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Abstract Treating bone defect concomitant with microbial infection poses a formidable clinical challenge. Addressing this dilemma necessitates the implementation of biomaterials exhibiting dual capabilities in anti-bacteria and bone regeneration. Of particular significance is the altered microenvironment observed in infected bones, characterized by acidity, inflammation, and an abundance of reactive oxygen species (ROS). These conditions, while challenging, present an opportunity for therapeutic intervention in the context of contaminated bone defects. In this study, we developed an oriented composite scaffold containing copper-coated manganese dioxide (MnO2) nanoparticles loaded with parathyroid hormone (PMPC/Gelatin). The characteristics of these scaffolds were meticulously evaluated and confirmed the high sensitivity to H+, responsive drug release and ROS elimination. In vitro antibacterial analysis underscored the remarkable ability of PMPC/Gelatin scaffolds to substantially suppressed bacterial proliferation and colony formation. Furthermore, this nontoxic material demonstrated efficacy in mitigating ROS levels, thereby fostering osteogenic differentiation of bone marrow mesenchymal stem cells and enhancing angiogenic ability. Subsequently, the infected models of bone defects in rat skulls were established to investigate the effects of composite scaffolds on anti-bacteria and bone formation in vivo. The PMPC/Gelatin treatment exhibited excellent antibacterial activity, coupled with enhanced vascularization and osteogenesis at the defect sites. These compelling findings affirm that the PMPC/Gelatin composite scaffold represents a promising avenue for anti-bacteria and bone regeneration.

Abstract Background The cell development atlas of transition stage from late Carnegie to fetal development (7–9 weeks) remain unclear. It can be seen that the early period of human embryos (7–9 weeks) is a critical research gap. Therefore, we employed single‑cell RNA sequencing to identify cell types and elucidate differentiation relationships. Results The single‑cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7–9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. Conclusions We provide the cell development atlas for human embryos (7–9 weeks). Two distinct cell development and differentiation pathways are revealed.

Abstract The mismanagement of waste is jeopardizing urban sustainability. Although polycentric waste governance (PWG) has been introduced, characterizing the PWG remains challenging. This paper employs game theory to illustrate polycentricity by investigating the equilibrium state from the stakeholders’ perspective. Shanghai, Tokyo, and Hong Kong are selected as target cities for comparative analysis. The findings reveal the heterogeneous characteristics in three megacities’ PWG—the collaboration by principal stakeholders (formal recyclers, informal recyclers, households) in Shanghai, the exclusion of informal recyclers in Tokyo, and the limited contribution provided by the formal recyclers in Hong Kong. The divergent PWG characteristics can be attributed to variations in governance patterns, socioeconomic factors, and policy formulation. Regarding urban sustainability, Tokyo and Shanghai’s PWG contribute to the circular economy’s expansion, while Hong Kong’ potential, in this regard, is undervalued. Despite Tokyo’s improved social recognition to practitioners, this PWG mode, primarily driven by formal recyclers and households, presents limited inclusion of low-income groups. Additionally, it is crucial for the authorities in Shanghai and Hong Kong to acknowledge the potential pollution of informal recyclers’ non-environmental behavior. This paper offers a valuable model for characterizing and analyzing PWG across different cities, facilitating knowledge aggregation and the implementation of PWG practice.

Abstract Background Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria. Methods A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment. Results Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group. Conclusion Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.

Abstract Carbon dots (CDs)‐based zero‐dimensional nanomaterials with dimensions ranging from 1 to 10 nm have shown tremendous potential in the application of regenerative medicine, because of their unique physicochemical properties and favorable attributes like good biocompatibility, unique biological functions, low cost and high stability. These newly synthesized CDs‐based nanomaterials could replace traditional semiconductor quantum dots, which have obvious toxicity drawbacks and higher costs. CDs not only show sustained fluorescent quality and biocompatibility, but also serve as superior carriers for drug delivery, as well as for bioimaging‐guided detection of cells, drugs, and growth factors. So, they have been shown to play a role in various fields such as chemical and biological sensing, bioimaging, drug delivery, and photocatalysis. Thus, they are considered potential candidates for regenerative medicine applications. In this review, we provide a comprehensive summary of the classification of CDs, focusing on their formation mechanisms, micro‐/nanostructures, and distinctive properties. We describe their properties and synthesis methods in detail. Furthermore, we systematically highlight recent remarkable advances in the applications of CDs in regenerative medicine, such as bone and cartilage repair, wound healing, nerve regeneration, and myocardial regeneration, are systematically highlighted. Finally, we discuss the key challenges that lie ahead, outline future research directions, and explore the prospects of CDs‐based materials in regenerative medicine.

IntroductionThis study investigates how parental styles, basic empathy, and family violence influence adolescents’ bystander behaviors in school bullying.MethodsA survey was conducted with 1,067 students from three middle schools in southern China. Multifactor logistic regression and a moderated mediation model were employed to analyze the relationships between positive and negative parental styles, basic empathy, and bystander behaviors.ResultsThe study found significant correlations and predictive relationships: Positive parental styles were strongly associated with increased basic empathy (r = 0.29, p < 0.01) and behaviors that protect victims (r = 0.29, p < 0.01). In contrast, negative parental styles correlated positively with behaviors that support bullying (r = 0.12, p < 0.01) and instances of family violence (r = 0.62, p < 0.01). Basic empathy negatively predicted behaviors that promote bullying (β = -0.098, p < 0.01) and positively predicted protective behaviors toward victims (β = 0.249, p < 0.001). Furthermore, family violence weakened the positive effects of positive parental styles on both empathy (β = -0.075, p < 0.001) and protective behaviors (β = -0.025, p < 0.01).ConclusionThe findings indicate that positive parental styles indirectly promote adolescents’ victim protector behaviors by enhancing their basic empathy, underscoring the importance of emotional cultivation. Meanwhile, family violence weakens the positive impact of these parental styles on basic empathy and protective behaviors, harming adolescents’ emotional security and behavioral norms.

ObjectiveThis study used finite element analysis to simulate four commonly used fixation methods for metacarpal shaft oblique fractures during finger motion and evaluate their biomechanical performance. The aim was to provide evidence for clinically selecting the optimal fixation method, guiding early rehabilitation treatment, and reducing the risk of complications.MethodsFinite element analysis simulated dynamic proximal phalanx motion (60° flexion, 20° extension, 20° adduction, and 20° abduction). We analysed stress, displacement, and distributions for dorsal plates, intramedullary nails, Kirschner wire, and screw fixation methods.ResultsAt 60° of finger flexion and 20° of abduction, plate fixation demonstrated greater stability and minimal displacement, with a peak displacement of 0.19 mm; however, it showed higher stress levels in all motion states, increasing the risk of failure. The stability of the intramedullary nail was similar to that of the dorsal plate, with a maximum displacement difference of 0.04 mm, and it performed better than the dorsal plate during adduction of 20°. Kirschner wire showed the highest stress levels of 81.6 Mpa during finger flexion of 60°, indicating a greater risk of failure and unstable displacement. Screws had lower stress levels in all finger motion states, reducing the risk of failure, but had poorer stability. Stress and displacement distributions showed that the dorsal plate, intramedullary nail, and Kirschner wire mainly bore stress on the implants, concentrating near the fracture line and the proximal metacarpal. In contrast, the screws partially bore stress in the screw group. The anterior end of the metacarpal mainly hosted the maximum displacement.ConclusionThis study demonstrates that under simulated finger motion states, the dorsal plate fixation method provides the best stability in most cases, especially during finger flexion and abduction. However, high stress levels also indicate a higher risk of failure. The intramedullary nail is similar to the dorsal plate in stability and performs better in certain motion states. Kirschner wire exhibits the highest risk of failure during flexion. Although screws have poorer stability in some motion states, they offer a lower risk of failure. These findings provide important reference and surgical selection strategies for treating metacarpal fractures.

Abstract Topographic Rossby waves (TRWs) dominate the low-frequency variability of deep ocean currents and play a crucial role in energy exchange and material mixing. On the continental slope of the southwestern South China Sea, a deep-water mooring was deployed to observe TRWs for a period of ~ 40 days. The TRWs, with a wavelength of 109 km, account for 41.3% of the subinertial variations. A ray-tracing model was applied to investigate the propagation and energy source. The results showed that the TRWs propagated from the northeast of the mooring location and were most likely caused by the mesoscale eddy disturbances off the Vietnam coast. This study provides a new perspective on examining the impact of mesoscale eddies off Vietnam on abyssal currents.

Iron ore tailings (IOT) are industrial solid wastes that pose environmental threats. This study prepared IOT-biochar composite materials as multifunctional soil conditioners through an in-situ growth method. Biochar served as a carrier to improve the dispersity and reactivity of IOT in soil. The IOT-biochar composite (FeOT-BC) showed balanced impacts on soil properties, increasing pH, organic matter and available nutrients compared to IOT alone. This was due to the buffering effects of biochar. In pot experiments, FeOT-BC significantly promoted rice plant growth compared to IOT alone. The improvements were attributed to the improved soil fertility and increased microbial activities induced by biochar. The results suggest that integrating IOT with biochar can mitigate the negative effects of tailings and convert them into a value-added product. The biochar component can optimize the performance of IOT by moderating soil acidification, enhancing nutrient release from iron minerals, and stimulating microbial activities. The IOT-biochar composite materials integrate the functionalities of both components for optimized soil conditioning effects, providing a promising strategy for comprehensive tailings utilization.

Objective:. Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence. Methods:. This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment. Results:. A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of anti-hypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11–1.72, P = 0.004). Conclusions:. HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients’ misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.

Abstract Patients with obstructive sleep apnea (OSA) are liable to have resistant hypertension (RH) associated with unfavorable cardiovascular events. It is of necessity to predict OSA patients who are susceptible to resistant hypertension. Hence, we conducted a retrospective study based on the clinical records of OSA patients admitted to Yixing Hospital Affiliated to Jiangsu University from January 2018 to December 2022. According to different time periods, patients diagnosed between January 2018 and December 2021 were included in the training set (n = 539) for modeling, and those diagnosed between January 2022 and December 2022 were enrolled into the validation set (n = 259) for further assessment. The incidence of RH in the training set and external validation set was comparable (P = 0.396). The related clinical data of patients enrolled were collected and analyzed through univariate analysis and least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a nomogram. Finally, five variables were confirmed as independent risk factors for OSA patients with RH, including smoking, heart disease, neck circumference, AHI and T90. The nomogram established on the basis of variables above was shown to have good discrimination and calibration in both the training set and validation set. Decision curve analysis indicated that the nomogram was useful for a majority of OSA patients. Therefore, our nomogram might be useful to identify OSA patients at high risk of developing RH and facilitate the individualized management of OSA patients in clinical practice.

Recent advancements in deep convolutional neural networks (DCNNs) have significantly improved landslides identification using remote sensing images. Pixel-wise semantic segmentation (PSS) and object-oriented detection (OOD) are two dominant approaches, wherein PSS are better as providing detailed delineation of landslide shapes. However, PSS are limited by the difficulty in labelling training data and low segmentation speed compared to OOD. In this paper, we propose an efficient DCNN-based landslide semantic segmentation method, the so-called Dynahead-YOLO-Otsu, to perform a PSS based on the OOD results. This is achieved by locating potential landslide regions in advance using the ODD-based Dynahead-YOLO model, which enhances the capacity for detecting landslides with variable proportions and complex background in the images. The preliminary results are then processed using the Otsu binarization algorithm to cluster pixels belonging to landslides from the images of potential regions for semantic segmentation. To validate the performance, we tested the proposed method using an open-source dataset containing 950 landslide images. We compared the results with three up-to-date DCNN-and PSS- based approaches, namely DeepLab v3+, PSPnet, and Unet. Results demonstrate that the proposed method achieves comparable Recall (71.80%) and F1 scores (75.80%), with an average improvement of 22% and 16% in Precision and IoU, respectively.

Abstract Accumulating evidence indicates that metabolic reprogramming of cancer cells supports the energy and metabolic demands during tumor metastasis. However, the metabolic alterations underlying lymph node metastasis (LNM) of cervical cancer (CCa) have not been well recognized. In the present study, it is found that lymphatic metastatic CCa cells have reduced dependency on glucose and glycolysis but increased fatty acid oxidation (FAO). Inhibition of carnitine palmitoyl transferase 1A (CPT1A) significantly compromises palmitate‐induced cell stemness. Mechanistically, FAO‐derived acetyl‐CoA enhances H3K27 acetylation (H3K27Ac) modification level in the promoter of stemness genes, increasing stemness and nodal metastasis in the lipid‐rich nodal environment. Genetic and pharmacological loss of CPT1A function markedly suppresses the metastatic colonization of CCa cells in tumor‐draining lymph nodes. Together, these findings propose an effective method of cancer therapy by targeting FAO in patients with CCa and lymph node metastasis.

Abstract Background Cervical cancer (CCa) is the fourth most common cancer among females, with high incidence and mortality rates. Circular RNAs (circRNAs) are key regulators of various biological processes in cancer. However, the biological role of circRNAs in cervical cancer (CCa) remains largely unknown. This study aimed to elucidate the role of circMAST1 in CCa. Methods CircRNAs related to CCa progression were identified via a circRNA microarray. The relationship between circMAST1 levels and clinicopathological features of CCa was evaluated using the clinical specimens and data of 131 patients with CCa. In vivo and in vitro experiments, including xenograft animal models, cell proliferation assay, transwell assay, RNA pull-down assay, whole-transcriptome sequencing, RIP assay, and RNA-FISH, were performed to investigate the effects of circMAST1 on the malignant behavior of CCa. Results CircMAST1 was significantly downregulated in CCa tissues, and low expression of CircMAST1 was correlated with a poor prognosis. Moreover, our results demonstrated that circMAST1 inhibited tumor growth and lymph node metastasis of CCa. Mechanistically, circMAST1 competitively sequestered N-acetyltransferase 10 (NAT10) and hindered Yes-associated protein (YAP) mRNA ac4C modification to promote its degradation and inhibit tumor progression in CCa. Conclusions CircMAST1 plays a major suppressive role in the tumor growth and metastasis of CCa. In particular, circMAST1 can serve as a potential biomarker and novel target for CCa.

In order to investigate the flavor properties of commercial plant-based meat alternatives (PMAs) and the similarity of PMAs with meat products, this experiment used solid-phase microextraction (SPME) in conjunction with gas chromatography-olfactometry-mass spectrometry (GC-O-MS) to identify and analyze the volatile flavor compounds in three types of commercial PMAs and corresponding animal meat products. There were 30, 35, and 30 flavor-active substances discovered in chicken PMAs, beef PMAs, and pork PMAs, respectively. According to instrument measurement and relative odor activity value (ROAV) analysis, the key flavor components thatmade up the three types of PMAs were aldehydes, including heptanal (rubber, meat tallow), (E)-2-octenal (delicate fragrance, meat tallow), (E)-2-nonenal (meat tallow, salt, sauce), and (E,E)-2,4-decadienal (meat tallow). Key flavor components of the chicken PMAs group also included nonanal (celery), decyl aldehyde (garlic, acid), and (E)-2,4-nonadienal (meat tallow). Key flavor components up the beef PMAs group included decyl aldehyde (beany flavor, roasted onion), ethyl hydride maltol (tallow, sauce), methyl furfuryl disulfide (roasted), and (E,E)-2,4 nonadienal (meat tallow). Key flavor components of the pork PMAs group were (E)-2-undecenal (fried), (E,Z)-2,4-decadienal (sauce), and 2-acetylthiazole (bean). This study demonstrated the primary aromatic substances that contributed to the overall olfactory features of PMAs were aldehydes. During processing, the flavorings from spices had masking and imitating impact. As a result, this work provides both theoretical and empirical support for further improving and maximizing the authenticity of PMAs flavor qualities.

On-chip electrostatic discharge (ESD) protection poses a challenge in the chip fabrication process. In this study, a novel electric fuse (E-fuse) device featuring a simple structure of Ni metal on a SiO2 dielectric for ESD protection was proposed, and the physical mechanism of its operation was investigated in detail. Experimental evaluations, utilizing transmission line pulse (TLP) testing and fusing performance analyses, reveal that the E-fuse, constructed with a Ni metal layer measuring 5 μm in width, 100 μm in length, and 5 nm in thickness, achieved a significant ESD protection voltage of 251 V (VHBM) and demonstrates low-voltage fusing at a bias voltage of 7 V. Compared to traditional ESD protection devices, the E-fuse boasts a smaller size and removability. To assess fusing performance, devices of varying sizes were tested using a fusing lifetime model. This study supports both theoretical and empirical evidence, enabling the adoption of cost-effective, straightforward E-fuse devices for ESD protection.

The improvement of landslide susceptibility assessment is a long-standing problem in hazard mitigation work, wherein previous studies have proposed various training models. However, the ratio of positive to negative samples and the selection of non-landslide samples have been shown to significantly influence results. These research directions have traditionally been focal points, while datasets are often overlooked, serving merely as auxiliary tools to support the validation process. Hence, this study proposes an approach to enhance datasets through the introduction of the side-sampling method. This technique focuses on individual research cells, conducting feature sampling training on fixed regions of length M, thereby enabling more precise identification of geographical clustering characteristics. Using evaluation metrics such as accuracy, precision, recall, F1 score, and ROC curve, this study conducts a comparative analysis between the side-sampling method and traditional sampling methods, using three distinct railway lines in China as the study areas. Results show substantial improvements beyond several exceptions: accuracy (+7.68%), precision (+7.19%), recall (+13.48%), F1 score (+9.92%), and ROC (+6.22%). The results demonstrate a significant overall improvement in the performance of the trained models based on the side-sampling method, providing a positive insight into mitigating landslide hazards along railways from the dataset perspective.

BackgroundThe pandemic has accelerated digital work transformation, yet little is known about individuals’ willingness to sustain such digital modes and its associated factors. A better understanding of this willingness and its drivers is crucial for guiding the development of future digital work infrastructure, training programs, and strategies to monitor and prevent related health issues. ObjectiveThis study aims to quantify the general population’s willingness to sustain pandemic-induced digital work, identify its associated factors, and examine how screen time moderates these relationships. MethodsA cross-sectional study was conducted targeting Hong Kong residents aged ≥18 years who have increased engagement in digital work since the pandemic. Data were collected through self-reported, web-based surveys. Descriptive statistics determined prevalence rates, while structured multiphase logistic regression identified associated factors and explored the moderating effects of screen hour levels. ResultsThis unfunded study enrolled 1014 participants from May 2 to June 24, 2022, and completed data analysis within 3 months after data collection. A total of 391 (38.6%; 95% CI 35.6%-41.6%) participants expressed willingness to sustain digital work. Positive factors associated with this willingness included being an employee (odds ratio [OR] 3.12, 95% CI 1.59-6.45; P=.001), being health professionals (OR 3.32, 95% CI 1.49-7.82; P=.004), longer screen hours (OR 1.09, 95% CI 1.03-1.15; P=.002), and higher depression levels (OR 1.20, 95% CI 1.01-1.44; P=.04). Conversely, negatively associated factors included older age (OR 0.87, 95% CI 0.81-0.94; P=.001), extroversion (OR 0.66, 95% CI 0.51-0.86; P=.002), higher eHealth literacy (OR 0.96, 95% CI 0.93-0.98; P8 h/d; low: ≤8 h/d) influenced the association among 10 factors related to willingness to sustain pandemic-induced digital work, including age, education level, household size, needs for regular medical care, BMI, frequency of both vigorous and moderate physical activities, perceived COVID-19 severity, immediate social circle COVID-19 presence, and fear of COVID-19 (all P values for interaction

Abstract Background The gut is an important site for human immunodeficiency virus (HIV) infection and immune responses. The role of gut mucosal immune cells in immune restoration in patients infected with HIV undergoing antiretroviral therapy remains unclear. Methods Ileocytes, including 54 475 immune cells, were obtained from colonoscopic biopsies of five HIV‐negative controls, nine immunological responders (IRs), and three immunological non‐responders (INRs) and were analyzed using single‐cell RNA sequencing. Immunohistochemical assays were performed for validation. The 16S rRNA gene was amplified using PCR in faecal samples to analyze faecal microbiota. Flow cytometry was used to analyze CD4+ T‐cell counts and the activation of T cells. Results This study presents a global transcriptomic profile of the gut mucosal immune cells in patients infected with HIV. Compared with the IRs, the INRs exhibited a lower proportion of gut plasma cells, especially the IGKC+IgA+ plasma cell subpopulation. IGKC+IgA+ plasma cells were negatively associated with enriched f. Prevotellaceae the INRs and negatively correlated with the overactivation of T cells, but they were positively correlated with CD4+ T‐cell counts. The INRs exhibited a higher proportion of B cells than the IRs. Follicular and memory B cells were significantly higher in the INRs. Reduced potential was observed in the differentiation of follicular or memory B cells into gut plasma cells in INRs. In addition, the receptor‐ligand pairs CD74_MIF and CD74_COPA of memory B/ follicular helper T cells were significantly reduced in the INRs, which may hinder the differentiation of memory and follicular B cells into plasma cells. Conclusions Our study shows that plasma cells are dysregulated in INRs and provides an extensive resource for deciphering the immune pathogenesis of HIV in INRs. Key points An investigation was carried out at the single‐cell‐level to analyze gut mucosal immune cells alterations in PLWH after ART. B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs. There are gaps in the transition from gut follicular or memory B cellsinto plasma cells in INRs.

The impact of the built environment and weather conditions on travel behavior has been widely studied. However, limited studies have focused on better understanding such effects in medium-sized cities with bus-oriented transit systems, particularly from a separate perspective of travelers’ origins and destinations. We took Weinan, China, as a representative of second-tier cities in developing countries that concentrate on bus-oriented development strategies. New evidence of feature importance and nonlinear effects of crucial factors were revealed by an interpretable machine learning-based approach combining XGBoost and Shapley Additive Explanation (SHAP) with multi-source data. Most key factors were critical at both origins and destinations, such as the density of residential and commercial facilities. However, several important factors, such as road density and boarding time, had strong imbalanced effects on travel behavior. These findings provide novel insights and empirical implications to support urban planning strategies in medium-sized cities.

The ongoing evolution of SARS-CoV-2 is a significant concern, especially with the decrease in clinical sequencing efforts, which impedes the ability of public health sectors to prepare for the emergence of new variants and potential COVID-19 outbreaks. Wastewater-based epidemiology (WBE) has been proposed as a surveillance program to detect and monitor the SARS-CoV-2 variants being transmitted in communities. However, research is limited in evaluating the effectiveness of wastewater collection at sentinel sites for monitoring disease prevalence and variant dynamics, especially in terms of inferring the epidemic patterns on a broader scale, such as at the state/province level. This study utilized a multiplexed tiling amplicon-based sequencing (ATOPlex) to track the longitudinal dynamics of variant of concern (VOC) in wastewater collected from municipalities in Queensland, Australia, spanning from 2020 to 2022. We demonstrated that wastewater epidemiology measured by ATOPlex exhibited a strong and consistent correlation with the number of daily confirmed cases. The VOC dynamics observed in wastewater closely aligned with the dynamic profile reported by clinical sequencing. Wastewater sequencing has the potential to provide early warning information for emerging variants. These findings suggest that WBE at sentinel sites, coupled with sensitive sequencing methods, provides a reliable and long-term disease surveillance strategy.

ObjectivesThe auditory spatial processing abilities mature throughout childhood and degenerate in older adults. This study aimed to compare the differences in onset cortical auditory evoked potentials (CAEPs) and location-evoked acoustic change complex (ACC) responses among children, adults, and the elderly and to investigate the impact of aging and development on ACC responses.DesignOne hundred and seventeen people were recruited in the study, including 57 typically-developed children, 30 adults, and 30 elderlies. The onset-CAEP evoked by white noise and ACC by sequential changes in azimuths were recorded. Latencies and amplitudes as a function of azimuths were analyzed using the analysis of variance, Pearson correlation analysis, and multiple linear regression model.ResultsThe ACC N1’-P2’ amplitudes and latencies in adults, P1’-N1’ amplitudes in children, and N1’ amplitudes and latencies in the elderly were correlated with angles of shifts. The N1’-P2’ and P2’ amplitudes decreased in the elderly compared to adults. In Children, the ACC P1’-N1’ responses gradually differentiated into the P1’-N1’-P2’ complex. Multiple regression analysis showed that N1’-P2’ amplitudes (R2 = 0.33) and P2’ latencies (R2 = 0.18) were the two most variable predictors in adults, while in the elderly, N1’ latencies (R2 = 0.26) explained most variances. Although the amplitudes of onset-CAEP differed at some angles, it could not predict angle changes as effectively as ACC responses.ConclusionThe location-evoked ACC responses varied among children, adults, and the elderly. The N1’-P2’ amplitudes and P2’ latencies in adults and N1’ latencies in the elderly explained most variances of changes in spatial position. The differentiation of the N1’ waveform was observed in children. Further research should be conducted across all age groups, along with behavioral assessments, to confirm the relationship between aging and immaturity in objective ACC responses and poorer subjective spatial performance.SignificanceACCs evoked by location changes were assessed in adults, children, and the elderly to explore the impact of aging and development on these differences.

Introduction Obesity has been identified as a significant risk factor for several chronic conditions, including diabetes, tumours and cardiovascular disease, and has been associated with increased mortality rates. Despite the well-established clinical practice of electroacupuncture (EA) as a potential treatment option for obesity, its efficacy remains questionable, primarily due to the paucity of empirical evidence supporting its therapeutic benefits.Methods and analysis The present study aims to investigate the efficacy and safety of EA for weight loss in obese individuals with pre-diabetes, using a randomised, placebo-controlled clinical trial design. A total of 256 eligible patients will be randomly assigned to one of two groups: EA (comprising EA treatment with health education) or superficial acupuncture (SA) (comprising SA treatment with health education). The intervention will be administered three times per week for the initial 12 weeks, two times per week for the subsequent 8 weeks and one time per week for the final 4 weeks, with a 24-week follow-up period. The primary outcome measure will be the percentage of patients who achieve a reduction of 10% or more in their body weight at week 24. Secondary outcome measures will include changes in body weight and body mass index, blood test results, data collected by the body composition analyser, size of adipose tissue scanned by MRI of the abdomen and the Impact of Weight on Quality of Life, the 21-item Three-Factor Eating Questionnaire-Revised and the Food Craving Questionnaire-Trait. The Treatment Emergent Symptom Scale will be employed to monitor every adverse reaction from baseline to follow-up.Ethics and dissemination This trial has received ethical clearance from the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine under the registration number 2021SHL-KY-74. All participants will provide their written informed consent prior to their enrolment. The findings of this investigation will be disseminated through peer-reviewed publications and scholarly conferences.Trial registration number NCT05237089.

The research focuses on and analyses the effect of government investment on income distribution by evaluating the effects of public spending on income variation in various fields, in various regions, and at different income levels in the Chinese economy. The study found that government investment in different fields substantially decreases income inequality. Increasing housing security, medical, agriculture, forestry and other expenditures has a significant impact on improving the income inequality between rural and urban inhabitants; the impact of government investment in the western, central, and eastern regions on the reduction of income variation is decreasing successively, with emphasis on government investment in the western and central regions. The effects of government investment on the decline of the income distribution are twofold: first, it influences the amount of low- and middle-income groups; second, it has an impact on the reduction of high-income organizations; however, the impact on the income equality of high-income and low-income organizations is not considerable. In investment, the study demonstrates that income inequality can be reduced without negatively affecting the financial status of higher-income individuals. It is significant to value providing adequate housing security for low-income populations as a critical policy implication. This study, utilizing novel indicators, contributes to the current body of research on the impact of fiscal policy in addressing income inequality in China.

In order to improve the yield of bacterial cellulose (BC), the fermentation medium of the Gluconacetobacter xylinus was optimized by response surface methodology. Based on the optimization results, the effects of sodium alginate (SA), sodium carboxymethyl cellulose (CMC-Na) and carboxymethyl cellulose (CMC) on the yield of BC, total sugar consumption, acetic acid and pyruvic acid were investigated. The results showed that when the amounts of addition of glucose was 4%, yeast extract powder was 1%, peptone was 0.8%, MgSO4 was 1.9%, Na2HPO4 was 0.2%, acetic acid was 0.4%, ethanol was 1.6%, the actual yield of BC could reach 5.19 g/L. After adding SA, CMC-Na and CMC, the total sugar consumption increased by 29.9%, 22.82% and 15.73%, and the yield of BC was 6.72, 6.01 and 5.1 g/L, respectively. The content of pyruvic acid in SA group and CMC-Na group was increased by 29.02% and 16.52% compared with the control group. SA and CMC-Na promoted the accumulation and utilization of pyruvate acid, the yield of BC accumulation was increased. The highest acetic acid accumulation (4.27 g/L) was observed in the CMC addition group, which had a certain relationship to the lower yield of BC than the control group.

Abstract Background The prevalence of diabetic foot ulcers, a common, more serious chronic diabetes-related complication, is increasing. Vacuum sealing drainage (VSD) constitutes an effective adjunctive treatment for diabetic foot ulcers. Factors, such as poor glycemic control, ischemia, and infection prolong wound healing time, and VSD products are expensive and unaffordable for many patients. Objective To compare the use of customized VSD and customized VSD in the treatment of diabetic foot ulcer. Method This retrospective study included 83 patients with diabetic foot ulcers in customized VSD (n = 44) and VSD (n = 39) groups. Baseline data, efficacy after 14 days, total treatment efficiency, final outcome (28 days after treatment, healing rate), average treatment cost, and hospitalization (days) of the two groups were compared. Factors affecting wound healing were analyzed. Results No significant intergroup differences in the baseline data were detected (VSD vs. customized VAD, p > 0.05). Treatment efficacy was higher in the customized VSD group than in the VSD group after 14 days (p

Abstract Background Traumatic brain injury (TBI) is a significant worldwide public health concern that necessitates attention. Apoptosis signal-regulating kinase 1 (ASK1), a key player in various central nervous system (CNS) diseases, has garnered interest for its potential neuroprotective effects against ischemic stroke and epilepsy when deleted. Nonetheless, the specific impact of ASK1 on TBI and its underlying mechanisms remain elusive. Notably, mutation of ATP-binding sites, such as lysine residues, can lead to catalytic inactivation of ASK1. To address these knowledge gaps, we generated transgenic mice harboring a site-specific mutant ASK1 Map3k5-e (K716R), enabling us to assess its effects and elucidate potential underlying mechanisms following TBI. Methods We employed the CRIPR/Cas9 system to generate a transgenic mouse model carrying the ASK1-K716R mutation, aming to investigate the functional implications of this specific mutant. The controlled cortical impact method was utilized to induce TBI. Expression and distribution of ASK1 were detected through Western blotting and immunofluorescence staining, respectively. The ASK1 kinase activity after TBI was detected by a specific ASK1 kinase activity kit. Cerebral microvessels were isolated by gradient centrifugation using dextran. Immunofluorescence staining was performed to evaluate blood–brain barrier (BBB) damage. BBB ultrastructure was visualized using transmission electron microscopy, while the expression levels of endothelial tight junction proteins and ASK1 signaling pathway proteins was detected by Western blotting. To investigate TBI-induced neuroinflammation, we conducted immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry analyses. Additionally, immunofluorescence staining and electrophysiological compound action potentials were conducted to evaluate gray and white matter injury. Finally, sensorimotor function and cognitive function were assessed by a battery of behavioral tests. Results The activity of ASK1-K716R was significantly decreased following TBI. Western blotting confirmed that ASK1-K716R effectively inhibited the phosphorylation of ASK1, JNKs, and p38 in response to TBI. Additionally, ASK1-K716R demonstrated a protective function in maintaining BBB integrity by suppressing ASK1/JNKs activity in endothelial cells, thereby reducing the degradation of tight junction proteins following TBI. Besides, ASK1-K716R effectively suppressed the infiltration of peripheral immune cells into the brain parenchyma, decreased the number of proinflammatory-like microglia/macrophages, increased the number of anti-inflammatory-like microglia/macrophages, and downregulated expression of several proinflammatory factors. Furthermore, ASK1-K716R attenuated white matter injury and improved the nerve conduction function of both myelinated and unmyelinated fibers after TBI. Finally, our findings demonstrated that ASK1-K716R exhibited favorable long-term functional and histological outcomes in the aftermath of TBI. Conclusion ASK1-K716R preserves BBB integrity by inhibiting ASK1/JNKs pathway in endothelial cells, consequently reducing the degradation of tight junction proteins. Additionally, it alleviates early neuroinflammation by inhibiting the infiltration of peripheral immune cells into the brain parenchyma and modulating the polarization of microglia/macrophages. These beneficial effects of ASK1-K716R subsequently result in a reduction in white matter injury and promote the long-term recovery of neurological function following TBI.

Abstract Various miRNAs have been shown to participate in the tumor progression and development of colorectal cancer (CRC). However, the role of miR-3913-5p in CRC are yet to be clearly defined. In the present study, we determine that miR-3913-5p is downregulated in CRC cell lines and CRC tissues. Exogenous miR-3913-5p expression weakens the CRC cells growth, migration and invasion. Mechanistically, miR-3913-5p directly targets the 3’UTR of CREB5. Overexpression of CREB5 reverses the suppression of CRC cells proliferation, migration and invasion induced by miR-3913-5p. Furthermore, ATF2 negatively regulates the transcription of miR-3913-5p by binding to its promoter. CREB5 can cooperate with ATF2. CREB5 is required for ATF2 in regulating miR-3913-5p. Finally, inverse correlations can be found between the expressions of miR-3913-5p and CREB5 or ATF2 in CRC tissues. Thus, a plausible mechanism of ATF2/miR-3913-5p/CREB5 axis regulating CRC progression is elucidated. Our findings suggest that miR-3913-5p functions as a tumor suppressor in CRC. ATF2/miR-3913-5p/CREB5 axis might be a potential therapeutic target against CRC progression.

The globally increasing frequency of extreme drought events exacerbates the contradiction between the supply of water and the demand for high-quality urban greening. However, the mechanism of the response of urban shrubs to drought stress remains unclear. In this study, three typical urban shrubs (Euonymus japonicus, golden vicary [Ligustrum × vicaryi], and Japanese purple barberry [Berberis thunbergii var. atropurpurea]) that are used for greening in northern China were exposed to three levels of water (full irrigation, natural rain-fed, and extreme drought) in different periods of the growing season (April to May, June to July, and August to September) to investigate the responses of leaf water potential and photosynthetic parameters. The main results were as follows: (1) all the leaf water potentials (Ψ) and photosynthetic parameters (Pn) showed a typical linear relationship along the water gradient in the middle of the growing season. Extreme drought decreased the photosynthetic rates by 1.26~11.03 μmol·m−2·s−1 compared with the irrigated groups. However, the responses were less pronounced in the early and late growing seasons. (2) Different shrubs responded with different intensities and mechanisms. B. thunbergii var. atropurpurea showed clear anisohydric behavior throughout the whole growing season, while L. × vicaryi and E. japonicus showed stronger isohydric behavior during the early and late growing seasons. These findings are important to improve the sustainability of maintenance of ornamental plants from the scope of the efficient utilization of urban water resources.

Low or insufficient testosterone levels caused by caponization promote fat deposition in animals. However, the molecular mechanism of fat deposition in caponized animals remains unclear. This study aimed to investigate the metabolomics and transcriptomic profiles of adipose tissues and study the effect of testosterone and leptin on the proliferation of adipocytes. We observed a significant enlargement in the areas of adipocytes in the abdominal fat tissues in capon, as well as increased luciferase activity of the serum leptin and a sharp decrease in the serum testosterone in caponized gander. Metabolomics and transcriptomic results revealed differentially expressed genes and differentially expressed metabolites with enhanced PARR signal pathway. The mRNA levels of peroxisome proliferators-activated receptor γ, fatty acid synthase, and suppressor of cytokine signaling 3 in goose primary pre-adipocytes were significantly upregulated with high leptin treatment and decreased significantly with increasing testosterone dose. Hence, reduced testosterone and increased leptin levels after caponization possibly promoted adipocytes proliferation and abdominal fat deposition by altering the expression of PPAR pathway related genes in caponized ganders. This study provides a new direction for the mechanism through which testosterone regulates the biological function of leptin and fat deposition in male animals.

It is well accepted that the high performance of wastewater treatment plants (WWTPs) relies on the microbial community in activated sludge (AS). Hence, it is crucial to illuminate the geographic distributions and influencing factors of the ecological strategies employed by the AS microbial community. Here, we investigated how the ecological strategies of AS microbial communities influenced their ecological characteristics in 60 WWTPs across 15 cities in China. Our study showed that the average rrn copy number of the whole AS microbial community across China was 2.25 ± 0.12. The highest average rrn copy number of the core community indicated that core members tend to be r-strategists with an advantage in rapid pollutant removal and recovery of the community after environmental disturbances. High nutrient availability promoted microorganisms with higher average rrn copy numbers, while long sludge retention time (SRT) was preferred to the microorganisms with lower average rrn copy numbers. Homogenous selection and dispersal limitation were the predominant assembling processes at the city level, with a shift from deterministic to stochastic processes with increasing average rrn copy numbers. Furthermore, more r-strategists participated in chemoheterotrophic functions, while more K-strategists were related to the nitrification processes. Overall, our findings enrich the knowledge of AS microbial ecology and lay the theoretical foundation for the precise regulation of WWTPs.

Background: MicroRNA (miRNA) and mRNA levels in matching specimens were used to identify miRNA–mRNA interactions. We aimed to integrate transcriptome, immunophenotype, methylation, mutation, and survival data analyses to examine the profiles of miRNAs and target mRNAs and their associations with breast cancer (BC) diagnosis. Methods: Based on the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), differentially expressed miRNAs and targeted mRNAs were screened from experimentally verified miRNA-target interaction databases using Pearson's correlation analysis. We used real-time quantitative reverse transcription polymerase chain reaction to verify BC and benign disease samples, and logistic regression analysis was used to establish a diagnostic model based on miRNAs and target mRNAs. Receiver operating characteristic curve analysis was performed to test the ability to recognize the miRNA-mRNA pairs. Next, we investigated the complex interactions between miRNA-mRNA regulatory pairs and phenotypic hallmarks. Results: We identified 27 and 359 dysregulated miRNAs and mRNAs, respectively, based on the GEO and TCGA databases. Using Pearson's correlation analysis, 10 negative miRNA-mRNA regulatory pairs were identified after screening both databases, and the related miRNA and target mRNA levels were assessed in 40 BC tissues and 40 benign breast disease tissues. Two key regulatory pairs (miR-205-5p/High mobility group box 3 (HMGB3) and miR-96-5p/Forkhead Box O1 (FOXO1)) were selected to establish the diagnostic model. They also had utility in survival and clinical analyses. Conclusions: A diagnostic model including two miRNAs and their respective target mRNAs was established to distinguish between BC and benign breast diseases. These markers play essential roles in BC pathogenesis.

Safely and appropriately disposing of metalworking fluids sludge (MFS) remains a challenge owing to its highly hazardous properties, this work investigated MFS pyrolysis at various temperatures (500, 600, 700, 800, and 900 °C) for energy recovery and safety treatment of MFS. The experimental results indicated that inherent minerals at higher temperatures could enhance the gas yields and promote the qualities of oil and gas from MFS pyrolysis. The highest pyrolysis gas yield was achieved at 18.86 wt% after MFS pyrolysis at 900 °C. GC-MS analysis revealed that the inherent minerals facilitated a decrease in oxygenated and nitrogenated compounds within the oil, while simultaneously leading to a substantial increase in hydrocarbon contents. Notably, the highest content of aromatics (61.16%) was attained during pyrolysis at 900 °C. Moreover, inherent minerals improved carbon sequestration and the characteristics of biochar during the MFS pyrolysis. The leaching contents of heavy metals in biochars were reduced, thereby reducing the heavy metals associated environmental risk. This research suggests that the pyrolysis process was a promising approach for simultaneous energy recovery and MFS disposal with low environmental risk.

Learners' anxiety and emotional engagement have attracted a surge of scholarly interest due to their considerable relevance to students' academic performance and psychological well-being. However, the two variables await more exploration in the English as a Foreign Language (EFL) context. To fill this gap, we aimed to investigate these two variables in online and offline English-speaking classes, respectively, at a university in China. We adopted a sequential mixed-methods research approach. First, we used questionnaires to measure and compare the level of anxiety and emotional engagement in the two classes. Then, we conducted semi-structured interviews to gain a deeper understanding of the factors affecting learners' online and offline learning experiences. Quantitative results showed that students had higher levels of anxiety and lower levels of emotional engagement in the online environment than in the offline context. The subsequent qualitative findings revealed a complexity of positive and negative factors affecting anxiety and emotional engagement in the two instructional contexts. Our findings can shed light on research and practices concerning learner emotions in online and offline EFL instruction. Strategies were also provided to help teachers mitigate learners' anxiety and enhance their emotional engagement, which includes formulating a learning community, providing emotional support, alleviating students' technical stress and distraction, and incorporating group-based interactive activities into the course.

Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.

AbstractThe improvement of the landslide susceptibility mapping (LSM) is a long-standing problem, as it provides basics for hazard mitigation. Recently, hybrid ensemble deep learning (DL) techniques have witnessed the potential for this purpose. In this paper, we proposed a novel ensemble DL model, namely GL-ResNet, which employs the conventional ResNet blocks for landslide feature extraction, long-short term memory (LSTM) structures for information storage, and a proposed GoogLeNet block (GBlk) to broaden model perception ability. To validate the model performance, a landslide inventory containing 1147 historical landslide polygons and the data of 12 landslide factors in the Wenchuan area in southwestern China, was presented and separated into training and validating dataset using a 7:3 randomly sampling ratio strategy. Based on AUC and Accuracy, GL-ResNet (0.96 and 0.909) outperformed logistic regression (0.92 and 0.851), support vector machines (0.94 and 0.884), deep belief networks (0.95 and 0.884), gated recurrent unit (0.94 and 0.884) and ResNet (0.95 and 0.894). We also explored the robustness of GL-ResNet for LSM. The results suggested that although GL-ResNet is sensitive to initial training conditions, it showed good robustness to model training method and sample ratios. In detail, GL-ResNet outperformed the conventional models in terms of fitting power and prediction performance by 0.03-0.04 and 0.02 respectively in most cases, with even greater differences in the limited training dataset.

Abstract Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXIP1-AS1 was transcriptionally repressed by homeobox D9 (HOXD9) and was significantly downregulated in GC tissues and cells. Decreased expression of PAXIP1-AS1 was positively correlated with tumour progression, while PAXIP1-AS1 overexpression inhibited cell growth and metastasis both in vitro and in vivo. PAXIP1-AS1 overexpression significantly attenuated HOXD9-enhanced epithelial-to-mesenchymal transition (EMT), invasion and metastasis in GC cells. Poly(A)-binding protein cytoplasmic 1 (PABPC1), an RNA-binding protein, was found to enhance the stability of PAK1 mRNA, leading to EMT progress and GC metastasis. PAXIP1-AS1 was found to directly bind to and destabilise PABPC1, thereby regulating EMT and metastasis of GC cells. In summary, PAXIP1-AS1 suppressed metastasis, and the HOXD9/PAXIP1-AS1/PABPC1/PAK1 signalling axis may be involved in the progression of GC.

Abstract Background Urolithiasis with high prevalence and recurrence rate, has impacts on kidney injury in patients, becomes a socioeconomic and healthcare problem in worldwide. However, the biology of kidney with crystal formation and proximal tubular injury remains essentially unclear. The present study aims to evaluate the cell biology and immune-communications in urolithiasis mediated kidney injury, to provide new insights in the kidney stone treatment and prevention. Results We identified 3 distinct injured-proximal tubular cell types based on the differentially expression injury markers (Havcr1 and lcn2) and functional solute carriers (slc34a3, slc22a8, slc38a3 and slc7a13), and characterized 4 main immune cell types in kidney and one undefined cell population, where F13a1+/high/CD163+/high monocyte & macrophage and Sirpa/Fcgr1a/Fcgr2a+/high granulocyte were the most enriched. We performed intercellular crosstalk analysis based on the snRNA-seq data and explored the potential immunomodulation of calculi stone formation, and founded that the interaction between ligand Gas6 and its receptors (Gas6-Axl, Gas6-Mertk) was specifically observed in the injured-PT1 cells, but not injured-PT2 and -PT3 cells. The interaction of Ptn-Plxnb2 was only observed between the injured-PT3 cells and its receptor enriched cells. Conclusions Present study comprehensively characterized the gene expression profile in the calculi rat kidney at single nucleus level, identified novel marker genes for all cell types of rat kidney, and determined 3 distinct sub-population of injured-PT clusters, as well as intercellular communication between injured-PTs and immune cells. Our collection of data provides a reliable resource and reference for studies on renal cell biology and kidney disease.

Abstract Background BI-RADS 4 breast lesions are suspicious for malignancy with a range from 2 to 95%, indicating that numerous benign lesions are unnecessarily biopsied. Thus, we aimed to investigate whether high-temporal-resolution dynamic contrast-enhanced MRI (H_DCE-MRI) would be superior to conventional low-temporal-resolution DCE-MRI (L_DCE-MRI) in the diagnosis of BI-RADS 4 breast lesions. Methods This single-center study was approved by the IRB. From April 2015 to June 2017, patients with breast lesions were prospectively included and randomly assigned to undergo either H_DCE-MRI, including 27 phases, or L_DCE-MRI, including 7 phases. Patients with BI-RADS 4 lesions were diagnosed by the senior radiologist in this study. Using a two-compartment extended Tofts model and a three-dimensional volume of interest, several pharmacokinetic parameters reflecting hemodynamics, including Ktrans, Kep, Ve, and Vp, were obtained from the intralesional, perilesional and background parenchymal enhancement areas, which were labeled the Lesion, Peri and BPE areas, respectively. Models were developed based on hemodynamic parameters, and the performance of these models in discriminating between benign and malignant lesions was evaluated by receiver operating characteristic (ROC) curve analysis. Results A total of 140 patients were included in the study and underwent H_DCE-MRI (n = 62) or L_DCE-MRI (n = 78) scans; 56 of these 140 patients had BI-RADS 4 lesions. Some pharmacokinetic parameters from H_DCE-MRI (Lesion_Ktrans, Kep, and Vp; Peri_Ktrans, Kep, and Vp) and from L_DCE-MRI (Lesion_Kep, Peri_Vp, BPE_Ktrans and BPE_Vp) were significantly different between benign and malignant breast lesions (P

Acute myeloid leukemia (AML) remains a most lethal hematological malignancy, partly because of its slow development of targeted therapies compared with other cancers. PLK1 inhibitor, volasertib (Vol), is among the few molecular targeted drugs granted breakthrough therapy status for AML; however, its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits. Here, we report that transferrin-guided polymersomes (TPs) markedly augment the targetability, potency and safety of Vol to AML. Vol-loaded TPs (TPVol) with 4% transferrin exhibited best cellular uptake, effective down-regulation of p-PLK1, p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells. Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow. The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood, bone marrow, liver and spleen, effectively enhanced mouse survival rate, and impeded bone loss. This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.

Intervertebral disc degeneration (IVDD) is a worldwide disease that causes low back pain and reduces quality of life. Biotherapeutic strategies based on tissue engineering alternatives, such as intervertebral disc scaffolds, supplemented by drug-targeted therapy have brought new hope for IVDD. In this study, to explore the role and mechanism of MnO2/GelMA composite hydrogels in alleviating IVDD, we prepared composite hydrogels with MnO2 and methacrylate gelatin (GelMA) and characterized them using compression testing and transmission electron microscopy (TEM). Annulus fibrosus cells (AFCs) were cultured in the composite hydrogels to verify biocompatibility by live/dead and cytoskeleton staining. Cell viability assays and a reactive oxygen species (ROS) probe were used to analyze the protective effect of the composite hydrogels under oxidative damage. To explore the mechanism of improving the microenvironment, we detected the expression levels of antioxidant and autophagy-related genes and proteins by qPCR and Western blotting. We found that the MnO2/GelMA composite hydrogels exhibited excellent biocompatibility and a porous structure, which promoted cell proliferation. The addition of MnO2 nanoparticles to GelMA cleared ROS in AFCs and induced the expression of antioxidant and cellular autophagy through the common SIRT1/NRF2 pathway. Therefore, the MnO2/GelMA composite hydrogels, which can improve the disc microenvironment through scavenging intracellular ROS and resisting oxidative damage, have great application prospects in the treatment of IVDD.

Due to anthropogenic emissions, the global CO2 concentration increases at a rate of approximately 2 ppm per year. With over 130 countries and regions committing to carbon neutrality goals and continuously reducing anthropogenic CO2 emissions, understanding how atmospheric CO2 concentrations will change globally and in other regions has become an intriguing question. Examining different regions’ efforts to reduce anthropogenic CO2 emissions through atmospheric CO2 observations is also meaningful. We used prior and posterior fluxes to drive the TM5 model. The posterior fluxes were based on the China Carbon Monitoring, Verification and Support System for Global (CCMVS-G), which assimilated the atmospheric CO2 concentration data from ground-based observation and satellite observation. We found that the CO2 concentration obtained using the posterior fluxes was more in line with the actual situation. Then, we presented some experiments to estimate how global and regional CO2 concentrations would change if certain key regions and the whole world achieved net zero emissions of anthropogenic CO2. After removing carbon fluxes from China, North America, and Europe, global CO2 concentrations decreased by around 0.58 ppm, 0.22 ppm, and 0.10 ppm, respectively. The most significant decrease occurred in the regions where fluxes were removed, followed by other areas at the same latitude affected by westerly winds. This indicates that fossil fuel flux is the main factor affecting CO2 concentrations, and that meteorological-driven transportation also significantly impacts CO2 concentrations. Most importantly, using this method, it is possible to quantitatively estimate the impact of achieving carbon neutrality in one region on CO2 concentrations in local regions as well as globally.

Bone metabolic homeostasis is dependent on coupled bone formation dominated by osteoblasts and bone resorption dominated by osteoclasts, which is a process of dynamic balance between bone formation and bone resorption. Notably, the formation of bone relies on the development of bone vasculature. Previous studies have shown that oxidative stress caused by disturbances in the antioxidant system of the whole organism is an important factor affecting bone metabolism. The increase in intracellular reactive oxygen species can lead to disturbances in bone metabolism, which can initiate multiple bone diseases, such as osteoporosis and osteoarthritis. Traditional Chinese medicine is considered to be an effective antioxidant. Cumulative evidence shows that the traditional Chinese medicine can alleviate oxidative stress-mediated bone metabolic disorders by modulating multiple signaling pathways, such as Nrf2/HO-1 signaling, PI3K/Akt signaling, Wnt/β-catenin signaling, NF-κB signaling, and MAPK signaling. In this paper, the potential mechanisms of traditional Chinese medicine to regulate bone me-tabolism through oxidative stress is summarized to provide direction and theoretical basis for future research related to the treatment of bone diseases with traditional Chinese medicine.

The purification effect of a natural wetland landscape is often low when the focus is placed on the landscape effect. The effective combination of constructed wetland technology with landscape construction is challenging. Taking the Yuhe Wetland Park in Datong, Shanxi Province, China, as an example, the COD, phosphorus, and nitrogen removal capacities of aquatic plant species were determined, as well as the effects of the soil and the microbial communities. The highest COD and P removal capacity was observed for Typha orientalis Presl. which the purification rate reached 76.9% and 76.6%, and the highest N removal capacities were found for Scirpus validus Vahl., the rate of purification was 83.4%. Gram-negative bacteria were dominant.

Vision transformer architectures attract widespread interest due to their robust representation capabilities of global features. Transformer-based methods as the encoder achieve superior performance compared to convolutional neural networks and other popular networks in many segmentation tasks for medical images. Due to the complex structure of the brain and the approximate grayscale of healthy tissue and lesions, lesion segmentation suffers from over-smooth boundaries or inaccurate segmentation. Existing methods, including the transformer, utilize stacked convolutional layers as the decoder to uniformly treat each pixel as a grid, which is convenient for feature computation. However, they often neglect the high-frequency features of the boundary and focus excessively on the region features. We propose an effective method for lesion boundary rendering called TransRender, which adaptively selects a series of important points to compute the boundary features in a point-based rendering way. The transformer-based method is selected to capture global information during the encoding stage. Several renders efficiently map the encoded features of different levels to the original spatial resolution by combining global and local features. Furthermore, the point-based function is employed to supervise the render module generating points, so that TransRender can continuously refine the uncertainty region. We conducted substantial experiments on different stroke lesion segmentation datasets to prove the efficiency of TransRender. Several evaluation metrics illustrate that our method can automatically segment the stroke lesion with relatively high accuracy and low calculation complexity.

Driven by the change in intense land use and land cover (LULC) due to fast urbanization, urban flooding events have become the most frequent and influential hazards over the last few decades. Accurately predicting possible flood-prone locations under the dynamic fluctuations of LULC is crucial for sustainable urban development. However, there has been sparse studies on systematic integration of LULC changes into anticipate urban development scenarios coupled with flooding vulnerability assessment. Therefore, this study proposed a robust and powerful cascade modeling chain consisting of Maximum Entropy, System Dynamics and Patch-generating Land Use Simulation in combination with shared socio-economic pathways for projecting temporal and spatial dynamic changes associated with urban flooding vulnerability. Taking Guangdong Hong Kong Macao Greater Bay Area (GBA) as case study, the results showed that the increase in urban flooding was largely caused by the expansion of construction land. Overall, a substantial distinction within the scenarios was observed and the flooding vulnerability was ranked in the order of SSP126

Lumbar fusion is a popular surgical procedure for the treatment of degenerative lumbar disc disease; however, it may be accompanied by complications, such as cage loosening, subsidence, and non-union. This study engineered and fabricated a three-dimensional (3D)-printed anisotropic biomimetic trabecular porous Ti-6Al-4V cage for lumbar interbody fusion. The study evaluated the structural design, manufacturability, mechanical properties, and cellular functions of the fabricated structures compared to currently available interbody cages. In vitro tests assessed the biofunctionality of the 3D-printed porous cage, which revealed anisotropic biomimetic trabecular porous Ti-6Al-4V cages with 65%-85% porosity, and 600 μm pore size. The microscopy analysis of surface properties indicated in situ micro- and nano-roughness. The mechanical properties decreased progressively with increasing porosity, and the optimized frame-reinforced porous cage achieved higher compressive strength and stiffness than the fully porous fusion. The 70% 3D-printed porous frame-reinforced cage had suitable mechanical performance compared with the polyether-ether-ketone (PEEK) cage. The anisotropic biomimetic trabecular porous structures and the surface micro- and nano-roughness modifications achieved excellent biological functions in vitro. In conclusion, our fabricated 70% 3D-printed porous frame-reinforced Ti-6Al-4V cage with anisotropic biomimetic trabeculae is a promising strategy for lumbar interbody fusion.

In recent years, motor imagery-based brain-computer interface (MI-BCI) has been applied to motor rehabilitation in patients with motor dysfunction. However, traditional MI-BCI is rarely used for foot motor intention recognition because the motor cortex regions of both feet are anatomically close to each other, and traditional event-related desynchronization (ERD) patterns for MI-BCI have insufficient spatial discrimination. This study introduced steady-state somatosensory evoked potentials (SSSEPs) by synchronous bilateral feet electrical stimulation at different frequencies, which were used as carrier signals modulated by unilateral foot motor intention. Fifteen subjects participated in MI and MI-SSSEP tasks. A Riemannian geometry classifier with a task-related component analysis (TRCA) spatial filter was proposed to demodulate the variation in SSSEP features and discriminate the left and right foot motor intentions. The feature outcomes indicated that the amplitude and phase synchronization of the SSSEPs could be well modulated by unilateral foot MI tasks under the MI-SSSEP paradigm. The classification results revealed that the modulated SSSEP features played an important role in the recognition of left-right foot discrimination. Moreover, the proposed TRCA-based method outperformed the other three methods and improved the foot average classification accuracy to 81.07± 13.29%, with the highest accuracy attained at 97.00%. Compared with the traditional MI paradigm, the foot motor intention recognition accuracy of the MI-SSSEP paradigm was significantly improved, from nearly 60% to more than 80%. This work provides a practical method for left-right foot motor intention recognition and expands the application of MI-BCI in the field of lower-extremity motor function rehabilitation.