OS) of elderly patients with hepatocellular carcinoma (HCC, ≥60 years old) and build a nomogram prediction model. MethodsClinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database. In accordance with the inclusion and exclusion criteria, the screened patients were randomly assigned to a training group (70%) and a validation group (30%). The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis. On the basis of the determined variables, nomograms were developed and verified to predict the OS of elderly patients with HCC at 6, 12, and 24 months. The consistency index (C index), calibration curve, receiver’s operating characteristic (ROC) curve, and area under curve (AUC) were used to evaluate the prediction efficiency and discrimination ability of the prediction model, and decision curve analysis (DCA) was used to evaluate the potential clinical application value of the nomogram. ResultsA total of 1134 elderly patients with HCC were included, with 793 in the training group and 341 in the validation group. Seven variables, including age, clinical grade, clinical stage, M stage, tumor size classification, and radiotherapy, were identified as independent prognostic factors of this population. The constructed nomogram shows excellent prediction performance, with C indices of 0.745 in the training group and 0.704 in the validation group. The AUC values of the training group at 6, 12, and 24 months were 0.785, 0.788, and 0.798, respectively, and those of the validation group were 0.780, 0.725, and 0.607, respectively. The calibration curve shows good consistency from the predicted survival probability to the actual probability. The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability. ConclusionAge, clinical grade, clinical stage, M stage, tumor size classification, and radiotherapy are important influencing factors for the survival of elderly patients with HCC. The prediction model of prognosis nomogram constructed in this study has good predictive value, and it can be used to predict the OS of elderly patients with HCC, which could be helpful for individualized survival assessment and clinical management of these patients.

Abstract Thorium biosorption by a green microalga, Chlorella Vulgaris, was studied in a stirred batch reactor to investigate the effect of initial solution pH, metal ion concentration, biomass dosage, contact time, kinetics, equilibrium and thermodynamics of uptake. The green microalgae showed the highest Th adsorption capacity at 45 °C for the solution with a thorium concentration of 350 mg L−1 and initial pH of 4. The amount of uptake raised from 84 to 104 mg g−1 as the temperature increased from 15 to 45 °C for an initial metal concentration of 75 mg L−1 at pH 4. Transformation Infrared Spectroscopy (FTIR) was employed to characterize the vibrational frequency changes for peaks related to surface functional groups. Also, the scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to determine the morphological changes and elemental analysis of the biosorbent before and after the sorption process. The Langmuir isotherm was in perfect agreement with the equilibrium empirical data of thorium biosorption and the highest sorption capacity of the Chlorella Vulgaris microalgae was determined as 185.19 mg g−1. Also, the results of kinetic studies show that the thorium biosorption process follows a pseudo-second-order kinetic model. The negative value of ΔG0 indicates spontaneity and the positive values of ΔH0 indicate the endothermic nature of the adsorption process.

Sepsis, a life-threatening syndrome of organ damage resulting from dysregulated inflammatory response, is distinguished by overexpression of inflammatory cytokines, excessive generation of reactive oxygen/nitrogen species (RONS), heightened activation of pyroptosis, and suppression of autophagy. However, current clinical symptomatic supportive treatment has failed to reduce the high mortality. Herein, we developed self-assembled multifunctional carbon monoxide nanogenerators (Nano CO), as sepsis drug candidates, which can release CO in response to ROS, resulting in clearing bacteria and activating the heme oxygenase-1/CO system. This activation strengthened endogenous protection and scavenged multiple inflammatory mediators to alleviate the cytokine storm, including scavenging RONS and cfDNA, inhibiting macrophage activation, blocking pyroptosis and activating autophagy. Animal experiments show that Nano CO has a good therapeutic effect on mice with LPS-induced sepsis, which is manifested in hypothermia recovery, organ damage repair, and a 50% decrease in mortality rates. Taken together, these results illustrated the efficacy of multifunctional Nano CO to target clearance of multiple mediators in sepsis treatment and act against other refractory inflammation-related diseases.

Artemisia argyi H. Lév. & Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of A. argyi, including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterpenoids in A. argyi remains underexplored. In this study, we identified four β-caryophyllene synthases from A. argyi. A high-yield β-caryophyllene engineered Saccharomyces cerevisiae cell factory has been built in this study. By fusing ERG20 and AarTPS88 with a flexible linker (GGGS)2 and enhancing metabolic flux in the MVA pathway (HIF-1, tHMGR, and UPC2-1), we achieved a titer of β-caryophyllene reached 15.6 g/L by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this represents the highest reported titer of β-caryophyllene in yeast to date. This study provides a valuable tool for the industrial-scale production of β-caryophyllene.

RNA-binding proteins (RBPs) are key post-transcriptional regulators, and the malfunctions of RBP-RNA binding lead to diverse human diseases. However, prediction of RBP binding sites is largely based on RNA sequence features, whereas in vivo RNA structural features based on high-throughput sequencing are rarely incorporated. Here, we designed a deep bimodal information fusion network called DeepFusion for unraveling protein-RNA interactions by incorporating structural features derived from DMS-seq data. DeepFusion integrates two sub-models to extract local motif-like information and long-term context information. We show that DeepFusion performs best compared with other cutting-edge methods with only sequence inputs on two datasets. DeepFusion’s performance is further improved with bimodal input after adding in vivo DMS-seq structural features. Furthermore, DeepFusion can be used for analyzing RNA degradation, demonstrating significantly different RBP-binding scores in genes with slow degradation rates versus those with rapid degradation rates. DeepFusion thus provides enhanced abilities for further analysis of functional RNAs. DeepFusion’s code and data are available at http://bioinfo.org/deepfusion/.

Abstract Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.

Abstract Sorghum ratooning, a time and labor-saving cultivation practice, is increasingly being adopted by farmers in Southwest China as an alternative. Efficient N fertilizer management is critical for economical production of sorghum and the long-term protection of the environment. To investigate the impact of N management on grain yield and nitrogen use efficiencies (NUEs) of ratoon sorghum system, a three-year field experiment was conducted for Jinyunuo3 (a hybrid cultivar) and Guojiaohong1 (an inbred cultivar) using 12 combinations of N rates and splitting ratios. The results showed that increasing N rate and splitting application times led to improvements in various growth parameters such as dry matter weight, crop growth rate (CGR), leaf area index (LAI), and photosynthetic potential (PP). The main, ratoon, and annual yields increased with N rate increase, but there was no significant difference between 225 and 150 kg N ha−1 in the ratoon and annual yields. Splitting the application of N fertilizer enhanced grain yield compared to a single dose application method, especially three-split applications yielded higher than two-split applications. Compared with N rates of 225 and 150 kg ha−1, N rate of 75 kg ha−1 increased apparent recovery rate of applied nitrogen (REN), agronomic efficiency of applied nitrogen (AEN), and partial factor productivity from applied nitrogen (PFPN) in both main season and whole year. But through splitting application methods at high N rates could achieve similar or even higher levels of NUEs compared to all applied as basal fertilizer at low N rates. Therefore, it could be recommended that applying 150 kg N ha−1 with a basal-jointing-heading fertilizer ratio of 2:4:4 represented an efficient N management practice to synchronously obtain high grain yield and NUEs in ratoon sorghum system in Southwest China.

Abstract Ranula is a mucous cyst that occurs in the sublingual gland (SLG) in the floor of the mouth. It can be classified into two types based on origins: One is the the lesser sublingual gland (LSLG) in the anterior segment and the Rivini duct, which is connected to it, and the other is the greater sublingual gland (GSLG) in the posterior segment. Because of the anatomical characteristics, surgical resection of the cysts carries the risk of damaging adjacent tissues and has a high recurrence rate. Intralesional injection of sclerotherapy may be a better alternative treatment. We summarized 65 cases of ranula treated with intralesional injections of bleomycin(BML). According to the origin of the ranula, 60 cases were from the LSLG and the Rivini duct, and 5 cases were from the GSLG. The results showed that 60 cases of ranula from LSLG and Rivini ducts were 100% cured during the follow-up period. The median number of injections for all patients was 1.16. All 5 cases of ranula from the GSLG did not wholly recover. This study confirmed that BLM intralesional injection is a safe and effective treatment modality for cysts from LSLG or the ducts of Rivini rather than GSLG. Therefore, before treatment, it is necessary to determine the type and origin of the cyst by characterizing its morphology to ensure the effectiveness of the treatment.

Aiming at the problem of traffic data distribution shift caused by new unknown attacks in the industrial Internet, a malicious traffic identification method based on neighborhood filtering and stable learning was proposed to enhance the effectiveness and robustness of the existing graph neural network model in identifying known malicious traffic. Firstly, the graph structure of the traffic data was modeled to capture the topological relationship and interaction mode in communication behavior. Secondly, the traffic subgraph was divided based on the neighborhood filtering mechanism of biased sampling to eliminate the pseudo-homogeneity between communication behaviors. Finally, the statistical independence of high-dimensional traffic features was realized by applying graph representation learning and stable learning strategies, combined with adaptive sample weighting and collaborative loss optimization methods. The experimental results on two benchmark datasets show that compared with the baseline method, the recognition performance of the proposed method is increased by more than 2.7% in the new unknown attack scenario, which shows its high efficiency and practicability in the industrial Internet environment.

Abstract Removal of heavy metal pollutants from wastewater is critical for preserving a clean environmental setting and guaranteeing universal well-being. Physical, chemical, and biological approaches have been devised for the removal of heavy metals from various wastewater sources. Methods used include electrocoagulation (EC) and adsorption (AD). Although both methods are reported to be efficiently applied in wastewater treatment, the EC method is impeded by high energy consumption, particularly when treating concentrated effluents, as it demands substantial current for coagulant formation. Alternatively, the AD process is hindered by adsorbent saturation and the competitive effects of specific chemicals. Here, we only found limited studies on integrated EC-AD combined process, where the AD and EC were either used in separate or combined system vessels to augment the removal efficiency of heavy metal ions from wastewater or synthetic solutions. It is imperative to conduct more studies on synergistic approaches that combine adsorption with other wastewater treatment methods to address current limits and optimize removal processes. The review identified current density, pH, time, temperature, and adsorbent dosages as factors influencing the EC-AD process in heavy in the removal of heavy metals from wastewater. Although electrocoagulation combined with adsorption has been explored in several studies which have been confined to synthetic effluents, limiting their relevance to real-world scenarios. Therefore, this review proposes for development and design of EC-AD combined technologies to exploit their strengths and minimize associated limitations. Overall, the combined strategies proved more effective and economical compared to individual adsorption and electrocoagulation methods.

Due to the substantial production and use of antibiotics, they inevitably remain in aquatic environments, posing a serious threat to aquatic ecosystems. However, there are currently no criteria of antibiotics for ecological risk in the water environment. In the present study, three types of antibiotics (tetracyclines, sulfonamides and quinolones) that are often detected in water environments were investigated. Toxicity data regarding bacteria, algae, plants, invertebrates and vertebrates were selected, and the species sensitivity distribution was used to obtain the ecological risk criteria of antibiotics to aquatic organisms. Animals are the least sensitive to antibiotics. The overall toxicity of antibiotics is most sensitive to bacteria and cyanobacteria, followed by green algae and plants. The recommended ecological criteria for tetracyclines, quinolones, and sulfonamides are 22, 17, and 94 μg/L, respectively. Ofloxacin needs to be used with caution because it has a small acute predicted no-effect concentration (PNEC) of 0.6 μg/L. The ecological risk criterion for chronic toxicity of total antibiotics was determined to be 1.4 μg/L. The PNECs measured for the quinolone, tetracycline, and sulfonamide antibiotics were 0.5, 2.2, and 2.4 μg/L, respectively. Norfloxacin had the highest chronic toxicity zone of 353, indicating that chronic poisoning is most likely to occur. Moreover, there was an exponential correlation between acute PNEC and chronic PNEC. In addition, a quantitative structure–activity relationship model was constructed for acute ecological risk criteria of antibiotics to aquatic organisms. These findings can expand the ecological risk threshold data on the effects of antibiotics on aquatic organisms, and provide a theoretical basis for the environmental risk assessment of antibiotics.

Soybean cyst nematode disease represents the major soil-borne disease of soybean. Identifying disease-resistant genes in soybean has a substantial impact on breeding of disease-resistant crops and genetic improvement. The present work created the F2 population with the disease-resistant line H-10 and disease-susceptible line Chidou4. 30 respective F2disease-resistant and disease-susceptible individuals for forming two DNA pools for whole-genome re-sequencing were selected. As a result, a total of 11,522,230 single nucleotide polymorphism (SNPs) markers from these two parental lines and two mixed pools were obtained. Accordng to SNP-index based association analysis, there were altogether 741 genes out of 99% confidence interval, which were mainly enriched into regions of 38,524,128∼39,849,988 bp with a total length of 1.33 Mb contain 111 genes on chromosome 2, 27,821,012∼29,612,574 bp with a total length of 1.79 Mb contain 92 genes on chromosome 3, 308∼348,214 bp with a total of length 0.35 Mb contain 34 genes on chromosome 10, and 53,867,581∼58,017, 852 bp with a total length of 4.15 Mb contain 504 genes on chromosome 18. Bulk segregant analysis in F2 generations (BSA-seq) was correlated with a disease resistance interval containing 15 genes. Then, using bioinformatics analysis and differential expression analysis, five candidate genes were identified: Glyma.02G211400, Glyma.18G252800, Glyma.18G285800, Glyma.18G287400 and Glyma.18G298200. Our results provides a key basis for analyzing the soybean resistance mechanism against soybean cyst nematode and cloning soybean resistance genes.

IntroductionIn clinical diagnosis of porcine diseases, co-infection with multiple viruses often leads to similar clinical symptoms. Postweaning multisystemic wasting syndrome (PMWS) can be caused by infections with TTSuV or PCV2, while PCV2, PRV, and PPV can cause respiratory and reproductive disorders in pigs. The overlapping clinical and pathological features of these infections necessitate the development of a rapid and specific method for differentiating and detecting these four DNA viruses.MethodsIn this study, four pairs of primers and TaqMan probes were designed targeting the conserved sequence of TTSuV, the Rep gene of PCV2, the gE gene of PRV, and the VP2 gene of PPV. After optimizing reaction conditions, including annealing temperature, primer concentration, and probe concentration, a quadruplex real-time PCR method was developed.ResultsThis method can specifically detect TTSuV1, PCV2, PRV, and PPV simultaneously, with no cross-reactivity with ASFV, CSFV, PRRSV, PEDV, PSV, and TGEV. The minimum detection limit for each virus was 10 copies/μl, and the inter-assay and intra-assay coefficients of variation ranged from 0.33% to 1.43%. Subsequently, 150 clinical samples were tested to evaluate the practical applicability of this method. The positive rates for TTSuV1, PCV2, PRV, and PPV were 8.6% (13/150), 10.67% (16/150), 14% (21/150), and 11.33% (17/150), respectively.DiscussionThe results indicate that the established quadruplex real-time PCR method can assist in the accurate and rapid diagnosis of TTSuV1, PCV2, PRV, and PPV in clinical settings, providing robust support for the prevention and control of these infections.

Rotenone (ROT), a widely used natural pesticide, has an uncertain effect on reproductive toxicity. In this study, we used 20 mice distributed randomly into four groups, with each group receiving ROT doses of 0, 2, 4, and 8 mg/kg/day for 28 days. The results demonstrated that ROT induced significant testicular damage, including impaired spermatogenesis, inhibition of testosterone synthesis, and apoptosis of Leydig cells. Additionally, ROT disrupted the normal ultrastructure of the endoplasmic reticulum (ER) in testicular tissue, leading to ER stress in Leydig cells. To further explore whether ROT-induced apoptosis in Leydig cells is related to ER stress, the mouse Leydig cell line (TM3 cells) was treated with ROT at 0, 250, 500, and 1000 nM. ROT inhibited TM3 cell viability, induced cytotoxicity, and reduced testosterone content in the culture supernatants. Furthermore, ROT treatment triggered apoptosis in TM3 cells by activating ER stress and the PERK-eIF2α-CHOP signalling pathway. Pre-treatment of TM3 cells exposed to ROT with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects, decreasing apoptosis and preserving testosterone levels. Further intervention with the PERK inhibitor GSK2606414 reduced ROT-induced apoptosis and testosterone reduction by inhibiting PERK activity. In summary, ROT-induced male reproductive toxicity is specifically driven by apoptosis, with the PERK-eIF2α-CHOP signalling pathway activated by ER stress playing a crucial role in the apoptosis of Leydig cells triggered by ROT.

The ventilation system is one of the essential safety systems in underground power spaces. Over the years, active ventilation has been widely employed for heat dissipation in underground power spaces. In operation, high-power equipment generates significant heat, necessitating sufficient heat dissipation for smooth and efficient functioning. The effectiveness of the ventilation system is influenced by airflow, making aerodynamics a crucial aspect of studying underground power spaces. This study establishes a comprehensive hybrid model (a combination of physical and data-driven models) representing underground power spaces. Ansys Fluent and MATLAB are used to simulate and calculate temperature fields for various structures. The physical model employs model order reduction to achieve efficient computation without compromising accuracy. For the data-driven model, a genetic neural network is developed for multifactor nonlinear optimisation to evaluate and analyse thermal behaviour within the space. The integrated hybrid model enables efficient and high-precision calculations for the underground power space’s ventilation system. The research outcomes provide a theoretical foundation for practical construction and design schemes of underground power spaces, contributing significantly to ensuring their safety and optimal functionality in real-world applications.

Tire wear particles (TWPs), common mixed particulate emerging contaminants in the environment, have global per capita emissions accounting for 0.23–1.9 kg/year, attracting global attention recently due to their wide detection, small size, mobility, and high toxicity. This review focuses on the occurrence characteristics of TWPs in multiple environmental media, adverse effects on organisms, potential toxicity mechanisms, and environmental risk prevention and control strategies of TWPs. The environmental fate of TWPs throughout the entire process is systematically investigated by the bibliometric analysis function of CiteSpace. This review supplements the gap in the joint toxicity and related toxicity mechanisms of TWPs with other environmental pollutants. Based on the risks review of TWPs and their additives, adverse impacts have been found in organisms from aquatic environments, soil, and humans, such as the growth inhibition effect on Chironomus dilutes. A multi-faceted and rationalized prevention and control treatment of ''source-process-end'' for the whole process can be achieved by regulating the use of studded tires, improving the tire additive formula, growing plants roadside, encouraging micro-degradation, and other methods, which are first reviewed. By addressing the current knowledge gaps and exploring prospects, this study contributes to developing strategies for reducing risks and assessing the fate of TWPs in multiple environmental media.

Abstract Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

Abstract As a progressive security strategy, the zero trust model has attracted notable attention and importance within the realm of network security, especially in the context of the Internet of Things (IoT). This paper aims to evaluate the current research regarding zero trust and to highlight its practical applications in the IoT sphere through extensive bibliometric analysis. We also delve into the vulnerabilities of IoT and explore the potential role of zero trust security in mitigating these risks via a thorough review of relevant security schemes. Nevertheless, the challenges associated with implementing zero trust security are acknowledged. We provide a summary of these issues and suggest possible pathways for future research aimed at overcoming these challenges. Ultimately, this study aims to serve as a strategic analysis of the zero trust model, intending to empower scholars in the field to pursue deeper and more focused research in the future.

Abstract The van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.

Abstract Background Wilms’ tumor (WT) is the most common renal tumor in childhood. Pyroptosis, a type of inflammation-characterized and immune-related programmed cell death, has been extensively studied in multiple tumors. In the current study, we aim to construct a pyroptosis-related gene signature for predicting the prognosis of Wilms’ tumor. Methods We acquired RNA-seq data from TARGET kidney tumor projects for constructing a gene signature, and snRNA-seq data from GEO database for validating signature-constructing genes. Pyroptosis-related genes (PRGs) were collected from three online databases. We constructed the gene signature by Lasso Cox regression and then established a nomogram. Underlying mechanisms by which gene signature is related to overall survival states of patients were explored by immune cell infiltration analysis, differential expression analysis, and functional enrichment analysis. Results A pyroptosis-related gene signature was constructed with 14 PRGs, which has a moderate to high predicting capacity with 1-, 3-, and 5-year area under the curve (AUC) values of 0.78, 0.80, and 0.83, respectively. A prognosis-predicting nomogram was established by gender, stage, and risk score. Tumor-infiltrating immune cells were quantified by seven algorithms, and the expression of CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages are positively or negatively correlated with risk score. Two single nuclear RNA-seq samples of different histology were harnessed for validation. The distribution of signature genes was identified in various cell types. Conclusions We have established a pyroptosis-related 14-gene signature in WT. Moreover, the inherent roles of immune cells (CD8( +) T cells, B cells, Th2 cells, dendritic cells, and type 2 macrophages), functions of differentially expressed genes (tissue/organ development and intercellular communication), and status of signaling pathways (proteoglycans in cancer, signaling pathways regulating pluripotent of stem cells, and Wnt signaling pathway) have been elucidated, which might be employed as therapeutic targets in the future.

Abstract To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P

HMGA2, a pivotal transcription factor, functions as a versatile regulator implicated in the progression of diverse aggressive malignancies. In this study, mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2, and USP48 was identified as a deubiquitinating enzyme of HMGA2. The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis. We discovered that USP48 undergoes SUMOylation at lysine 258, which enhances its binding affinity to HMGA2. Through subsequent phenotypic screening of small molecules, we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48. Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2. Clinically, upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer (CRC). Collectively, our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC, but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

Craniomaxillofacial (CMF) reconstruction is a challenging clinical dilemma. It often necessitates skin replacement in the form of autologous graft or flap surgery, which differ from one another based on hypodermal/dermal content. Unfortunately, both approaches are plagued by scarring, poor cosmesis, inadequate restoration of native anatomy and hair, alopecia, donor site morbidity, and potential for failure. Therefore, new reconstructive approaches are warranted, and tissue engineered skin represents an exciting alternative. In this study, we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting (IOB), which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting. Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix (adECM) and stem cells (ADSCs), skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies. adECM, even at a very low concentration such as 2 % or less, has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo. Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects, accomplishing near-complete wound closure within two weeks. More importantly, both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame. Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.

Coal is the main energy source in China, and the western region in China is the main coal production area. The protection and utilization of coal mine water is the major technical challenge in the coal mining. The coal green mining research team of China Energy Group has pioneered the technology of underground coal mine reservoirs, which has been widely implemented in the Shendong mining area in Western China, providing over 95% of water needed for mining and ensuring the sustainable development of the mining area. To further enrich and improve the theoretical and technical system of underground coal mine reservoirs, this technology has been promoted and applied under different geological and working conditions in the western coal mining areas to ensure national energy security and water resources protection. The research team has built the original technology experimental platform system for coal mine underground reservoirs, including the comprehensive intelligent experimental platform for underground water transport and protection, the physical modelling platform for coal mine underground reservoirs under multiple coal seams, the dam structure experimental platform for coal mine underground reservoirs, the simulation experimental platform for deep well construction in western areas, the water-rock coupling mechanism experimental platform for underground water reservoirs, the integrated water treatment process experimental platform, and the impact experimental platforms for coal mine underground reservoirs, etc. On these platforms, the researches can be carried out consisting of the transport law of underground water, the optimization of dam structure parameters, the safety and stability of reservoirs, water-rock coupling mechanism, the optimization of mine water treatment, and the impact of caving rock mass on the dam structure under different coal seam occurrence conditions in the western mining areas of China. These platform systems provide a theoretical support and technical verification for the construction, operation, and safety of coal mine underground reservoirs. By utilizing these experimental platforms, various experimental research studies have been conducted, including the stability and seepage of coal mine underground reservoirs under multiple coal seams, the structural safety of coal mine underground reservoirs dam, and the water-rock coupling mechanism of coal mine underground reservoirs. These research results have been applied in actual engineering practice to ensure the safe and stable operation of coal mine underground reservoirs.

Abstract Background Drought severely limits sunflower production especially at the seedling stage. To investigate the response mechanism of sunflowers to drought stress, we utilized two genotypes of sunflower materials with different drought resistances as test materials. The physiological responses were investigated under well-watered (0 h) and drought-stressed conditions (24 h, 48 h, and 72 h). Results ANOVA revealed the greatest differences in physiological indices between 72 h of drought stress and 0 h of drought stress. Transcriptome analysis was performed after 72 h of drought stress. At 0 h, there were 7482 and 5627 differentially expressed genes (DEGs) in the leaves of K55 and K58, respectively, and 2150 and 2527 DEGs in the roots of K55 and K58, respectively. A total of 870 transcription factors (TFs) were identified among theDEGs, among which the high-abundance TF families included AP2/ERF, MYB, bHLH,and WRKY. Five modules were screened using weighted gene coexpressionnetwork analysis (WGCNA), three and two of which were positively and negatively, respectively, related to physiological traits. KEGG analysis revealedthat under drought stress, “photosynthesis”, “carotenoid biosynthesis”, “starch and sucrose metabolism”, “ribosome”, “carotenoid biosynthesis”, “starch and sucrose metabolism”, “protein phosphorylation” and “phytohormone signaling” are six important metabolic pathways involved in the response of sunflower to drought stress. Cytoscape software was used to visualize the three key modules, and the hub genes were screened. Finally, a total of 99 important candidate genes that may be associated with the drought response in sunflower plants were obtained, and the homology of these genes was compared with that in Arabidopsis thaliana. Conclusions Taken together, our findings could lead to a better understanding of drought tolerance in sunflowers and facilitate the selection of drought-tolerant sunflower varieties.

Skeletal muscle diseases, a broad category encompassing a myriad of afflictions such as acute muscle injury and muscular dystrophies, pose a significant health burden globally. These conditions often lead to muscle weakness, compromised mobility, and a diminished quality of life. In light of this, innovative and effective therapeutic strategies are fervently sought after. Exosomes, naturally extracellular vesicles with a diameter of 30–150 nm, pervade biological fluids. These microscopic entities harbor a host of biological molecules, including proteins, nucleic acids, and lipids, bearing a significant resemblance to their parent cells. The roles they play in the biological theater are manifold, influencing crucial physiological and pathological processes within the organism. In the context of skeletal muscle diseases, their potential extends beyond these roles, as they present a promising therapeutic target and a vehicle for targeted drug delivery. This potentially paves the way for significant clinical applications. This review aims to elucidate the mechanisms underpinning exosome action, their myriad biological functions, and the strides made in exosome research and application. A comprehensive exploration of the part played by exosomes in skeletal muscle repair and regeneration is undertaken. In addition, we delve into the use of exosomes in the therapeutic landscape of skeletal muscle diseases, providing a valuable reference for a deeper understanding of exosome applications in this realm. The concluding section encapsulates the prospective avenues for exosome research and the promising future they hold, underscoring the tremendous potential these diminutive vesicles possess in the field of skeletal muscle diseases.The Translational Potential of this Article.The comprehensive exploration of exosome's diverse biological functions and translational potential in the context of skeletal muscle diseases presented in this review underscores their promising future as a therapeutic target with significant clinical applications, thus paving the way for innovative and effective therapeutic strategies in this realm.

Abstract Background Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. Methods Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. Results A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn’s disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn’s disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. Conclusions Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn’s disease, and ulcerative colitis).

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a leading public health problem worldwide. Approximately one fourth of patients with nonalcoholic fatty liver (NAFL) progress to nonalcoholic steatohepatitis (NASH), an advanced stage of NAFLD. Hence, there is an urgent need to make a better understanding of NAFLD heterogeneity and facilitate personalized management of high-risk NAFLD patients who may benefit from more intensive surveillance and preventive intervene. Methods In this study, a series of bioinformatic methods were performed to identify NAFLD progression-specific pathways and genes, and three machine learning approaches were combined to construct a risk-stratification gene signature to quantify risk assessment. In addition, bulk RNA-seq, single-cell RNA-seq (scRNA-seq) transcriptome profiling data and whole-exome sequencing (WES) data were comprehensively analyzed to reveal the genomic alterations and altered pathways between distinct molecular subtypes. Results Two distinct subtypes of NAFL were identified with the NAFLD progression-specific genes, and one subtype has a high similarity of the inflammatory pattern and fibrotic potential with NASH. The established risk-stratification gene signature could discriminate advanced samples from overall NAFLD. COL1A2, one key gene closely related to NAFLD progression, is specifically expressed in fibroblasts involved in hepatocellular carcinoma (HCC), and significantly correlated with EMT and angiogenesis in pan-cancer. Moreover, the β-catenin/COL1A2 axis might play a critical role in fibrosis severity and inflammatory response during NAFLD-HCC progression. Conclusion In summary, our study provided evidence for the necessity of molecular classification and established a risk-stratification gene signature to quantify risk assessment of NAFLD, aiming to identify different risk subsets and to guide personalized treatment.

Abstract Background Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. Methods A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. Results In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. Conclusions Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

Abstract Reactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H2O2) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO2@Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO2) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H2O2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO2@Dex into biofilms, while CaO2 generated a substantial amount of H2O2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H2O2 into hydroxyl radicals (•OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO2@Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.

Laser soldering has attracted attention in microbumps joining field due to its noncontact and localized heating, a short joining time, fluxless and easy automation. In this study, Sn-3.0Ag-0.5Cu/Ni–P microbumps were prepared by laser soldering and reflow soldering respectively, then the effects of isothermal aging and multiple reflowing on microstructure and shear properties of the microbumps were compared and analyzed. The results show that a small granular and loose (Cu, Ni)6Sn5 intermetallic compounds and striated Sn grains were formed in laser-soldered microbumps, while a long and needlelike (Cu, Ni)6Sn5 intermetallic compounds and intertwined twins Sn grains were generated in reflow-soldered microbumps. During isothermal aging at 150 °C, the morphology of (Cu, Ni)6Sn5 particles changed to scallop with a large aspect ratio in the laser-soldered microbumps, which evolve to short rod-like in reflow-soldered microbumps, and the IMCs thickness in laser-soldered microbumps was always much thinner than that in reflow-soldered microbumps. The shear strength of as-soldered microbumps by laser soldering was slightly higher than that by reflow soldering ones, which sharply decreased from 0 to 100 h for both cases, and then was maintained at a similar level with increasing aging time. During multiple reflowing, the thickness of IMCs gradually increased in both cases, and the morphology of (Cu, Ni)6Sn5 particles changed to a dense short rod in laser soldered microbumps, which evolved to an irregular lumpy and long rod-like in reflow soldered microbumps. The shear strength for both laser and reflow soldered microbumps decreased with increasing reflowing times, but the decrease amplitude was all small. Moreover, the (Cu, Ni)6Sn5 IMCs transformed from granular to rod-like related to the content Ni atoms, and which critical value was evaluated to be 6–10 at%, based on the Jackson parameter α. Therefore, laser soldering is effective for reducing the thickness of IMCs and ensuring the mechanical property after isothermal aging and multiple reflowing of the microbumps was similar to reflow soldering.

Porous materials with excellent load-bearing capacity are essential for aerospace, shipbuilding, and biomedical devices where lightweight structures are required. In this study, a design strategy of mechanical metamaterials with a shell-based structure is proposed. By re-filling curved surfaces in the tetrahedral wireframe, closed cavities inside the structure are eliminated and the manufacturability is improved. The modified tetrahedron is mirrored, cut with specific proportions (25%, 50%, and 75%), and arrayed to form different structures. The compression performance of the structure is investigated using stereolithographic specimens and numerical methods. Compared with the mechanical metamaterials based on triply periodic minimal surfaces (TPMS) and strut-based structures, the new shell-based structures exhibit excellent strength and stiffness. The compressive strength and Young’s modulus of the structure with 50% cutting proportion are increased by 65% and 80%, respectively, compared with the Gyroid structure. This study offers a new design strategy for mechanical metamaterials with excellent compression-resistant capability.

IntroductionHepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Traditional Chinese Medicine (TCM) is widely utilized as an adjunct therapy, improving patient survival and quality of life. TCM categorizes HCC into five distinct syndromes, each treated with specific herbal formulae. However, the molecular mechanisms underlying these treatments remain unclear.MethodsWe employed a network medicine approach to explore the therapeutic mechanisms of TCM in HCC. By constructing a protein-protein interaction (PPI) network, we integrated genes associated with TCM syndromes and their corresponding herbal formulae. This allowed for a quantitative analysis of the topological and functional relationships between TCM syndromes, HCC, and the specific formulae used for treatment.ResultsOur findings revealed that genes related to the five TCM syndromes were closely associated with HCC-related genes within the PPI network. The gene sets corresponding to the five TCM formulae exhibited significant proximity to HCC and its related syndromes, suggesting the efficacy of TCM syndrome differentiation and treatment. Additionally, through a random walk algorithm applied to a heterogeneous network, we prioritized active herbal ingredients, with results confirmed by literature.DiscussionThe identification of these key compounds underscores the potential of network medicine to unravel the complex pharmacological actions of TCM. This study provides a molecular basis for TCM’s therapeutic strategies in HCC and highlights specific herbal ingredients as potential leads for drug development and precision medicine.

Volatile fatty acid derivatives (VFADs) play a significant role in contributing to flowery–fruity flavor black tea. Innovative black tea is typically crafted from aroma-intensive tea cultivars, such as Jinmudan, using defined production methodologies. In this study, the during-processing tea leaves of innovative black tea were applied as materials, and we selected a total of 45 VFADs, comprising 11 derived aldehydes, nine derived alcohols, and 25 derived esters. Furthermore, the dynamic variations of these VFADs were uncovered. Transcriptome analysis was performed to identify genes involved in the LOX (lipoxygenase) pathway, resulting in the identification of 17 CsLOX genes, one hydrogen peroxide lyase (CsHPL) gene, 11 alcohol dehydrogenases (CsADH) genes, 11 genes as acyl CoA oxidase (CsACOX) genes, and three allene oxide synthase (CsAOS) genes. Additionally, the expression levels of these genes were measured, indicating that the processing treatments of innovative black tea, particularly turn-over and fermentation, had a stimulation effect on most genes. Finally, qRT-PCR verification and correlation analysis were conducted to explain the relationship between VFADs and candidate genes. This study aims to provide a reference for illuminating the formation mechanisms of aroma compounds in innovative black tea, thereby inspiring the optimization of innovative processing techniques and enhancing the overall quality of black tea.

Porcine epidemic diarrhea virus (PEDV) is associated with severe enteritis, which contributes to high mortality in piglets. The aim of this study was to describe molecular mechanisms associated with proinflammatory cytokine(s) production during PEDV infection. We showed that infection of porcine intestine epithelial cell clone J2 (IPEC-J2) with PEDV induces a gradual increase in interleukin 8 (IL-8) production at different time points, as well as infection of Vero E6 with PEDV. The secretion of IL-8 in these two cell lines infected with PEDV is related to the activation of NF-κB. Furthermore, the cells expressing PEDV M or E protein can induce the upregulation of IL-8. These findings suggest that the IL-8 production can be the initiator of inflammatory response by the host cells upon PEDV infection.

We herein present a case of a ruptured giant omphalocele with congenital short small intestine. Vacuum-sealing drainage and carboxymethylcellulose silver dressing promoted wound healing after repair, avoided abdominal compartment syndrome, and reduced the risks of multiple procedures. We review the perioperative management of omphaloceles in congenital short small intestines.

Ischemic heart disease (IHD) can trigger responses from the innate immune system, provoke aseptic inflammatory processes, and result in the recruitment and accumulation of neutrophils. Excessive recruitment of neutrophils is a potential driver of persistent cardiac inflammation. Once recruited, neutrophils are capable of secreting a plethora of inflammatory and chemotactic agents that intensify the inflammatory cascade. Additionally, neutrophils may obstruct microvasculature within the inflamed region, further augmenting myocardial injury in the context of IHD. Immune-related molecules mediate the recruitment process of neutrophils, such as immune receptors and ligands, immune active molecules, and immunocytes. Non-immune-related molecular pathways represented by pro-resolving lipid mediators are also involved in the regulation of NR. Finally, we discuss novel regulating strategies, including targeted intervention, agents, and phytochemical strategies. This review describes in as much detail as possible the upstream molecular mechanism and external intervention strategies for regulating NR, which represents a promising therapeutic avenue for IHD.

BackgroundThis research explores the causal association between circulating inflammatory markers and the development of sciatica, a common and debilitating condition. While previous studies have indicated that inflammation may be a factor in sciatica, but a thorough genetic investigation to determine a cause-and-effect relationship has not yet been carried out. Gaining insight into these interactions may uncover novel treatment targets.MethodsWe utilized data from the OpenGWAS database, incorporating a large European cohort of 484,598 individuals, including 4,549 sciatica patients. Our study focused on 91 distinct circulating inflammatory markers. Genetic variations were employed as instrumental variables (IVs) for these markers. The analysis was conducted using inverse variance weighting (IVW) as the primary method, supplemented by weighted median-based estimation. Validation of the findings was conducted by sensitivity studies, utilizing the R software for statistical computations.ResultsThe analysis revealed that 52 out of the 91 inflammatory markers studied showed a significant causal association with the risk of developing sciatica. Key markers like CCL2, monocyte chemotactic protein-4, and protein S100-A12 demonstrated a positive correlation. In addition, there was no heterogeneity or horizontal pleiotropy in these results. Interestingly, a reverse Mendelian randomization analysis also indicated potential causative effects of sciatica on certain inflammatory markers, notably Fms-related tyrosine kinase 3 ligands.DiscussionThe study provides robust evidence linking specific circulating inflammatory markers with the risk of sciatica, highlighting the role of inflammation in its pathogenesis. These findings could inform future research into targeted treatments and enhance our understanding of the biological mechanisms underlying sciatica.

A 60-day feeding trial was conducted to investigate the effects of dietary a Chinese herbal compound (CHC) including Pulsatillae Radix, Coptidis Rhizoma, Cortex Phellodendri Amurensis and Fraxini Cortex on the growth performance, intestinal and liver histology, antioxidative capacity and immunity of juvenile large yellow croaker (Larimichthys crocea) with the initial body weight of 17.00 ± 0.03 g. Four experimental diets were formulated to contain 0 mg/kg (CHC0), 250 mg/kg (CHC250), 500 mg/kg (CHC500), and 750 mg/kg (CHC750) of CHC, respectively. Results showed that dietary CHC did not significantly affect the survival of large yellow croaker (P > 0.05). Compared with the control, the CHC500 group showed higher weight gain and protein efficiency ratio, along with a lower feed conversion ratio (P < 0.05). Furthermore, increasing levels of dietary CHC linearly decreased the activities of aspartate aminotransferase and alanine aminotransferase, and malondialdehyde content in serum. Moreover, dietary CHC significantly increased the total antioxidative capacity and complement levels in serum (P < 0.05). The relative expressions of sod1, nrf2, il-10 and tnf-α in liver and intestine were upregulated in the CHC500 group (P < 0.05). Additionally, the activities of digestive and absorptive enzymes in intestine were significantly increased in the CHC500 group (P < 0.05). The length of intestinal villus height, villus width and perimeter ratio were higher in the CHC supplemented diets. In conclusion, CHC supplementation in diet could improve growth performance, anti-oxidative capacity and immunity of large yellow croaker.

The present study aims to investigate the effects of dietary Chinese herbs mixture (CHM) including Artemisia capillaris, Gardenia jasminoides, Scutellaria baicalensis, Reynoutria japonica and Uncaria rhynchophylla on the growth performance, anti-oxidative and immune responses, and intestine and liver histology of juvenile large yellow croaker Larimichthys crocea (initial body weight: 17.03 ± 0.03 g), which were fed graded levels of CHM (0 (control group), 250, 500 and 750 mg/kg, respectively) for 60 days. The results indicated that supplementing 250 and 500 mg/kg CHM in diet significantly increased the weight gain rate and decreased the feed conversion ratio of juvenile large yellow croaker (P < 0.05). The activities of lipase, chymotrypsin, γ-glutamyl transferase and Na+, K+-ATPase were significantly increased in CHM250 and/or CHM500 groups (P < 0.05). Besides, the levels of total anti-oxidative capacity, immunoglobulin M, complement 3 and complement 4 were significantly increased in the CHM250 and/or CHM500 groups (P < 0.05). The expressions of anti-oxidation gene (nuclear factor erythroid 2-related factor 2, nrf2), anti-inflammatory cytokines (interleukin-10, il-10 and transforming growth factor-β, tgf-β) and anti-apoptotic gene (B-cell lymphoma-2, bcl-2) in liver were significantly up-regulated, while the malondialdehyde content and the expressions of kelch like ECH associated protein 1 (keap1) and nuclear factor κB p65 (nf-κb p65) were significantly down-regulated after supplementing 250 and/or 500 mg/kg CHM in diet (P < 0.05). The histological analysis of liver and intestine showed the better morphology in CHM250 and CHM500 groups than the control group. In conclusion, above results indicated that dietary CHM (250 – 500 mg/kg) significantly improved the growth performance, anti-oxidative capacity, immunity and histology of liver and intestine of juvenile large yellow croaker.

PurposeTo evaluate the visual and refractive outcomes of astigmatic cataract patients following opposite clear corneal incision (OCCI) combined with rotationally asymmetric multifocal intraocular lens (IOL) implantation.SettingDepartment of Ophthalmology, Zhongshan Hospital (Xiamen), Fudan University, People’s Republic of China.DesignRetrospective cohort study.MethodsThis study comprised 58 cataract eyes of 54 patients with corneal astigmatism who underwent phacoemulsification and rotationally asymmetric multifocal IOL implantation which received either OCCI (OCCI group) or a single clear corneal incision (SCCI group). The follow-up period was 3 months after surgery. Distance, intermediate and near visual acuity, refractive outcomes, and corneal anterior keratometry were compared between the two groups. Vector analysis was used to evaluate astigmatism correction.ResultsThree months after surgery, the distance, intermediate and near visual acuity, and sphere remained comparable between the two groups, but a significant difference was detected in residual astigmatism and anterior corneal keratometric astigmatism. In the OCCI group, the residual astigmatism and keratometric astigmatism were −0.60 ± 0.29 D and 0.59 ± 0.28 D, respectively, which were lower than those in SCCI groups (−1.18 ± 0.47 D and 1.15 ± 0.45 D, both p < 0.05). In vector analysis, the difference vector (DV), angle of error (AoE), absolute AoE, index of success (IoS) and correction index (CI) were statistically significantly different between the two groups (p < 0.05).ConclusionOCCI combined with rotationally asymmetric multifocal intraocular lens implantation showed predictable and desirable efficacy in treating cataract patients with astigmatism.

Abstract The development of efficient and durable non‐precious hydrogen evolution reaction (HER) catalysts for scaling up alkaline water/seawater electrolysis is highly desirable but challenging. Amorphous‐crystalline (A‐C) heterostructures have garnered attention due to their unusual atomic arrangements at hetero‐interfaces, highly exposed active sites, and excellent stability. Here, a heterogeneous synthesis strategy for constructing A‐C non‐homogeneous interfacial centers of electrocatalysts on nanocages is presented. Isolated PdCo clusters on nanoscale islands in conjunction with Co3S4 A‐C, functioning as a bifunctional site “island‐sea” synergy, enable the dynamic confinement design of metal active atoms, resulting in excellent HER catalytic activity and durability. The hierarchical structure of hollow porous nanocages and nanoclusters, along with their large surface area and multi‐dimensional A‐C boundaries and defects, provides the catalyst with abundant active centers. Theoretical calculations demonstrate that the combination of PdCo and Co3S4 regulates the redistribution of interface electrons effectively, promoting the sluggish water‐dissociation kinetics at the cluster Co sites. Additionally, PdCo‐Co3S4 heterostructure nanocages exhibit outstanding HER activity in alkaline seawater and long‐term stability for 100 h, which can be powered by commercial silicon solar cells. This finding significantly advances the development of alkaline seawater electrolysis for large‐scale hydrogen production.

The objective of this study is to investigate methodologies concerning enterprise financial sharing and risk identification to mitigate concerns associated with the sharing and safeguarding of financial data. Initially, the analysis examines security vulnerabilities inherent in conventional financial information sharing practices. Subsequently, blockchain technology is introduced to transition various entity nodes within centralized enterprise financial networks into a decentralized blockchain framework, culminating in the formulation of a blockchain-based model for enterprise financial data sharing. Concurrently, the study integrates the Bi-directional Long Short-Term Memory (BiLSTM) algorithm with the transformer model, presenting an enterprise financial risk identification model referred to as the BiLSTM-fused transformer model. This model amalgamates multimodal sequence modeling with comprehensive understanding of both textual and visual data. It stratifies financial values into levels 1 to 5, where level 1 signifies the most favorable financial condition, followed by relatively good (level 2), average (level 3), high risk (level 4), and severe risk (level 5). Subsequent to model construction, experimental analysis is conducted, revealing that, in comparison to the Byzantine Fault Tolerance (BFT) algorithm mechanism, the proposed model achieves a throughput exceeding 80 with a node count of 146. Both data message leakage and average packet loss rates remain below 10 %. Moreover, when juxtaposed with the recurrent neural networks (RNNs) algorithm, this model demonstrates a risk identification accuracy surpassing 94 %, an AUC value exceeding 0.95, and a reduction in the time required for risk identification by approximately 10 s. Consequently, this study facilitates the more precise and efficient identification of potential risks, thereby furnishing crucial support for enterprise risk management and strategic decision-making endeavors.

Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical pursuit. Currently used traditional block-shaped or mesh patches, typically incorporating a positive Poisson's ratio, often fall short of matching the deformation characteristics of cardiac tissue satisfactorily, thus often diminishing their repairing capability. By introducing auxeticity into the cardiac patches, this study is trying to present a beneficial approach to address these shortcomings of the traditional patches. The patches, featuring the auxetic effect, offer unparalleled conformity to the cardiac complex mechanical challenges. Initially, scaffolds demonstrating the auxetic effect were designed by merging chiral rotation and concave angle units, followed by integrating scaffolds with a composite hydrogel through thermally triggering, ensuring excellent biocompatibility closely mirroring heart tissue. Tensile tests revealed that auxetic patches possessed superior elasticity and strain capacity exceeding cardiac tissue's physiological activity. Notably, Model III showed an equivalent modulus ratio and Poisson's ratio closely toward cardiac tissue, underscoring its outstanding mechanical potential as cardiac patches. Cyclic tensile loading tests demonstrated that Model III withstood continuous heartbeats, showcasing outstanding cyclic loading and recovery capabilities. Numerical simulations further elucidated the deformation and failure mechanisms of these patches, leading to an exploration of influence on mechanical properties with alternative design parameters, which enabled the customization of mechanical strength and Poisson's ratio. Therefore, this research presents substantial potential for designing cardiac auxetic patches that can emulate the deformation properties of cardiac tissue and possess adjustable mechanical parameters.