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Abstract Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is marked by impaired immune tolerance and heightened activity in both innate and adaptive immune systems. Hallmarks of SLE include elevated type I interferons and autoantibody production, though the exact causes of SLE remain elusive despite advances in research techniques. Crucial to SLE research is understanding its pathogenesis and developing effective diagnostic and therapeutic methods. Recent studies have highlighted a significant link between mitochondrial abnormalities and SLE's development and progression. Mitochondrial dysfunction plays a key role in SLE pathogenesis through various mechanisms such as mitochondrial DNA mutations, oxidative stress, immune metabolic reprogramming, and cellular death. These factors collectively contribute to the loss of self‐tolerance, increased autoantibody production, and impaired clearance of immune complexes, leading to their deposition. This triggers sustained inflammatory responses and damages multiple organs. This review focuses on the diagnostic and therapeutic approaches related to mitochondrial abnormalities in SLE. Targeting mitochondrial pathways presents a promising strategy for treating SLE, potentially improving prognosis and quality of life for those affected. Future research should further investigate the role of mitochondria in the onset and progression of SLE, providing new avenues for understanding and managing this complex disease.

Abstract Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.

Cetaceans play a crucial role in marine ecosystems; however, research on their gastrointestinal microbiota remains limited due to sampling constraints. In this study, we collected hindgut samples from 12 stranded cetaceans and performed 16S rRNA gene amplicon sequencing to investigate microbial composition and functional potentials. Analysis of ZOTUs profiles revealed that the phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated all hindgut samples. However, unique microbial profiles were observed among different cetacean species, with significant separation of gut microbiota communities according to biological evolutionary lineages. Different genera that contain pathogens were observed distinguishing delphinids from physeteroids/ziphiids. Delphinid samples exhibited higher abundances of Vibrio, Escherichia, and Paeniclostridium, whereas physeteroid and ziphiid samples showed higher abundances of Pseudomonas, Enterococcus, and Intestinimonas. Functional analysis indicated convergence in the gut microbiota among all cetaceans, with shared bacterial infection pathways across hindgut samples. In addition, a comparison of the gastrointestinal microbial composition between a stranded short-finned pilot whale (Globicephala macrorhynchus) and a stranded rough-toothed dolphin (Steno bredanensis) using 16S rRNA gene sequencing revealed distinct microbial community structures and functional capacities. To the best of our knowledge, this study represents the first report on the gastrointestinal microbiota of the pantropical spotted dolphin (Stenella attenuata), Blainville’s beaked whale (Mesoplodon densirostris), and rough-toothed dolphin, with various comparisons conducted among different cetacean species. Our findings enhance the understanding of microbial composition and diversity in cetacean gastrointestinal microbiota, providing new insights into co-evolution and complex interactions between cetacean microbes and hosts.

The transformation of energy structure has brought about new changes in the power system, and the environmentally friendly gas switchgear with the goal of low carbon and environmental protection has been widely spread and applied, but due to its short application time and the accumulation of related research, it continues to carry out life prediction to improve the related operation and maintenance system. The article proposes the environmental protection gas switchgear data processing technology based on data enhancement technology, proposes the environmental protection gas switchgear life prediction technology based on approximate dynamic planning, and verifies the algorithm through case analysis, which proves the effectiveness and accuracy of the proposed method.

Hemihydrate phosphogypsum (HPG), obtained as a cementitious material from the dewatering of phosphogypsum, can be widely used in the preparation of construction materials owing to its low cost and environmental friendliness. However, current reports on HPG mainly focus on hydration behavior, mechanical properties, and durability, and there are few studies focusing on the enhancement of HPG toughness. In this work, glass fibers (GF) and fly ash (FA), as composite reinforcement, were mixed with HPG during its preparation to obtain eco-friendly, high-toughness gypsum. The workability, mechanical, microstructural, financial and environmental properties of the HPG-based composites with different GF volume dosages (0, 0.5, 1.0, and 1.5 vol%) and FA weight percentages (0, 10, 20, and 30 wt%) were comparatively investigated. The results show that the addition of an appropriate amount of FA can improve the interface transition zone between GF and the matrix and effectively increase the flexural strength and toughness of the composites. For the optimal mixture containing 1.5 vol% GF and 20 wt% FA, the flexural strength and toughness were 50.7% and 82.2% higher, respectively, than those of the mixture without FA and 99.2% and 675.3% higher, respectively, than those of the control sample (without GF and FA). Cost-benefit and environmental impact analyses also indicated that this composite was the most economical and environmentally friendly. Thus, this work provides an effective approach to achieve the high-value utilization of two major industrial by-products.

Abstract Background Diarrheal diseases caused by viral agents have led to a great morbidity, mortality, and economic loss in global pig industry. Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and group A porcine rotavirus (RVA) are main causative agents of swine viral diarrhea with similar clinical signs on Chinese farms and their co-infection is also common. However, it is still lack of a convenient method to detect these four agents. Methods A TaqMan multiplex qPCR method was developed to detect PEDV, TGEV, PDCoV, and RVA, simultaneously. This method was then applied to investigate 7,342 swine fecal samples or rectal swabs, as well as 1,246 swine intestinal samples collected from 2075 farms in China in 2022. Results Minimum detection limits of this method were 3 copies/µL for PEDV, 4 copies/µL for TGEV, 8 copies/µL for RVA, and 8 copies/µL for PDCoV, suggesting a good sensitivity. No signals were observed by using this method detecting other viral agents commonly prevalent in pigs, which is suggestive of a good specificity. Application of this method on investigating clinical samples demonstrated a relatively high positive rate for PEDV (22.21%, 1907/8588) and RVA (44.00%, 3779/8588). In addition, co-infection between PEDV and RVA was observed on 360 investigated farms, accounting for 17.35% (360/2075) of the farms where co-infection events were screened. Conclusions A TaqMan multiplex qPCR method targeting PEDV, TGEV, PDCoV, and RVA was developed in this study. This method demonstrated a good specificity and sensitivity on investigating these four common viruses responsible for viral diarrhea on Chinese pig farms, which represents a convenient method for the monitoring and differential diagnosis of swine viral diarrhea.

The massive use of antibiotics has led to the aggravation of bacterial resistance and also brought environmental pollution problems. This poses a great threat to human health. If the dosage of antibiotics is reduced by increasing its bactericidal performance, the emergence of drug resistance is certainly delayed, so that there's not enough time for developing drug resistance during treatment. Therefore, we selected typical representative materials of metal Ag and semiconductor ZnO nano-bactericides to design and synthesize Ag/ZnO hollow core–shell structures (AZ for short). Antibiotics are grafted on the surface of AZ through rational modification to form a composite sterilization system. The research results show that the antibacterial efficiency of the composite system is significantly increased, from the sum (34.7% + 22.8% = 57.5%) of the antibacterial efficiency of AZ and gentamicin to 80.2%, net synergizes 22.7%, which fully reflects the effect of 1 + 1 > 2. Therefore, the dosage of antibiotics can be drastically reduced in this way, which makes both the possibility of bacterial resistance and medical expenses remarkably decrease. Subsequently, residual antibiotics can be degraded under simple illumination using AZ-self as a photocatalyst, which cuts off the path of environmental pollution. In short, such an innovative route has guiding significance for drug resistance.

One of the main diseases that adversely impacts the global citrus industry is citrus bacterial canker (CBC), caused by the bacteria Xanthomonas citri subsp. citri (Xcc). Response to CBC is a complex process, with both protein-DNA as well as protein–protein interactions for the regulatory network. To detect such interactions in CBC resistant regulation, a citrus high-throughput screening system with 203 CBC-inducible transcription factors (TFs), were developed. Screening the upstream regulators of target by yeast-one hybrid (Y1H) methods was also performed. A regulatory module of CBC resistance was identified based on this system. One TF (CsDOF5.8) was explored due to its interactions with the 1-kb promoter fragment of CsPrx25, a resistant gene of CBC involved in reactive oxygen species (ROS) homeostasis regulation. Electrophoretic mobility shift assay (EMSA), dual-LUC assays, as well as transient overexpression of CsDOF5.8, further validated the interactions and transcriptional regulation. The CsDOF5.8–CsPrx25 promoter interaction revealed a complex pathway that governs the regulation of CBC resistance via H2O2 homeostasis. The high-throughput Y1H/Y2H screening system could be an efficient tool for studying regulatory pathways or network of CBC resistance regulation. In addition, it could highlight the potential of these candidate genes as targets for efforts to breed CBC-resistant citrus varieties.

Abstract Increased global floating populations is an important driver of local social‐ecological systems change, especially in ecologically fragile areas. However, the limitations of accurate data and specific methods have prevented the exploration of spatial visitation of floating populations and its risk of negative effects on fragile ecosystems. Here, we contribute to filling the knowledge gap in Tibet by adopting large‐scale geolocation data and incorporating factors such as landscape aesthetic value, ecological vulnerability and traffic accessibility. We found that 89.97% of the digital footprints of floating populations in Tibet have entered nature areas with low density of resident population, and 40.57% of them have entered ecologically fragile areas, leading to increased ecological risks. Nature‐based tourism is the main motive for floating populations to enter the ecologically fragile areas, accounting for 65.56%. The central government inadvertently exacerbated ecological risks by leading road construction, resulting in 64.62% of the ecological risks being located in areas with high traffic accessibility. The floating populations entering Tibet have the dual effects of promoting economic development and causing ecological risks. Therefore, it is urgent to put forward strategies to promote the sustainable development in Tibet based on the complex system of “nature‐based tourism–ecological protection–economic income–government behavior”. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease characterized by clinical and pathological diversity. Mitochondrial dysfunction has been identified as a critical pathogenetic factor in SLE. However, the specific molecular aspects and regulatory roles of this dysfunction in SLE are not fully understood. Our study aims to explore the molecular characteristics of mitochondria-related genes (MRGs) in SLE, with a focus on identifying reliable biomarkers for classification and therapeutic purposes. Methods We sourced six SLE-related microarray datasets (GSE61635, GSE50772, GSE30153, GSE99967, GSE81622, and GSE49454) from the Gene Expression Omnibus (GEO) database. Three of these datasets (GSE61635, GSE50772, GSE30153) were integrated into a training set for differential analysis. The intersection of differentially expressed genes with MRGs yielded a set of differentially expressed MRGs (DE-MRGs). We employed machine learning algorithms—random forest (RF), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) logistic regression—to select key hub genes. These genes’ classifying potential was validated in the training set and three other validation sets (GSE99967, GSE81622, and GSE49454). Further analyses included differential expression, co-expression, protein-protein interaction (PPI), gene set enrichment analysis (GSEA), and immune infiltration, centered on these hub genes. We also constructed TF-mRNA, miRNA-mRNA, and drug-target networks based on these hub genes using the ChEA3, miRcode, and PubChem databases. Results Our investigation identified 761 differentially expressed genes (DEGs), mainly related to viral infection, inflammatory, and immune-related signaling pathways. The interaction between these DEGs and MRGs led to the identification of 27 distinct DE-MRGs. Key among these were FAM210B, MSRB2, LYRM7, IFI27, and SCO2, designated as hub genes through machine learning analysis. Their significant role in SLE classification was confirmed in both the training and validation sets. Additional analyses included differential expression, co-expression, PPI, GSEA, immune infiltration, and the construction of TF-mRNA, miRNA-mRNA, and drug-target networks. Conclusions This research represents a novel exploration into the MRGs of SLE, identifying FAM210B, MSRB2, LYRM7, IFI27, and SCO2 as significant candidates for classifying and therapeutic targeting.

Investigating the spatiotemporal variation of human activity intensity and its determinants is a crucial basis for further revealing the mechanism of human-environment interaction and optimizing the human development mode. In this study, the human activity intensity on the Qinghai–Tibet Plateau (QTP) from 1990 to 2020 was measured based on the quantitative model of land use data and the actual regional background, and the underlying natural and socioeconomic determinants were investigated using spatial econometric methods. The results demonstrate that (1) the human activity intensity in QTP has increased by 11.96%, and there are differences in different spatial scales; the areas with high human activity intensity are distributed in the Hehuang Valley where Xining City and its surrounding areas are located, as well as the One-River and Two-River Area where Lhasa City and surrounding areas are located. (2) Human activity intensity has significant positive spatial spillover, suggesting that local changes will cause changes in the same direction in adjacent areas. (3) The human activity intensity in QTP is affected by various determinants. Concerning socioeconomic factors, the economic level has no significant impact on the human activity intensity in QTP, which differs from the general regional law. Both urbanization and traffic conditions have a significant positive effect, and the impact intensity continues to increase. Concerning natural factors, topographic relief has a significant positive effect; the impacts of temperature and vegetation coverage have changed from insignificant to a significant positive effect; the impacts of precipitation and river network density have not been verified; there is no linear relationship between altitude and human activity intensity in the entire QTP, while it exists in local regions. Finally, this study proposes three policy implications for the realization of a more harmonious human-environment relationship in QTP.

Abstract Vaccination is a fundamental tool in preventing infectious diseases. However, due to the wide array of vaccines available, comprehending the entire vaccine landscape can be a daunting task. To tackle this complexity, this study employs advanced network analysis methods capable of capturing the intricate relationships within multivariate datasets. The objective is to investigate how the vaccination landscape has evolved both before and after the COVID-19 pandemic. This study examined vaccination data in the Nanan District of Chongqing, China, spanning from 2016 to 2022. Additionally, the network topological characteristics were computed and scrutinized across 2326 sliding windows. The investigation focused on assessing alterations in the topological structure of the vaccination network before and after the COVID-19 pandemic, encompassing analyses at both macro and mesoscale levels. Furthermore, at the micro level, this study delved into the correlation degrees of selected vaccine nodes within the vaccination network. The analysis unveiled that the correlation and activity within the vaccination network showed a noticeable enhancement in strength in the wake of the COVID-19 pandemic, especially during the spring and winter months. However, the community structure and the average interactions between vaccines displayed a diminishing trend post-pandemic. Among the analyzed vaccines, the HepA vaccine emerged as the one with the highest average node-degree centrality rank. A closer examination of the node-degree centrality ranking chart within the vaccination network disclosed fluctuations in the rankings of various vaccine types across different time periods and seasons. In contrast, vaccines incorporated into NIP exhibited a remarkable degree of consistency, which is attributed to children adhering to a fixed vaccination schedule, rendering NIP vaccines less susceptible to disruptions and enhancing their stability within the vaccination network. This study offers valuable insights into the dynamics of the vaccination network, shedding light on the impact of the COVID-19 pandemic, seasonal variations, and the ever-shifting correlation patterns among different vaccine types. These discoveries enrich our comprehension of vaccination trends and have the potential to guide forthcoming endeavors aimed at refining vaccination strategies and enhancing public health outcomes, not only in the Nanan District but also in analogous settings.

Abstract Aims Atrial fibrillation (AF) and heart failure (HF) often co‐exist and are closely intertwined. The impact of AF on the outcome of patients with heart failure with mildly‐reduced ejection fraction (HFmrEF) is not fully clear. This study aimed to investigate the impact of AF on the outcomes of hospitalized HFmrEF patients. Methods and results The study included 1691 consecutive patients with HFmrEF (mean 68.2 years, 64.8% male) including 296 AF patients. Patients completed 1 year and mean of 33 month clinical follow‐up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was cerebro‐cardiovascular events (CCE, composite of HF rehospitalization, stroke, or cardiovascular death). After propensity score matching, 296 patients were included into the AF group (mean 71.5 years) and 592 patients into the non‐AF group (mean 70.6 years). After propensity score matching, CCE at 1 year (59.1% vs. 48.5%, P = 0.003) and at a mean of 33 month (77.0% vs. 70.6%, P = 0.043). AF was independently associated with increased CCE within 1 year (HR = 1.31, 95% CI 1.07 to 1.61, P = 0.010) and at 33 months (HR = 1.20, 95% CI 1.00 to 1.43, P = 0.050) post‐discharge after adjusted for other clinical confounders including discharge heart rate, NT‐proBNP, haemoglobin, and uric acid. Conclusions AF is independently associated with an increased risk of CCE in HFmrEF patients within 1 year and at a mean of 33 months after discharge.

In optical remote sensing image object detection, discontinuous boundaries often limit detection accuracy, particularly at high Intersection over Union (IoU) thresholds. This paper addresses this issue by proposing the Spatial Adaptive Angle-Aware (SA3) Network. The SA3 Network employs a hierarchical refinement approach, consisting of coarse regression, fine regression, and precise tuning, to optimize the angle parameters of rotated bounding boxes. It adapts to specific task scenarios using either class-aware or class-agnostic strategies. Experimental results demonstrate its effectiveness in significantly improving detection accuracy at high IoU thresholds. Additionally, we introduce a Gaussian transform-based IoU factor during angle regression loss calculation, leading to the development of Edge-aware Skewed Bounding Box Loss (EAS Loss). The EAS loss enhances the loss gradient at the final stage of angle regression for bounding boxes, addressing the challenge of further learning when the predicted box angle closely aligns with the real target box angle. This results in increased training efficiency and better alignment between training and evaluation metrics. Experimental results show that the proposed method substantially enhances the detection accuracy of ReDet and ReBiDet models. The SA3 Network and EAS loss not only elevate the mAP of the ReBiDet model on DOTA-v1.5 to 78.85% but also effectively improve the model’s mAP under high IoU threshold conditions.

Cell chirality is crucial for the chiral morphogenesis of biological tissues, yet its underlying mechanism remains unclear. Cell organelle polarization along multiple axes in a cell body, namely, apical–basal, front–rear, and left–right, is known to direct cell behavior such as orientation, rotation, and migration. Among these axes, the left–right bias holds significant sway in determining the chiral directionality of these behaviors. Normally, mouse myoblast (C2C12) cells exhibit a strong counterclockwise chirality on a ring-shaped micropattern, whereas they display a clockwise dominant chirality under Latrunculin A treatment. To investigate the relationship between multicellular chirality and organelle positioning in single cells, we studied the left–right positioning of cell organelles under distinct cell chirality in single cells via micropatterning technique, fluorescent microscopy, and imaging analysis. We found that on a “T”-shaped micropattern, a C2C12 cell adopts a triangular shape, with its nucleus–centrosome axis pointing toward the top-right direction of the “T.” Several other organelles, including the Golgi apparatus, lysosomes, actin filaments, and microtubules, showed a preference to polarize on one side of the axis, indicating the universality of the left–right asymmetrical organelle positioning. Interestingly, upon reversing cell chirality with Latrunculin A, the organelles correspondingly reversed their left–right positioning bias, as suggested by the consistently biased metabolism and contractile properties at the leading edge. This left–right asymmetry in organelle positioning may help predict cell migration direction and serve as a potential marker for identifying cell chirality in biological models.

Proliferative enteropathy caused by Lawsonia intracellularis is an important economic associated disease to pig industry, but the knowledge about the prevalence of L. intracellularis in pig farms in China is limited. In addition, there is no complete genome sequence available for L. intracellularis isolates from China. In this study, we developed a TaqMan qPCR for the screening of L. intracellularis by targeting the bacterial 16S rDNA gene. Laboratory evaluations revealed a good sensitivity and specificity on detecting L. intracellularis nucleic acid. Using this method, we investigated 891 fecal samples from apparently healthy pigs in 47 farms. The results demonstrated a screening positive rate of 37.3% (95% CI, 34.1–40.5%) for the samples, and a farm screening positive rate of 93.6% (95% CI, 65.3–94.4%). The screening positive rate at herd level ranged from 6.67% (95% CI, 0.2–31.9%) to 40% (95% CI, 38–79.6%), while at animal level, the highest screening positive rate was found in 12-week-old pigs [85.7% (95% CI, 67.3–96.0%)]. Investigation of 705 diarrheal or bloody feces from symptomatic pigs revealed that the highest positive rate was found in replacement gilts which was 37.18% (95% CI, 45.1–89.5%). Secondly, we conducted the complete genome sequence of a L. intracellularis PPE-GX01-2022 from China through PacBio sequencing. The genome of PPE-GX01-2022 consisted of a chromosome of 1,439,110 bp in length and three plasmids of 193,063, 39,799, and 27,067 bp, respectively. This genome encoded 1,428 predicted proteins, 44 tRNAs, and 6 rRNAs. Sequence comparisons demonstrated that the genome sequence of PPE-GX01-2022 was highly homologous to those of two isolates from US, and these three isolates shared 1,378 core genes. The screening results suggest a high prevalence rate of L. intracellularis in Chinese pig farms. In addition, the genome sequence of the Chinese isolate was highly homologous to those of the field isolates from the US.

Objective Gastrointestinal (GI) involvements were scarcely reported in adult anti-nuclear matrix protein 2 (NXP2) dermatomyositis (NXP2+DM). In this study, we investigated the clinical, pathological and molecular features as well as treatment options of this rare yet life-threatening disease.Methods We retrospectively collected the data of the cohort of NXP2+ DM from 2012 to 2022 in our hospital. RNA sequencing was performed in intestinal samples of perforated patients compared with healthy controls data set.Results A total of 56 patients with adult NXP2+DM were collected including 10 cases with GI involvements. Abdominal pain and melena were the initial manifestations for GI involvements with a median 10-month time lag after the diagnosis of NXP2+DM when myositis largely subsided. Within weeks, GI perforation occurred in 8 of 10 patients, while five patients underwent eight surgical interventions subsequently. The short-term mortality was observed in four patients. NXP2+DM with GI involvements presented with more extramuscular systemic manifestations such as interstitial lung disease and subcutaneous calcinosis. The GI pathological features encompassed vasculitis/vasculopathy with high MxA expression, intestinal smooth muscle necrosis and serosal calcinosis. Gene expression profile validated the type-I interferon activation and revealed that epithelial mesenchymal transition and focal adhesion pathway may also contribute. Finally, vedolizumab, an anti-α4β7-integrin monoclonal antibody, exhibited promising therapeutic signals which should be further investigated.Conclusions GI involvement is a unique complication in patients with adult NXP2+DM. Timely recognition and targeted therapy may turn out to be lifesaving.

Determination of the cracking behavior during crack propagation helps to better understand damage and fracture processes in brittle rocks. The paper studies the cracking behavior of rocks on three scales: macro-deformation (or macro-cracking), internal micro-fracture, and surface crack coalescence. Under uniaxial compression, the cracking behavior of two types of sandstone specimens having single flaws was experimentally and systematically investigated. Acoustic emission (AE) and three-dimensional digital image correlation (3D-DIC) techniques were utilized to continuously monitor the acoustic shock signals generated by micro-fracture events inside the specimen and the specimen surface cracking process. The experimental results show that at the crack initiation stage, many micro-tensile fractures within the rock are initiated and coalesced, and small strain localized zones (SLZs) appear on the specimen surface. In the crack propagation stage, micro-fractures coalesce into macro-fractures that propagate in tensile mode to form surface cracks, which finally break in tension or slide against each other in shear mode. The formation of SLZs is related to the dip angle of pre-existing flaws, which determines the direction and mode of crack propagation. In conclusion, the strong acoustic-optical evidence accompanying different cracking behaviors is discussed in detail. From both acoustic and optical perspectives, it reveals and explains how flaws and material properties affect the strength and cracking mechanisms of brittle rocks. The study aids comprehension of the potential relation between internal micro-fracture and surface cracking in the process of engineering rock mass failure.

The Guangdong-Hong Kong-Macao Greater Bay Area (GBA) represents a significant economic zone with a diverse financial landscape. Understanding the spatial distribution of financial resources within this area is crucial for promoting balanced economic growth and financial development. This study investigates the spatial patterns of financial agglomeration in the GBA, identifying key influencing factors and assessing their impact on the region's financial landscape. We employ the entropy value method to evaluate financial agglomeration levels across the GBA's cities. Additionally, we use spatial econometric techniques to analyze the spatial correlations and the Geo-Detector model to determine the primary factors influencing financial agglomeration. The analysis reveals an overall increase in financial agglomeration, with significant disparities among cities. Key factors driving this agglomeration include transportation infrastructure, overseas trade, foreign direct investment (FDI), and technological advancements. Hong Kong and Shenzhen display notable unevenness in the distribution of financial industries. The interplay between finance, technology, and industrial sectors suggests considerable development potential. Understanding and optimizing the spatial distribution of financial resources is essential for fostering high-quality financial development and sustainable economic growth in the GBA. This study provides insights that can inform policy decisions aimed at enhancing financial integration and cooperation within the region.

Abstract Background Worsening of heart failure (HF) symptoms is the leading cause of medical contact and hospitalization of patients with mildly reduced ejection fraction (HFmrEF). The prognostic value of signs and symptoms for patients with HFmrEF is currently unclear. This study investigated the prognostic impact of signs and symptoms in HFmrEF patients. Methods A Cox proportional risk regression model analyzed the relationship between the number of signs/symptoms and outcomes in 1691 hospitalized HFmrEF patients. Ten significant signs and symptoms were included. Patients were divided into three groups (A: ≤2, B: 3–5, C: ≥6 signs/symptoms). Stratified analysis on male and female patients was performed. The primary endpoint was all-cause mortality, and the secondary outcome was a composite of cardiovascular death and heart failure readmission (CV events) post-discharge. Results After a median follow-up of 33 months, all-cause mortality occurred in 457 patients and CV events occurred in 977 patients. Incidence of all-cause mortality was 20.7%, 32.3%* and 49.4%*† in group A, B and C of male patients, (*P

Abstract Papillary thyroid carcinoma (PTC) is one of the most common thyroid carcinomas. The gross extrathyroidal extension and extensive metastases of PTC lead to high rates of recurrence and poor clinical outcomes. However, the mechanisms underlying PTC development are poorly understood. In this study, using single-cell RNA sequencing, the transcriptome profiles of two PTC patients were addressed, including PTC1 with low malignancy and good prognosis and PTC2 with high malignancy and poor prognosis. We found that epithelial subcluster Epi02 was the most associated with the malignant development of PTC cells, with which the fold change of Chitinase 3-like 1 (CHI3L1) is on the top of the differentially expressed genes between PTC1 and PTC2 (P

With the increase in regional economic development disparities, a regional coordinated development strategy is put forward that prioritizes human welfare and holistic social progress over a purely materialistic growth model. To address the challenges of balanced regional development, this paper has developed a multidimensional assessment framework of social development encompassing education, healthcare, culture, and social security. Using the entropy weight TOPSIS method, this study measures the social development level across 296 Chinese prefecture-level cities from 1990 to 2020. It explores the spatio-temporal evolution characteristics of China’s social development level through the Dagum Gini coefficient decomposition method and exploratory spatial data analysis. The results indicate that (1) the level of social development in China exhibits a fluctuating upward trend over the time series, showing a phase-wise pattern of decline–rise–rise; (2) there is a clear heterogeneity in the level of social development, with a general hierarchy of Eastern, Northeastern, Western, and Central regions in terms of social development; (3) spatially, China’s social development level has evolved from a patchy distribution in 1990 to a clustered distribution around urban agglomerations by 2020, with pronounced characteristics of spatial imbalance; (4) the level of social development in China displays varying degrees of spatial clustering, with this trend intensifying over time; and (5) over the period 1990–2020, the overall disparity in China’s social development level presents a fluctuating trend, with a notable reduction after an initial increase, and regional disparities following the order of Central, Western, Eastern, and Northeastern regions. This research offers valuable insights for policymakers and scholars seeking to understand and enhance China’s social development landscape.

Path planning is an indispensable component in guiding unmanned ground vehicles (UGVs) from their initial positions to designated destinations, aiming to determine trajectories that are either optimal or near-optimal. While conventional path-planning techniques have been employed for this purpose, planners utilizing reinforcement learning (RL) exhibit superior adaptability within exceedingly complex and dynamic environments. Nevertheless, existing RL-based path planners encounter several shortcomings, notably, redundant map representations, inadequate feature extraction, and limited adaptiveness across diverse environments. In response to these challenges, this paper proposes an innovative and highly self-adaptive path-planning approach based on Transformer encoder feature extraction coupled with incremental reinforcement learning (IRL). Initially, an autoencoder is utilized to compress redundant map representations, providing the planner with sufficient environmental data while minimizing dimensional complexity. Subsequently, the Transformer encoder, renowned for its capacity to analyze global long-range dependencies, is employed to capture intricate correlations among UGV statuses at continuous intervals. Finally, IRL is harnessed to enhance the path planner’s generalization capabilities, particularly when the trained agent is deployed in environments distinct from its training counterparts. Our empirical findings demonstrate that the proposed method outperforms traditional uniform-sampling-based approaches in terms of execution time, path length, and trajectory smoothness. Furthermore, it exhibits a fivefold increase in adaptivity compared to conventional transfer-learning-based fine-tuning methodologies.

Abstract Introduction Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions with high morbidity and mortality and not clearly established treatment protocol. This meta-analysis aimed to evaluate the efficacy and safety of three biologic TNF-α inhibitors (infliximab, etanercept, adalimumab) in the treatment of SJS, SJS-TEN overlap, and TEN. Methods Electronic databases were searched for original studies containing human participants diagnosed with SJS/TEN and treated with biologic TNF-α inhibitors. Individual patient data were collected and summarized to provide a comprehensive overview on therapeutic efficacy of different biologic TNF-α inhibitors for SJS, SJS-TEN overlap, and TEN, respectively. Meta-analyses on aggregated study data were conducted using random-effects model. Results Overall, 55 studies with 125 sets of individual patient data were included. Infliximab was used to treat 3 patients with SJS-TEN overlap and 28 patients with TEN, and the actual mortality rate was 33.3% and 17%, respectively. Etanercept was administered to 17 patients with SJS, 9 patients with SJS-TEN overlap, and 64 patients with TEN, and mortality rate was reported to be 0%, 0%, and 12.5%, respectively. For participants with TEN, no significant difference was found in time of reepithelialization, hospitalization time, and mortality rate comparing etanercept with infliximab. More sequelae were reported in patients receiving infliximab than in patients treated with etanercept (39.3% versus 6.4%). Adalimumab was administered to four patients with TEN, and mortality rate was 25%. Meta-analyses on aggregated study data revealed significantly shortened hospitalization time in etanercept compared with non-etanercept groups [weighted mean differences (WMD) −5.30; 95% confidence interval (CI) −8.65 to −1.96]. Etanercept was associated with a survival benefit for patients when compared with non-etanercept treatment, however, the analysis was not statistically significant (odds ratio 0.55; 95% CI 0.23–1.33). Conclusions On the basis of the current findings, etanercept is currently the most promising biologic therapy for SJS/TEN. Further evaluation in prospective studies is required to confirm its efficacy and safety.

Abstract We demonstrate that superconducting gatemon qubits based on superconductor-semiconductor-superconductor Josephson junctions can be constructed on hole-type Ge/Si core/shell nanowires. The frequency of the qubit can be set firstly by controlling the diffusion of Al in the nanowire via thermal annealing, which yields a suitable critical supercurrent allowing the qubit frequency to be within the experimentally accessible range, and then by fine tuning of a gate voltage, by which an accurate adjustment of the frequency can be realized. On the resulted qubit, Rabi oscillation with an energy relaxation time $${T}_{1} \sim 180\,{\rm{ns}}$$ T 1 ~ 180 ns was observed in the time domain, an average decoherence time $${T}_{2}^{* } \sim 15\,{\rm{ns}}$$ T 2 * ~ 15 ns was obtained, and the gate voltage dependence of both $${T}_{1}$$ T 1 and $${T}_{2}^{* }$$ T 2 * was investigated. Such a hole-type superconducting gatemon qubit, based on materials with strong spin-orbit coupling and potentially the absence of hyperfine interaction after isotope purification, could be used for exploring the quantum coherence phenomena of hole-gas and even Majorana physics in Ge-based quantum devices.

Abstract Clinical studies on heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) have gradually increased. However, studies on the prognostic differences between men and women among patients with HFmrEF are few, and no evidence on sex differences in such patients exists. Therefore, we retrospectively assessed the data of patients with HFmrEF using propensity score-matched analysis (PSMA). A total of 1691 patients with HFmrEF were enrolled in the Outcome of Discharged HFmrEF Patients study (OUDI-HF study), which included 1095 men and 596 women. After propensity score matching, we compared the difference in cardiovascular (CV) events (cardiovascular death or heart failure readmission) and all-cause mortality at 90 days and 1 year after discharge between men and women using Kaplan–Meier analysis and Cox regression. After PSMA, men with HFmrEF were 2.2 times more likely to die at 90 days than women with HFmrEF [hazard ratio (HR) 1.88; 95% confidence interval (95% CI) 1.03–3.46; P = 0.041]. However, there was no difference in the 90-day CV events (HR 0.96; 95% CI 0.75–1.22; P = 0.718). Similarly, there was no difference in all-cause mortality (HR 1.16; 95% CI 0.81–1.65; P = 0.417) and CV events (HR 0.98; 95% CI 0.83–1.16; P = 0.817) between men and women after 1 year. Among the patients with HFmrEF, men had a higher 90-day risk of all-cause mortality than women after hospital discharge, and this risk disappeared after 1 year. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT05240118 (ESC Heart Failure. (2022). doi: https://doi.org/10.1002/ehf2.14044 ).

Objectives Prognostic impact of lung ultrasound-derived B-lines (LUS-BL) in heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) patients remains elusive. We evaluated the correlation between LUS-BL and prognosis in HFmrEF patients.Methods This is a subgroup analysis based on our previously published retrospective study with 1691 HFmrEF patients. This subgroup analysis involved 574 patients with LUS-BL results at admission. After discharge, patients underwent clinical follow-up for a minimum of 1 year through telephone, clinical visits or community visits. The primary endpoint was defined as cardiovascular (CV) event, including CV-related mortality or HF hospitalisation at 90 days and 1 year after discharge.Results CV event at 90 days was significantly increased with higher LUS-BL number (0, 1–2, 3–9 and ≥10: 20%, 14%, 18% and 33%, p=0.008), while CV event rate at 1 year was similar among groups (45% vs 45% vs 42% vs 50%, p=0.573). Older age, hypertension (HR=2.06, 95% CI 1.31 to 3.25), higher right ventricular diameter (>23 mm, HR=2.008, 95% CI 1.37 to 2.94), increased ratio of early transmitral flow velocity to early mitral annular velocity (>24, HR=1.79, 95% CI 1.11 to 2.26) and higher LUS-BL number (>11, HR=1.510, 95% CI 1.01 to 2.26) were identified as independent determinants associated with increased risk of CV event at 90 days after discharge. The Harrell’s C-Statistic analysis, based on the Cox regression models, demonstrated a significant improvement in the predictive ability of the model that incorporated both clinical and echocardiographic risk factors along with LUS-BL (areas under the curve (AUC)=0.72) compared with the model comprising only clinical risk factors and LUS-BL (AUC=0.69, p=0.036), or to the model with echocardiographic risk factors and LUS-BL (AUC=0.68, p=0.025).Conclusion In HFmrEF patients with ischaemic heart disease, admission LUS-BL>11 is independently associated with an increased risk of CV event at 90 days following discharge.

To maximize the expected profits and manage the risks of renewable energy system under electricity market environment, scenario-based- stochastic optimization model can be established to generate energy bidding strategies, in which the probabilistic scenarios of risk parameters are usually obtained by using statistical or machine learning methods. This paper proposes a practical multivariate statistical method for risk parameter scenario generation, which is used by a wind energy system faced with uncertain electricity prices and wind power productions, and it considers the correlation between dependent risk parameters by using historical data directly. The probabilities of scenarios containing correlated risk parameters are calculated by using multivariate histograms, in which the asymmetric correlation between different parameters existing in the historical data are preserved. Additionally, in order to make the stochastic optimization problem with large numbers of scenarios tractable, a multivariate scenario reduction method is used to trim down the scenario number. By solving the stochastic optimization problem, optimal day-ahead bidding curves for the wind energy system are generated, and Douglas–Peucker algorithm is used to fit the bidding curves according to market requirements. Case studies based on real world data in electricity markets are performed to prove the effectiveness of the proposed risk parameter scenario generation method and energy bidding strategies. Finally, conclusions and practical suggestions on future research works are provided.

Abstract Neural interfaces for stable access to the spinal cord (SC) electrical activity can benefit patients with motor dysfunctions. Invasive high‐density electrodes can directly extract signals from SC neuronal populations that can be used for the facilitation, adjustment, and reconstruction of motor actions. However, developing neural interfaces that can achieve high channel counts and long‐term intraspinal recording remains technically challenging. Here, a biocompatible SC hyperflexible electrode array (SHEA) with an ultrathin structure that minimizes mechanical mismatch between the interface and SC tissue and enables stable single‐unit recording for more than 2 months in mice is demonstrated. These results show that SHEA maintains stable impedance, signal‐to‐noise ratio, single‐unit yield, and spike amplitude after implantation into mouse SC. Gait analysis and histology show that SHEA implantation induces negligible behavioral effects and Inflammation. Additionally, multi‐unit signals recorded from the SC ventral horn can predict the mouse's movement trajectory with a high decoding coefficient of up to 0.95. Moreover, during step cycles, it is found that the neural trajectory of spikes and low‐frequency local field potential (LFP) signal exhibits periodic geometry patterns. Thus, SHEA can offer an efficient and reliable SC neural interface for monitoring and potentially modulating SC neuronal activity associated with motor dysfunctions.

Cancer is a devastating disease with a high global mortality rate and is projected to increase further in the coming years. Current treatment options, such as chemotherapy and radiation therapy, have limitations including side effects, variable effectiveness, high costs, and limited availability. There is a growing need for alternative treatments that can target cancer cells specifically with fewer side effects. Phages, that infect bacteria but not eukaryotic cells, have emerged as promising cancer therapeutics due to their unique properties, including specificity and ease of genetic modification. Engineered phages can transform cancer treatment by targeting cancer cells while sparing healthy ones. Phages exhibit versatility as nanocarriers, capable of delivering therapeutic agents like gene therapy, immunotherapy, and vaccines. Phages are extensively used in vaccine development, with filamentous, tailed, and icosahedral phages explored for different antigen expression possibilities. Engineered filamentous phages bring benefits such as built in adjuvant properties, cost-effectiveness, versatility in multivalent formulations, feasibility of oral administration, and stability. Phage-based vaccines stimulate the innate immune system by engaging pattern recognition receptors on antigen-presenting cells, enhancing phage peptide antigen presentation to B-cells and T-cells. This review presents recent phage therapy advances and challenges in cancer therapy, exploring its versatile tools and vaccine potential.

Viruses existed in wastewaters might pose a biosecurity risk to human and animal health. However, it is generally difficult to detect viruses in wastewater directly as they usually occur in low numbers in water. Therefore, processing large volumes of water to concentrate viruses in a much smaller final volume for detection is necessary. Glass wool has been recognized as an effective material to concentrate multiple in water, and in this study, we assessed the use of glass wools on concentrating pseudorabies virus (PRV), African swine fever virus (ASFV), and porcine epidemic diarrhea virus (PEDV) in water samples. The influence of pH values, water matrix, water volume, filtration rate, temperature on the effect of the method concentrating these viruses for detection was evaluated in laboratory. Our results revealed that glass wool was suitable for the concentration of above-mentioned viruses from different water samples, and demonstrated a good application effect for water with pH between 6.0–9.0. Furthermore, glass wool also showed a good recovery effect on concentrating viral nucleic acids and viral particles, as well as living viruses. In addition, combining use of glass wool with skim milk, polyethylene glycol (PEG)-NaCl, or ultracentrifuge had good effects on concentrating ASFV, PRV, and PEDV. Detection of wastewater samples (n = 70) collected from 70 pig farms in 13 regions across Hubei Province in Central China after glass-wool-concentration determined one sample positive for ASFV, eighteen samples positive for PRV, but no sample positive for PEDV. However, these positive samples were detected to be negative before glass wool enrichment was implemented. Our results suggest that glass wool-based water concentration method developed in this study represents an effective tool for detecting viruses in wastewater.

Despite their high surface reactivity, the gas sensor based on Co3O4 nanoparticles frequently suffers from a low response to volatile organic compounds (VOCs) due to high-temperature sintering and inefficient resistance modulation. Herein, halloysite nanotubes (HNTs) were incorporated as the additive into the Co3O4 nanoparticle matrix to enhance the sensing property toward VOCs in terms of gas response (Rg/Ra) and operation stability. Co3O4 nanoparticles intimately attached on HNTs were achieved by a facile deposition-precipitation method followed by calcination. The best-performing Co3O4/0.3HNTs-based sensor had a high gas response of 22.9 to 50 ppm triethylamine at 240 °C, which was 4.9 times than that of Co3O4 alone. The enhanced sensitivity could be attributed to the HNT incorporation that facilitated effective resistance modulation, surface property tuning, as well as surface defect formation. These results bring new insight into an enhancement of gas sensing property of a p-type metal oxide with insensitive materials. They also provide a potential to expand the application of aluminosilicate clays to gas sensors.

Wasted tofu rich in protein was subject to hydrothermal pretreatment (HTPT) under different conditions (at 120, 140, 160 and 180 ℃; for 0, 30, 60 and 90 min) followed by biochemical methane potential (BMP) tests, and 140 ℃ and 0 min were found to be respectively the best temperature and duration for HTPT of tofu in terms of its biogas production. Under the under the optimal conditions (140 ℃, 0 min) the accumulative methane yield reached up to 510.9 mL·(gVS)-1, which was 26.98 % higher than that without HTPT (402.3 mL·(gVS)-1). The start-up process of continuous anerobic digestion (AD) of the tofu before and after hydrothermal treated (HT) at the optimal HTPT conditions (140 ℃, 0 min) was examined, to investigate and compare how their consequent AD responded to HTPT. It was found that, for start-up of continuous AD, the HT tofu delivered more balanced nutrients and thus led to more stable AD and quicker biogas production. Unavoidably, HTPT generated products refractory to biodegradation, to slightly decrease the total biogas production. During AD of HT tofu some weak ammonia-tolerant microbes, such as methylotrophic methanogens, survived and played indispensable roles. Analyses of living microbial community structure indicated that, some hydrolytic acidification bacteria intolerant to ammonia nitrogen (such as Proteobacteria) were always active and appeared at high proportion. The viable methylotrophic methanogens, e. g. RumEn M2, took obvious responsibilities in start-up of the AD for HT tofu.

Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test. However, whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established. Therefore, in this study, we simulated perimenopausal depression via an ovariectomy in mice, and subjected them to a single 9-hour fasting 7 days later. We found that the ovariectomy increased the time spent immobile in the forced swimming test, inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefrontal cortex, and decreased the density of dendritic spines in the hippocampus. The 9-hour acute fasting alleviated the above-mentioned phenomena. Furthermore, all of the antidepressant-like effects of 9-hour fasting were reversed by an inhibitor of the mammalian target of rapamycin complex 1. Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting. These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus. Thus, fasting may be a potential treatment for depression.

Oxidative dehydrogenation of alkanes over boron nitride catalysts provides a new opportunity for efficient olefin production. Here, the authors discover in situ formed olefins can promote parent alkane conversion, and achieve activation of ethane by propane-derived olefins at a lower temperature.

Analyzing the spatio-temporal relationship between socio-economics and land-use structure at the micro-scale is crucial for effective spatial governance in large cities. This paper focuses on Beijing, utilizing long time-series remote sensing images and multi-source data spanning 30 years. We employ spatio-temporal clustering based on kilometer grid cells and a community-scale multi-factor aggregation method to categorize the linkages and spatio-temporal matching of population, GDP, land development, and ecological protection at the community level in a problem-oriented approach. Results indicate significant changes in Beijing’s population, GDP, and land use, with a 11.53% increase in land development intensity. We identify significant temporal and spatial disparities between population–GDP dynamics, population–land development trends, and GDP–land development patterns, underscoring the multifaceted challenges inherent in urban governance. Areas characterized by lagging population concentration, sluggish economic growth, rampant land development, and ecological fragility collectively encapsulate notable portions of Beijing’s expansive urban terrain. Mismatches pose governance risks, with medium to high-risk communities comprising 18.08% of community units and high-risk types representing 4.27% in Beijing. These discrepancies pose formidable governance risks, with communities ranging from moderate to high-risk categories, necessitating tailored interventions to address their unique challenges. This systematic exploration of comprehensive governance issues within mega-cities promises to furnish decision-makers with invaluable insights, facilitating nuanced and strategic urban governance approaches tailored to the intricacies of urban dynamics and challenges.

Citrus bacterial canker (CBC) is a severe bacterial infection caused by Xanthomonas citri subsp. citri (Xcc), which continues to adversely impact citrus production worldwide. Members of the GATA family are important regulators of plant development and regulate plant responses to particular stressors. This report aimed to systematically elucidate the Citrus sinensis genome to identify and annotate genes that encode GATAs and evaluate the functional importance of these CsGATAs as regulators of CBC resistance. In total, 24 CsGATAs were identified and classified into four subfamilies. Furthermore, the phylogenetic relationships, chromosomal locations, collinear relationships, gene structures, and conserved domains for each of these GATA family members were also evaluated. It was observed that Xcc infection induced some CsGATAs, among which CsGATA12 was chosen for further functional validation. CsGATA12 was found to be localized in the nucleus and was differentially upregulated in the CBC-resistant and CBC-sensitive Kumquat and Wanjincheng citrus varieties. When transiently overexpressed, CsGATA12 significantly reduced CBC resistance with a corresponding increase in abscisic acid, jasmonic acid, and antioxidant enzyme levels. These alterations were consistent with lower levels of salicylic acid, ethylene, and reactive oxygen species. Moreover, the bacteria-induced CsGATA12 gene silencing yielded the opposite phenotypic outcomes. This investigation highlights the important role of CsGATA12 in regulating CBC resistance, underscoring its potential utility as a target for breeding citrus varieties with superior phytopathogen resistance.

The disruption of endothelial heparan sulfate (HS) is an early event in tumor cell metastasis across vascular barriers, and the reinforcement of endothelial HS reduces tumor cell adhesion to endothelium. Our recent study showed that while vascular endothelial growth factor (VEGF) greatly reduces HS at an in vitro blood–brain barrier (BBB) formed by human cerebral microvascular endothelial cells (hCMECs), it significantly enhances HS on a breast cancer cell, MDA-MB-231 (MB231). Here, we tested that this differential effect of VEGF on the HS favors MB231 adhesion and transmigration. We also tested if agents that enhance endothelial HS may affect the HS of MB231 and reduce its adhesion and transmigration. To test these hypotheses, we generated an in vitro BBB by culturing hCMECs on either a glass-bottom dish or a Transwell filter. We first quantified the HS of the BBB and MB231 after treatment with VEGF and endothelial HS-enhancing agents and then quantified the adhesion and transmigration of MB231 across the BBB after pretreatment with these agents. Our results demonstrated that the reduced/enhanced BBB HS and enhanced/reduced MB231 HS increase/decrease MB231 adhesion to and transmigration across the BBB. Our findings suggest a therapeutic intervention by targeting the HS-mediated breast cancer brain metastasis.

Abstract Aims Clinical data on the prognostic determinants over varying periods within the same cohort of heart failure with mid‐range or mildly reduced ejection fraction (HFmrEF) remain scarce. This study aimed to identify the short‐term, intermediate‐term, and long‐term risk factors of adverse cardiovascular (CV) outcomes in patients hospitalized for HFmrEF. Methods and results This retrospective study included 1691 consecutive HFmrEF patients admitted to our hospital between January 2015 and August 2020. Baseline data including clinical characteristics, laboratory and cardiac imaging examinations were obtained. Patients completed at least 1 year clinical follow‐up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was defined as a composite of CV death or rehospitalization for heart failure (CV events) at 3, 12, and 33 months after the diagnosis of HFmrEF. Mean age of the whole cohort was 69 (61–77) years and 64.8% were male. The median clinical follow‐up was 33 (20–50) months. CV events were 17.5%, 28.2%, and 57.8% at 3, 12, and 33 months after discharge, respectively. Independent risk factors for CV events were uric acid >382 μmol/L, creatinine >100 μmol/L, N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) > 3368 pg/mL and haemoglobin 35 mmHg and the ratio of early transmitral flow velocity to early mitral annular velocity >18 served as independent risk factors for CV events at 12 months. At 33 months, uric acid > 382 μmol/L, NT‐proBNP >3368 pg/mL, and pulmonary artery systolic pressure >35 mmHg were the independent risk factors of CV events. Conclusions Higher uric acid, creatinine, NT‐proBNP, and lower haemoglobin levels at baseline are valuable serum biomarkers for risk stratification of short‐term and long‐term CV outcomes of HFmrEF patients. Future studies are needed to verify if intensive heart failure therapy for identified high‐risk HFmrEF patients based on these four serum biomarkers could improve their short‐term and long‐term CV outcomes or not.

Bacteria–algae consortia in the light bring the benefit of O2 production and CO2 reduction for wastewater treatment, while the bottleneck for application is how it behaves in the dark. In this study, inoculum ratio and sludge retention time (SRT) affected nutrient removal rather than chemical oxygen demand (COD) removal. Dark conditions (with a sludge/Chlorella inoculum ratio of 1:2 at a SRT of 15 d) achieved comparable performance to those of light conditions, due to bacteria contribution and mechanical aeration. Compared with light conditions, the ratio of Chla/Chlb decreased and Caro/(Chla + Chlb) increased to response oxidative stress. In the dark, algae were associated with Nitrosomonas and Dechloromonas. Flavobacterium disassociated with Chlorella in the dark but associated with Chlorella in the light. Moreover, nitritation genes (amo and Hao) and denitrifying gene (narH) were up-regulated, while P metabolism genes (PPX and PPK) were down-regulated. It is proposed to enrich Nitrosomonas in the night and denitrify polyphosphate accumulating organisms (DPAO) in the daytime to establish short-cut nitrification and denitrifying phosphorus removal in practical applications. HIGHLIGHTS Bacteria–algae inoculum ratio affected N and P removal, while SRT affected P removal.; Bacteria contributed more than algae towards COD, NH4+, and P removal.; Caro/(Chla + Chlb) increased and Chla/Chlb decreased.; Dark co-culture favored Nitrosomonas but was adverse to Flavobacterium.; N-related genes (amo, Hao, narH) were up-regulated, while P-related genes (PPX, PPK) were down-regulated.;

Abstract Natural disasters occur when environmental systems have a disruptive effect on the socio-economic system. In recent years, particular unreasonable human behaviours have amplified losses from natural disasters as result of the increasing complexity of human systems. Because of the lack of both quantitative calculation of this amplification, and analysis of the root cause of these behaviours, existing risk assessment and management research rarely includes unreasonable human behaviour as a critical factor. This study therefore creates three simulation scenarios, each based on a twenty-first-century catastrophe in China, and calculates the disaster losses that are amplified when such behaviour increases exposure (the 2008 Wenchuan earthquake), vulnerability (the 2014 Ludian earthquake) and hazard (the 2021 Zhengzhou rainstorm) levels. In doing so, it intuitively demonstrates the amplification effect caused by unreasonable human behaviour. The results show that these behaviours amplified disaster losses significantly: increased exposure due to unscientific planning nearly doubled the death toll in the Wenchuan earthquake; high vulnerability caused by the low economic level of residents increased the disaster losses of the Ludian earthquake more than tenfold; and the elevated hazard intensity caused by anthropogenic climate change resulted in a 1.44-times expansion of the area severely affected by the Zhengzhou rainstorm. These behaviours have become an important cause of disasters, and the main driving factors behind them—such as neglecting disaster risk; the inability to cope with disasters; and a lack of certainty about how to deal with extreme events—are the inevitable outcomes of societal development. On this basis, we constructed an extended risk framework that included unreasonable behavioural factors and a disaster mechanism, to analyse in depth the relationship between human behaviours and disaster risk prevention in different developmental stages. The results provide an important reference for the development of risk management policies to control these unreasonable behaviours.

Abstract Background Salmonella is a leading foodborne and zoonotic pathogen, and is widely distributed in different nodes of the pork supply chain. In recent years, the increasing prevalence of antimicrobial resistant Salmonella poses a threat to global public health. The purpose of this study is to the prevalence of antimicrobial resistant Salmonella in pig slaughterhouses in Hubei Province in China, and explore the effect of using lytic bacteriophages fighting against antimicrobial resistant Salmonella. Results We collected a total of 1289 samples including anal swabs of pigs (862/1289), environmental swabs (204/1289), carcass surface swabs (36/1289) and environmental agar plates (187/1289) from eleven slaughterhouses in seven cities in Hubei Province and recovered 106 Salmonella isolates. Antimicrobial susceptibility testing revealed that these isolates showed a high rate of antimicrobial resistance; over 99.06% (105/106) of them were multidrug resistant. To combat these drug resistant Salmonella, we isolated 37 lytic phages using 106 isolates as indicator bacteria. One of them, designated ph 2–2, which belonged to the Myoviridae family, displayed good capacity to kill Salmonella under different adverse conditions (exposure to different temperatures, pHs, UV, and/or 75% ethanol) and had a wide lytic spectrum. Evaluation in mouse models showed that ph 2–2 was safe and saved 80% (administrated by gavage) and 100% (administrated through intraperitoneal injection) mice from infections caused by Salmonella Typhimurium. Conclusions The data presented herein demonstrated that Salmonella contamination remains a problem in some pig slaughter houses in China and Salmonella isolates recovered in slaughter houses displayed a high rate of antimicrobial resistance. In addition, broad-spectrum lytic bacteriophages may represent a good candidate for the development of anti-antimicrobial resistant Salmonella agents.

Summary: During chronic viral infection and cancer, it has been established that a subset of progenitor CD8+ T cells continuously gives rise to terminally exhausted cells and cytotoxic effector cells. Although multiple transcriptional programs governing the bifurcated differentiation trajectories have been previously studied, little is known about the chromatin structure changes regulating CD8+ T cell-fate decision. In this study, we demonstrate that the chromatin remodeling complex PBAF restrains expansion and promotes exhaustion of CD8+ T cells during chronic viral infection and cancer. Mechanistically, transcriptomic and epigenomic analyses reveal the role of PBAF in maintaining chromatin accessibility of multiple genetic pathways and transcriptional programs to restrain proliferation and promote T cell exhaustion. Harnessing this knowledge, we demonstrate that perturbation of PBAF complex constrained exhaustion and promoted expansion of tumor-specific CD8+ T cells resulting in antitumor immunity in a preclinical melanoma model, implicating PBAF as an attractive target for cancer immunotherapeutic.

ObjectivesMass vaccination campaigns can rapidly increase the vaccination rate for the COVID-19 vaccine, the establishment of mass vaccination centers is indispensable. At the beginning of March 2021, China began to carry out COVID-19 vaccination activities nationwide. Here, we aimed to evaluate the criteria established by mass vaccination centers, COVID-19 vaccination experience, the incidence of adverse events following immunization and opinions.MethodsWe describe the layout and functioning of Nan’an District mass vaccination center, the working mechanism, experience and effectiveness. Distribution of COVID-19 vaccine vaccination and adverse events following immunization reported in the mass vaccination center of Nan’an District were evaluated.ResultsFrom March 26, 2021 to April 28, 2022, the mass vaccination center has inoculated about 381,364 doses of COVID-19 vaccine to the population. The study found that the incidence of adverse events following immunization (AEFI) was very low (1.04/100000). The chances of having AEFI were significantly higher in COVID-19 vaccine (CHO cell) than COVID-19 vaccine (Vero cell).ConclusionThe mass vaccination center was running successfully. It was effective and safe, providing vaccination services and increasing COVID-19 vaccination rates among the population. The experience of the mass vaccination center for COVID-19 in China can provide a reference for other countries and regions to carry out COVID-19 vaccination.

Neutrophil extracellular traps (NETs) is an important process involved in the pathogenesis of systemic lupus erythematosus (SLE), but the potential mechanisms of NETs contributing to SLE at the genetic level have not been clearly investigated. This investigation aimed to explore the molecular characteristics of NETs-related genes (NRGs) in SLE based on bioinformatics analysis, and identify associated reliable biomarkers and molecular clusters. Dataset GSE45291 was acquired from the Gene Expression Omnibus repository and used as a training set for subsequent analysis. A total of 1006 differentially expressed genes (DEGs) were obtained, most of which were associated with multiple viral infections. The interaction of DEGs with NRGs revealed 8 differentially expressed NRGs (DE-NRGs). The correlation and protein-protein interaction analyses of these DE-NRGs were performed. Among them, HMGB1, ITGB2, and CREB5 were selected as hub genes by random forest, support vector machine, and least absolute shrinkage and selection operator algorithms. The significant diagnostic value for SLE was confirmed in the training set and three validation sets (GSE81622, GSE61635, and GSE122459). Additionally, three NETs-related sub-clusters were identified based on the hub genes’ expression profiles analyzed by unsupervised consensus cluster assessment. Functional enrichment was performed among the three NETs subgroups, and the data revealed that cluster 1 highly expressed DEGs were prevalent in innate immune response pathways while that of cluster 3 were enriched in adaptive immune response pathways. Moreover, immune infiltration analysis also revealed that innate immune cells were markedly infiltrated in cluster 1 while the adaptive immune cells were upregulated in cluster 3. As per our knowledge, this investigation is the first to explore the molecular characteristics of NRGs in SLE, identify three potential biomarkers (HMGB1, ITGB2, and CREB5), and three distinct clusters based on these hub biomarkers.

Abstract Lignin is a renewable bioresource that can be used for a variety of value-added applications. However, the effective separation of lignin from lignocellulosic biomass remains an ongoing challenge. In this study, lignin was extracted from waste palm fiber and successfully converted into a dehumidifying material. The following four process parameters of lignin extraction from palm fiber were optimized systematically and comprehensively using the response surface methodology: reaction time, extraction temperature, ethanol concentration and solid/liquid ratio. The results revealed that under the optimum processing conditions (111 min of extraction at 174 °C using 73% ethanol at 1/16 g/mL solid/liquid ratio), the extraction yield of lignin was 56.2%. The recovery of ethanol solvent was as high as 91.8%. Further, the lignin could be directly used without purification to produce lignin-based activated carbon fibers (LACFs) with specific surface area and total pore volume of 1375 m2/g and 0.881 cm3/g, respectively. Compared with the commercial pitch-based activated carbon fiber, the LACF has a higher specific area and superior pore structure parameters. This work provides a feasible route for extracting lignin from natural palm fiber and demonstrates its use in the preparation of activated carbon fiber with a remarkable performance as a solid dehumidification agent. Graphical Abstract

Abstract Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells; we named this “in-cell killing” which displays the efficacy superior to the canonical way of “kiss-killing” from outside. By profiling isogenic cells, CD44 on tumor cells was identified as a negative regulator of “in-cell killing” via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and by enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated “in-cell killing” as a promising strategy for cancer immunotherapy.

ObjectivesPatients with minor ischemic stroke (MIS) frequently suffer from early neurological deterioration (END) and become disabled. Our study aimed to explore the association between serum neurofilament light chain (sNfL) levels and END in patients with MIS.MethodsWe conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score 0–3] admitted within 24 h from the onset of symptoms. sNfL levels were measured at admission. The primary outcome was END, defined as an increase in the NIHSS score by ≥2 points within 5 days after admission. Univariate and multivariate analyses were performed to explore the risk factors associated with END. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between sNfL levels and END.ResultsA total of 152 patients with MIS were enrolled, of which 24 (15.8%) developed END. The median sNfL level was 63.1 [interquartile range (IQR), 51.2–83.4] pg/ml on admission, which was significantly higher than that of 40 age- and sex-matched healthy controls (median 47.6, IQR 40.8–56.1 pg/ml; p < 0.001). Patients with MIS with END had a higher level of sNfL (with ND: median 74.1, IQR 59.5–89.8 pg/ml; without END: median 61.2, IQR 50.5–82.2 pg/ml; p = 0.026). After adjusting for age, baseline NIHSS score, and potential confounding factors in multivariate analyses, an elevated sNfL level (per 10 pg/mL) was associated with an increased risk of END [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.04–1.77; p = 0.027). Stratified analyses and interaction tests demonstrated that the association between sNfL and END did not change by age group, sex, baseline NIHSS score, Fazekas' rating scale, hypertension, diabetes mellitus, intravenous thrombolysis, and dual antiplatelet therapy in patients with MIS (all p for interaction > 0.05). END was associated with an increased risk of unfavorable outcomes (modified Rankin scale score ranging from 3 to 6) at 3 months.ConclusionEarly neurological deterioration is common in minor ischemic stroke and is associated with poor prognosis. The elevated sNfL level was associated with an increased risk of early neurological deterioration in patients with minor ischemic stroke. sNfL might be a promising biomarker candidate that can help to identify patients with minor ischemic stroke at high risk of neurological deterioration, for reaching individual therapeutic decisions in clinical practice.