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Abstract Background Despite the use of targeted therapeutic approaches, T-cell acute lymphoblastic leukemia (T-ALL) is still associated with a high incidence of complications and a poor prognosis. Indisulam (also known as E7070), a newly identified molecular glue compound, has demonstrated increased therapeutic efficacy in several types of cancer through the rapid degradation of RBM39. This study aimed to evaluate the therapeutic potential of indisulam in T-ALL, elucidate its underlying mechanisms and explore the role of the RBM39 gene. Methods We verified the anticancer effects of indisulam in both in vivo and in vitro models. Additionally, the construction of RBM39-knockdown cell lines using shRNA confirmed that the malignant phenotype of T-ALL cells was dependent on RBM39. Through RNA sequencing, we identified indisulam-induced splicing anomalies, and proteomic analysis helped pinpoint protein changes caused by the drug. Comprehensive cross-analysis of these findings facilitated the identification of downstream effectors and subsequent validation of their functional roles. Results Indisulam has significant antineoplastic effects on T-ALL. It attenuates cell proliferation, promotes apoptosis and interferes with cell cycle progression in vitro while facilitating tumor remission in T-ALL in vivo models. This investigation provides evidence that the downregulation of RBM39 results in the restricted proliferation of T-ALL cells both in vitro and in vivo, suggesting that RBM39 is a potential target for T-ALL treatment. Indisulam’s efficacy is attributed to its ability to induce RBM39 degradation, causing widespread aberrant splicing and abnormal translation of the critical downstream effector protein, THOC1, ultimately leading to protein depletion. Moreover, the presence of DCAF15 is regarded as critical for the effectiveness of indisulam, and its absence negates the ability of indisulam to induce the desired functional alterations. Conclusion Our study revealed that indisulam, which targets RBM39 to induce tumor cell apoptosis, is an effective drug for treating T-ALL. Targeting RBM39 through indisulam leads to mis-splicing of pre-mRNAs, resulting in the loss of key effectors such as THOC1.

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or ?at anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P

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 In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress–strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.

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.

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.

Abstract RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA‐ and other RNA‐processing machineries in the nucleus. However, these established couplings are all major spliceosome‐related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural‐related defects. The 65K‐ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle‐uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin‐binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11‐KD are due to the decreased common chromatin‐binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression.

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.

ObjectiveTangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD).MethodsThe mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction.ResultsMass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-β, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD.ConclusionTBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD.

Aims and objectives: During the new coronavirus disease 2019 (COVID-19) outbreak period, there was increasing presentation in the number of patients with acute primary angle closure (APAC). This study aimed to report the occurrence of APAC during the COVID-19 post-restriction period and investigate the related characteristics of these patients with APAC. Methods: This retrospective, multi-center study included consecutive patients seeking APAC treatment at two eye centers in China from December 7, 2022 to January 13, 2023 (post-restriction period) and from December 7, 2021 to January 13, 2022 (control period). Electronic medical records were reviewed, and ocular data of the affected eye(s) were analyzed for patients with unilateral or bilateral APAC. Information including COVID-19 related symptoms, medications used for COVID-19 infection, and living habits and emotions related to the COVID-19 outbreak during the post restriction period were collected using a questionnaire. Results: Overall, 189 (219 APAC eyes) and 51 (54 APAC eyes) patients with APAC were identified during the post-restriction and control periods, respectively. The patients identified during the post-restriction period were younger (P = 0.043) and had a longer duration from symptoms to treatment (P = 0.039), shorter axial length (P = 0.002), larger pupil diameter (P = 0.004), larger vertical cup disc ratio (P = 0.004), poorer mean deviation values (P = 0.003), and more glaucomatous optic neuropathy diagnoses (P = 0.032) compared with the patients with APAC identified during the control period. Among 151 included patients with APAC who completed the questionnaires, 130 patients with APAC were diagnosed with concurrent COVID-19 infection, of which 54 (41.5 %) had coughing and/or vomiting as the main symptoms. Of these, 89.2 % spent 0 h per day on outdoor activity; 44.6 % drank more water than usual, with 14.6 % drinking more than twice the amount of water than usual; 91.5 % used antipyretics; and 20.0 % had mood swings, including anxiety, depression, and tension, during the concurrent COVID-19 infection. Conclusion: In our study, a significant increase in the number of patients presenting with APAC with certain characteristics was observed during the COVID-19 post-restriction period. And whether COVID-19 symptoms, such as coughing and vomiting, and behavioral and psychological changes caused by COVID-19 infection contributing to the concurrence of APAC and COVID-19 recurrence require further investigation.

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.

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.

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.

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 Background Gait impairment is common in Parkinson’s disease (PD) patients, which greatly reduces their quality of life. Executive dysfunction is associated with gait impairment. Compensatory strategies, including visual cues, have been shown to be effective in improving PD gait. In this study, we aimed to understand whether carpets with visual cues could improve PD gait, and how the improvement varies across patients with different executive function state. Methods We designed carpets with chessboard and stripe cues. A total of 65 Chinese PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, L-dopa equivalent daily dosage, Hoehn & Yahr stage, Frontal Assessment Battery, Mini Mental State Examination Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were evaluated. Gait parameters including stride length, gait speed and fall risk were recorded by a wearable electronic device. Results The stride length and gait speed were significantly improved and the fall risk was significantly mitigated when PD patients walked on carpets with chessboard and stripe patterns. Further analysis showed the amelioration of gait parameters was independent of executive dysfunction. Conclusions Our study demonstrates that carpets with visual cues can improve the gait of PD patients even in those with mild executive dysfunction.

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.

Porcine proliferative enteropathy (PPE), an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis, is commonly associated with diarrhea and reduced weight gain in growing pigs widespread. An accurate method for detecting L. intracellularis is particularly important for preventing and controlling PPE. Heat shock protein 60 (Hsp60) is an immunodominant bacterial antigen found in all eukaryotic and prokaryotic organisms. Thus, the purpose of the current investigation was to produce a novel L. intracellularis Hsp60 monoclonal antibody (mAb) useful for immunodiagnostics. Three hybridomas secreted anti-Hsp60 termed 3E5, 4E2, and 9G6 were generated, and the titers of ascitic fluids of 3E5, 4E2, 9G6 were 1:1 024 000, 1:2 048 000 and 1:2 048 000, respectively. The Western blotting analysis demonstrated that recombinant Hsp60 (rHsp60) was recognized by mAbs 3E5, 4E2 and 9G6. Subsequently, analyses of specificity showed all the mAbs were highly specific to L. intracellularis while could not significantly react with other enteric bacteria commonly found in the ileum of pigs, such as Escherichia coli, Salmonella Choleraesuis, Salmonella Typhimurium, and Brachyspira hyodysenteriae. Furthermore, the mAbs were useful for detecting L. intracellularis in the infected monolayer cells and histological sections of the ileum from PPE-affected pigs. Our research will provide a foundation for the development of immunological diagnostic tests.

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.

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 Tuberculous meningitis (TBM) is a severe infectious disease affecting the central nervous system, causing high mortality and disability. However, current diagnostic methods for TBM using cerebrospinal fluid (CSF) lack sensitivity and predictive biomarkers for prognosis. We conducted a study on cytokine profiles in CSF and serum samples from TBM patients to identify disease-specific biomarkers. Patients were categorized into three groups: TBM (n = 17), cryptococcal meningitis (n = 10), and non-infection (n = 6), and cytokine levels were quantified using a 48-plex panel. After treatment, we observed a significant reduction in the levels of 12 cytokines, indicating their potential use as biomarkers for treatment monitoring. Among them, monokine induced by interferon-γ (MIG) and interleukin-18 showed significant differences in serum or CSF cytokine levels compared to the control groups. CSF levels of MIG in TBM patients were negatively correlated with the CSF/blood glucose ratio (r = −0.4728, P = 0.0475). Positive correlations were found between CSF leukocyte counts and several cytokines, including fibroblast growth factor-basic, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-3, macrophage inflammatory protein 1 alpha (MIP-1α), and tumor necrosis factor alpha. G-CSF and MIP-1α were also positively correlated with CSF protein levels. Receiver operating characteristic curve analysis revealed that MIG exhibited the highest area under the curve of 0.92 [95% confidence interval (CI) 0.82–1.00] with a sensitivity of 0.85 (95% CI 0.58–0.97) and a specificity of 0.87 (95% CI 0.62–0.98), making it a promising diagnostic biomarker for TBM. Our study provides valuable insights into TBM’s pathogenesis and identifies potential biomarkers for diagnosis and evaluating treatment monitoring. IMPORTANCE Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study’s findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.

BackgroundMinimally invasive surgery, in particular endoscopic surgery, has revolutionized the benefits for patients, but poses greater challenges for surgeons in terms of ergonomics. Integrating ergonomic assessments and interventions into the multi-stage endoscopic procedure contributes to the surgeon’s musculoskeletal health and the patient’s intraoperative safety and postoperative recovery.ObjectiveThe purpose of this study was to overview the objective assessment techniques, tools and assessment settings involved in endoscopic procedures over the past decade and to identify the potential factors that induce differences in high workloads in endoscopic procedures and ultimately to design a framework for ergonomic assessment in endoscopic surgery.MethodsLiterature searches were systematically conducted in the OVID, pubmed and web of science database before October 2022, and studies evaluating ergonomics during the process of endoscopic procedures or simulated procedures were both recognized.ResultsOur systematic review of 56 studies underscores ergonomic variations in endoscopic surgery. While endoscopic procedures, predominantly laparoscopy, typically incur less physical load than open surgery, extended surgical durations notably elevate ergonomic risks. Surgeon characteristics, such as experience level and gender, significantly influence these risks, with less experienced and female surgeons facing greater challenges. Key assessment tools employed include electromyography for muscle fatigue and motion analysis for postural evaluation.ConclusionThis review aims to provide a comprehensive analysis and framework of objective ergonomic assessments in endoscopic surgery, and suggesting avenues for future research and intervention strategies. By improving the ergonomic conditions for surgeons, we can enhance their overall health, mitigate the risk of WMSDs, and ultimately improve patient outcomes.

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

For improving the corrosion resistance of 904L stainless steel under high Cl- concentration environment with different pH values condition，the corrosion behavior of 904L austenitic stainless steel in 100 g/L NaCl solution at different pH values was studied by cyclic polarization curves，electrochemical impedance spectroscopy，Olympus confocal microscopy，scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS).Results showed that the corrosion resistance of 904L stainless steel increased with the increase of pH value，EIS consisted of two capacitive reactance arcs，and the radius of capacitive reactance arc increased with the increase of pH value，and the capacitive reactances were all in the same order of magnitude.Meanwhile，lower pH value conditions could enhance the destructive effect of Cl- on the passive film.With the decrease of pH value，the range of passive region of the material decreased.When the pH＝2，slight pitting occurred on the surface of the material.

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.

Mechanical interfaces are prevalent in industries like aerospace and maritime, where the normal contact stiffness on these surfaces is a crucial component of the overall stiffness of mechanical structures. From the perspective of structural mechanics, normal contact stiffness significantly affects the dynamic response of mechanical structures and must be considered in mechanical design and simulation analysis. Essentially, the mechanical interface represents a typical type of nonlinear contact, characterized by both its non-uniform distribution and its frequency-dependent properties under external excitations. A plate structure was designed to study the distribution and frequency-dependent characteristics of normal contact stiffness on the mechanical interface. Experiments validated that the normal contact stiffness not only significantly increases the fundamental frequency of the plate but also alters its mode shapes. To replicate the experimental results in simulations, the BUSH elements were used to model the normal contact stiffness within the plate structure, arranging it non-uniformly and setting it to vary with frequency according to the plate’s mode shapes and frequency response. This method accurately replicated the plate’s mode shapes and response curves within the 0–1000 Hz range in simulations.

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.

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 For some new mines, the utilization rate of tailings is not satisfactory when using unclassified tailings as backfill aggregate for cemented backfill. At the same time, with the progress of mineral processing technology, the tailings discharged by the concentrator gradually become finer. Therefore, cemented filling with fine-grained tailings as aggregate will become the development direction of filling technology in the future. In this paper, the feasibility of fine particle tailings backfill is studied by taking the particle tailings of-200 mesh as aggregate in Shaling gold mine. The calculation shows that the utilization rate of tailings is increased from 45.1% to 90.3% by using-200 mesh tailings as filling aggregate. The response surface central composite design method (RSM-CCD) was used to study the strength of backfill with alkali-activated cementitious material as binder by taking the mass concentration of backfill slurry and sand-binder ratio as input factors. The results show that the 28-day strength of the backfill with graded fine-grained tailings as filling aggregate can reach 5.41 MPa when the sand-binder ratio is 4, which can fully meet the needs of the mine for the strength of the backfill. The thickening test of-200 mesh fine particle tailings was carried out by static limit concentration test and dynamic thickening test. In the case of adding 35 g/t BASF 6920 non-ionic flocculant, the concentration of 64.74% tail mortar can reach 67.71% after 2 h of static thickening, and the concentration can reach 69.62% after 2 h of static thickening. The feeding speed of thickener should be controlled between 0.4 and 0.59 t/(m2 h). In this case, the underflow concentration of thickener is relatively high, which is 64.92–65.78%, and the solid content of overflow water is less than 164 ppm. The conventional full tailings thickening process was improved by using the design of high-efficiency deep cone thickener and vertical sand silo. The feasibility of fine-grained tailings as filling aggregate was demonstrated by combining the filling ratio test of fine-grained tailings, the data of thickening test and the improved thickening process. The research results can provide reference for other mines to use fine-grained tailings as filling aggregate to design filling system.

Streptococcus agalactiae is one of the most common pathogens that cause bovine mastitis worldwide. Identifying pathogen prevalence and virulence factors is critical for developing prevention and control approaches. Herein, 1 161 milk samples from various dairy farms in China (n=558) and Pakistan (n=603) were collected between 2019–2021 and were subjected to S. agalactiae isolation. Prevalence, serotyping, virulence genes, and antibiotic-resistant genes of S. agalactiae were evaluated by PCR assay. All isolates were characterized for haemolysis, biofilm production, cytotoxicity, adhesion, and invasion on bovine mammary epithelial cells. The prevalence of S. agalactiae-induced mastitis in cattle was found to be considerably higher in Pakistan than in China. Jiangsu and Sindh provinces had the highest area-wise prevalence in China and Pakistan, respectively. Serotypes Ia and II were prevalent in both countries, whereas serotype III was found only in Pakistan. Moreover, all isolates tested positive for PI-2b gene but negative for PI-1 and PI-2a genes. All isolates harboured cfb, cylE, hylB, and fbsB virulent genes, whereas many of them lacked bibA, rib and bca. However, the absence of bac and scp genes in Chinese isolates and cspA in Pakistani isolates was noted, while spb1 and lmb were not detected in isolates of both countries. Pakistani isolates, particularly serotype Ia-positive, had a considerably higher ability to produce biofilm, haemolysis, cytotoxicity, adhesion, and invasion than Chinese isolates. Most of the isolates were phenotypically resistant to tetracycline, erythromycin, and clindamycin and genotypic resistance was confirmed by the presence of ermA, ermB, tetM and tetO genes. Our study highlights the antimicrobial resistance profile and virulence-related factors contributing to the epidemiological spread of mastitis-causing S. agalactiae in China and Pakistan. The findings may facilitate future studies designed to develop improved treatment and control strategies against this pathogen.

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 ).

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.