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The Northern Extended Millimeter Array (NOEMA) formIng Cluster survEy (NICE) is a NOEMA large programme targeting 69 massive galaxy group candidates at z > 2 over six deep fields with a total area of 46 deg2. Here we report the spectroscopic confirmation of eight massive galaxy groups at redshifts 1.65 ≤ z ≤ 3.61 in the Cosmic Evolution Survey (COSMOS) field. Homogeneously selected as significant overdensities of red IRAC sources that have red Herschel colours, four groups in this sample are confirmed by CO and [CI] line detections of multiple sources with NOEMA 3 mm observations, three are confirmed with Atacama Large Millimeter Array (ALMA) observations, and one is confirmed by Ha emission from Subaru/FMOS spectroscopy. Using rich ancillary data in the far-infrared and sub-millimetre, we constructed the integrated farinfrared spectral energy distributions for the eight groups, obtaining a total infrared star formation rate (SFR) of 260-1300 M⊙ yr-1. We adopted six methods for estimating the dark matter masses of the eight groups, including stellar mass to halo mass relations, overdensity with galaxy bias, and NFW profile fitting to radial stellar mass densities. We find that the radial stellar mass densities of the eight groups are consistent with a NFW profile, supporting the idea that they are collapsed structures hosted by a single dark matter halo. The best halo mass estimates are log(Mh/M⊙) = 12.8-13.7 with a general uncertainty of 0.3 dex. Based on the halo mass estimates, we derived baryonic accretion rates (BARs) of (1-8) × 103 M⊙/yr for this sample. Together with massive groups in the literature, we find a quasi-linear correlation between the integrated SFR/BAR ratio and the theoretical halo mass limit for cold streams, Mstream/Mh, with SFR/BAR = 10-0.46±0.22 (Mstream/Mh)0.71±0.16 with a scatter of 0.40 dex. Furthermore, we compared the halo masses and the stellar masses with simulations, and find that the halo masses of all structures are consistent with those of progenitors of Mh(z = 0) > 1014 M⊙ galaxy clusters, and that the most massive central galaxies have stellar masses consistent with those of the brightest cluster galaxy progenitors in the TNG300 simulation. Above all, the results strongly suggest that these massive structures are in the process of forming massive galaxy clusters via baryonic and dark matter accretion.

ABSTRACT The primary objective of this paper is to propose a method for predicting the safe mud weight window within the Bozi gas field situated in the Tarim Basin and establish a 3D wellbore stability model. The approach combines Mogi–Coulomb criterion using intermediate stress for wellbore shear failure. It considers rock shear breakdown in fracture pressure calculations and predicts reservoir shear slip with Jaeger criterion and drilling fluid invasion on the weak surface in calculating wellbore tensile failure. The study finds that instability in the well wall of this block is not solely due to the intermediate stress criterion or shear fracture of intact rock. Instead, during drilling with high‐density fluid, the weak surface (fracture) undergoes shear‐slip damage before intact rock. The collapse is a result of the interplay between bit replacement, dynamic drilling loads, and drilling fluid intrusion, causing tensile rupture on the weak surface and repeated fluid leakage. Analysis of wellbore instability in 16 wells within ultra‐deep complex formations shows that the collapse pressure prediction accuracy is 87.5%, and the loss pressure prediction accuracy is 93.7%. Compared to traditional methods, this approach is more accurate and practical, providing essential guidance for resolving wellbore instability issues in drilling operations. In conclusion, this paper introduces a novel and more precise method for predicting the safe mud weight window in the Bozi gas field.

In order to solve the problem of difficult deployment of existing deep learning-based defect detection models in terminal equipment with limited computational capacity, a lightweight steel surface defect testing model LSKA-YOLOv8 was proposed based on the YOLOv8n target detection framework. The model uses KernelWarehouse Conv (KWConv) with lower computational volumes, which significantly reduces the required computational resources. By updating the traditional Feature Pyramid Network (FPN) structure to Bi-directional Feature Pyramid Network (BiFPN), enhance the capture of contextual information and reduce the number of parameters of the model. In addition, the Spatial Pyramid Pooling Fast (SPPF) module was replaced with a more accurate Receptive Field Block (RFB) module, expanding the model’s sensory field and improving characteristic representation. At the same time, the Large Separable Kernel Attention (LSKAttention) module was introduced in the detection head, effectively enhancing the understanding and capture of the target characteristics, thus significantly improving the overall detection performance. Experiments on the NEU-DET dataset showed that the average accuracy of LSKA-YOLO increased by 4.4% on the map@0.5 indicator compared to the benchmark model, while the number of parameters and calculations of the model decreased by 26.7% and 50%, respectively. Provides valuable references and practical applications for deployment of defect detection models on computing-resource-limited terminal devices.

Abstract Machine-learned potentials (MLPs) have exhibited remarkable accuracy, yet the lack of general-purpose MLPs for a broad spectrum of elements and their alloys limits their applicability. Here, we present a promising approach for constructing a unified general-purpose MLP for numerous elements, demonstrated through a model (UNEP-v1) for 16 elemental metals and their alloys. To achieve a complete representation of the chemical space, we show, via principal component analysis and diverse test datasets, that employing one-component and two-component systems suffices. Our unified UNEP-v1 model exhibits superior performance across various physical properties compared to a widely used embedded-atom method potential, while maintaining remarkable efficiency. We demonstrate our approach’s effectiveness through reproducing experimentally observed chemical order and stable phases, and large-scale simulations of plasticity and primary radiation damage in MoTaVW alloys.

Abstract Background Dendrobium catenatum is a perennial herb of the genus Dendrobium orchidaceae. It has been known as “Golden Grass, Soft Gold” since ancient times with effects of strengthening the body, benefiting the stomach, generating body fluid, nourishing Yin and clearing internal heat. The flowers of D. catenatum have anti-oxidation, immune regulation and other biological activities. The composition analysis of flowers showed that flavonoid glycosides were significantly accumulated in floral tissue. However, in the flowers of D. catenatum, there was only one case of the UDP-glycosyltransferase (UGT) responsible for the glycosylation of flavonoids has been reported. Result In this study, a new UGT (named UGT708S6) was cloned from D. catenatum flowers rich in O-glycosides and C-glycosides, and its function and biochemical properties were characterized. Through homology comparison and molecular docking, we identified the key amino acid residues affecting the catalytic function of UGT708S6. The glycosyltransferase UGT708S6 was characterized and demonstrated C-glycosyltransferase (CGT) activity in vitro assay using phloretin and 2-hydroxynaringenin as sugar acceptors. The catalytic promiscuity assay revealed that UGT708S6 has a clear sugar donor preference, and displayed O-glycosyltransferase (OGT) activity towards luteolin, naringenin and liquiritigenin. Furthermore, the catalytic characteristics of UGT708S6 were explored, shedding light on the structural basis of substrate promiscuity and the catalytic mechanism involved in the formation of flavonoid C-glycosides. R271 was a key amino acid residue site that sustained the catalytic reaction. The smaller binding pocket resulted in the production of new O-glycosides and the reduction of C-glycosides. This highlighted the importance of the binding pocket in determining whether C-glycosides or O-glycosides were produced. Conclusions The findings suggest that UGT708S6 holds promise as a new glycosyltransferase for synthesizing flavonoid glycosides and offer valuable insights for further understanding the catalytic mechanisms of flavonoid glycosyltransferases.

Abstract Background To ensure workforce stability in China’s healthcare system and maintain high-quality care, it is essential to comprehensively understand the interplay of factors contributing to turnover intention of healthcare workers. This study aims to examine the associations between potential factors and turnover intention in healthcare workers and explore the mediating effect of job satisfaction and work engagement in the association between them. Methods In this cross-sectional study, a random sample of 1060 healthcare workers working in 98 public medical institutions were recruited to rate their turnover intention in 2018 in Shenzhen, China. Information on socio-demographic characteristics, job-related factors, turnover intention, job satisfaction, work engagement, work stress and doctor-patient relationship of participants were collected. Pearson’s chi-squared tests and binary logistic regression analyses were performed to explore the association between these factor and turnover intention. Mediation analysis was used to explore the roles of potential mediators and moderators. Results The results showed that age (OR: 0.35, 95%CI: 0.16 to 0.72), tenure (OR: 0.98, 95%CI: 0.96 to 0.99), administrative positions (OR: 0.33, 95%CI: 0.16 to 0.63), and night shift frequency (OR: 1.84, 95%CI: 1.26 to 2.67) were significantly associated with turnover intention. We identified the mediating effect of job satisfaction and work engagement in the relationship between administrative positions and turnover intention, while the suppressing effect in the relationship between professional titles and turnover intention. Additionally, we found that monthly income plays a moderating role in the relationship between work engagement and turnover intention, and in the association between professional titles and turnover intention. Conclusions Greater job satisfaction and engagement, along with reasonable remuneration, were found to be associated with lower turnover intention among healthcare workers. Employers should proactively monitor the dynamic interactions among these factors and then develop more tailored interventions in order to alleviate the ongoing loss of healthcare workers.

Abstract Objective The relationship between blood glucose levels and osteoarthritis (OA) is unclear. This study aimed to investigate the genetic causal relationship between blood glucose-related traits and OA. Methods We first performed univariate Mendelian randomization (UVMR) analyses using published genome-wide association study (GWAS) datasets with fasting glucose (FG), 2 h-glucose post-challenge glucose (2hGlu), and glycosylated hemoglobin (HbA1c) as exposures, and hip osteoarthritis (HOA) and knee osteoarthritis (KOA) as outcomes; then, we performed inverse analyses of them. We used Inverse-variance weighted (IVW) analysis as the primary analysis, and sensitivity analyses were performed. Moreover, we performed multivariate Mendelian randomization (MVMR) to estimate the independent effect of exposure on outcome after adjusting for body mass index (BMI). Summarized data for blood glucose-related traits were obtained from the MAGIC Consortium study of the glucose trait genome and for OA from the UK Biobank and arcOGEN. Summarized data for BMI were obtained from the GIANT Consortium meta-analysis of individuals of European ancestry. A two-sided p value

Abstract Inflammation underlies many conditions causing excess morbidity and mortality among people with HIV (PWH). A handful of single-trait epigenome-wide association studies (EWAS) have suggested that inflammation is associated with DNA methylation (DNAm) among PWH. Multi-trait EWAS may further improve statistical power and reveal pathways in common between different inflammatory markers. We conducted single-trait EWAS of three inflammatory markers (soluble CD14, D-dimers and interleukin-6) in the Veterans Aging Cohort Study (n = 920). The study population was all male PWH with an average age of 51 years, and 82.3% self-reported as Black. We then applied two multi-trait EWAS methods—CPASSOC and OmniTest—to combine single-trait EWAS results. CPASSOC and OmniTest identified 189 and 157 inflammation-associated DNAm sites, respectively, of which 112 overlapped. Among the identified sites, 56% were not significant in any single-trait EWAS. Top sites were mapped to inflammation-related genes including IFITM1, PARP9 and STAT1. These genes were significantly enriched in pathways such as “type I interferon signaling” and “immune response to virus.” We demonstrate that multi-trait EWAS can improve the discovery of inflammation-associated DNAm sites, genes and pathways. These DNAm sites might hold the key to addressing persistent inflammation in PWH.

Abstract Objective This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). Methods Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. Results Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29–41), DCR was 67% (95%CI 58–76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11–9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78–100) and 37% (95%CI 19–57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68–91), 74% (57–88), 73% (35–98) and 57% (46–68), respectively. Conclusion As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation.

Abstract Background The purpose of this study is to explore the feasibility and accuracy of a robot-assisted technique in four-corner fusion compared with traditional freehand operation. Methods Twenty cadaver specimens were randomly assigned to the robot-assisted group and freehand groups. Three screws were placed percutaneously to fix the capitate-lunate joint, lunate-triquetrum joint, and triquetrum-hamate-capitate joint in each specimen by robot-assisted or freehand technique. The offset between the actual and planned screw positions was determined by merging the images of intraoperative and postoperative CT scans in the robot-assisted group. The centrality of the screw, time-consuming, drilling attempts, and radiation exposure were compared between the two groups. Results The mean offset between the actual and planned screw position was 1.09 (SD: 0.56) mm. The offset at the start point of the screw was significantly lower than that at the endpoint. There was no significant difference in the centrality of the screws, surgical time between the two groups. The number of drilling attempts and the radiation dose received by surgeons were significantly lower in the robot-assisted group. Conclusions Although there was no significant difference in screw centrality between the two groups, the slight offset between the actual and planned screw positions confirmed the feasibility of the robot-assisted technique in four-corner fusion. The robot-assisted technique has advantages in reducing the difficulty of surgery and protecting the surgeon from exposure to large doses of radiation.

Abstract Background Calcaneal fractures are the most common type of tarsal fractures. The sustentaculum tali (ST) offers anatomical stability in calcaneal fractures, and recently, ST screws have been widely used in their treatment. This study aimed to investigate the clinical efficacy and value of ST screw fixation via a modified sinus tarsi approach (MSTA) for treating displaced intraarticular calcaneal fractures (DIACFs). Methods This study enrolled 64 patients (64 feet): 32 patients in the calcaneal locking plate combined with the ST screw group (CLP-STS Group) and 32 patients in the simple calcaneal locking plate internal fixation group (CLP Group). The minimum follow-up duration was 18 months. Ankle function was evaluated using VAS, AOFAS, and Short Form-36 scores. Imaging evaluation included the Böhler angle, Gissane angle, length, height, and width of the calcaneus, and the Böhler angle in both groups 1 year after surgery. Results Functional evaluation revealed that postoperative AOFAS and VAS scores in the CLP-STS Group were significantly better than those in the CLP Group. After surgery, the Böhler angle, Gissane angle, and length, height, and width of the calcaneus were significantly corrected compared to the preoperative values; however, the difference in these indicators between the two groups was not significant. Nevertheless, at the 1-year postoperative follow-up, the calcaneal Böhler angle loss in the CLP-STS Group was significantly better than that in the CLP Group. Conclusion Compared to simple calcaneal locking plate internal fixation, combining the plate with the additionally free ST screw can resolve the limited intraoperative exposure of MSTA, reduce postoperative foot pain in patients, and improve clinical efficacy.

Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.

Abstract Background Children with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors. Method CMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors. Results Cardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P

Abstract Background The widespread acceptance of early surgery as a treatment for acute intertrochanteric fracture (ITF) has been accompanied by ongoing controversy due to conflicting conclusions presented in previous studies. This study aims to compare the occurrence of perioperative complications and mortality, as well as functional outcomes in older patients with ITF who underwent either early or delayed surgery. Methods A retrospective multicenter cohort study involving 7414 patients with ITF between Jan. 2017 and Dec. 2021 was conducted. After predefined participants selection inclusion and exclusion criteria, 2323 surgically treated ITF patients were included and analyzed utilizing propensity score matching (PSM) method. Their demographics, injury-related data, surgery-related data, and perioperative adverse outcomes during hospitalization were collected and compared between the early or delayed surgery groups by PSM with a 1:4 ratio. All participants received a minimum of two-year follow-up and perioperative outcomes, functional outcomes, and survival analyses were conducted and compared. Results After adjustment for potential confounders, there were no significant difference in surgery duration, intraoperative blood loss, transfusion rate, mortality rates, functional outcomes, and perioperative complications rates including severe complications, cardiac complications, pulmonary complications, and neurological complications regardless of whether the patient was treated with early or delayed surgery (all P > 0.05). Although length of hospital stay (mean, 11.5 versus 14.4 days, P

Abstract High‐dose melphalan followed by stem cell rescue is the standard consolidative therapy for transplant‐eligible patients with multiple myeloma (MM) in the United Kingdom. A melphalan dose of 200 mg/m2 (Mel200) is considered the “gold standard” for autologous stem cell transplant (ASCT) conditioning for fit patients ≤70 years old; however, with a peak diagnosis incidence at 80–89 years old in the UK dose adjustments will be inevitable to limit toxicities. In this single‐centre UK‐based retrospective analysis, data was collected from patients with plasma cell dyscrasias who underwent a first reduced‐intensity, Mel140, ASCT from 2006 to 2019, a total of 81 patients. We found that the procedure was overall safe with seven (9%) of patients requiring ITU admission and a single transplant‐related death within the initial autograft admission. The progression‐free survival (PFS) and overall survival were comparable with those previously reported in the literature with median PFS for our cohort of 31 months. Univariate analysis of our data showed an inferior PFS for patients aged ≥70 years. In conclusion, although this is a retrospective analysis, it demonstrates that dose‐reduced melphalan conditioning is safe and effective in patients deemed unfit for standard‐intensity conditioning.

Abstract Methylation quantitative trait loci (meQTLs) quantify the effects of genetic variants on DNA methylation levels. However, most published studies utilize bulk methylation datasets composed of different cell types and limit our understanding of cell-type-specific methylation regulation. We propose a hierarchical Bayesian interaction (HBI) model to infer cell-type-specific meQTLs, which integrates a large-scale bulk methylation data and a small-scale cell-type-specific methylation data. Through simulations, we show that HBI enhances the estimation of cell-type-specific meQTLs. In real data analyses, we demonstrate that HBI can further improve the functional annotation of genetic variants and identify biologically relevant cell types for complex traits.

Abstract Background This study aimed to analyze the epidemic characteristics and influencing factors of school influenza outbreaks in Jiangsu Province, China from 2020 to 2023,following the COVID-19 pandemic, to inform prevention and control strategies. Methods Data on influenza-like illness(ILI) outbreaks from the Chinese Influenza Surveillance Information System and national-level influenza surveillance sentinel hospitals were analyzed. The temporal distribution, school type, virus strains, and outbreak scales were examined using descriptive statistics. Results From 2020 to 2023, 1142 influenza outbreaks occurred in schools, with primary schools(ages 6 to 12) accounting for 71.80%. Most large outbreaks were caused by A(H1N1) and A(H3N2), responsible for 8.99% of total outbreaks. Outbreaks were predominantly reported in the pre-peak periods of B(Victoria) and A(H1N1) circulation, accounting for 86.31% and 92.32% of their respective total outbreaks. No concurrent influenza and COVID-19 outbreaks were observed during the study period. Conclusion Primary and secondary schools are high-risk settings for influenza outbreaks. A(H3N2) shows higher adaptability and is more likely to co-circulate with other subtypes/lineages, especially A(H1N1), leading to larger outbreaks. B(Victoria)-caused outbreaks are more frequent but smaller in scale. School influenza outbreaks are more likely to occur during the early stages of seasonal peaks, particularly for B(Victoria) and A(H1N1). This suggests that influenza outbreaks in schools may play a crucial role in seeding and accelerating the spread of the virus within the broader community.

Abstract Gliomas are the most common primary malignant tumours of the central nervous system (CNS), which are highly aggressive, with increasing morbidity and mortality rates year after year, posing a serious threat to the quality and expected survival time of patients. The treatment of gliomas is a major challenge in the field of neuro-oncology, especially high-grade gliomas such as glioblastomas (GBMs). Despite considerable progress in recent years in the study of the molecular and cellular mechanisms of GBMs, their prognosis remains bleak. Tumour-associated macrophages (TAMs) account for up to 50% of GBMs, and they are a highly heterogeneous cell population whose role cannot be ignored. Here, we focus on reviewing the contribution of classically activated M1-phenotype TAMs and alternatively activated M2-phenotype TAMs to GBMs, and exploring the research progress in reprogramming M1 TAMs into M2 TAMs.

Abstract Currently, despite the vast amounts of time and money invested in cancer treatment, cancer remains one of the primary threats to human life. The primary factor contributing to the low treatment efficacy is cancer heterogeneity. The unclear molecular mechanisms underlying tumorigenesis, coupled with the complexity of human physiology, and the inability of animal models to accurately replicate the human tumor microenvironment, pose significant hurdles in the development of novel cancer therapies. Tumor-microenvironment-on-chip (TMOC) represents a research platform that integrates three-dimensional cell culture with microfluidic systems, simulating the essential components and physiological traits of the in vivo tumor microenvironment. It offers a dynamic setting within the chip system to study tumor progression, potentially heralding a breakthrough in cancer research. In this review, we will summarize the current advancements in this platform, encompassing various types of TMOCs and their applications in different types of cancer. From our perspective, the TMOC platform necessitates enhanced integration with tissue engineering techniques and microphysiological environments before it can evolve into a more refined preclinical model for cancer research.

To further elucidate the mechanism of acoustic emission (AE) response when a fractured rock is compressed, a new method for calculating the AE characteristics from the perspective of relative particle motion based on the moment tensor theory in seismology was proposed in discrete element simulation. The crack expansion process and mechanical-deformation characteristics were simulated by the particle flow code (PFC). Based on the new AE response simulation method, the spatial evolution of AE events, magnitude distribution and the orientation of the moment tensor were calculated. The results showed that the stress of the pre-cracked rock under uniaxial compressive conditions drops dramatically after the peak, the cracks expanded rapidly into a macroscopic crack, the acoustic emission events surge, and the brittle damage characteristics after the peak are obvious. The number of tensile and shear cracks obtained from PFC showed a similar growth trend temporally, while the number of tensile cracks was more than that of shear cracks. The acoustic emission magnitudes obtained based on seismology principally concentrated in the range of [−6.9, −5.9], and the slope of the G-R statistical relationship (b value) was 1.81. The spatial orientation of the AE moment tensor coincided with the tensile-shear cracks: the moment tensor is mainly transverse in the wing crack region, with more tensile cracks than shear cracks; while in the main crack region, the moment tensor was heterogeneous, and the percentage of tensile and shear cracks is close to each other. The tensile and shear properties of microcracks were determined based on the T-k diagram and R-value theory of moment tensor. The trends of the percentage of tensile and shear cracks were basically consistent with those obtained by PFC, while the comparison revealed that using [−20, 20] as the interval of tensile-shear crack was more reasonable than that suggested by Feignier et al. The findings provide beneficial reference for accurate analysis of the characteristics of rock cracking seismic sources and the identification of tensile shear properties.

Abstract Herein, we report polyphosphonate covalent organic frameworks (COFs) constructed via P-O-P linkages. The materials are synthesized via a single-step condensation reaction of the charge-assisted hydrogen-bonded organic framework, which is constructed from phenylphosphonic acid and 5,10,15,20‐tetrakis[p‐phenylphosphonic acid]porphyrin and is formed by simply heating its hydrogen-bonded precursor without using chemical reagents. Above 210 °C, it becomes an amorphous microporous polymeric structure due to the oligomerization of P-O-P bonds, which could be shown by constant-time solid-state double-quantum 31P nuclear magnetic resonance experiments. The polyphosphonate COF exhibits good water and water vapor stability during the gas sorption measurements, and electrochemical stability in 0.5 M Na2SO4 electrolyte in water. The reported family of COFs fills a significant gap in the literature by providing stable microporous COFs suitable for use in water and electrolytes. Additionally, we provide a sustainable synthesis route for the COF synthesis. The narrow pores of the COF effectively capture CO2.

Abstract Background Respiratory infectious diseases have the highest incidence among infectious diseases worldwide. Currently, global monitoring of respiratory pathogens primarily focuses on influenza and coronaviruses. This study included influenza and other common respiratory pathogens to establish a local respiratory pathogen spectrum. We investigated and analyzed the co-infection patterns of these pathogens and explored the impact of lifting non-pharmaceutical interventions (NPIs) on the transmission of influenza and other respiratory pathogens. Additionally, we used a predictive model for infectious diseases, utilizing the commonly used An autoregressive comprehensive moving average model (ARIMA), which can effectively forecast disease incidence. Methods From June 2023 to February 2024, we collected influenza-like illness (ILI) cases weekly from the community in Xuanwu District, Nanjing, and obtained 2046 samples. We established a spectrum of respiratory pathogens in Nanjing and analysed the age distribution and clinical symptom distribution of various pathogens. We compared age, gender, symptom counts, and viral loads between individuals with co-infections and those with single infections. An autoregressive comprehensive moving average model (ARIMA) was constructed to predict the incidence of respiratory infectious diseases. Results Among 2046 samples, the total detection rate of respiratory pathogen nucleic acids was 53.37% (1092/2046), with influenza A virus 479 cases (23.41%), influenza B virus 224 cases (10.95%), and HCoV 95 cases (4.64%) being predominant. Some pathogens were statistically significant in age and number of symptoms. The positive rate of mixed infections was 6.11% (125/2046). There was no significant difference in age or number of symptoms between co-infection and simple infection. After multiple iterative analyses, an ARIMA model (0,1,4), (0,0,0) was established as the optimal model, with an R2 value of 0.930, indicating good predictive performance. Conclusions The spectrum of respiratory pathogens in Nanjing, Jiangsu Province, was complex in the past. The primary age groups of different viruses were different, causing various symptoms, and the co-infection of viruses did not correlate with the age and gender of patients. The ARIMA model estimated future incidence, which plateaued in subsequent months.

Abstract Predicting the corrosion rate for soil-buried steel is significant for assessing the service-life performance of structures in soil environments. However, due to the large amount of variables involved, existing corrosion prediction models have limited accuracy for complex soil environment. The present study employs three machine learning (ML) algorithms, i.e., random forest, support vector regression, and multilayer perception, to predict the corrosion current density of soil-buried steel. Steel specimens were embedded in soil samples collected from different regions of the Wisconsin state. Variables including exposure time, moisture content, pH, electrical resistivity, chloride, sulfate content, and mean total organic carbon were measured through laboratory tests and were used as input variables for the model. The current density of steel was measured through polarization technique, and was employed as the output of the model. Of the various ML algorithms, the random forest (RF) model demonstrates the highest predictability (with an RMSE value of 0.01095 A/m2 and an R 2 value of 0.987). In light of the feature selection method, the electrical resistivity is identified as the most significant feature. The combination of three features (resistivity, exposure time, and mean total organic carbon) is the optimal scenario for predicting the corrosion current density of soil-buried steel.

Abstract The issue of brightness in strong ambient light conditions is one of the critical obstacles restricting the application of augmented reality (AR) and mixed reality (MR). Gallium nitride (GaN)-based micro-LEDs, renowned for their exceptional brightness and stability, are considered the foremost contenders for AR applications. Nevertheless, conventional heteroepitaxial growth micro-LED devices confront formidable challenges, including substantial wavelength shifts and efficiency droop. In this paper, we firstly demonstrated the high-quality homoepitaxial GaN-on-GaN micro-LEDs micro-display, and thoroughly analyzed the possible benefits for free-standing GaN substrate from the material-level characterization to device optoelectronic properties and micro-display application compared with sapphire substrate. The GaN-on-GaN structure exhibits a superior crystal quality with ultra-low threading dislocation densities (TDDs) of ~ 105 cm−2, which is three orders of magnitude lower than that of GaN-on-Sapphire. Through an in-depth size-dependent optoelectronic analysis of blue/green emission GaN-on-GaN/ Sapphire micro-LEDs from 100 × 100 shrink to 3 × 3 μm2, real that a lower forward voltage and series resistance, a consistent emission wavelength (1.21 nm for blue and 4.79 nm for green @ 500 A/cm2), coupled with a notable reduction in efficiency droop ratios (15.6% for blue and 28.5% for green @ 500 A/cm2) and expanded color gamut (103.57% over Rec. 2020) within GaN-on-GaN 10 μm micro-LEDs. Last but not least, the GaN-on-GaN micro-display with 3000 pixels per inch (PPI) showcased enhanced display uniformity and higher luminance in comparison to its GaN-on-Sapphire counterpart, demonstrating significant potentials for high-brightness AR/MR applications under strong ambient light.

Abstract Background Given that viral infections can increase the risk of adverse pregnancy outcomes, such as spontaneous miscarriage, preterm premature rupture of membranes, and preterm birth, the effects of COVID-19, a novel emerging coronavirus disease rapidly spreading globally, on pregnancy outcomes have garnered significant attention. Methods We conducted a review of studies related to pregnant women infected with SARS-CoV-2 over the past five years (December 2019 to April 2023), utilizing search engines such as PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI). This study was registered with PROSPERO with ID: CRD42024540849. Results A total of 218 articles were screened, with 15 studies meeting the inclusion criteria for this research, including 12 cohort studies, one cross-sectional study, one case-control study, and one case series. Six studies found that the preterm birth rate was higher in the infected group compared to the control group; five studies showed that the cesarean section rate was higher in the infected group; three studies found that the APGAR scores of newborns were higher in the control group than in the infected group; three studies indicated that the mortality rate of newborns in the infected group was higher than that in the control group. Conclusions Our retrospective review suggests that compared to pregnant women not infected with SARS-CoV-2, those diagnosed with COVID-19 are more likely to experience adverse outcomes such as preterm birth, cesarean delivery, and low birth weight in newborns.

Background: Osteoarthritis (OA) and obstructive sleep apnea (OSA) are prevalent chronic conditions with emerging evidence suggesting a potential link. However, the causality of this association remains unclear, possibly influenced by confounders like high body mass index (BMI). This study aimed to explore causal relationships between OA and OSA using Mendelian randomization (MR). Methods: MR analysis was performed to assess causality between OA and OSA. Inverse variance weighting (IVW) was the primary MR method, complemented by sensitivity analyses, including MR steiger, MR-Egger, MR-PRESSO, weighted median, heterogeneity tests, and leave-one-out approaches to evaluate pleiotropy and confirm the robustness of the causal estimates. To exclude confounding effects of BMI, we also used a multivariate MR (MVMR). Results: After adjusting for BMI through MVMR, no significant causal relationship was identified between genetically predicted OSA and OA phenotypes, including knee (KOA) and hip osteoarthritis (HOA), suggesting that obesity largely drives the observed relationship between these conditions. Similarly, MR steiger doesn't support a causal effect from OA on OSA. Sensitivity analyses confirmed the robustness of these results, with no significant evidence of horizontal pleiotropy or heterogeneity affecting outcomes. The findings indicate that BMI acts as a critical confounder in the relationship between OSA and OA, rather than OSA directly contributing to OA development. Conclusions: Our findings indicate that there is no significant causal relationship between genetically predicted OSA and OA after adjusting for BMI. These findings underscore obesity as the primary shared risk factor, highlighting the importance of weight management as a key strategy for mitigating the risks of both conditions. Future research should aim to validate these findings in diverse populations and explore other metabolic pathways that may contribute to these complex associations.

Lightweight structures are ubiquitous in nature and extensively applied in high-end industries for load-bearing purpose. Parametric design is superior for its rapid generation of complex geometries controlled by user-specified parameters, thus has been increasingly explored in structural optimization. Conventional parametric design approaches for lightweight structure are primarily focus on size and shape, while the topology still requires lengthy iterative process. The major issues that hinder parametric control of topological design include singularity of the stress field and the lack of proper operators for discretized geometry. This paper introduced an implicit neural representation for parametric design of stress-oriented cellular structure, which exhibited great potential to resolve the aforementioned issues by harnessing the universal approximation and resolution invariant capability of a neural network. The structure was implicitly trained to smoothly align with the principal stress field of the input geometry under arbitrary loading condition. A tailored wave projection function together with morphological operators were employed for parametric control of the output cellular structure. The proposed framework enables the parametric design and fabrication of various cellular structures, resulting in enhanced load-bearing capacity compared to structures designed using conventional methods. This advancement opens up new possibilities for the effective design of lightweight structures.

BackgroundAcute myeloid leukemia (AML) is a hematologic tumor with poor prognosis and significant clinical heterogeneity. By integrating transcriptomic data, single-cell RNA sequencing data and independently collected RNA sequencing data this study aims to identify key genes in AML and establish a prognostic assessment model to improve the accuracy of prognostic prediction.Materials and methodsWe analyzed RNA-seq data from AML patients and combined it with single-cell RNA sequencing data to identify genes associated with AML prognosis. Key genes were screened by bioinformatics methods, and a prognostic assessment model was established based on these genes to validate their accuracy.ResultsThe study identified eight key genes significantly associated with AML prognosis: SPATS2L, SPINK2, AREG, CLEC11A, HGF, IRF8, ARHGAP5, and CD34. The prognostic model constructed on the basis of these genes effectively differentiated between high-risk and low-risk patients and revealed differences in immune function and metabolic pathways of AML cells.ConclusionThis study provides a new approach to AML prognostic assessment and reveals the role of key genes in AML. These genes may become new biomarkers and therapeutic targets that can help improve prognostic prediction and personalized treatment of AML.

Abstract Lung cancer (LC) is the leading cause of cancer‐related death worldwide. Recent studies have shown that tripartite motif 13 (TRIM13) play important regulatory roles in the progression of different tumors. In this study, we focused on the role of TRIM13 in LC tumorigenesis and its underlying molecular mechanisms. The study demonstrated TRIM13 was identified as a novel tumor suppressor gene of LC and its overexpression suppressed LC progression in vitro and in vivo. Mechanistically, TRIM13 interacted with RPS27A, increasing RPS27A ubiquitination and degradation. Furthermore, RPS27A overexpression reversed the inhibitory effect of TRIM13 overexpression on LC progression. By binding to RPS27A and encouraging its ubiquitination and degradation, TRIM13 hindered LC advancement. We also found that RPS27A overexpression reversed the inhibitory effect of TRIM13 overexpression on NF‐κB signaling, thereby further promoting the proliferation and metastasis of LC cell lines. Therefore, targeting the TRIM13/RPS27A/NF‐κB signaling axis may be a promising target for LC treatment.

Additively manufactured (AM) Al alloys have widespread applications. Their high-temperature mechanical behaviors are also of significant interest. In this study, we investigated the microstructure and mechanical behavior of Al-2Ti-2Fe-2Co-2Ni (at%) alloy processed by laser powder bed fusion. The as-printed alloy contains a distinctive heterogeneous microstructure characterized by nanoscale intermetallic lamellae arranged in rosette patterns in the Al matrix. Notably, this alloy exhibits high tensile strength and thermal stability up to 500 °C as revealed by in-situ tension studies in a scanning electron microscope. The enhanced high temperature performance can be attributed to a substantial volume fraction of well-dispersed, nanoscale stable intermetallic particles.

Objective To evaluate whether ultrasound-guided radiofrequency ablation (RFA) is reliable for unifocal T1aN0M0 papillary thyroid carcinoma in the isthmus (PTCI).Methods 431 patients who underwent ultrasound-guided RFA for unifocal T1aN0M0 papillary thyroid carcinoma (PTC) were divided by location of the lesion into the PTCI group (52 females, 7 males, mean age 43.79 ± 12.04 years, range 22-74 years) and the PTCL group ((291 females, 81 males, mean age 43.42 ± 10.87 years, range 18-75 years) for comparative analysis. The efficacy of ultrasound-guided RFA was evaluated by volume reduction rate (VRR), complete disappearance rate (CDR) and disease progression, and the safety was evaluated by incidence of complications.Results The two groups exhibited a consistent trend of change, with the PTCI group performing better in volume, VRR and CDR at all follow-up time points expect 1 month, but the differences were not statistically significant (p > 0.05). The mean initial volume of the PTCI group vs the PTCL group decreased significantly from 65.4 ± 69.79 vs 86.38 ± 87.09 mm³ (range 10.92-427.58 vs 3.05-471.6 mm³) to 0 vs 0 mm³ at a mean follow-up time of 31.12 ± 12.5 months (range 12-60 months); their VRR increased significantly from −618.62 ± 655.61% vs −789.85 ± 1135.07% at 1 month to 100% vs 100% at 48 months. No disease progression was found in the two groups. The PTCI group had no complications, whereas the PTCL group had a total of 7 complications (1.88%).Conclusions Ultrasound-guided RFA is reliable for unifocal T1aN0M0 PTCI. It can be promoted as an alternative to immediate surgery for selected PTC patients.

Not available.

Animal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, ACE2 with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR – Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3 × 105 PFU) or low (2.5 × 102 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arteriovenous thrombosis and pathological pregnancy, accompanied by persistent antiphospholipid antibodies, (aPL). The incidence of APS is increasing year by year, clinicians lack of understanding of this type of disease, easy to misdiagnose and miss the diagnosis. Therefore, it is extremely important to establish a suitable animal model to reduce the process of disease development as much as possible and improve clinicians’ understanding and understanding. This review will summarize the animal models of APS from the aspects of modeling methods, modeling mechanism, evaluation indicators and advantages and disadvantages of methods, providing a reference for finding an animal model highly similar to human APS, helping researchers to further clarify the pathogenesis of APS and find potential therapeutic targets, so as to achieve early diagnosis, early intervention, and ultimately improve the prognosis of patients.

Objective Gut microbiota was closely involved in the pathogenesis of depression, but the underlying molecular mechanisms in depression remained unclear. This study was conducted to investigate the relationship between neurotransmitters/inflammatory factors and gut microbiota in depressed mice.Materials and methods A chronic social defeat stress (CSDS) depression model was established. Gut microbial composition was detected in faeces, neurotransmitters were detected in faeces, colon, blood and hippocampus, and inflammatory factors were detected in hippocampus. After a key neurotransmitter was identified, intervention experiment was conducted to explore whether it could improve depressive-like behaviours.Results Six differential genera in faeces, 14 differential neurotransmitters in gut-brain axis, and two differential inflammatory factors (interleukin-1 beta (IL-1β) and interleukin-6 (IL-6)) in hippocampus were identified in depressed mice. There were significant correlations among differential genera, differential neurotransmitters and IL-1β/IL-6. Among these differential neurotransmitters, 3-O-Methyldopa (3-OMDP) was found to be consistently decreased in faeces, colon, blood and hippocampus, and 3-OMDP was significantly correlated to Limosilactobacillus and IL-1β. After receiving 3-OMDP, the depressive-like behaviours in depressed mice were improved and the increased IL-1β/IL-6 levels were reversed.Conclusions These results indicated that gut microbiota might affect host’s inflammation levels in brain through regulating neurotransmitters, eventually leading to the onset of depression. ‘Limosilactobacillus-3-OMDP-IL-1β/IL-6’ might be a potential pathway in the crosstalk of gut and brain, and 3-OMDP held the promise as a therapeutic target for depression.

Irradiation-induced cascade collisions produce numerous point defects within materials, which can severely deteriorate their thermo-mechanical properties and overall performance. We propose a computational scheme that combines molecular dynamic (MD) simulations with a denoising diffusion probabilistic model (DDPM) to rapidly and accurately predict the spatial coordinates of point defects at any given primary knock atom (PKA) energy, ranging from 0 to 100.0 keV. Importantly, this capability extends to PKA energies that are exclusive from the training data set, demonstrating the robustness and generalizability of the model. The proposed scheme has been thoroughly validated by several designed indicators, including the Fréchet inception distance, the number of point defects, the distance from vacancies and self-interstitial atoms (SIAs) to their respective centroids, the inter-centroid distance between the vacancies and SIAs, the probability density of clustered defect sizes, and the sub-cascade number. Compared to MD simulations, the DDPM can generate point defects at a specific PKA energy at least ten thousand times faster. By offering a rapid and reliable means to model defect distributions across various energy levels, the proposed scheme benefits the comprehension of the cascade process and provides a valuable database for both experimental investigations and large-scale simulations.

Selective area heteroepitaxy provides an alternate solution for the monolithic integration of high-performance III-V lasers on Si with effective management of crystalline defects. Here, we report large-area single-crystal InP grown on (001) patterned silicon-on-insulator (SOI) wafers using the lateral aspect ratio trapping (LART) method by metal-organic chemical vapor deposition. The InP grown on SOI features a length of hundreds of micrometers and a width of up to 8.5 μm with an “in-plane” configuration. Based on fine-tuned growth conditions, especially in the InP nucleation layer on the Si interface, crystalline defects have been minimized resulting in large-area high-quality materials for active devices. Growth mechanisms describing each stage of epitaxy are presented to explain the difference of lateral growth in small and large material volumes. Comprehensive material characterizations and device implementations were performed on the InP/SOI to characterize its viability as an integration platform for photonics. III-V lasers with micro-cavity and Fabry–Perot cavity were fabricated and statistically analyzed to demonstrate the feasibility of providing photonic function. Attaining large-area InP/SOI addresses the bottleneck of limited III-V material volume in selective epitaxy leading to a critical step toward monolithic integration of III-V on Si. Furthermore, the high-quality InP/SOI could serve as a mini template for regrowth to construct various photonic building blocks. Large-area and high-quality III-V on SOI here ensure LART as an easy, flexible, and tolerable method for the potential realization of fully integrated Si photonics.

Background Gastric carcinomas (GC) are aggressive malignancies, and only ~15% of patients respond to anti-programmed cell death (ligand) 1 (PD-(L)1) monotherapy. However, Epstein-Barr virus (EBV)-associated GCs (~5–10% of GCs) often harbor PD-L1 and PD-L2 chromosomal amplifications and robust CD8+ T cell infiltrates, and respond at a high rate to anti-PD-1. The current study compares the tumor immune microenvironments (TiMEs) of EBV+ versus EBV(−) GCs.Methods Over 1000 cases of primary invasive GCs were screened to identify 25 treatment-naïve specimens for study (11 EBV+, 14 EBV(−)). Quantitative immunohistochemistry (IHC) was conducted for markers of immune cell subsets and co-regulatory molecules. Gene expression profiling (GEP) was performed on RNAs isolated from macrodissected areas of CD3+ T cell infiltrates abutting PD-L1+ stromal/tumor cells, using multiplex quantitative reverse transcriptase PCR for a panel of 122 candidate immune-related genes.Results IHC revealed that 17/25 GCs contained PD-L1+ stromal cells, with no significant difference between EBV+/- specimens; however, only 3/25 specimens (all EBV+) contained PD-L1+ tumor cells. CD8+ T cell densities were higher in EBV+ versus EBV(−) tumors (p=0.044). With GEP normalized to the pan-leukocyte marker PTPRC/CD45, EBV+ GCs overexpressed ITGAE (CD103, marking intraepithelial T cells and a dendritic cell subset) and the interferon-inducible genes CXCL9 and IDO1. In contrast, EBV(−) tumors overexpressed several functionally-related gene groups associated with myeloid cells (CD163, IL1A, NOS2, RIGI), immunosuppressive cytokines/chemokines (CXCL2, CXCR4, IL10, IL32), coinhibitory molecules (HAVCR2/TIM-3 and VSIR/VISTA), and adenosine pathway components (ENTPD1/ CD39 and NT5E/CD73). Notably, compared with EBV+ GCs, EBV(−) GCs also overexpressed components of the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway associated with cancer-promoting inflammation, including PTGS2/COX-2 (most highly upregulated gene, 32-fold, p=0.005); prostaglandin receptors PTGER1 (EP1; up 21-fold, p=0.015) and PTGER4 (EP4; up twofold, p=0.022); and the major COX-2-inducing cytokine IL1B (up 11-fold, p=0.019). Consistent with these findings, COX-2 protein expression trended higher in EBV(−) versus EBV+ GCs (p=0.068).Conclusions While certain markers of immunosuppression are found in the GC TiME regardless of EBV status, EBV(−) GCs, which are much more common than EBV+ GCs, overexpress components of the COX-2/PGE2 pathway. These findings provide novel insights into the immune microenvironments of EBV+ and EBV(−) GC, and offer potential targets to overcome resistance to anti-PD-(L)1 therapies.

Ischemic stroke (IS) is the predominant subtype of stroke and a leading contributor to global mortality. The mitochondrial-associated endoplasmic reticulum membrane (MAM) is a specialized region that facilitates communication between the endoplasmic reticulum and mitochondria, and has been extensively investigated in the context of neurodegenerative diseases. Nevertheless, its precise involvement in IS remains elusive. This literature review elucidates the intricate involvement of MAM in mitophagy and endoplasmic reticulum stress during IS. PINK1, FUNDC1, Beclin1, and Mfn2 are highly concentrated in the MAM and play a crucial role in regulating mitochondrial autophagy. GRP78, IRE1, PERK, and Sig-1R participate in the unfolded protein response (UPR) within the MAM, regulating endoplasmic reticulum stress during IS. Hence, the diverse molecules on MAM operate independently and interact with each other, collectively contributing to the pathogenesis of IS as the covert orchestrator.

Pancreatic cancer (PC) is a very aggressive digestive system tumor, known for its high mortality rate, low cure rate, low survival rate and poor prognosis. In particular, pancreatic ductal adenocarcinoma (PADC), which accounts for more than 90% of PC cases, has an overall 5-year survival rate of only 5%, which is an extremely critical situation. Early detection and effective treatment of PC is extremely difficult, which leads many patients to despair. In the current medical context, targeted therapy, as an important strategy for cancer treatment, is expected. However, the problems of immune escape and drug resistance in PC have become two major obstacles that are difficult to be overcome by targeted therapy. How to break through these two difficulties has become a key issue to be solved in the field of PC therapy. In recent years, non-coding RNAs (ncRNAs) have continued to heat up in the field of cancer research. NcRNAs play a pivotal role in gene regulation, cell differentiation, development, and disease processes, and their important roles in the genesis, development, and therapeutic response of PC have been gradually revealed. More importantly, ncRNAs have many advantages as therapeutic targets, such as high specificity and low side effects, making them a new favorite in the field of PC therapy. Therefore, the aim of this paper is to provide new ideas and methods for the targeted therapy of PC by reviewing the mechanism of action of four major ncRNAs (circRNAs, lncRNAs, miRNAs, siRNAs) in both immune escape and drug resistance of PC. It is expected that an effective way to overcome immune escape and drug resistance can be found through in-depth study of ncRNA, bringing a ray of hope to PC patients.

Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats’ reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor β1 (TGF-β1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-β1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.

Abstract BackgroundEvidence has shown that HIV prevalence among young people, especially college students, has increased disproportionately. Preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) are two of the most effective ways to prevent HIV, which are vital for college students with sexual experiences who have sexual risks. ObjectiveTo provide evidence for effective intervention to reduce the risk of HIV infection among young students, this study aimed to analyze the awareness and uptake of HIV PrEP and PEP among college students with sexual experiences. MethodsAn institutional-based cross-sectional study design was used to collect data through an electronic questionnaire from college students in 5 colleges located in Zhejiang Province. A total of 21,962 college students were investigated, of which 2605 students with sexual experiences were included in the data analysis with the following information collected: sociodemographic characteristics, awareness and uptake of HIV PrEP and PEP, sexual behaviors, and HIV tests. Binary logistic regression analysis was used to explore the factors on seeking PrEP and PEP. ResultsThe average age of college students with sexual experiences was 21.25 (SD 2.75) years. Overall, 61.4% (n=1600) of the participants were aware of PrEP, and 53.0% (n=1380) of them were aware of PEP. Moreover, 5.6% (n=146) of them have sought PrEP or/and PEP, and 89.1% (n=2321) have not sought PrEP or PEP. College students who had more than 6 sexual partners, have always had unprotected sex, have subjective perceived risk behavior, and undergo HIV testing were more likely to seek PrEP or/and PEP. The main ways for the participants to learn PrEP and PEP were through school clubs, the internet, and the Centers for Disease Control and Prevention. Moreover, senior students and those who had not undergone an HIV test had a lower likelihood of seeking PrEP and PEP. College students who did not have risky sexual behaviors (odds ratio 0.468, PP ConclusionsCollege students with sexual experiences rarely seek PrEP and PEP, with a relatively low awareness of PrEP and PEP. It is very important to increase the knowledge and uptake of PrEP and PEP by educational and behavioral interventions among young students at risk for HIV infection.

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvβ3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.

Abstract Ulcerative colitis (UC) is a persistent inflammatory condition that specifically targets the colon and rectum. Existing therapies fail to adequately address the clinical requirements of people suffering from this ailment. Despite the acknowledged potential of nanomedicines in the field of anti-inflammatory treatment, their widespread use in clinical settings is impeded by their expensive nature and the uncertainty surrounding their safety profiles. This study illustrates that two naturally occurring phytochemicals, Costunolide (COS) and Glycyrrhizic acid (GA), form carrier-free, multifunctional spherical nanoparticles (NPs) through noncovalent interactions, such as π–π stacking and hydrogen bonding. The COS-GA NPs displayed a synergistic anti-inflammatory effect, providing much more evidently improved therapeutic benefits for dextran sodium sulfate (DSS)-induced UC mice due to more effective reduction in inflammation and oxidative stress than did equal dosages of COS or GA used alone. In addition, COS-GA NPs have biocompatibility and biosafety properties unique to them. This study will serve as affirmation of the potential of COS-GA NPs as innovative natural anti-inflammatory and antioxidant activities and also such agents as drug discovery in UC, leading possibly to better outcomes in people living with this disabling condition.

Abstract Electrocaloric refrigeration which is environmentally benign has attracted considerable attention. In distinction to ferroelectric materials, which exhibit an extremely high positive electrocaloric effect near the Curie temperature, antiferroelectric materials represented by PbZrO3 have a specific negative electrocaloric effect, i.e., electric field decreases the temperature of the materials. However, the explanation of the microscopic mechanism of the negative electrocaloric effect is still unclear, and further research is still needed to provide a theoretical basis for the negative electrocaloric effect enhancement. Herein, the antiferroelectric phase-field model has been proposed to design polar boundaries enhancing antiferroelectric negative electrocaloric performance in PbZrO3-based materials. Based on this, we have simulated the polarization response and domain switching process of the temperature and electric field-induced antiferroelectric—ferroelectric phase transition. It is shown that the temperature range tends to increase as the density of polar boundaries increases from the antiferroelectric stripe domain, polymorphic domain to the nanodomain. Among them, the peak adiabatic temperature change of antiferroelectric nanodomains can reach −13.05 K at 84 kV/cm, and a wide temperature range of about 75 K can be realized at 42 kV/cm. We expect these discoveries to spur further interest in the potential applications of antiferroelectric materials for next-generation refrigeration devices.