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Most acute ischemic stroke patients with large vessel occlusion require stent implantation for complete recanalization. Yet, due to ischemia-reperfusion injury, over half of these patients still experience poor prognoses. Thus, neuroprotective treatment is imperative to alleviate the ischemic brain injury, and a proof-of-concept study was conducted on “biodegradable neuroprotective stent”. This concept is premised on the hypothesis that locally released Mg2+/H2 from Mg metal within the bloodstream could offer synergistic neuroprotection against reperfusion injury in distant cerebral ischemic tissues. Initially, the study evaluated pure Mg's neuroactive potential using oxygen-glucose deprivation/reoxygenation (OGD/R) injured neuron cells. Subsequently, a pure Mg wire was implanted into the common carotid artery of the transient middle cerebral artery occlusion (MCAO) rat model to simulate human brain ischemia/reperfusion injury. In vitro analyses revealed that pure Mg extract aided mouse hippocampal neuronal cell (HT-22) in defending against OGD/R injury. Additionally, the protective effects of the Mg wire on behavioral abnormalities, neural injury, blood-brain barrier disruption, and cerebral blood flow reduction in MCAO rats were verified. Conclusively, Mg-based biodegradable neuroprotective implants could serve as an effective local Mg2+/H2 delivery system for treating distant cerebral ischemic diseases.

Multi-targeted tyrosine kinase inhibitor QLNC-3A6 Di-maleate, a structurally novel small molecule compound, has therapeutic efficacy for the treatment of canine cutaneous mast cell tumor (CMCT) caused by mutations in the c-Kit gene. Since pharmacokinetic (PK) information plays an important role in the development and application of new drugs, etc., a rapid, highly sensitive and selective UHPLC-MS/MS analytical method was developed and validated for the first time in this study for the quantitative detection of QLNC-3A6 in canine plasma. 100 µL of plasma was precipitated using 350 µL of acetonitrile, and Chromatographic separation was performed on a Phenomenex Kinetex C18 column (50 × 2.1 mm, 2.6 µm) at a flow rate of 0.4 mL/min, the mobile phases were set to 0.1% formic acid aqueous solution (A) and 0.1% formic acid acetonitrile (B). The calibration curve linear range was 0.5–100 ng/mL (R2>0.99). The intraday and interday precision values (relative standard deviation, RSD) were 2.06–13.57% and 6.90–9.14%. Intraday and interday accuracies were −10.73 to 9.54% and −3.86 to 0.70% respectively. The dilution integrity RSD value and stability RSD value were less than 3.77 and 7.45%, respectively. Subsequently, the pharmacokinetics were investigated in canine after oral administration of QLNC-3A6 Di-maleate tablets at a dose of 3 mg/kg BW using this method. The results showed that QLNC-3A6 showed fast absorption rate, rapid distribution and slow metabolic elimination in canine plasma. The results of the main PK parameters including λz, T1/2λz, Cmax, Tmax and AUClast were 0.07 ± 0.01/h, 11.00 ± 2.57 h, 50.88 ± 31.94 ng/mL, 9.08 ± 11.57 h and 836.48 ± 230.53 ng h/mL, respectively.

Work-related musculoskeletal disorders (WMSDs) are common and serious occupational health problems faced by primary and secondary school teachers around the world. The high prevalence of WMSD brings great harm to the physical health, psychology, daily work and life of primary and secondary school teachers. This project systematically reviewed the basic situation of WMSDs in primary and secondary school teachers at home and abroad, summarized the prevalence rate, involved body parts and main hazards of WMSDs in primary and secondary school teachers, and concluded the personal factors, occupational factors and social psychological factors leading to WMSDs. Based on this, a set of basic prevention and control measures of WMSDs were proposed from five perspectives: organizational training, organizational management, ergonomic design, individual behavior and social psychology, in order to provide a scientific basis for the prevention and treatment of WMSDs.

In this paper, a symplectic fission scheme for the association scheme of $ m\times n $ rectangular matrices over the finite field $ \mathbb{F}_q $, denoted by $ {\rm{SMat}}(m\times n, q) $, is constructed, where $ q $ is a power of a prime number. We discuss its association classes and inner automorphism group. In particular, we determine the intersection numbers and automorphism group of $ {\rm{SMat}}(m\times n, q) $ for $ m = 1 $ and $ m = 2 $.

Abstract Respiratory infections caused by coronaviruses have posed serious and unpredictably public health threats; reliable animal models continue to be essential for advancing our understanding of the virus’s transmission, pathophysiology, and immunological mechanisms. In response to the critical need for centralized resources in coronavirus research, the COVID-AMD database (Coronavirus Disease Animal Model Database, https://www.uc-med.net/CoV-AMD ) has been developed as an integrated platform. Data was gathered from public literature databases, refined and integrated using ETL (Extract, Transform, Load) methodology. After data conversion and cleaning, COVID-AMD was implemented using MySQL relational database with jQuery and JBoss. COVID-AMD database consolidates comprehensive data on animal models infected with various CoVs, including MERS-CoV, SARS-CoV, and SARS-CoV-2, featuring methodologies for establishing infection models, clinical features, and phenotypic data. It catalogs 869 animal models across 29 species and 312 virus strains, covering five diseases and ten infection routes. With global and advanced search capabilities, it facilitated data preprocessing, integration, analysis, and visualization, and provided tools for comparative analysis, model recommendation and omics analysis based on model and phenotype data. The open access to this rich repository aims to enable rapid identification of animal models for CoVs, thereby accelerating the development and clinical trial progression of prospective therapeutics and vaccines.

Abstract Sand gradation is an important reference factor for concrete proportion design, which has a significant impact on the strength and workability of concrete. The efficiency of using the traditional vibrating sieving method to measure the gradation is low, and the machine vision-based sand gradation inspection method can realize the automation of sand gradation inspection, which can significantly improve the inspection efficiency and reduce the inspection cost. The particle size of construction sand is usually between 0.075 and 4.75 mm, and to capture images of sand below 0.15 mm requires a high-resolution camera that can only maintain a small object distance and a small shooting field of view, so it is difficult for the image acquisition system to capture images of all the sand particles, and this is a challenging problem in sand grading inspection. In order to solve this problem, this study proposes a sand gradation detection method based on localized sampling, and develops a hardware system for localized sampling and a software system for gradation detection. The hardware system uses a flexible vibrating disk to uniformly disperse the sand particles, realizing random local sampling of sand particles, and calculating the grain size gradation of the test samples based on the local data of multiple local sampling. The experimental results show that the local sampling gradation and the sample gradation have a similar distribution, and the local gradation detection error of multiple sampling is smaller. This study provides an effective method for the automated detection of sand grain size gradation between 0.075 and 4.75 mm, which can significantly increase the frequency of construction sand gradation detection, improve the quality control level of construction sand, and improve the quality of construction.

Abstract Background The role of neurons in central post-stroke pain (CPSP) following thalamic hemorrhage remains unclear. This study aimed to identify key genes associated with post-thalamic hemorrhage pain and to explore their functions in neurons. Single-nucleus RNA sequencing (snRNA-seq) data from a mouse model was used for this analysis. Methods First, snRNA-seq data were analyzed to identify cell types associated with CPSP induced by thalamic hemorrhage. Differentially expressed genes (DEGs) in neurons were then screened between control and model groups, followed by the construction of a protein-protein interaction (PPI) network for the DEGs. CytoNCA was used to assess node connectivity in the PPI network, and the top 5 key genes were identified. Subsequently, transcription factor (TF)-mRNA and miRNA-mRNA networks were constructed, and small-molecule drugs potentially targeting these key genes were predicted. Finally, the expression differences of key genes in neurons were compared between the model and control groups. Results A total of 13 cell clusters were identified, categorized into 8 cell types: T cells, endothelial cells, monocytes, neural progenitor cells (NPCs), microglia, astrocytes, neurons, and oligodendrocytes. A total of 228 DEGs were detected in neurons when comparing the model group with the control group. The PPI network of the DEGs consisted of 126 nodes and 209 edges, identifying the top 5 key genes: Dlgap1, Cacna1c, Gria2, Hsp90ab1, and Gapdh. The miRNA-mRNA network included 68 miRNA-mRNA pairs, 62 miRNAs, and 5 mRNAs, while the TF-mRNA network consisted of 66 TF-mRNA pairs, 56 TFs, and 5 mRNAs. Drug prediction identified 110 small-molecule drugs (e.g., purpurogallin, nifedipine, and novobiocin) potentially targeting these key genes. Additionally, Cacna1c were significantly upregulated in model mice. Conclusion This study identified the role of key genes in thalamic hemorrhage-induced CPSP through snRNA-seq, providing a scientific basis for further exploration of the molecular mechanisms underlying CPSP.

Abstract Moiré superlattices of semiconducting transition metal dichalcogenide heterobilayers are model systems for investigating strongly correlated electronic phenomena. Specifically, WSe2/WS2 moiré superlattices have emerged as a quantum simulator for the two-dimensional extended Hubbard model. Experimental studies of charge transport have revealed correlated Mott insulator and generalized Wigner crystal states, but spin transport of the moiré heterostructure has not yet been sufficiently explored. Here, we use spatially and temporally resolved circular dichroism spectroscopy to directly image the spin transport as a function of carrier doping and temperature in WSe2/WS2 moiré heterostructures. We observe diffusive spin transport at all hole concentrations at 11 Kelvin — including the Mott insulator at one hole per moiré unit cell — where charge transport is strongly suppressed. At elevated temperatures the spin diffusion constant remains unchanged in the Mott insulator state, but it increases significantly at finite doping away from the Mott state. The doping- and temperature-dependent spin transport can be qualitatively understood using a t–J model, where spins can move via the hopping of spin-carrying charges and via the exchange interaction.

Abstract Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck, associated with high recurrence and poor prognosis. We performed an integrated analysis of single-cell RNA and spatial transcriptomic data from cancerous and normal tissues to create a comprehensive atlas of epithelial cells and cancer-associated fibroblasts (CAFs). Our findings show that AKR1C3+ epithelial cells, located at the tumor’s stromal front, exhibit significant copy number variation and poor prognostic indicators, suggesting a role in tumor invasion. We also identified a distinct group of early-stage CAFs (named OSCC_Normal, characterized by ADH1B+, MFAP4+, and PLA2G2A+) that interact with AKR1C3+ cells, where OSCC_Normal may inhibit the FOXO1 redox switch in these epithelial cells via the IGF1/IGF1R pathway, causing oxidative stress overload. Conversely, AKR1C3+ cells use ITGA6/ITGB4 receptor to counteract the effects of OSCC_Normal, promoting cancer invasion. This study unveils complex interactions within the OSCC tumor microenvironment.

Abstract Background Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, Dysbiosis of intestinal microbiota and their metabolites has been linked to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear.In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and metabolomics. Methods Based on diet and modeling, rats were divided into normal group (Con), CIA model group, HFD group (HFD), and HFD + CIA group (HCIA). The effect of HFD on arthritis in CIA rats were investigated based on the arthritis index (AI), weight, blood lipid levels, and inflammatory cytokines. Moreover, HE staining and micro-CT were performed to evaluated the effect of HFD on the pathology of joints and synovial tissues in CIA rats.16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry (LC–MS) were employed to explore changes in gut microbiota and short-chain fatty acids (SCFAs). Results The AI scores, inflammatory cytokines and bone destruction parameters in the HCIA group were significantly higher than those in the other three groups. The results of 16S rRNA amplicon sequencing and metabolomics showed that compared with the other three groups, the expression of g_Muribaculaceae and butyric acid were reduced in the HCIA group. Spearman and linear correlation analyses revealed a positive correlation between g_Muribaculaceae abundance and butyric acid levels. Conclusions HFD stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in CIA rats.

Abstract The efficacy of flipped classroom in ophthalmology education has not been well proved. This study aimed to investigate the efficacy of flipped classroom on diabetic retinopathy (DR) and glaucoma in ophthalmology education. Ninety-three medical students in Peking Union Medical College participated and were randomly assigned into two groups. Students in “Group A” participated in a flipped classroom on diabetic retinopathy (DR) and a regular course on glaucoma, while students in “Group B” had a flipped classroom on glaucoma and a regular one on DR. The primary outcome measure of this study was the exam score after class. The secondary outcome measure was the result of a post-classroom questionnaire. The final exam revealed numerically better scores for questions in the same section as flipped classroom that students joined with no statistical significance. The post-class questionnaire revealed an overall satisfaction rate of 93.48%. Most students thought the flipped classroom enhance personal abilities compared with the traditional lecture-based class. However, further amendments should also be made to improve defects such as students’ comprehension of basic knowledge and the overall degree of involvement of students. The concept of the flipped classroom could be applied to diabetic retinopathy and glaucoma with satisfactory results.

Abstract Soft robotics has emerged as a highly promising field, particularly for handling interactions in unstructured environments such as food factories and agricultural warehouses. This potential is largely attributed to the inherent flexibility and compliance of soft robots. A critical aspect in the development of these robots lies in the selection and utilization of appropriate soft actuators and materials. Nevertheless, the modeling of soft robots presents considerable challenges owing to their intricate properties and continuum nature. In this article, we focus on the design and modeling of a three dimensional (3D) printed soft bellows actuator. The primary objective is to assess its efficacy in creating suitable soft grippers for handling various practical products. We propose an empirical model to predict the output forces of the soft bellows actuator. This model comprehensively integrates parameters such as bellows geometry and material properties, thereby providing valuable insights for the actuator’s design and control. To ascertain the precision of our model, we conducted a series of finite element simulations considering different designed parameters of the bellows, and performed experimental validations using 3D printed bellows actuators. The empirical model demonstrated high accuracy in predicting the output forces of the bellows actuator, with average absolute and relative errors of $$1.35\,$$ 1.35 N and $$3.5\%$$ 3.5 % , respectively. As an application, a robotic gripper with two parallel bellows actuators was developed, and its grasping force was validated using the empirical model. Building on this, a robotic gripper incorporating three bellows actuators was designed and fabricated based on the empirical model, and pick-and-place experiments were effectively conducted for handling a range of products.

Abstract Background Heart failure combined with hypertension is a major contributor for elderly patients (≥ 65 years) to in-hospital mortality. However, there are very few models to predict in-hospital mortality in such elderly patients. We aimed to develop and test an individualized machine learning model to assess risk factors and predict in-hospital mortality in in these patients. Methods From January 2012 to December 2021, this study collected data on elderly patients with heart failure and hypertension from the Chongqing Medical University Medical Data Platform. Least absolute shrinkage and the selection operator was used for recognizing key clinical variables. The optimal predictive model was chosen among eight machine learning algorithms on the basis of area under curve. SHapley Additive exPlanations and Local Interpretable Model-agnostic Explanations was employed to interpret the outcome of the predictive model. Results This study ultimately comprised 4647 elderly individuals with hypertension and heart failure. The Random Forest model was chosen with the highest area under curve for 0.850 (95% CI 0.789–0.897), high accuracy for 0.738, recall 0.837, specificity 0.734 and brier score 0.178. According to SHapley Additive exPlanations results, the most related factors for in-hospital mortality in elderly patients with heart failure and hypertension were urea, length of stay, neutrophils, albumin and high-density lipoprotein cholesterol. Conclusions This study developed eight machine learning models to predict in-hospital mortality in elderly patients with hypertension as well as heart failure. Compared to other algorithms, the Random Forest model performed significantly better. Our study successfully predicted in-hospital mortality and identified the factors most associated with in-hospital mortality.

Abstract Background Circular RNAs (circRNAs) function as essential regulatory elements with pivotal roles in various biological processes. However, their expression profiles and functional regulation during the differentiation of goat myoblasts have not been thoroughly explored. This study conducts an analysis of circRNA expression profiles during the proliferation phase (cultured in growth medium, GM) and differentiation phase (cultured in differentiation medium, DM1/DM5) of skeletal muscle satellite cells (MuSCs) in goats. Results A total of 2,094 circRNAs were identified, among which 84 were differentially expressed as determined by pairwise comparisons across three distinct groups. Validation of the expression levels of six randomly selected circRNAs was performed using reverse transcription PCR (RT-PCR) and quantitative RT-PCR (qRT-PCR), with confirmation of their back-splicing junction sites. Enrichment analysis of the host genes associated with differentially expressed circRNAs (DEcircRNAs) indicated significant involvement in biological processes such as muscle contraction, muscle hypertrophy, and muscle tissue development. Additionally, these host genes were implicated in key signaling pathways, including Hippo, TGF-beta, and MAPK pathways. Subsequently, employing Cytoscape, we developed a circRNA-miRNA interaction network to elucidate the complex regulatory mechanisms underlying goat muscle development, encompassing 21 circRNAs and 47 miRNAs. Functional assays demonstrated that circTGFβ2 enhances myogenic differentiation in goats, potentially through a miRNA sponge mechanism. Conclusion In conclusion, we identified the genome-wide expression profiles of circRNAs in goat MuSCs during both proliferation and differentiation phases, and established that circTGFβ2 plays a role in the regulation of myogenesis. This study offers a significant resource for the advanced exploration of the biological functions and mechanisms of circRNAs in the myogenesis of goats.

Abstract Immunoglobulin diversity encompasses B-cell receptor, T-cell receptor, and antibody diversity. Existing studies have focused more on the role of B-cell and T-cell receptor diversity in tumor immunity, while the role of antibody diversity is less understood. This study examined and compared the blood extracellular vesicles (EVs) of lung cancer patients and healthy individuals using proteomics and bioinformatics analyses. The results revealed that among the 270 identified proteins, those involved in defense mechanisms were the most abundant. Most of these were antibody subtypes, accounting for 50.00%. Similarly, of the 40 identified EVs differentially expressed proteins (DEPs), 29 were involved in defense mechanisms (72.50%), with a higher proportion being antibody subtypes (82.76%). Furthermore, 24 DEP antibody subtypes were implicated in 18 immune reaction-related signaling pathways. These findings suggest that human serum EVs contain a significant number of antibody subtypes, and the antibody subtypes from lung cancer serum EVs differ from those of healthy controls (HCs). The variations in antibody diversity may be closely associated with lung cancer tumor immunity.

Abstract Background Adolescents with secondary hyperaldosteronism often present with severe and treatment-resistant hypertension, along with hypokalemia. Renovascular hypertension is frequently caused by renal artery stenosis, primarily due to atherosclerosis and fibromuscular dysplasia (FMD). The presence of an accessory renal artery (ARA) is a common anatomical variation that can contribute to secondary renal vascular hypertension. However, FMD occurring in the ARA is a rare cause of renal vascular hypertension. Juxtaglomerular cell tumor (JGCT) represents a rare etiology of renal hypertension. The co-occurrence of the pathogenic ARA with JGCT is infrequently reported in the existing literature. Case presentations This case study presents a young individual with a 12-year history of resistant hypertension, initially diagnosed with pathogenic ARA but later confirmed as JGCT 4 years later. Following surgery for JGCT, the patient experienced only temporary stabilization of blood pressure without anti-hypertensive medication. Stenosis of the ARA was definitively diagnosed one and a half years post-surgery, with FMD occurring on the ARA strongly suspected. The patient underwent balloon dilatation angioplasty 3 years later, leading to sustained blood pressure stability with the use of two medications. Conclusions The case study discussed herein involves a patient with resistant hypertension initially diagnosed with ARA but later determined to have late-onset JGCT and renal artery stenosis. It is imperative to consider atypical JGCT in young patients exhibiting resistant hypertension, hypokalemia, and hyperreninemia. Adequate management of renal artery stenosis is crucial in the management of hyperreninemic hypertension.

Abstract HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation. Additionally, HBO1 catalyzes the modification of proteins through acylation with propionyl, butyryl, crotonyl, benzoyl, and acetoacetyl groups. HBO1 undergoes ubiquitination and degradation by two types of ubiquitin complexes and can also act as an E3 ubiquitin ligase for the estrogen receptor α (ERα). Moreover, HBO1 participates in the expansion of medullary thymic epithelial cells (mTECs) and regulates the expression of peripheral tissue genes (PTGs) mediated by autoimmune regulator (AIRE), thus inducing immune tolerance. Furthermore, HBO1 influences the renewal of hematopoietic stem cells and the development of neural stem cells significantly. Importantly, the overexpression of HBO1 in various cancers suggests its carcinogenic role and potential as a therapeutic target. This review summarizes recent advancements in understanding HBO1’s involvement in acylation modification, DNA replication, ubiquitination, immunity, and stem cell renewal.

Abstract Background Recent research has demonstrated that the use of artificial intelligence (AI) in radiotherapy (RT) has significantly streamlined the process for physicians to treat patients with tumors; however, bibliometric studies examining the correlation between AI and RT are not available. Providing a thorough overview of the knowledge structure and research hotspots between AI and RT was the main goal of the current study. Method A search was conducted on the Web of Science Core Collection (WoSCC) database for publications pertaining to AI and RT between 2003 and 2023. VOSviewers, CiteSpace, and the R program “bibliometrix” were used to do the bibliometric analysis. Results The analysis comprised 615 publications from 64 countries, with USA and China leading the pack. Since 2017, there have been more and more publications about RT and AI every year. The research center that made the biggest contribution to this topic was Maastricht University. The most articles published journal in this field was Frontiers in Oncology, while Medical Physics received the greatest number of citations. Dekker Andre is the author with the greatest number of published articles, while Philippe Lambin was the most often co-cited author. In the newly identified research hotspots, “autocontouring algorithm”, “deep learning”, and “machine learning” stand out as the main terms. Conclusion In fact, our bibliometric analysis offers insightful information on current research directions and advancements pertaining to the use of AI in RT. For academics looking to understand the connection between AI and RT, this study is a great resource because it highlights current research frontiers and hot trends.

Abstract Purpose It is a central goal in current ecology to investigate the effects of global changes on ecosystem productivity, which includes above- and below-ground plant productivity as well as soil microbial productivity, but most studies focus on aboveground plant productivity. As plant and microbial communities have different attributes, it is intuitive to hypothesize that belowground plant root productivity will respond to global changes more similarly as aboveground stem/leaf productivity than soil microbial productivity; however, this hypothesis remains largely unexplored. Methods Here we conducted a long-term nitrogen deposition experiment in the Eurasian steppe, manipulating nine rates (0–50 g N m− 2 yr− 1) at two frequencies under two management strategies (fencing or mowing). Results Belowground plant productivity was found to respond similarly as soil microbial productivity rather than aboveground plant productivity, contrary to the hypothesis. And this pattern was more obvious under mowing than fencing, because mowing decreased soil water content and caused another pressure beyond the decreased pH induced by N addition. Conclusions Overall, our results demonstrated the importance of microhabitat (below- or above-ground) relative to community attribute (plants or microorganisms) in determining productivity response to nitrogen deposition, emphasizing the necessity to integratively study the response of both above- and below-ground productivities to global changes.

Abstract Surgical site infection (SSI) following lumbar disc herniation (LDH) surgery leads to prolonged hospital stays, increased costs and reoperations. Therefore, we aim to develop and validate a nomogram to predict the risk of SSI following LDH surgery, thereby helping spine surgeons design personalized prevention strategies and promote early recovery. Data from 647 patients with SSI who underwent LDH surgery at the First Affiliated Hospital of Air Force Medical University (AFMU) from 2020 to 2023 were collected. Ultimately, 241 patients with SSI were selected based on inclusion and exclusion criteria. Patients were randomly divided into training and validation sets with a ratio of 7:3. LASSO regression, univariate, and multivariate logistic regression were utilized to identify target variables and establish the prediction model, which was subsequently validated. Six factors—Age, Body Mass Index (BMI), Postoperative Suction Drainage (PSD), Gelatin Sponge (GS), None-Preoperative Antibiotic (NPTA), and Thrombin Time (TT)—were selected to construct the nomogram model. In the training set, the area under the curve (AUC) for the nomogram was 0.818 (95% CI 0.779–0.857). In the validation set, the AUC was 0.782 (95% CI 0.717–0.846). Calibration curves for both sets showed satisfactory agreement between predicted and actual SSI probabilities. Decision curve analysis indicated that the nomogram is clinically useful with a threshold range of 1–90%. The Clinical Impact Curve (CIC) demonstrated an acceptable cost-benefit ratio. The developed nomogram model effectively predicts the risk of SSI following LDH surgery, enabling spine surgeons to formulate more professional and rational clinical prevention strategies.

Abstract Robust deep learning models have demonstrated significant applicability in real-world scenarios. The utilization of adversarial attacks plays a crucial role in assessing the robustness of these models. Among such attacks, transfer-based attacks, which leverage white-box models to generate adversarial examples, have garnered considerable attention. These transfer-based attacks have demonstrated remarkable efficiency, particularly under the black-box setting. Notably, existing transfer attacks often exploit input transformations to amplify their effectiveness. However, prevailing input transformation-based methods typically modify input images indiscriminately, overlooking regional disparities. To bolster the transferability of adversarial examples, we propose the Local Transformation Attack (LTA) based on forward class activation maps. Specifically, we first obtain future examples through accumulated momentum and compute forward class activation maps. Subsequently, we utilize these maps to identify crucial areas and apply pixel scaling for transformation. Finally, we update the adversarial examples by using the average gradient of the transformed image. Extensive experiments convincingly demonstrate the effectiveness of our proposed LTA. Compared to the current state-of-the-art attack approaches, LTA achieves an increase of 7.9% in black-box attack performance. Particularly, in the case of ensemble attacks, our method achieved an average attack success rate of 98.3%.

Sintering flue gas is the waste gas produced in the sintering process of steel production, containing NOx, SO2, dioxins, volatile organic compounds, and other pollutants. The sintering flue gas can replace the air of the coal-burning circulating fluidized bed (CFB) boiler for incineration treatment, which can effectively reuse CO and residual oxygen in the waste gas, and remove SOx, NOx, and other pollutants in the sintering flue gas together with pollutants from coal combustion by the high-temperature atmosphere and desulfurization and denitrification facilities in the CFB boiler. It is expected to become an efficient integrated treatment technology for sintering flue gas. However, the research on removing dioxins and volatile organic compounds from sintering flue gas by coal-fired circulating fluidized bed boilers is still limited. The coal combustion process of sintering flue gas as an accelerant was studied through chemical reaction kinetics simulation. It is found that hydrogen radicals and other free radicals produced in the combustion process are the main mechanisms of dioxin removal, and the increase in combustion reaction temperature can significantly promote the removal of dioxins and volatile organic compounds. The decrease of residual oxygen in burned flue gas can also encourage the removal of dioxins. The operation of a coal-fired CFB boiler with sintering flue gas as the accelerant is simulated by calculating particle fluid dynamics. It is found that the fluidized state of the combustion process is good, and the low-concentration CO in the sintering flue gas is burned out with the cyclone separator outlet mass concentration of CO at around 100 mg/m3. The combustion temperature also satisfies the temperature requirement for removing pollutants. The feasibility of using sintering flue gas as the accelerant in the coal-fired CFB boiler is verified. The engineering verification of the CFB incineration method for sintering flue gas is conducted in a steel plant in Tangshan. The test on the flue gas at the outlet of the low-temperature economizer shows that the dioxin removal rate exceeds 99.5%, as low as 0.005 7 ng TEQ/m3 and the mass concentration of CO is as low as 108 mg/m3. The concentrations of NOx and SO2 in the flue gas are as low as 38 and 24 mg/m3, meeting the ultra-low emission requirements. The effectiveness of the integrated CFB sintering flue gas incineration treatment is proven.

Abstract The accuracy of a fuzzy system’s approximation is closely tied to the performance of fuzzy control systems design, while this system’s interpretability depends on the description of a mechanical model using human language. This research introduces a quasi-Gaussian membership function characterized by a pair of parameters to achieve the sensitivity of a triangular membership function along with the interpretability of Gaussian membership functions. Consequently, a two-dimensional (2-D) quasi-Gaussian membership function is derived, and a method for establishing quasi-Gaussian fuzzy systems (QGFS) using a rectangular grid is proposed. After validating the approximation properties using the sine function for the one-dimensional (1-D) and 2-D QGFS, the systems are applied to approximate the depyrogenation tunnel, a significant piece of equipment in the pharmaceutical industry with various mechanical designs. Validation results indicate that the 1-D and 2-D QGFS can achieve an approximation error varying within a ± 5% range. Meanwhile, the 1-D and 2-D QGFSs are applied to mechanical models of the depyrogenation tunnel with satisfactory final approximation results. Lastly, the 2-D QGFS is capable of demonstrating an excellent description of models with coupled parameters.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging global infectious disease with a high mortality rate. Clinicians lack a convenient tool for early identification of critically ill SFTS patients. The aim of this study was to construct a simple and accurate nomogarm to predict the prognosis of SFTS patients. Methods We retrospectively analyzed the clinical data of 372 SFTS patients collected between May 2015 and June 2023, which were divided 7:3 into a training set and an internal validation set. We used LASSO regression to select predictor variables and multivariable logistic regression to identify independent predictor variables. Prognostic nomograms for SFTS were constructed based on these factors and analysed for concordance index, calibration curves and area under the curve (AUC) to determine the predictive accuracy and consistency of the model. Results In the training set, LASSO and multivariate logistic regression analyses showed that age, SFTSV RNA, maximum body temperature, pancreatitis, gastrointestinal bleeding, pulmonary fungal infection (PFI), BUN, and PT were independent risk factors for death in SFTS patients. There was a strong correlation between neurological symptoms and mortality (P

Abstract Paphiopedilum armeniacum, Paphiopedilum wenshanense and Paphiopedilum emersonii are critically endangered wild orchids. Their populations are under severe threat, with a dramatic decline in the number of their natural distribution sites. Ex situ conservation and artificial breeding are the keys to maintaining the population to ensure the success of ex situ conservation and field return in the future. The habitat characteristics and soil nutrient information of the last remaining wild distribution sites of the three species were studied. ITS high-throughput sequencing was used to reveal the composition and structure of the soil fungal community, analyze its diversity and functional characteristics, and reveal its relationship with soil nutrients. The three species preferred to grow on low-lying, ventilated and shaded declivities with good water drainage. There were significant differences in soil alkali-hydrolyzed nitrogen and available phosphorus among the three species. There were 336 fungal species detected in the samples. On average, there were different dominant groups in the soil fungal communities of the three species. The functional groups of soil fungi within their habitats were dominated by saprophytic fungi and ectomycorrhizae, with significant differences in diversity and structure. The co-occurrence network of habitat soil fungi was mainly positive. Soil pH significantly affected soil fungal diversity within their habitats of the three paphiopedilum species. The study confirmed that the dominant groups of soil fungi were significantly correlated with soil nutrients. The three species exhibit comparable habitat inclinations, yet they display substantial variations in the composition, structure, and diversity of soil fungi. The fungal functional group is characterized by a rich presence of saprophytic fungi, a proliferation of ectomycorrhizae, and a modest occurrence of orchid mycorrhizae. The symbiotic interactions among the soil fungi associated with these three species are well-coordinated, enhancing their resilience against challenging environmental conditions. There is a significant correlation between soil environmental factors and the composition of soil fungal communities, with pH emerging as a pivotal factor regulating fungal diversity. Our research into the habitat traits and soil fungal ecosystems of the three wild Paphiopedilum species has established a cornerstone for prospective ex situ conservation measures and the eventual reestablishment of these species in their native landscapes.

Abstract Dental and maxillofacial diseases are always accompanied by complicated hard and soft tissue defects, involving bone, teeth, blood vessels and nerves, which are difficult to repair and severely affect the life quality of patients. Recently, extracellular vesicles (EVs) secreted by all types of cells and extracted from body fluids have gained more attention as potential solutions for tissue regeneration due to their special physiological characteristics and intrinsic signaling molecules. Compared to stem cells, EVs present lower immunogenicity and tumorigenicity, cause fewer ethical problems, and have higher stability. Thus, EV therapy may have a broad clinical application in regenerative dentistry. Herein, we reviewed the currently available literature regarding the functional roles of EVs in oral and maxillofacial tissue regeneration, including in maxilla and mandible bone, periodontal tissues, temporomandibular joint cartilage, dental hard tissues, peripheral nerves and soft tissues. We also summarized the underlying mechanisms of actions of EVs and their delivery strategies for dental tissue regeneration. This review would provide helpful guidelines and valuable insights into the emerging potential of EVs in future research and clinical applications in regenerative dentistry.

Abstract To assess the level of both pro-inflammatory and anti-inflammatory cytokines in the aqueous humor (AH) of patients suffering from uveitis, with or without coexisting glaucoma, and compare them with patients diagnosed with primary open-angle glaucoma (POAG) and those with age-related cataract (ARC). By using Luminex xMAP® multiplex assays analyses, we assessed levels of 11 cytokines and chemokines, and compared them across groups, including uveitis-secondary glaucoma (USG) (n = 16), uveitis without glaucoma (UwoG), (n = 16), POAG (n = 16), and ARC (n = 16) to explore the correlation between these cytokines and the presence of uveitis, as well as intraocular pressure (IOP). Pro-inflammatory factors MCP-1, MIP-1β, IL-6, IL-8, and transforming growth factors TGF-β1 and TGF-β2 were significantly elevated in the AH of USG eyes. In the case of enhanced anti-inflammatory in the perioperative period, the pro-inflammatory factors remained notably elevated in the USG group compared to the UwoG group (P

Abstract The contradiction between high piezoelectricity and uniquely poor temperature stability generated by polymorphic phase boundary is a huge obstacle to high-performance (K, Na)NbO3 -based ceramics entering the application market as Pb-based substitutes. We possess the phase boundary by mimicking Pb(Zr, Ti)O3’s morphotropic phase boundary structure via the synergistic optimization of diffusion phase boundary and crystal orientation in 0.94(Na0.56K0.44)NbO3−0.03Bi0.5Na0.5ZrO3−0.03(Bi0.5K0.5)HfO3 textured ceramics. As a result, a prominent comprehensive performance is obtained, including giant d 33 of 550 ± 30 pC/N and ultrahigh temperature stability (d 33 change rate less than 1.2% within 25-150 °C), representing a significant breakthrough in lead-free piezoceramics, even surpassing the Pb-based piezoelectric ceramics. Within the same temperature range, the d 33 change rate of the commercial Pb(Zr, Ti)O3−5 ceramics is only about 10%, and more importantly, its d 33 (~ 350 pC/N) is much lower than that of the (K, Na)NbO3-based ceramics in this work. This study demonstrates a strategy for constructing the phase boundary with MPB feature, settling the problem of temperature instability in (K, Na)NbO3-based ceramics.

Abstract The Riemerella anatipestifer bacterium is known to cause infectious serositis in ducklings. Moreover, its adherence to the host’s respiratory mucosa is a critical step in pathogenesis. Membrane cofactor protein (MCP; CD46) is a complement regulatory factor on the surface of eukaryotic cell membranes. Bacteria have been found to bind to this protein on host cells. Outer membrane proteins (OMPs) are necessary for adhesion, colonisation, and pathogenicity of Gram-negative bacteria; however, the mechanism by which R. anatipestifer adheres to duck cells remains unclear. In this study, pull-down assays and LC–MS/MS identified eleven OMPs interacting with duck CD46 (dCD46), with OMP71 exhibiting the strongest binding. The ability of an omp71 gene deletion strain to bind dCD46 is weaker than that of the wild-type strain, suggesting that this interaction is important. Further evidence of this interaction was obtained by synthesising OMP71 using an Escherichia coli recombinant protein expression system. Adhesion and invasion assays and protein and antibody blocking assays confirmed that OMP71 promoted the R. anatipestifer YM strain (RA-YM) adhesion to duck embryo fibroblasts (DEFs) by binding to CD46. Tests of the pathogenicity of a Δomp71 mutant strain of RA-YM on ducks compared to the wild-type parent supported the hypothesis that OMP71 was a key virulence factor of RA-YM. In summary, the finding that R. anatipestifer exploits CD46 to bind to host cells via OMP71 increases our understanding of the molecular mechanism of R. anatipestifer invasion. The finding suggests potential targets for preventing and treating diseases related to R. anatipestifer infection.

Abstract Background Although whole-body vibration (WBV) training is acknowledged for its benefits in enhancing motor functions across several neurological disorders, its precise influence on ankle joint proprioception and balance in stroke patients is still not well understood. This research seeks to assess the impact of WBV training on ankle joint proprioception and balance in stroke patients, thereby filling this important research void. Methods In this prospective cohort study, thirty-five stroke patients were randomly assigned to either the WBV group (n = 17) or a control group (n = 18) using a random number table method. The control group received daily general rehabilitation for four weeks, while the WBV group received an additional 30 min of WBV training each day with the Trunsan S110 Vibration Training System. Blinded outcome assessments were conducted at baseline and post-treatment, utilizing the Berg balance scale (BBS), Functional reach test (FRT), Romberg test length (RTL) and area (RTA), and completion rates of ankle joint dorsiflexion-plantar flexion (DP) and inversion-eversion (IE) tests. Follow-up assessments were performed after four weeks of intervention, focusing on RTL, RTA, DP, and IE as primary outcomes. Results Analysis of intra-group changes from baseline to post-treatment revealed significant improvements across the BBS, FRT, RTL, RTA, and DP and IE assessments (p 0.05). Conclusions This study demonstrates that WBV therapy is equally effective as conventional methods in enhancing proprioception and balance in stroke patients, but it does not provide additional benefits for balance recovery. WBV significantly improves proprioceptive functions, particularly in DP and IE parameters. However, it does not surpass traditional rehabilitation methods in terms of balance recovery. These findings indicate that WBV should be incorporated into stroke rehabilitation primarily to enhance proprioception rather than to optimize balance recovery. Trial registration This study was retrospectively registered in the ISRCTN Registry on 29/07/2024 ( https://www.isrctn.com/ , ISRCTN64602845).

Abstract Epilepsy is one of the most common symptoms in patients with gliomas; however, the mechanisms underlying its interaction are not yet clear. Moreover, epidemiological studies have not accurately identified patients with glioma-related epilepsy (GRE), and there is an urgent need to identify the molecular mechanisms and markers of its occurrence. We analyzed the demographics, transcriptome, whole-genome, and methylation sequences of 997 patients with glioma, to determine the genetic differences between glioma and GRE patients and to determine the upregulated molecular function, cellular composition, biological processes involved, signaling pathways, and immune cell infiltration. Twelve machine learning algorithms were refined into 113 combinatorial algorithms for building diagnostic recognition models. A total of 342 patients with GRE were identified with WHO grade 2 (174), grade 3 (107), and grade 4 (61). The mean age of the patients with GREs, with IDH mutations (n = 217 [63%]) and 1p19q non-codeletion (n = 169 [49%]), was 38 years old. GRE molecular functions were mainly passive transmembrane transporter protein activity, ion channel activity, and gated channel activity. Cellular components were enriched in the cation-channel and transmembrane transporter complexes. Cerebral cortical development regulates the membrane potential and synaptic organization as major biological processes. The signaling pathways mainly focused on cholinergic, GABAergic, and glutamatergic synapses. LASSO, combined with Random Forest, was the best diagnostic model and identified nine diagnostic genes. This study provides new insights and future perspectives for resolving the molecular mechanisms of GRE.

Abstract Background EYA4 variants are responsible for DFNA10 deafness. Due to its insidious onset and slow progression, hearing loss in autosomal dominant non-syndromic hearing loss (ADNSHL) is usually challenging to detect early in clinical settings, with limited intervention options. Genetic testing can aid in early detection of hearing loss, enabling timely intervention to reduce disability rates and improve the quality of life. Methods In this study, we report the case of a Chinese family with postlingual and progressive hearing loss that was passed down for four generations. Whole-exome sequencing (WES) was performed on DNA samples from the proband. Candidate variants identified in the proband and family members were confirmed via Sanger sequencing. In silico prediction tools and co-segregation analyses were used to assess the pathogenicity of identified variants. A literature review of known EYA4 variants was performed, analysing variant frequency, distribution characteristics across different populations, and genotype-phenotype correlations. Results We identified a novel EYA4 variant, c.1745_1748del (p.Glu582ValfsTer6), in a Chinese family with ADNSHL, and co-segregation with the family’s phenotype was confirmed. The audiometry showed mid-to-high frequency downsloping hearing loss. To date, 52 pathogenic variants of EYA4 have been reported, with majority identified in Asian populations. Most observed are the missense and frameshift variants. Conclusions A novel variant of EYA4 was identified in a Chinese family with postlingual hearing loss, contributing to the expanding spectrum of EYA4 variants. The audiological features of EYA4 variants are highly heterogeneous and often challenging to detect early in clinical settings. Our findings highlight the significance of genetic testing in patients presenting with postlingual hearing loss.

Abstract In heavy oil reservoirs, favorable reservoir properties have a positive impact on the production performance during CO2 huff-n-puff. It is significant to study the screening method of applicable conditions for CO2 huff-n-puff in actual reservoirs. To solve these problems, this paper introduced the orthogonal design method to analyze the main factors based on numerical simulation. The technical analysis and the economic evaluation were both employed to obtain the applicable conditions of selecting oil layers or injection wells during CO2 huff-n-puff. And a new algorithms of machine learning, the random forest algorithm, was introduce to find the weighted factors and the scoring standards that were suitable for CO2 huff-n-puff. Finally, a set of method for screening suitable reservoir conditions was established. Based on the introduction of orthogonal analysis method and random forest algorithm, a software was established to achieve the purpose of analyzing the feasibility of CO2 huff-n-puff considering different reservoir geological parameters. This method increased the accuracy and efficiency in screening reservoir conditions that was suitable for CO2 huff-n-puff.

Achieving thermal cycle stability is an imperative challenge for the successful commercialization of solid oxide cell (SOC) technology. Ruddlesden‒Popper (R‒P) oxides, whose thermal expansion coefficient (TEC) is compatible with common electrolytes, are promising candidates for SOC applications. However, the two-dimensional conduction characteristic of R‒P oxides leads to insufficient catalytic activity, which hinders their performance. Here, we propose a win‒win strategy for self-assembly decoration by employing a one-pot method to address this issue. By using a single perovskite oxide (La0.4Sr0.6FeO3) to modify R‒P oxide (La0.8Sr1.2FeO4+δ), we enhanced the electrochemical performance without compromising the stability of the composite electrode. The strategic incorporation of a 10 mol% perovskite phase at 800 °C resulted in a significant 49% reduction in the polarization resistance (Rp), an impressive 86% increase in the maximum power density under power generation mode, and a notable 33% increase in the electrolysis current density under electrolysis mode. Furthermore, the perovskite-decorated R‒P oxide composite also exhibited high thermal and chemical stability, with negligible performance degradation observed under both thermal cycling and charge/discharge cycling conditions. Our results demonstrate that such dual-phase composites, which are simultaneously produced by a one-step process with outstanding catalytic activity and stability, can be considered an effective strategy for the advancement of SOCs.

In recent years, the research on high-speed vehicles has become a hot spot, among which the research on hypersonic vehicles is particularly important. Multihypersonic vehicles will inevitably work cooperatively in the future under the weaponization and armament acquisition processes of hypersonic vehicles. However, the characteristics of hypersonic vehicles, such as without thrust and with strong nonlinearity, strong coupling, and multiple constraints, have led to considerable difficulties and challenges in the cooperative formation control problem of multihypersonic vehicles. This paper proposes a time-coordination entry trajectory planning method for multihypersonic vehicles for scenarios where multihypersonic vehicles arrive at a designated area with cooperative time constraints. First, the coupling problem between the re-entry flight time and lateral maneuvering of a vehicle is solved by reasonably simplifying the motion equation of the vehicle in the longitudinal plane, and a longitudinal trajectory planning method considering arrival time and range constraints is designed based on the binary Newton iteration method. Then, the inverse logic of the bank angle is designed based on the heading angle deviation corridor; thus, the terminal flight range constraint and heading angle deviation constraint can be satisfied, and the three-dimensional trajectory of the vehicle is obtained. However, the impact of the lateral motion will inevitably result in a certain deviation between the final and expected flight times. Therefore, a strategy for compensation and renewal is designed and the entry trajectory is planned iteratively until meeting the flight range and arrival time constraints. Simultaneously, the impact of different bank angle profiles on the flight range, flight time, and terminal height in trajectory planning of vehicles is investigated, and on this basis, a method for determining the collaborative flight time, terminal altitude, and flight range of the vehicles is introduced. Finally, the numerical simulation is conducted to verify the trajectory planning problem of multiple vehicles with time coordination, and the simulation results show that multihypersonic vehicles can simultaneously arrive at the terminal area using the method proposed in this study, which can satisfy the flight range, arrival time, and terminal height constraints and has good calculation accuracy. Meanwhile, varying degrees of uncertainty can be detected in the initial altitude, speed, longitude, latitude, flight path angle, heading angle, and other initial conditions and various disturbances, such as atmospheric density and aircraft mass, during the actual flight of the hypersonic vehicle. Moreover, the Monte Carlo simulation verified that the trajectory planning method with time coordination has strong robustness to various disturbances and remarkable application prospects.

BACKGROUND AND AIMS: Neuroprotection plays an important role in the treatment of brain disorders. In recent years, studies using rat models and clinical trials have demonstrated the positive effects of hydrogen treatment on neurological disorders and brain injuries. Hence, it is of great significance to shed light on this issue. In this article, CiteSpace is employed for visualization and bibliometric analysis of the research frontiers and evolving trends related to the neuroprotective effect of hydrogen. METHODS: All articles published from 2009 to 2023 that discussed the neuroprotective effects of hydrogen in cerebrovascular diseases were retrieved from the Web of Science. Using CiteSpace, a visualization analysis was conducted on aspects such as countries, institutions, authors, keywords, and Co cited references, which enables an intuitive observation of current research hotspots. RESULTS: After manual screening, a total of 106 articles were retrieved. Over time, The number of publications has increased annually. Regarding national contributions, the top three countries with the highest number of publications include China, the United States, and Japan. The Second Military Medical University is the institution that publishes the most articles and has significant influence in the field of hydrogen neuroprotection. Sun, Xuejun and Domoki, Ferenc were the most productive. The most common keywords include hydrogen, oxidative stress, inflammation, and apoptosis. Potential areas of focus for future research consist of early brain injury, hydrogen, ischemia-reperfusion injury and hypothermia treatment. CONCLUSION: The bibliometric study presented herein offers insights into the current status and trends of research on hydrogen in the field of cerebrovascular diseases. Future research trends suggest that hydrogen contributes significantly to the cerebrovascular domain through its anti-inflammatory, antioxidative, and anti-apoptotic mechanisms. This study can aid researchers in identifying hot topics and exploring new research directions.

Abstract Nitrate can be electrolyzed mainly into N2, but the generated ammonia, as its secondary intermediate, is soluble and remained in the wastewater yet, which affects negatively the degradation of nitrate and total nitrogen. In this work, an electrolytic reactor constructed with Ti/RuSn anode and Fe cathode, was applied to electrolyze nitrate, and magnesium chloride was used as electrolyte and precipitant simultaneously, while disodium hydrogen phosphate (DSP) was added only as precipitant of ammonia. The results indicated that, most part of generated ammonia could be precipitated as magnesium ammonium phosphate (MAP) and some residual ammonia may be transformed into N2 by breakpoint chlorination. Thus, the nitrate and total nitrogen (TN) degradation efficiencies could be enhanced obviously by the combined electrolysis precipitation process.

Abstract The nodal-line semiconductor Mn3Si2Te6 is generating enormous excitment due to the recent discovery of a field-driven insulator-to-metal transition and associated colossal magnetoresistance as well as evidence for a new type of quantum state involving chiral orbital currents. Strikingly, these qualities persist even in the absence of traditional Jahn-Teller distortions and double-exchange mechanisms, raising questions about exactly how and why magnetoresistance occurs along with conjecture as to the likely signatures of loop currents. Here, we measured the infrared response of Mn3Si2Te6 across the magnetic ordering and field-induced insulator-to-metal transitions in order to explore colossal magnetoresistance in the absence of Jahn-Teller and double-exchange interactions. Rather than a traditional metal with screened phonons, the field-driven insulator-to-metal transition leads to a weakly metallic state with localized carriers. Our spectral data are fit by a percolation model, providing evidence for electronic inhomogeneity and phase separation. Modeling also reveals a frequency-dependent threshold field for carriers contributing to colossal magnetoresistance which we discuss in terms of polaron formation, chiral orbital currents, and short-range spin fluctuations. These findings enhance the understanding of insulator-to-metal transitions in new settings and open the door to the design of unconventional colossal magnetoresistant materials.

Abstract In the healing process of myocardial infarction, cardiac fibroblasts are activated to produce collagen, leading to adverse remodeling and heart failure. Our previous study showed that ASPP1 promotes cardiomyocyte apoptosis by enhancing the nuclear trafficking of p53. We thus explored the influence of ASPP1 on myocardial fibrosis and the underlying mechanisms. Here, we observed that ASPP1 was increased after 4 weeks of MI. Both global and myofibroblast knockout of ASPP1 in mice mitigated cardiac dysfunction and fibrosis after MI. Strikingly, ASPP1 produced the opposite influence on p53 level and cell fate in cardiac fibroblasts and cardiomyocytes. Knockdown of ASPP1 increased p53 levels and inhibited the activity of cardiac fibroblasts. ASPP1 accumulated in the cytoplasm of fibroblasts while the level of p53 was reduced following TGF-β1 stimulation; however, inhibition of ASPP1 increased the p53 level and promoted p53 nuclear translocation. Mechanistically, ASPP1 is directly bound to deubiquitinase OTUB1, thereby promoting the ubiquitination and degradation of p53, attenuating myofibroblast activity and cardiac fibrosis, and improving heart function after MI.

Abstract Cyclo (Phe-Pro) (cFP), a cyclic dipeptide with notable antifungal, antibacterial, and antiviral properties, shows great promise for biological control of plant diseases. Produced as a byproduct by non-ribosomal peptide synthetases (NRPS), the regulatory mechanism of cFP biosynthesis remains unclear. In a screening test of 997 Tn5 mutants of Burkholderia seminalis strain R456, we identified eight mutants with enhanced antagonistic effects against Fusarium graminearum (Fg). Among these, mutant 88’s culture filtrate contained cFP, confirmed through HPLC and LC-MS, which actively inhibited Fg. The gene disrupted in mutant 88 is part of the Dct transport system (Dct-A, -B, -D), responsible for C4-dicarboxylate transport. Knockout mutants of Dct genes exhibited higher cFP levels than the wild type, whereas complementary strains showed no significant difference. Additionally, the presence of exogenous C4-dicarboxylates reduced cFP production in wild type R456, indicating that these substrates negatively regulate cFP synthesis. Given that cFP synthesis is related to NRPS, we previously identified an NRPS cluster in R456, horizontally transferred from algae. Specifically, knocking out gene 2061 within this NRPS cluster significantly reduced cFP production. A Fur box binding site was predicted upstream of gene 2061, and yeast one-hybrid assays confirmed Fur protein binding, which increased with additional C4-dicarboxylates. Knockout of the Fur gene led to up-regulation of gene 2061 and increased cFP production, suggesting that C4-dicarboxylates suppress cFP synthesis by enhancing Fur-mediated repression of gene 2061.

Abstract Background Poplar canker caused by Botryosphaeria dothidea is one of the most severe plant disease of poplars worldwide. In our study, we aimed to investigate the modes of antagonism by fermentation broth supernatant (FBS) of Streptomyces spiroverticillatus HS1 against B. dothidea. Results In vitro, the strain and FBS of S. spiroverticillatus HS1 significantly inhibited mycelial growth and biomass accumulation, and also disrupted the mycelium morphology of B. dothidea. On the 3rd day after treatment, the inhibition rates of colony growth and dry weight were 80.72% and 52.53%, respectively. In addition, FBS treatment damaged the plasma membrane of B. dothidea based on increased electrical conductivity in the culture medium, and malondialdehyde content of B. dothidea mycelia. Notably, the analysis of key enzymes in glycolysis pathway showed that the activity of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK), Ca2+Mg2+-ATPase were significantly increased after FBS treatment. But the glucose contents were significantly reduced, and pyruvate contents were significantly increased in B. dothidea after treatment with FBS. Conclusions The inhibitory mechanism of S. spiroverticillatus HS1 against B. dothidea was a complex process, which was associated with multiple levels of mycelial growth, cell membrane structure, material and energy metabolism. The FBS of S. spiroverticillatus HS1 could provide an alternative approach to biological control strategies against B. dothidea.

Abstract Genome differential positioning within interphase nuclei remains poorly explored. We extended and validated Tyramide Signal Amplification (TSA)-seq to map genomic regions near nucleoli and pericentric heterochromatin in four human cell lines. Our study confirmed that smaller chromosomes localize closer to nucleoli but further deconvolved this by revealing a preference for chromosome arms below 36-46 Mbp in length. We identified two lamina associated domain subsets through their differential nuclear lamina versus nucleolar positioning in different cell lines which showed distinctive patterns of DNA replication timing and gene expression across all cell lines. Unexpectedly, active, nuclear speckle-associated genomic regions were found near typically repressive nuclear compartments, which is attributable to the close proximity of nuclear speckles and nucleoli in some cell types, and association of centromeres with nuclear speckles in human embryonic stem cells (hESCs). Our study points to a more complex and variable nuclear genome organization than suggested by current models, as revealed by our TSA-seq methodology.

Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Abstract Background Blotched snakehead (Channa maculata) displays significant sexual dimorphism, with males exhibiting faster growth rates and larger body sizes compared to females. The cultivation of the all-male population of snakeheads holds substantial economic and ecological value. Nonetheless, the intricate processes governing the development of bipotential gonads into either testis or ovary in C. maculata remain inadequately elucidated. Therefore, it is necessary to determine the critical time window of sex differentiation in C. maculata, providing a theoretical basis for sex control in production practices. Methods The body length and weight of male and female C. maculata were measured at different developmental stages to reveal when sexual dimorphism in growth initially appears. Histological observations and spatiotemporal comparative transcriptome analyses were performed on ovaries and testes across various developmental stages to determine the crucial time windows for sex differentiation in each sex and the sex-related genes. Additionally, qPCR and MG2C were utilized to validate and locate sex-related genes, and levels of E2 and T were quantified to understand sex steroid synthesis. Results Sexual dimorphism in growth became evident starting from 90 dpf. Histological observations revealed that morphological sex differentiation in females and males occurred between 20 and 25 dpf or earlier and 30–35 dpf or earlier, respectively, corresponding to the appearance of the ovarian cavity or efferent duct anlage. Transcriptome analyses revealed divergent gene expression patterns in testes and ovaries after 30 dpf. The periods of 40–60 dpf and 60–90 dpf marked the initiation of molecular sex differentiation in females and males, respectively. Male-biased genes (Sox11a, Dmrt1, Amh, Amhr2, Gsdf, Ar, Cyp17a2) likely play crucial roles in male sex differentiation and spermatogenesis, while female-biased genes (Foxl2, Cyp19a1a, Bmp15, Figla, Er) could be pivotal in ovarian differentiation and development. Numerous biological pathways linked to sex differentiation and gametogenesis were also identified. Additionally, E2 and T exhibited sexual dimorphism during sex differentiation and gonadal development. Based on these results, it is hypothesized that in C. maculata, the potential male sex differentiation pathway, Sox11a–Dmrt1–Sox9b, activates downstream sex-related genes (Amh, Amhr2, Gsdf, Ar, Cyp17a2) for testicular development, while the antagonistic pathway, Foxl2/Cyp19a1a, activates downstream sex-related genes (Bmp15, Figla, Er) for ovarian development. Conclusions This study provides a comprehensive overview of gonadal dynamic changes during sex differentiation and gametogenesis in C. maculata, establishing a scientific foundation for sex control in this species.

Abstract Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e–118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6′-sialyllactose (P = 2.2e–9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P

Introduction: Cytochrome P450 enzymes (P450s) are recognized as the most versatile catalysts worldwide, playing vital roles in numerous biological metabolism and biosynthesis processes across all kingdoms of life. Despite the vast number of P450 genes available in databases (over 300,000), only a small fraction of them (less than 0.2 %) have undergone functional characterization. Objectives: To provide a convenient platform with abundant information on P450s and their corresponding reactions, we introduce the P450Rdb database, a manually curated resource compiles literature-supported reactions catalyzed by P450s. Methods: All the P450s and Reactions were manually curated from the literature and known databases. Subsequently, the P450 reactions organized and categorized according to their chemical reaction type and site. The website was developed using HTML and PHP languages, with the MySQL server utilized for data storage. Results: The current version of P450Rdb catalogs over 1,600 reactions, involving more than 590 P450s across a diverse range of over 200 species. Additionally, it offers a user-friendly interface with comprehensive information, enabling easy querying, browsing, and analysis of P450s and their corresponding reactions. P450Rdb is free available at http://www.cellknowledge.com.cn/p450rdb/. Conclusions: We believe that this database will significantly promote structural and functional research on P450s, thereby fostering advancements in the fields of natural product synthesis, pharmaceutical engineering, biotechnological applications, agricultural and crop improvement, and the chemical industry.

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl3 for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8+ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.