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Abstract Objective This study aimed to investigate the risk factors affecting the presence of carotid plaque in asymptomatic adults. Methods Asymptomatic adults (age > 40 years, no symptoms of cardiovascular and cerebrovascular diseases) undergoing routine health examinations from physical examination department were included in this study. Carotid plaque was measured by Resona 7OB and Resona 8EXP color Doppler ultrasound and L9-3U and L4-5WU probes. The focal carotid intima–media thickness was greater than 1.1 mm, and the local protrusion of the artery wall into the artery lumen suggested the presence of carotid atherosclerotic plaque. According to their ultrasound results, 1077 asymptomatic adults were divided into a group with carotid plaque (477) and a group without carotid plaque (600). Results A total of 1077 asymptomatic adults were included in this study, of whom 44.3% had carotid plaque. The proportion of men with carotid plaque was 84.5%. Multifactorial logistic analysis suggested that age, fasting blood glucose (FBG), total cholesterol (TC), homocysteine (Hcy) and male gender were risk factors for carotid atherosclerosis. The predictive probability of these risk factor indicators derived from the multifactorial model was calculated using receiver operating characteristic (ROC) curves with SPSS 25.0 software. The calculated area under the receiver operating characteristic curve (AUC) was 0.715 (95% CI, 0.685–0.746). Conclusion Age, FBG, TC, Hcy and male gender are risk factors for carotid atherosclerosis in asymptomatic adults. Gender differences in carotid atherosclerosis deserve further attention.

Abstract Background We studied the characteristics of carotid ultrasound plaque in a healthy physical-examination population and analyzed the risk factors for hypoechoic carotid plaque for early control and prevention of stroke. Results A total of 1333 healthy physical-examination individuals were included in this study, including 457 females and 876 males. According to the results of carotid artery ultrasound, they were divided into hyperechoic carotid plaque (n = 940) and hypoechoic carotid plaque (n = 393). Multivariate logistic analysis showed that male, alcohol consumption, and low-density lipoprotein were risk factors for hypoechoic carotid plaque. SPSS 25.0 software was used to draw the receive operating characteristic curve and calculate the prediction probability of the risk factor indicators obtained by the multifactor model. The area under the curve was also calculated to be 0.623 (95% CI = 0.591–0.655). Conclusion Male, alcohol consumption, and low-density lipoprotein are risk factors for hypoechoic carotid plaque in a healthy physical-examination population.

Abstract Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions.

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin β1 expression. Subsequently, integrin β1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

Abstract Background Spatiotemporal analysis is a vital method that plays an indispensable role in monitoring epidemiological changes in diseases and identifying high-risk clusters. However, there is still a blank space in the spatial and temporal distribution of tuberculosis (TB) incidence rate in Pudong New Area, Shanghai. Consequently, it is crucial to comprehend the spatiotemporal distribution of TB in this district, this will guide the prevention and control of TB in the district. Methods Our research used Geographic Information System (GIS) visualization, spatial autocorrelation analysis, and space-time scan analysis to analyze the TB incidence reported in the Pudong New Area of Shanghai from 2014 to 2023, and described the spatiotemporal clustering and seasonal hot spot distribution of TB incidence. Results From 2014 to 2023, the incidence of TB in the Pudong New Area decreased, and the mortality was at a low level. The incidence of TB in different towns/streets has declined. The spatial autocorrelation analysis revealed that the incidence of TB was spatially clustered in 2014, 2016–2018, and 2022, with the highest clusters in 2014 and 2022. The high clustering area was mainly concentrated in the northeast. The space-time scan analysis indicated that the most likely cluster was located in 12 towns/streets, with a period of 2014–2018 and a radiation radius of 15.74 km. The heat map showed that there was a correlation between TB incidence and seasonal variations. Conclusions From 2014 to 2023, the incidence of TB in the Pudong New Area of Shanghai declined, but there were spatiotemporal clusters and seasonal correlations in the incidence area. Local departments should formulate corresponding intervention measures, especially in high-clustering areas, to achieve accurate prevention and control of TB within the most effective time and scope.

Abstract Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.

Abstract Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair. Graphical Abstract

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn–Mg–Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.

Abstract The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Abstract Triple-negative breast cancer (TNBC) is more aggressive and has a higher metastasis rate compared with other subtypes of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is now the only available systemic treatment for TNBC. However, some patients might still develop drug resistance and have poor prognosis. Therefore, novel molecular biomarkers and new treatment targets are urgently needed for patients with TNBC. To provide molecular insights into TNBC progression, we investigated the function and the underlying mechanism of Defective in cullin neddylation 1 domain containing 5 (DCUN1D5) in the regulation of TNBC. By TCGA dataset and surgical specimens with immunohistochemical (IHC) staining method, DCUN1D5 was identified to be significantly upregulated in TNBC tumor tissues and negatively associated with prognosis. A series of in vitro and in vivo experiments were performed to confirm the oncogenic role of DCUN1D5 in TNBC. Overexpression of FN1 or PI3K/AKT activator IGF-1 could restore the proliferative and invasive ability induced by DCUN1D5 knockdown and DCUN1D5 could act as a novel transcriptional target of transcription factor Yin Yang 1 (YY1). In conclusion, YY1-enhanced DCUN1D5 expression could promote TNBC progression by FN1/PI3K/AKT pathway and DCUN1D5 might be a potential prognostic biomarker and therapeutic target for TNBC treatment.

Abstract Background The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. Methods OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. Results Pla-Exos derived from active TAO patients (Pla-ExosTAO−A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO−A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO−A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. Conclusion Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.

Perennial ryegrass (Lolium perenne L.) has potential in the phytoremediation of cadmium (Cd)-contaminated soil due to its strong Cd accumulation capacity and high biomass. In this study, we investigated the growth physiology, Cd accumulation, and metabolites of L. perenne roots under different soil acid stress levels (pH 4.0, 4.5, 5.0 and 6.0) and Cd concentrations (100 and 0 mg/kg) after 90 days of growth. The results showed that soil acid stress significantly impacts the remediation capability and physiological metabolic properties of L. perenne. Based on root Cd content and enrichment coefficient, soil pH between 4.5 and 5.0 was more conducive to Cd accumulation. The growth physiology and Cd accumulation of L. perenne were inhibited under high soil acid stress (pH 4.0). High soil acid stress caused a decrease in root length, root volume, and root biomass of L. perenne. Root malondialdehyde (MDA) content and the activity of antioxidant enzymes (catalase (CAT) and peroxidase (POD)) increased significantly in response to high soil acid stress to enhance tolerance. Metabolomics analysis revealed that acid stress resulted in significant changes in certain metabolites. Tartaric acid, fructose and amino acids (glutamate and lysine) in the roots of L. perenne were compatible solutes under acid stress. This study indicated that L. perenne has strong physiological and metabolic tolerance, as well as Cd accumulation ability, in response to soil acid stress.

Abstract Dielectric elastomer actuators (DEAs) with large actuation strain and high energy density are highly desirable for actuating soft robots. However, DEAs usually require high driving electric fields (>100 MV m−1) to achieve high performances due to the low dielectric constant and high stiffness of dielectric elastomers (DEs). Here, we introduce polar fluorinated groups and nanodomains aggregated by long alkyl side chains into DE design, simultaneously endowing DE with a high dielectric constant and desirable modulus. Our DE exhibits a maximum area strain of 253% at a low driving electric field of 46 MV m−1. Notably, it achieves an ultrahigh specific energy of 225 J kg−1 at only‍‌ ‌‌40‍‌ MV m−1, around 6 times higher than natural muscle and twice higher than the state-of-the-art DE. Using our DE, soft robots reach an ultrafast running speed of 20.6 BL s−1, 60 times higher than that of commercial VHB 4910, representing the fastest DEA-driven soft robots ever reported.

Panoptic segmentation plays a crucial role in enabling robots to comprehend their surroundings, providing fine-grained scene understanding information for robots' intelligent tasks. Although existing methods have made some progress, they are prone to fail in areas with weak textures, small objects, etc. Inspired by biological vision research, we propose a cascaded contour-enhanced panoptic segmentation network called CCPSNet, attempting to enhance the discriminability of instances through structural knowledge. To acquire the scene structure, a cascade contour detection stream is designed, which extracts comprehensive scene contours using channel regulation structural perception module and coarse-to-fine cascade strategy. Furthermore, the contour-guided multi-scale feature enhancement stream is developed to boost the discrimination ability for small objects and weak textures. The stream integrates contour information and multi-scale context features through structural-aware feature modulation module and inverse aggregation technique. Experimental results show that our method improves accuracy on the Cityscapes (61.2 PQ) and COCO (43.5 PQ) datasets while also demonstrating robustness in challenging simulated real-world complex scenarios faced by robots, such as dirty cameras and rainy conditions. The proposed network promises to help the robot perceive the real scene. In future work, an unsupervised training strategy for the network could be explored to reduce the training cost.

Abstract Toremifene, a selective estrogen receptor modulator, is commonly used in China for premenopausal breast cancer patients. This real‐world study aimed to compare patient‐reported outcome (PRO) and survival between toremifene and aromatase inhibitor (AI) plus ovarian function suppression (OFS) in patients with moderate‐/high‐risk premenopausal hormone receptor (HR)‐positive breast cancer. The primary endpoint was PROs, assessed using SF‐36 and EQ‐5D‐5L questionnaires between January and March 2023. A total of 392 patients were included, with 171 receiving toremifene and 221 receiving AI. The toremifene group showed significantly higher scores in the role physical (p = 0.034) and mental health (p = 0.009) dimensions of SF‐36 and lower anxiety/depression (AD) scores (p = 0.038) in EQ‐5D‐5L compared to AI group. The estimated 5‐ and 8‐year disease‐free survival (DFS) rates were similar in toremifene and AI groups: 96.5% versus 91.9%, and 87.4% versus 87.8% (p = 0.39), respectively. Adverse event rates were similar in two groups, except for a greater risk of endometrial thickening (p

This study aimed to investigate the effect of L-theanine in regulating the intestinal antioxidant of weaned piglets and its underlying mechanism. We found that L-theanine increased the activities of antioxidant enzymes and the level of GSH, while decreased the MDA content of weaned piglet jejunum mucosa and H2O2-induced IPEC-J2 cells. In addition, the mRNA expression of SOD1, SOD2, GPx1, CAT, HO-1 and NQO1 was also significantly increased in jejunum mucosa and H2O2-induced IPEC-J2 cells by L-theanine treatment. Furthermore, L-theanine promoted the nuclear Nrf2 expression and decreased the keap1 expression. However, blocking of Nrf2 signaling by ML385 (the Nrf2 inhibitor) repressed the promoting effects of L-theanine on the activities of antioxidative enzymes and the expression of antioxidant related genes, while increased the MDA content and keap1 expression in IPEC-J2 cells. These data provided the first evidence that L-theanine improved intestinal antioxidant ability of weaned piglets by activating Nrf2 signaling pathway.

The impact of CEO ability on corporate behavior is dual-faceted. Based on the “rent-seeking hypothesis”, this paper focuses on the “dark side” of CEO ability and suggests that CEO ability may hurt corporate behavior. Using the DEA method to measure CEO ability and selecting Chinese A-share listed companies from 2007 to 2017 as a sample, we examine the relationship, mechanisms, and boundary conditions between CEO ability and stock price crash risk. Our study finds that CEO ability exacerbates stock price crash risk positively. Mechanism tests based on CEO tenure, agency conflict, and litigation risk reveal that CEO ability intensifies stock price crash risk for alleviating career concerns, seeking private gains, and risk avoidance, supporting the “rent-seeking hypothesis”. Boundary condition tests based on internal and external governance environments show that internal control quality and external audit supervision can play a governance role in mitigating the exacerbating effect of CEO ability on stock price crash risk. The conclusions are of significant importance for companies, relevant departments, and global market participants to strengthen governance and supervision to prevent the negative impact of CEO ability on stock prices, thereby promoting the stable development of global financial markets.

Minks, cats, and some other species of carnivores are susceptible of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have a high risk of transmitting SARS-CoV-2 to humans. The development of animal vaccines can be an effective measure to protect animals against SARS-CoV-2 and reduce the potential risk of human infection. We previously developed a messenger ribonucleic acid (mRNA) vaccine SYS6006 that has been proven to be an efficient coronavirus disease 2019 (COVID-19) vaccine widely used in humans. Here, we further evaluated the safety and immunogenicity of SYS6006 as an animal COVID-19 vaccine candidate for SARS-CoV-2 susceptible animals or wild animals. SYS6006 was safe and immunogenic in mice and completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. SYS6006 was able to induce neutralizing antibodies against the SARS-CoV-2 wild-type, Delta, and Omicron BA.2 strain on day 7 after prime immunization, and two doses of immunization could enhance the neutralizing antibody responses and produce long-lasting potent antibodies for more than 8 months in minks and cats, blue foxes, and raccoon dogs, while all immunized animals had no abnormal clinical signs during immunization. These results provided here warrant further development of this safe and efficacious mRNA vaccine platform against animal COVID-19.

BackgroundMicrobial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized.ObjectiveOur objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis.MethodsWe analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes.ResultsOur findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients.ConclusionThe study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome’s role in HPVI ECA.

Cellular senescence, a permanent halt in cell division due to stress, spurs functional and structural changes, contributing to vascular aging characterized by endothelial dysfunction and vascular remodeling. This process raises the risk of ischemic stroke (IS) in older individuals, with its mechanisms still not completely understood despite ongoing research efforts. In this review, we have analyzed the impact of vascular aging on increasing susceptibility and exacerbating the pathology of IS. We have emphasized the detrimental effects of endothelial dysfunction and vascular remodeling influenced by oxidative stress and inflammatory response on vascular aging and IS. Our goal is to aid the understanding of vascular aging and IS pathogenesis, particularly benefiting older adults with high risk of IS.

Background: Alveolar bone destruction due to periodontal disease often requires a bone graft substitute to reconstruct the anatomical structures and biological functions of the bone tissue. Despite significant advances in the development of foreign ion-doped nonstoichiometric wollastonite bioceramics (CaSiO3, nCSi) for alveolar bone regeneration over the past decade, the in vivo biosafety and osteogenesis of nCSi scaffolds remain uncertain. In this study, we developed a customized porous nCSi scaffold to investigate the in vivo biocompatibility and osteogenic properties of nCSi bioceramics. Methods: Six percent Mg-doped nCSi bioceramic scaffolds were fabricated by digital light processing (DLP), and the scaffold morphology, pore architecture, compressive strength, in vitro biodegradation, and apatite-forming ability of the bioceramic scaffolds were investigated systematically. Subsequently, an alveolar bone defect rabbit model was used to evaluate the biocompatibility and osteogenic efficacy of the nCSi bioceramics. Animal weight, hematological test, blood biochemical test, wet weight of the main organs, and pathological examination of the main organs were conducted. Micro-CT and histological staining were performed to analyze the osteogenic potential of the personalized bioceramic scaffolds. Results: The nCSi scaffolds exhibited appreciable initial compressive strength (>30 MPa) and mild mechanical decay over time during in vitro biodissolution. In addition, the scaffolds induced apatite remineralization in SBF. Bioceramic scaffolds have been proven to have good biocompatibility in vivo after implantation into the alveolar bone defect of rabbits. No significant effects on the hematological indices, blood biochemical parameters, organ wet weight, or organ histopathology were detected from 3 to 180 days postoperatively. The porous scaffolds exhibited strong bone regeneration capability in the alveolar bone defect model of rabbits. Micro-CT and histological examination showed effective maintenance of bone morphology in the bioceramic scaffold group; however, depressed bone tissue was observed in the control group. Conclusions: Our results suggest that personalized nCSi bioceramic scaffolds can be fabricated using the DLP technique. These newly developed strong bioceramic scaffolds exhibit good biocompatibility and osteogenic capability in vivo and have excellent potential as next-generation oral implants. The translational potential of this article: Tissue-engineered strategies for alveolar bone repair require a bone graft substitute with appreciable biocompatibility and osteogenic capability. This article provides a systematic investigation of the in vivo biosafety and osteogenic property of nCSi to further development of a silicate-based bioceramics materials for clinical applications.

Background and objective Lung cancer is the malignant tumor with the highest incidence rate and the heaviest disease burden in China. In recent years, lung cancer has shown a high incidence trend, seriously affecting the health of the population. In this paper, we analyze the characteristics of lung cancer incidence in 2019 and the trend of incidence rate from 2010-2019 in the tumor registration area of Gansu province, in order to provide a reference basis for the development of lung cancer prevention and control strategies in Gansu province. Methods By analyzing the cases of lung cancer incidence in the tumor registration area of Gansu province in 2019, we calculated the incidence rate, medium incidence rate, world incidence rate and other related indexes; we used Joinpoint to calculate the annual percentage change (APC) for trend analysis. Results In 2019, a total of 3757 new cases of lung cancer were reported in Gansu province, accounting for 14.96% of all new malignant tumors. The incidence rate, medium incidence rate and world incidence rate and world rate of lung cancer were 40.52/105, 25.78/105, 25.86/105; and the cumulative rate of 0-74 years old, and the truncation rate of 35-64 years old were 3.23%, 40.03/105, respectively. The incidence of lung cancer rises with age, and is high in the age group of 40 years and above, and the incidence peaks in the male and female populations in the group of 75 years and above, and the group of 80 years and above, respectively. The crude incidence rate of lung cancer in the tumor registration area of Gansu province from 2010-2019 showed an overall increasing trend, and the rate of increase was relatively fast, with an APC 5.39% (P

Abstract The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients’ orthodontic treatment.

The advent of the digital era has transformed E-commerce platforms into critical tools for industry, yet traditional recommendation systems often fall short in the specialized context of the electric power industry. These systems typically struggle with the industry's unique challenges, such as infrequent and high-stakes transactions, prolonged decision-making processes, and sparse data. This research has developed a novel recommendation engine tailored to these specific conditions, such as to handle the low frequency and long cycle nature of Business-to-Business (B2B) transactions. This approach includes algorithmic enhancements to better process and interpret the limited data available, and data pre-processing techniques designed to enrich the sparse datasets characteristic of this industry. This research also introduces a methodological innovation that integrates multi-dimensional data, combining user E-commerce activities, product specifics, and essential non-tendering information. The proposed engine employs advanced machine learning techniques to provide more accurate and relevant recommendations. The results demonstrate a marked improvement over traditional models, offering a more robust and effective tool for facilitating B2B transactions in the electric power industry. This research not only addresses the sector's unique challenges but also provides a blueprint for adapting recommendation systems to other industries with similar B2B characteristics.

Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/μL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/μL for SFGR-ompA, 1.075 copies/μL for SFTSV-L and 1.006 copies/μL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.

All organisms have various circadian, behavioral, and physiological 24-h periodic rhythms, which are controlled by the circadian clock. The circadian clock controls various behavioral and physiological rhythms. In mammals, the primary circadian clock is present in the suprachiasmatic nucleus of the hypothalamus. The rhythm of the circadian clock is controlled by the interaction between negative and positive feedback loops, consisting of crucial clock regulators (including Bmal1 and Clock), three cycles (mPer1, mPer2, and mPer3), and two cryptochromes (Cry1 and Cry2). The development of early mammalian embryos is an ordered and complex biological process that includes stages from fertilized eggs to blastocysts and undergoes important morphological changes, such as blastocyst formation, cell multiplication, and compaction. The circadian clock affects the onset and timing of embryonic development. The circadian clock affects many biological processes, including eating time, immune function, sleep, energy metabolism, and endocrinology, therefore, it is also crucial for overall health, growth and development after birth. This review summarized the effects of the circadian clock in the body’s physiological activities. A new strategy is proposed for the prevention of malformations or diseases by regulating the circadian clock or changing circadian rhythms.

Abstract Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio‐based hydrogel microspheres ‘micro‐cage’, termed mPDA‐PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique ‘micro‐cage’ construct is designed to non‐contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into ‘micro‐cage’ along with wound exudation, and cationic mPDA‐PEI immobilizes them inside the ‘micro‐cage’ through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non‐contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

Sakuranetin, a flavonoid phytoalexin in rice, plays a crucial role in defense against pathogen infection. While MYB-type transcription factors are well-known to regulate plant growth, development, secondary metabolism, and adaptation to environmental stresses, the function of rice MYB-related transcription factors in sakuranetin biosynthesis and sakuranetin-mediated defense remains unclear. In this study, we identified and characterized OsMYB1R, a novel single repeat MYB transcription factor that acts as a transcriptional activator in sakuranetin biosynthesis. Protein-DNA binding and activation assays revealed that OsMYB1R directly regulates the gene promoter of OsNOMT, a key enzyme in sakuranetin synthesis. Molecular analyses and infection studies using OsMYB1R-overexpressing (OsMYB1R-OE) and OsMYB1R-knockout (Osmyb1r, generated using CRISPR/Cas9) plants demonstrated that OsMYB1R increases sakuranetin production and decreases Magnaporthe oryzae infection by transcriptionally regulating OsNOMT expression. This finding indicates a positive regulation of sakuranetin biosynthesis and antifungal resistance by the OsMYB1R-OsNOMT crosstalk. Interestingly, the alteration of OsMYB1R expression did not affect yield-related agronomic traits. Our results reveal a novel and positive role of 1R-MYB in secondary metabolite biosynthesis and pathogen defense, suggesting that OsMYB1R is a potential gene for effectively enhancing rice resistance without compromising yield.

Abstract Background Insulin resistance is associated with chronic complications of diabetes, including diabetic peripheral neuropathy (DPN). Estimated glucose disposal rate (eGDR), calculated by the common available clinical factors, was proved to be an excellent tool to measure insulin resistance in large patient population. Few studies have explored the association between eGDR and DPN longitudinally. Therefore, we performed the current study to analyze whether eGDR could predict the risk of DPN. Methods In this prospective study, 366 type 2 diabetes (T2DM) subjects without DPN were enrolled from six communities in Shanghai in 2011–2014 and followed up until 2019–2020. Neuropathy was assessed by Michigan Neuropathy Screening Instrument (MSNI) at baseline and at the end of follow‐up. Findings After 5.91 years, 198 of 366 participants progressed to DPN according to MNSI examination scores. The incidence of DPN in the low baseline eGDR (eGDR

In Human-Robot Interaction (HRI), accurate 3D hand pose and mesh estimation hold critical importance. However, inferring reasonable and accurate poses in severe self-occlusion and high self-similarity remains an inherent challenge. In order to alleviate the ambiguity caused by invisible and similar joints during HRI, we propose a new Topology-aware Transformer network named HandGCNFormer with depth image as input, incorporating prior knowledge of hand kinematic topology into the network while modeling long-range contextual information. Specifically, we propose a novel Graphformer decoder with an additional Node-offset Graph Convolutional layer (NoffGConv). The Graphformer decoder optimizes the synergy between the Transformer and GCN, capturing long-range dependencies and local topological connections between joints. On top of that, we replace the standard MLP prediction head with a novel Topology-aware head to better exploit local topological constraints for more reasonable and accurate poses. Our method achieves state-of-the-art 3D hand pose estimation performance on four challenging datasets, including Hands2017, NYU, ICVL, and MSRA. To further demonstrate the effectiveness and scalability of our proposed Graphformer Decoder and Topology aware head, we extend our framework to HandGCNFormer-Mesh for the 3D hand mesh estimation task. The extended framework efficiently integrates a shape regressor with the original Graphformer Decoder and Topology aware head, producing Mano parameters. The results on the HO-3D dataset, which contains various and challenging occlusions, show that our HandGCNFormer-Mesh achieves competitive results compared to previous state-of-the-art 3D hand mesh estimation methods.

Abstract Background The study aims to update the specific classification of mechanisms of death in swimming and to demonstrate these categories are reasonable, by analyzing more characteristics of death cases, evaluating the available evidence and determining their quality. Methods Original articles were queried from PubMed, Web of Science, Embase databases, Cochrane Library, and Scopus. Included studies, which were evaluated as level 4 evidence or higher according to the Oxford Centre for Evidence-Based Medicine, discussed hypothesized mechanisms of death in swimming. Parameters analyzed in this study included decedents’ characteristics, outcome measures, findings, methodological index for non-randomized studies (MINORS), and critical evaluation of each study classified by death mechanism. Results A total of twenty-five studies were included for further analysis: fourteen were associated with cardiovascular diseases, two were about cerebrovascular diseases, two contained respiratory diseases, seven were about hazardous conditions and three contained other drownings, which provided evidence for mechanisms of death. Conclusions It is found that cardiovascular disease is the main cause or contributing factor of death in swimming. Respiratory diseases and cerebrovascular diseases are difficult to be definitive mechanism categories due to insufficient evidence. Hazardous conditions appear to be one of the possible risk factors because there are more cases of deaths from unsafe environments in swimming, but further statistics and research are still needed to support this view. Our study may have important implications for developing potential prevention strategies for sports and exercise medicine. Trial registration PROSPERO ID (CRD42021267330). Registered Aug 13th 2021.

Abstract Inspired by the brilliant prospects of the ongoing B meson experiments, the hadronic charmless B $${\rightarrow }$$ → SS decays are studied by considering the next-to-leading (NLO) contributions with the QCD factorization approach, where S denotes the scalar mesons $$K_{0}^{*}(1430)$$ K 0 ∗ ( 1430 ) and $$a_{0}(1450)$$ a 0 ( 1450 ) . Branching ratios and CP violating asymmetries are estimated with the updated values of hadronic parameters obtained from a covariant light-front quark model, for two scenarios where the scalar mesons are the $$1^{3}P_{0}$$ 1 3 P 0 and $$2^{3}P_{0}$$ 2 3 P 0 states. It is found that the NLO contributions are very important for the B $${\rightarrow }$$ → SS decays. For the B $${\rightarrow }$$ → $$a_{0}(1450)K_{0}^{*}(1430)$$ a 0 ( 1450 ) K 0 ∗ ( 1430 ) and $$B_{s}$$ B s $${\rightarrow }$$ → $$K_{0}^{*}(1430)\overline{K}_{0}^{*}(1430)$$ K 0 ∗ ( 1430 ) K ¯ 0 ∗ ( 1430 ) decays, branching ratios can reach up to the order of $${\mathcal {O}}(10^{-5})$$ O ( 10 - 5 ) by assuming that the scalar mesons are the 1P states, and should first be investigated in the future experiments.

Soil salinization and alkalinization are pervasive environmental issues that severely restrict plant growth and crop yield. Utilizing plant growth-promoting rhizobacteria (PGPR) is an effective strategy to enhance plant tolerance to saline–alkaline stress, though the regulatory mechanisms remain unclear. This study employed biochemical and RNA-Seq methods to uncover the critical growth-promoting effects of Trichoderma spp. on Salix linearistipularis under saline–alkaline stress. The results showed that, during saline–alkaline stress, inoculation with Trichoderma sp. M4 and M5 significantly increased the proline and soluble sugar contents in Salix linearistipularis, enhanced the activities of SOD, POD, CAT, and APX, and reduced lipid peroxidation levels, with M4 exhibiting more pronounced effects than M5. RNA-Seq analysis of revealed that 11,051 genes were upregulated after Trichoderma sp. M4 inoculation under stress conditions, with 3532 genes primarily involved in carbon metabolism, amino acid biosynthesis, and oxidative phosphorylation—processes that alleviate saline–alkaline stress. Additionally, 7519 genes were uniquely upregulated by M4 under stress, mainly enriched in secondary metabolite biosynthesis, amino acid metabolism, cyanamide metabolism, and phenylpropanoid biosynthesis. M4 mitigates saline–alkaline stress-induced damage in Salix linearistipularis seedlings by reducing oxidative damage, enhancing organic acid and amino acid metabolism, and activating phenylpropanoid biosynthesis pathways to eliminate harmful ROS. This enhances the seedlings’ tolerance to saline–alkaline stress, providing a basis for studying fungi–plant interactions under such conditions.

Traditionally, Tibetan sheep only graze pastures without any supplementary feed. However, in recent years, feedlots are being used for fattening Tibetan sheep. The present study compared the growth rates, blood parameters, rumen fermentation, and bacterial communities in Tibetan sheep fattened by pasture grazing (PG) versus those fattened by stall feeding (SF). Twenty 18-month-old Tibetan sheep wethers (42.6 ± 2.11 kg) were divided randomly into PG (n = 10) and SF (n = 10) groups. The PG sheep grazed the grasslands without any supplementary feed, while the SF sheep were offered a commercial total mixed ration (TMR) at a crude protein content of 16.2% DM and an ME of 10.59 MJ/kg. The sheep were on their treatments for 70 days, which included 10 days for adaptation and 60 days for measurements. The average daily gain, white blood cell and lymphocyte counts were greater (p < 0.05), while the platelet count was lower (p < 0.05) in the SF group than in the PG group. The serum glutathione peroxidase activity, and concentrations of total proteins and albumin were greater (p < 0.05), while glucose was lower (p < 0.01) in the PG group compared to the SF group. The concentrations of ruminal ammonia–N and total volatile fatty acids (VFAs) were greater (p < 0.05), while the pH was lower (p < 0.05) in the SF group compared to the PG group. The molar proportion of acetate and the ratio of acetate to propionate were greater (p < 0.01) in the PG sheep than in the SF sheep, but the molar proportion of propionate and iso-VFAs did not differ (p > 0.05) between the groups. Based on the PCoA, the ruminal bacterial communities were distinct between groups, and the alpha diversity was greater (p < 0.001) in the PG sheep than in the SF sheep. The dominant phyla of the rumen bacteria were Firmicutes and Bacteroidetes, while the Firmicutes to Bacteroidetes ratio was greater (p < 0.001) in the SF group than in the PG group. At the genus level, the relative abundance of Ruminococcus was greater (p < 0.05) in the SF group, while the abundances of Prevotella, the Rikenellaceae_RC9_gut_group, Butyrivibrio, and unclassified_f_Lachnospiraceae were greater (p < 0.05) in the PG group. It was concluded that the Tibetan sheep adopted a short-term intensive fattening strategy when stall fed which altered the rumen bacterial community and blood parameters, enhanced rumen fermentation, and, ultimately, improved their average daily gain.

N6-methyladenosine (m6A), an RNA post-transcriptional modification, plays a crucial role in spermatogenesis. Cattle-yaks are interspecific hybrid offsprings of yak and cattle, and male cattle-yaks are sterile. This study aims to investigate the role of m6A modification in male cattle-yak infertility. Herein, testicular tissues were analyzed via histological observations, immunohistochemical assays, reverse-transcription quantitative polymerase chain reaction, Western blotting, and immunofluorescence assays. The results revealed that male cattle-yaks presented smaller testes (5.933 ± 0.4885 cm vs. 7.150 ± 0.3937 cm), with only single cell layers in seminiferous tubules, and weakened signals of m6A regulators such as METTL14 (methyltransferase-like 14), ALKBH5 (alpha-ketoglutarate-dependent hydroxylase homolog 5), FTO (fat mass and obesity-associated protein), and YTHDF2 (YTH N6-methyladenosine RNA binding protein F2), both at the RNA and protein levels, compared with those of yaks. Altogether, these findings suggest that m6A modification may play a crucial role in male cattle-yak sterility, providing a basis for future studies.

IntroductionThe programmed cell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3′-untranslated region of the PCD pathway genes and breast cancer outcomes.MethodsIn this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs) in 23 PCD pathway genes in 1,177 patients with early-stage breast cancer (EBC) from a Han Chinese population. The median follow-up period was 174 months.ResultsAmong all the candidate SNPs, four independent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS) and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreased as the number of unfavorable genotypes increased (Ptrend = 1.0 × 10−6, 8.5 × 10−8, 3.6 × 10−4, and 1.3 × 10−4 for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristic curve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P = 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively). Additionally, rs6753785 and rs2213181 were associated with BCL2L11 and c-Kit mRNA expression, respectively.ConclusionsOur results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes.

Background: Bibliometrics can trace general research trends in a particular field. Mucopolysaccharidoses (MPS), as a group of rare genetic diseases, seriously affect the quality of life of patients and their families. Scholars have devoted themselves to studying MPS’s pathogenesis and treatment modalities and have published many papers. Therefore, we conducted a bibliometric and visual study of the top 100 most highly cited articles to provide researchers with an indication of the current state of research and potential directions in the field.Methods: The Web of Science Core Collection was searched for articles on MPS from 1 January 1900, to 8 November 2023, and the top 100 most cited articles were screened. The title, year of publication, institution, country, and first author of the articles were extracted and statistically analyzed using Microsoft Excel 2007. Keyword co-occurrence and collaborative networks were analyzed using VOSviewer 1.6.16.Results: A total of 9,273 articles were retrieved, and the top 100 most cited articles were filtered out. The articles were cited 18,790 times, with an annual average of 188 citations (122–507). Forty-two journals published these articles, with Molecular Genetics and Metabolism and Proceedings of the National Academy of Sciences of the United States being the most published journal (N = 8), followed by Pediatrics (N = 7), Blood (N = 6). The United States (N = 68), the UK (N = 25), and Germany (N = 20) were the top contributing countries. The Royal Manchester Children’s Hospital (N = 20) and the University of North Carolina (N = 18) were the most contributing institutions. Muenzer J was the most prolific author (N = 14).Conclusion: We conducted a bibliometric and visual analysis of the top 100 cited articles in MPS. This study identifies the most influential articles currently available in the field of MPS, which provides a good basis for a better understanding of the disease and informs future research directions.

Summary: Neuromodulation is pivotal in modifying neuronal properties and motor states. CKR-1, a homolog of the cholecystokinin receptor, modulates robust escape steering and undulation body bending in C. elegans. Nevertheless, the mechanisms through which CKR-1 governs these motor states remain elusive. We elucidate the head motoneuron SMD as the orchestrator of both motor states. This regulation involves two neuropeptides: NLP-12 from DVA enhances undulation body curvature, while NLP-18 from ASI amplifies Ω-turn head curvature. Moreover, synthetic NLP-12 and NLP-18 peptides elicit CKR-1-dependent currents in Xenopus oocytes and Ca2+ transients in SMD neurons. Notably, CKR-1 shows higher sensitivity to NLP-18 compared to NLP-12. In situ patch-clamp recordings reveal CKR-1, NLP-12, and NLP-18 are not essential for neurotransmission at C. elegans neuromuscular junction, suggesting that SMD independently regulates head and body bending. Our studies illustrate that a single motoneuron SMD utilizes a cholecystokinin receptor CKR-1 to integrate two motor states.

Eravacycline (ERV) has emerged as a therapeutic option for the treatment of carbapenem-resistant pathogens. However, the advent of heteroresistance (HR) to ERV poses a challenge to these therapeutic strategies. This study aimed to investigate ERV HR prevalence among common clinical isolates and further characterize ERV HR in carbapenem-resistant Klebsiella pneumoniae (CRKP). A total of 280 clinical pathogens from two centers were selected for HR and analyzed using population analysis profiling (PAP) and modified E-tests. The PAP assay revealed an overall ERV HR prevalence of 0.7% (2/280), with intermediate heterogeneity observed in 24.3% (68/280) of strains. The proportion of heteroresistant strains was 18.3% according to modified E-test results. A time-killing assay demonstrated that CRKP CFU increased significantly after 10 h of ERV treatment, contributing to the reduced bactericidal effect of ERV in vitro. Interestingly, dual treatment with ERV and polymyxin B effectively inhibited the total CFU, simultaneously reducing the required polymyxin B concentration. Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.

Abstract Resistance to immunotherapy in colorectal cancer (CRC) is associated with obstruction of FAS (Apo‐1 or CD95)‐dependent apoptosis, a hallmark of cancer. Here it is demonstrated that the upregulation of pirin (PIR) protein in colon cancers promotes tumorigenesis. Knockout or inhibition of PIR dramatically increases FAS expression, FAS‐dependent apoptosis and attenuates colorectal tumor formation in mice. Specifically, NFκB2 is a direct transcriptional activator of FAS and robustly suppressed by PIR in dual mechanisms. One is the disruption of NFκB2 complex (p52‐RELB) association with FAS promoter, the other is the inhibition of NIK‐mediated NFκB2 activation and nuclear translocation, leading to the inability of active NFκB2 complex toward the transcription of FAS. Furthermore, PIR interacts with FAS and recruits it in cytosol, preventing its membrane translocation and assembling. Importantly, knockdown or knockout of PIR dramatically sensitizes cells to FAS mAb‐ or active CD8+ T cells‐triggered cell death. Taken together, a PIR‐NIK‐NFκB2‐FAS survival pathway is established, which plays a key role in supporting CRC survival.

The chemical recycling of polyolefin presents a considerable challenge, especially as upcycling methods struggle with the reality that plastic wastes typically consist of mixtures of polyethylene (PE), polystyrene (PS), and polypropylene (PP). We report a catalytic aerobic oxidative approach for polyolefins upcycling with the corresponding carboxylic acids as the product. This method encompasses three key innovations. First, it operates under atmospheric pressure and mild conditions, using O2 or air as the oxidant. Second, it is compatible with high-density polyethylene, low-density polyethylene, PS, PP, and their blends. Third, it uses an economical and recoverable metal catalyst. It has been demonstrated that this approach can efficiently degrade mixed wastes of plastic bags, bottles, masks, and foam boxes.

In the context of promoting the integration of smart cities, the pace of construction of smart chemical parks is gradually accelerating.Since accidents in China’s chemical industry have occurred frequently in recent years, causing great damage and loss to public safety, improving the safety management and emergency response capability of chemical parks is an urgent need to be solved.For this kind of safety problems, this paper proposed a game patrol strategy for hazardous gas leakage in chemical parks.Firstly, the convective diffusion model was used to describe the process of hazardous gas leakage.Secondly, game theory was introduced to model the confrontation process between the attacking and defending parties in the patrol problem, and the response time of the defenders to a safety incident was correlated with its benefit.Then, a multilinear programming-based GGC algorithm was proposed to solve this game model.Finally, the gains of the game model in this paper were compared with the other two basic methods in the scenarios of three real chemical park case with different sizes.The results show that the model can effectively improve the gains of the defender and reduce the gains of the attacker.

Abstract Background To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. Methods A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. Results Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. Conclusions Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. Clinical relevance statement Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. Key points • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77. Graphical Abstract

The relationship between distinct dietary selenium intake and type 2 diabetes (T2D) is still a topic of uncertainty. This study examined the relationship between dietary selenium intake and T2D risk among middle-aged and older Chinese adults. Dietary selenium intake was assessed through three 24 h recalls, using data from the China Health and Nutrition Survey. To investigate the relationship and the potential dose–response pattern between selenium intake and the likelihood of developing T2D, we employed both the restricted cubic spline analysis and the Cox proportional hazards model as our analytical tools. A cohort of 5970 participants aged ≥ 50 years was followed for an average of 5.44 years. The results revealed a V-shaped correlation between selenium intake and T2D risk, with the lowest risk observed at approximately 45 µg/day. Below this level, the risk decreased with an increasing selenium intake, while the risk increased between 45 and 100 µg/day. No significant association was found beyond 100 µg/day. These findings suggest that both low and high selenium consumption may increase T2D risk, highlighting the importance of maintaining a balanced selenium intake for T2D prevention.

Polar codes have garnered significant attention since they were proposed due to their capacity-achieving properties and their low-complexity decoding process, and they were selected as the coding scheme for the control channel in 5G mobile communication technology. A successive cancellation list (SCL) decoder, aided by a cyclic redundancy check (CRC), performs the competitive error correcting performance for polar codes compared to other sophisticated codes. The SCL-Flip decoding algorithm is proposed to enhance the error correction performance of the SCL. However, the SCL-Flip is hampered by a high decoding complexity due to the necessary selection and sorting process of path metrics (PMs). Additionally, it requires a large number of iterations to achieve a good error correction performance. In this paper, we propose the error segment bit-flip (ES-SCL-Flip) decoding algorithm, a simplified bit-flip approach for the SCL decoder based on analyzing the distributions of the first error bit. Firstly, we construct an index set with a high probability of the first erroneous bit. Second, a bit-flip criterion is introduced to prevent the costly operation of the PM selection and sorting without compromising the error correction performance. Finally, a search strategy is employed that utilizes segmented error indication to target and rectify the initial error segment sequentially. The simulation results demonstrate that the ES-SCL-Flip decoder provides an improved error correction performance with only a minimal increase in decoding complexity compared to the conventional CRC-aided SCL decoder. This algorithm attains a commendable equilibrium between the error correction performance and decoding complexity.

Bone defects caused by trauma, tumor resection, and infections are significant clinical challenges. Excessive reactive oxygen species (ROS) usually accumulate in the defect area, which may impair the function of cells involved in bone formation, posing a serious challenge for bone repair. Due to the potent ROS scavenging ability, as well as potential anti-inflammatory and immunomodulatory activities, antioxidants play an indispensable role in the maintenance and protection of bone health and have gained increasing attention in recent years. This narrative review aims to give an overview of the main research directions on the application of antioxidant compounds in bone defect repair over the past decade. In addition, the positive effects of various antioxidants and their biomaterial delivery systems in bone repair are summarized to provide new insights for exploring antioxidant-based strategies for bone defect repair.

Ambient particulate matter (PM) pollution is a leading environmental health threat worldwide. PM with an aerodynamic diameter ≤ 1.0 μm, also known as PM1, has been implicated in the morbidity and mortality of several cardiorespiratory and cerebrovascular diseases. However, previous studies have mostly focused on analyzing fine PM (PM2.5) associated with disease metrics, such as emergency department visits and mortality, rather than ultrafine PM, including PM1. This study aimed to evaluate the association between short-term PM1 exposure and hospital admissions (HAs) for all-cause diseases, chronic obstructive pulmonary disease (COPD), and respiratory infections (RIs), as well as the associated expenditures, using Beijing as a case study. Here, based on air pollution and hospital admission data in Beijing from 2015 to 2017, we performed a time-series analysis and meta-analysis. It was found that a 10 μg/m3 increase in the PM1 concentration significantly increased all-cause disease HAs by 0.07% (95% Confidence Interval (CI): [0, 0.14%]) in Beijing between 2015 and 2017, while the COPD and RI-related HAs were not significantly associated with short-term PM1 exposure. Meanwhile, we estimated the attributable number of HAs and hospital expenditures related to all-cause diseases. This study revealed that an average of 6644 (95% CI: [351, 12,917]) cases of HAs were attributable to ambient PM1, which was estimated to be associated with a 106 million CNY increase in hospital expenditure annually (95% CI: [5.6, 207]), accounting for 0.32% (95% CI: [0.02, 0.62%]) of the annual total expenses. The findings reported here highlight the underlying impact of ambient PM pollution on health risks and economic burden to society and indicate the need for further policy actions on public health.

There is a long sequence of periodic characteristics of reservoir water storage and discharge in large hydropower stations. The unloaded rock mass formed by blasting and excavation in the reservoir slope of the reservoir fluctuation zone is not only subjected to the penetration erosion caused by the change of the water level of the reservoir slope, but also the dry–wet cycle caused by the reservoir water storage and discharge. There is an obvious process of crack derivation and pore structure expansion, and the subsequent strength degradation breeds reservoir slope risks, which is one of the important factors restricting the operation safety of power stations. To study the pore structure evolution law of unloaded rock mass in reservoir slope excavation of reservoir fluctuation zones, the dry–wet cycle test simulating the periodic storage and discharge environment was carried out with samples of equal unloading amount obtained by indoor triaxial unloading test. The variation law of mesoscopic parameters such as wave velocity, mass, and nuclear magnetic resonance spectrum under dry–wet cycle was compared and analyzed, and the physical and mechanical mechanism of the pore structure evolution of the unloaded specimen under dry–wet cycles was explored. The results show that: (1) With the increase of dry–wet cycles, the evolution of wave velocity and dry mass of unloaded samples has obvious stage characteristics, which generally presents a rapid change in the early stage, moderate in the middle stage, and gradually stable in the late stage; (2) nuclear magnetic resonance (NMR) shows that the number of macropore structures in unloaded samples increases gradually with the dry–wet cycles; (3) the smaller the initial confining pressure, the larger the first peak area and the peak value of unloaded samples, and the spectral area corresponding to each peak under low confining pressure is significantly larger than that under medium and high confining pressure; (4) the unloading amount affects the overall proportion of macropores in the sample, which determines the deterioration process and evolution law of the mesostructure of the sample under dry–wet cycles.

Abstract For bone defect repair under co-morbidity conditions, the use of biomaterials that can be non-invasively regulated is highly desirable to avoid further complications and to promote osteogenesis. However, it remains a formidable challenge in clinical applications to achieve efficient osteogenesis with stimuli-responsive materials. Here, we develop polarized CoFe2O4@BaTiO3/poly(vinylidene fluoridetrifluoroethylene) [P(VDF-TrFE)] core-shell particle-incorporated composite membranes with high magnetoelectric conversion efficiency for activating bone regeneration. An external magnetic field force conduct on the CoFe2O4 core can increase charge density on the BaTiO3 shell and strengthens the β-phase transition in the P(VDF-TrFE) matrix. This energy conversion increases the membrane surface potential, which hence activates osteogenesis. Skull defect experiments on male rats showed that repeated magnetic field applications on the membranes enhanced bone defect repair, even when osteogenesis repression is elicited by dexamethasone or lipopolysaccharide-induced inflammation. This study provides a strategy of utilizing stimuli-responsive magnetoelectric membranes to efficiently activate osteogenesis in situ.