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Abstract Background Nephrotic syndrome (NPHS), characterized by proteinuria, hypoalbuminemia, and edema, can be caused by genetic variations. TBC1D8B was recently discovered as a novel disease-causing gene for X-linked NPHS. With only a few reported cases, the clinical manifestations associated with variants of this gene need to be further examined. Methods We recruited a newborn with NPHS complicated by acute kidney injury (AKI) and his parents and tested the potential genetic cause of the disease through trio-whole exome sequencing and Sanger sequencing. Western blotting (WB) was performed using a mutant plasmid to evaluate mutant protein expression levels. Since the TBC1D8B protein interacts with RAB proteins to catalyze the GTPase hydrolysis process, immunofluorescence (IF) can be used to verify the interaction between the TBC1D8B mutant protein and RAB11A/RAB11B, and thus to confirm its effect on the endocytosis and vesicle recycling functions of RAB proteins within the cell. Results The child, at 1 month, showed severe edema and proteinuria and unexplained coma with epilepsy. Ultrasound examination revealed multiple organ enlargement, and MRI showed nonspecific high diffusion-weighted imaging signal characteristics in the splenium of the corpus callosum. Hematoxylin and eosin staining showed diffuse inflammatory cell infiltration in the renal interstitium and multifocal renal tubule lumen expansion. Diffuse fusion of podocyte foot processes was observed under electron microscopy, indicating glomerular podocyte lesions. Genetic testing revealed a maternally inherited novel hemizygous variant, NM_017752: c.628 A > T, p.Lys210Ter, in TBC1D8B. In vitro functional experiments showed that this variant may lead to TBC1D8B protein degradation. IF results showed disrupted interaction with RAB11A/RAB11B, that then affects the biological function of RAB proteins in the process of cell intimal vesicle formation and intracellular transport. Conclusion This study will enrich the mutational and phenotypic spectra of TBC1D8B and demonstrate the potential of this gene variants to cause early-onset NPHS leading to severe kidney disease.

Abstract Background Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. Methods We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Results Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. Conclusions These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

Abstract Neurogenic bladder often occurs after pelvic ganglia injury. Its symptoms, like severe urinary retention and incontinence, have a significant impact on individuals’ quality of life. Unfortunately, there are currently no effective treatments available for this type of injury. Here, we designed a fiber-enhanced tissue bandage for injured pelvic ganglia. Tight junctions formed in tissue bandages create a mini tissue structure that enhances resistance in an in vivo environment and delivers growth factors to support the healing of ganglia. Strength fibers are similar to clinical bandages and guarantee ease of handling. Furthermore, tissue bandages can be stored at low temperatures over 5 months without compromising cell viability, meeting the requirements for clinical products. A tissue bandage was applied to a male rat with a bilateral major pelvic ganglia crush injury. Compared to the severe neurogenic bladder symptoms observed in the injury and scaffold groups, tissue bandages significantly improved bladder function. We found that tissue bandage increases resistance to mechanical injury by boosting the expression of cytoskeletal proteins within the major pelvic ganglia. Overall, tissue bandages show promise as a practical therapeutic approach for ganglia repair, offering hope for developing more effective treatments for this thorny condition.

Abstract Bearing‐fault diagnosis in rotating machinery is essential for ensuring the safety and reliability of mechanical systems. However, under complicated working conditions, the number of normal mechanical equipment samples can far exceed the number of faulty ones. When the data are so imbalanced, data fault diagnosis cannot be easily conducted using conventional deep learning methods. This study proposes a fault diagnosis method based on a dual‐branch interactive fusion network, which improves the accuracy and stability of bearing‐fault diagnosis. First, a dual‐branch feature representation network comprising an iterative attention‐feature fusion residual neural network and a long short‐term memory network is designed for extracting different modal features. Meanwhile, intermodal fusion of the extracted features is performed through multilayer perception. Based on the cost‐sensitive regularization loss, a new joint loss function is then designed for network training. Finally, the effectiveness of the proposed method is verified through comparative experiments, visualization analyses, ablation experiments, and generalization performance experiments.

Abstract Background The acute levodopa challenge test (ALCT) is a universal method for evaluating levodopa response (LR). Assessment of Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) is a key step in ALCT, which is some extent subjective and inconvenience. Methods This study developed a machine learning method based on instrumented Timed Up and Go (iTUG) test to evaluate the patients’ response to levodopa and compared it with classic ALCT. Forty-two patients with parkinsonism were recruited and administered with levodopa. MDS-UPDRS III and the iTUG were conducted in both OFF-and ON-medication state. Kinematic parameters, signal time and frequency domain features were extracted from sensor data. Two XGBoost models, levodopa response regression (LRR) model and motor symptom evaluation (MSE) model, were trained to predict the levodopa response (LR) of the patients using leave-one-subject-out cross-validation. Results The LR predicted by the LRR model agreed with that calculated by the classic ALCT (ICC = 0.95). When the LRR model was used to detect patients with a positive LR, the positive predictive value was 0.94. Conclusions Machine learning based on wearable sensor data and the iTUG test may be effective and comprehensive for evaluating LR and predicting the benefit of dopaminergic therapy.

Abstract Treatment of Mycobacterium abscessus (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti‐Mab drugs. In this study, we explored an intrinsic resistance mechanism through which Mab resists echinomycin (ECH). ECH showed activity against Mab at a minimum inhibitory concentration (MIC) of 2 µg/ml. A ΔembC strain in which the embC gene was knocked out showed hypersensitivity to ECH (MIC: 0.0078–0.0156 µg/ml). The MICs of ECH‐resistant strains screened with reference to ΔembC ranged from 0.25 to 1 µg/ml. Mutations in EmbB, including D306A, D306N, R350G, V555I, and G581S, increased the Mab's resistance to ECH when overexpressed in ΔembC individually (MIC: 0.25–0.5 µg/ml). These EmbB mutants, edited using the CRISPR/Cpf1 system, showed heightened resistance to ECH (MIC: 0.25–0.5 µg/ml). The permeability of these Mab strains with edited genes and overexpression was reduced, as evidenced by an ethidium bromide accumulation assay, but it remained significantly higher than that of the parent Mab. In summary, our study demonstrates that ECH exerts potent anti‐Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH. Mutation in EmbB may partially compensate for a loss of EmbC function.

Highlights We propose the novel concept of a tough hydrogel scaffold within the realm of tissue engineering. This scaffold combines exceptional strength (6.66 MPa), customization capabilities, and superior biocompatibility in a manner not previously achieved in existing research. These tough hydrogel scaffolds possess functional surface structures and can effectively enhance cell-guided growth and prompt regeneration of muscle tissue in vivo. This is a universal manufacturing method for tough hydrogel scaffolds in tissue engineering.

Abstract Background Emerging evidence has highlighted the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) in chemotherapy-induced premature ovarian failure (POF). This study was designed to investigate the appropriate timing and molecular mechanism of UC-MSCs treatment for chemotherapy-induced POF. Methods Ovarian structure and function of mice were assessed every 3 days after injections with cyclophosphamide (CTX) and busulfan (BUS). UC-MSCs and UC-MSCs-derived extracellular vesicles (EVs) were infused into mice via the tail vein, respectively. Ovarian function was analyzed by follicle counts, the serum levels of hormones and ovarian morphology. The apoptosis and proliferation of ovarian granulosa cells were analyzed in vitro and in vivo. Label-free quantitative proteomics was used to detect the differentially expressed proteins in UC-MSC-derived EVs. Results After CTX/BUS injection, we observed that the ovarian function of POF mice was significantly deteriorated on day 9 after CTX/BUS infusion. TUNEL assay indicated that the number of apoptotic cells in the ovaries of POF mice was significantly higher than that in normal mice on day 3 after CTX/BUS injection. Transplantation of UC-MSCs on day 6 after CTX/BUS injection significantly improved ovarian function, enhanced proliferation and inhibited apoptosis of ovarian granulosa cells, whereas the therapeutic effect of UC-MSCs transplantation decreased on day 9, or day 12 after CTX/BUS injection. Moreover, EVs derived from UC-MSCs exerted similar therapeutic effects on POF. UC-MSCs-derived EVs could activate the PI3K/AKT signaling pathway and reduce ovarian granulosa cell apoptosis. Quantitative proteomics analysis revealed that clusterin (CLU) was highly expressed in the EVs of UC-MSCs. The supplementation of CLU proteins prevented ovarian granulosa cells from chemotherapy-induced apoptosis. Further mechanistic analysis showed that CLU-knockdown blocked the PI3K/AKT signaling and reversed the protective effects of UC-MSCs-derived EVs. Conclusions Administration of UC-MSCs and UC-MSCs-derived EVs on day 6 of CTX/BUS injection could effectively improve the ovarian function of POF mice. UC-MSCs-derived EVs carrying CLU promoted proliferation and inhibited apoptosis of ovarian granulosa cells through activating the PI3K/AKT pathway. This study identifies a previously unrecognized molecular mechanism of UC-MSCs-mediated protective effects on POF, which pave the way for the use of cell-free therapeutic approach for POF. Graphical Abstract

The filamentous fungus Talaromyces liani (Kamyschko) Yilmaz, Frisvad & Samson, 2014, has attracted considerable interest in biotechnology due to its diverse industrial applications and physiological characteristics. However, the mitochondrial genome of T. liani remains uncharacterized. Here, we present the complete mitochondrial genome of T. liani, comprising 38,000 bp with a GC content of 24.61%. This genome includes 15 core protein-coding genes, 4 independent ORFs, 6 intronic ORFs, 26 tRNAs, and 2 rRNA genes. Phylogenetic analysis using Bayesian inference (BI) revealed the evolutionary relationships among 15 fungi from Eurotiales, strongly supporting distinct clades and indicating that T. liani most closely related to T. pinophilus.

Abstract Background The clinical significance of the presence or absence of Mycoplasma pneumoniae (MP) in pleural effusion in Mycoplasma pneumoniae pneumonia (MPP) children has not yet been elucidated. Herein, we investigated the clinical implication of pleural fluid MP positive in children with MPP. Methods A total of 165 MPP children with pleural effusion requiring thoracocentesis were enrolled in this study. They were subsequently divided into two groups according to the presence or absence of MP in pleural effusion, namely positive group (n = 38) and negative group (n = 127). Information on their clinical manifestations, laboratory findings, radiological characteristics and treatment modalities was retrospectively collected from medical chart reviews. Results The length of hospitalization (15.00 (10.75–19.25) vs. 11.00 (9.00–14.00) days, p=0.001) and total course of illness (23.00 (18.00–28.00) vs. 20.00 (17.00–24.00) days, p=0.010) were significantly longer in the positive group than in the negative group. The occurrence of pericardial effusion (23.7% vs. 7.9%, p=0.017), atelectasis (73.7% vs. 53.5%, p=0.027) and necrotizing pneumonia (23.7% vs. 7.9%, p=0.017) were more frequent in the positive group compared to the negative group. The levels of neutrophil percentages (82.35% (75.40%-85.78%) vs. 72.70% (64.30%-79.90%), p 7.33 mg/L was significantly associated with the incidence of MP positive pleural effusion in MPP (OR=3.517). Conclusions The presence of MP in pleural fluid in MPP children with pleural effusion indicated a more serious clinical course. D-dimer > 7.33 mg/L was a related factor for MP positive pleural effusion in MPP. The results of the present study would help in the creation of a therapeutic plan and prediction of the clinical course of MPP in children.

ABSTRACT: Milk contains abundant polar lipids, which are vital constituents of biological membranes. These polar lipids are present in the human diet as phospholipids and sphingolipids. Nevertheless, the limited focus has been on the attributes and role of camel milk polar lipids (MPL). In this study, camel MPL were isolated, and the composition of their lipidome was determined using ultra-high-performance liquid chromatography-tandem MS. This study characterized a total of 333 polar lipids, which encompassed glycerophospholipids and sphingolipids. Camel milk is rich in polar lipids, mainly phosphatidylethanolamine, sphingomyelin, and phosphatidylcholine. The results indicated that MPL intervention relieved the clinical symptoms and colon tissue damage in mice with dextran sulfate sodium-induced colitis, along with suppressing the expression of proinflammatory cytokines. Moreover, the administration of MPL partially alleviated mouse gut microbiota dysbiosis by increasing the abundance of probiotics (such as Lachnospiraceae_NK4A136_group and Muribaculaceae) and decreasing the number of harmful bacteria (such as Bacteroides and Parabacteroides). This study was conducted to investigate the potent protective effects of MPL in camel milk treatments on a mouse model of colitis and provided new ideas for the application of camel milk.

In the current information society, digital literacy has become an indispensable part of individuals’ overall literacy. Thus, investigating the factors influencing digital literacy is of theoretical and practical significance, especially for developing children. Against this background, the present study examined the association between family socioeconomic status and children’s digital literacy and the mediating roles of active and restrictive parental internet mediation in this association. A total of 1050 Chinese students ranging from Grades 4 to 8 completed questionnaires in their classrooms. Regression-based analyses showed that (1) family socioeconomic status was positively associated with digital literacy and (2) active parental mediation could significantly mediate this relationship, but the mediating effect of restrictive parental mediation was insignificant. This research not only deepens our understanding of the factors affecting digital literacy but also provides an empirical reference point for interventions to improve children’s digital literacy.

Abstract Background Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. Methods Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5–84 years), year (1990–2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. Results In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from −0.54% (−0.61%, −0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. Conclusions Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.

Abstract Solution-processable 2D semiconductor inks based on electrochemical molecular intercalation and exfoliation of bulk layered crystals using organic cations has offered an alternative pathway to low-cost fabrication of large-area flexible and wearable electronic devices. However, the growth of large-piece bulk crystals as starting material relies on costly and prolonged high-temperature process, representing a critical roadblock towards practical and large-scale applications. Here we report a general liquid-metal-assisted approach that enables the electrochemical molecular intercalation of low-cost and readily available crystal powders. The resulted solution-processable MoS2 nanosheets are of comparable quality to those exfoliated from bulk crystals. Furthermore, this method can create a rich library of functional 2D electronic inks ( >50 types), including 2D wide-bandgap semiconductors of low electrical conductivity. Lastly, we demonstrated the all-solution-processable integration of 2D semiconductors with 2D conductors and 2D dielectrics for the fabrication of large-area thin-film transistors and memristors at a greatly reduced cost.

Abstract Background This study explored similarities and differences among Chinese patients and rheumatologists in their attitudes towards and perceptions of traditional Chinese medicine (TCM) for Sjögren’s syndrome (SS), including analyzing factors that influenced their decision making. Methods An anonymous questionnaire was used to conduct a multicenter survey among patients with SS at three tertiary care medical centers in Beijing and among rheumatology clinicians at several hospitals across China. Results were analyzed using descriptive statistics. Results There were 942 valid questionnaires from patients from 31 provinces and cities in China, with a male-to-female ratio of approximately 1:14, a mean age of 48.81 years, and a median disease duration of 7 (4, 10) years. There were 320 valid questionnaires from rheumatologists, covering 30 provinces and cities in China, with a male-to-female ratio of approximately 0.87:1, a mean age of 48 years, and a median work duration of 10.5 (6, 15) years. The rheumatologists treated a median of 15 (11, 50) SS cases per month, and the median proportion of SS to all rheumatic diseases was 6.66% (6–10%). Many patients believed TCM could cure the root of the disease, and the most expected TCM therapies were TCM patent prescriptions and medicinal teas. Conversely, rheumatologists placed high value on the efficacy of TCM, and most commonly prescribed Chinese herbal decoctions. Most doctor-patient groups were positive about TCM treatment, citing the low side effects as the major advantage. Regression analysis showed that for patients over 40 years old with a course of disease > 4 years, the probability of using TCM has increased by 1–6 times; the probability of recommending TCM in clinical work of doctors who have worked for more than 15 years, TCM and integrated traditional Chinese and western medicine has increased 1–2 times. Conclusions TCM has become widely accepted and earned attention from doctor-patient groups, especially among older patients and experienced rheumatologists. However, negative prejudices and absence of accurate information about TCM treatments and SS itself require improvement. The contradiction between TCM dosage form and efficacy is a major problem, and patient demand for convenient and efficient TCM patent preparations suggests future work should focus on developing TCM patent preparations with clear compositions and mechanisms.

Abstract Reforming sustainable 3d-metal-based visible light catalytic platforms for inert bulk chemical activation is highly desirable. Herein, we demonstrate the use of a Brønsted acid to unlock robust and practical iron ligand-to-metal charge transfer (LMCT) photocatalysis for the activation of multifarious inert haloalkylcarboxylates (CnXmCOO−, X = F or Cl) to produce CnXm radicals. This process enables the fluoro-polyhaloalkylation of non-activated alkenes by combining easily available Selectfluor as a fluorine source. Valuable alkyl fluorides including potential drug molecules can be easily obtained through this protocol. Mechanistic studies indicate that the real light-harvesting species may derive from the in situ-assembly of Fe3+, CnXmCOO−, H+, and acetonitrile solvent, in which the Brønsted acid indeed increases the efficiency of LMCT between the iron center and CnXmCOO− via hydrogen-bond interactions. We anticipate that this Brønsted acid-unlocked iron LMCT platform would be an intriguing sustainable option to execute the activation of inert compounds.

Abstract Background The potential involvement of circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m6A-modified circMARK2 and its role in WT progression. Methods We identified dysregulated circRNAs through deep sequencing and validated their expression by qRT-PCR in WT tissues. The biological functions of circMARK2 were assessed using clone formation, transwell migration, and orthotopic animal models. To dissect the underlying mechanisms, we employed RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, Western blotting, and immunofluorescence and immunohistochemical staining. Results CircMARK2, upregulated in WT tissues, was found to be m6A-modified and promoted cytoplasmic export. It facilitated WT progression by stabilizing LIN28B mRNA through the circMARK2/IGF2BP2 interaction. In vitro and in vivo studies demonstrated that circMARK2 enhances the malignant behavior of WT cells. Clinically, higher circMARK2 levels in tumor tissues of WT patients were linked to increased tumor aggressiveness and reduced survival rates. Conclusions Our study provides the first comprehensive evidence that m6A-modified circMARK2 contributes to WT progression by enhancing LIN28B mRNA stability, promoting cellular aggressiveness. CircMARK2 emerges as a potential biomarker for prognosis and a promising target for therapeutic intervention in WT, underscoring the clinical relevance of m6A modification in pediatric renal cancer.

The scarcity of public resources and environmental pollution caused by rapid urbanization highlight the practical significance of parks in ensuring the sustainable development of a city. Therefore, the social equity of parks warrants further study. This paper proposes a fine-grained comprehensive evaluation framework that combines geographic accessibility models, geo-statistical analysis, and machine learning algorithms to explore social inequity in Taiyuan, China. In this framework, gini coefficient and lorentz curve express spatial equality, accessibility shows spatial equity, and ridge regression model handles the interdependence of variables with different dimensions to quantify the relative effects of local participants on changes in park accessibility. On this basis, the imbalance between vulnerable groups and park supply is analyzed to further understand the core concept of social equity. Results highlight serious spatial inequality in all three types of parks allocation of six urban areas, especially in community parks. The actual access level of people to parks is also stratified by their demographic and socioeconomic characteristics, revealing the social inequity in access to parks. Park distribution is indeed not conducive to some social vulnerable groups, whose contradiction between supply and demand is highly prominent in urban – rural junctions and new urban areas. This paper also confirms the unfair layout of public facilities can be observed in second-tier cities of China by highlighting the social inequity of parks in Taiyuan. The findings of this work have profound implications for urban planning and sustainable development.

Reasonable distribution of braking force is a factor for a smooth, safe, and comfortable braking of trains. A dynamic optimal allocation strategy of electric-air braking force is proposed in this paper to solve the problem of the lack of consideration of adhesion difference of train wheelsets in the existing high-speed train electric-air braking force optimal allocation strategies. In this method, the braking strategy gives priority to the use of electric braking force. The force model of a single train in the braking process is analyzed to calculate the change of adhesion between the wheel and rail of each wheelset after axle load transfer, and then the adhesion of the train is estimated in real time. Next, with the goal of maximizing the total adhesion utilization ratio of trailer/motor vehicles, a linear programming distribution function is constructed. The proportional coefficient of adhesion utilization ratio of each train and the application upper limit of braking force in the function is updated according to the change time point of wheelset adhesion. Finally, the braking force is dynamically allocated. The simulation results of Matlab/Simulink show that the proposed algorithm not only uses the different adhesion limits of each trailer to reduce the total amount of braking force undertaken by the motor vehicle, but also considers the adhesion difference of each wheelset. The strategy can effectively reduce the risk and time of motor vehicles during the braking process and improve the stability of the train braking.

Multisensor data fusion method can improve the accuracy of bearing fault diagnosis, in order to address the problems of single-sensor data types and the insufficient exploration of redundancy and complementarity between different modal data in most existing multisensor data fusion methods for bearing fault diagnosis, a bearing fault diagnosis method based on a Multiple-Constraint Modal-Invariant Graph Convolutional Fusion Network (MCMI-GCFN) is proposed in this paper. Firstly, a Convolutional Autoencoder (CAE) and Squeeze-and-Excitation Block (SE block) are used to extract features of raw current and vibration signals. Secondly, the model introduces source domain classifiers and domain discriminators to capture modal invariance between different modal data based on domain adversarial training, making use of the redundancy and complementarity between multimodal data. Then, the spatial aggregation property of Graph Convolutional Neural Networks (GCN) is utilized to capture the dependency relationship between current and vibration modes with similar time step features for accurately fusing contextual semantic information. Finally, the validation is conducted on the public bearing damage current and vibration dataset from Paderborn University. The experimental results showed that the delivered fusion method achieved a bearing fault diagnosis accuracy of 99.6 %, which was about 9 %–11.4 % better than that with nonfusion methods.

Objective:. To evaluate the feasibility, safety, and effectiveness of a novel edge-to-edge mitral valve repair system (the NovoClasp system) in patients with severe mitral regurgitation. Methods:. In this prospective, single-arm, first-in-human study conducted at Beijing Anzhen Hospital, data were collected from patients undergoing transcatheter edge-to-edge repair using the NovoClasp system. The study candidates were patients exhibiting a mitral regurgitation severity of 3+ or more and were at high-risk or contraindicated for surgical intervention. Technical success and device success according to the Mitral Valve Academic Research Consortium definitions were used as primary outcomes. Other safety and efficacy outcomes were prospectively assessed at device implantation, discharge, and 30 d, 6 months, and 12 months post-procedure. Results:. Between October 1, 2021, and January 31, 2022, 11 patients were treated for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the NovoClasp system. All patients had a baseline New York Heart Association functional class of III–IV, with 7/11 exhibiting complex mitral valve disease. All patients achieved the primary endpoints of technical and device success, with a post-operative 30-d mitral regurgitation grade reduction to 2+ or lower, which was maintained at 12 months. One patient had minor bleeding and hematoma at the access site before discharge, and 2 patients were readmitted due to fast atrial fibrillation within 12 months post-discharge. No additional cases of death, adverse cerebral or cardiovascular events, or device-related complications was observed during the follow-up. Conclusion:. This study suggested the potential feasibility and safety of the NovoClasp system, showing a promising technical and device success rate, along with a decrease in mitral regurgitation severity. A further pivotal study is needed to assess the procedural and long-term outcomes.

Abstract Background Wilms tumor is the most prevalent embryonal kidney malignancy in children worldwide. Previous genome-wide association study (GWAS) identified that LIM domain only 1 (LMO1) gene polymorphisms affected the susceptibility to develop certain tumor types. Apart from LMO1, the LMO gene family members also include LMO2-4, each of which has oncogenic potential. Methods We conducted this five-center case‒control study to assess the correlations between single nucleotide polymorphisms in LMO family genes and Wilms tumor susceptibility. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association. Results We found LMO1 rs2168101 G > T and rs11603024 C > T as well as LMO2 rs7933499 G > A were significantly associated with Wilms tumor risk. Stratified analysis demonstrated a protective role of rs2168101 GT/TT genotypes against Wilms tumor in the subgroups of age ≤ 18 months, males and clinical stages I/II compared to the rs2168101 GG genotype. Nevertheless, carriers with the rs11603024 TT genotype were more likely to have an increased risk of Wilms tumor than those with rs11603024 CC/CT genotypes in age > 18 months. And the rs11603024 was identified as a protective polymorphism for reducing the risk of Wilms tumor in the sex- and gender- subgroup. Likewise, carriers with the rs7933499 GA/AA genotypes were at significantly elevated risk of Wilms tumor in age ≤ 18 months and clinical stages I/II. Conclusion Overall, our study identified the importance of LMO family gene polymorphisms on Wilms tumor susceptibility in Chinese children. Further investigations are needed to validate our conclusions. Graphical Abstract

Abstract Lifestyles maybe associated with the immune and inflammatory state of human body. We aimed to comprehensively explore the relationship between lifestyles and circulating immune-inflammatory markers in the general population. Data from NHANES 1999–2014 was used. Lifestyle factors included leisure-time physical activity (LTPA), diet quality (Healthy Eating Index-2015, HEI-2015), alcohol consumption, cigarettes smoking, sleep hour and sedentary time. Immune makers included C-reactive protein (CRP), neutrophil–lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet–lymphocyte ratio (PLR) and monocyte–lymphocyte ratio (MLR). Generalized linear regression models were used to adjust confounders. Regressions of restricted cubic splines were utilized to evaluate the potentially non-linear relationships between exposures and outcomes. As results, HEI was negatively associated with CRP (P

Abstract Background Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. Methods We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. Results We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. Conclusions S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.

To solve the problem that it is difficult to track the desired control target of a heavy load train accurately under the input saturation constraint, an anti-windup compensated terminal sliding mode control algorithm for a heavy load train is proposed in this work. First, based on an analysis of the train coupling force and an uncertain disturbance force, a multi-particle dynamic model of a single train is established. Second, an improved unbounded anti-windup compensator is designed and the saturation deviation correction method is used to cause the compensation factor to converge to zero, which means that the compensation factor limit problem that occurs in traditional anti-saturation compensators is eliminated. Then, in combination with the terminal sliding mode control algorithm, an unbounded anti-windup terminal sliding mode controller is constructed. This control method attenuates the effect of input saturation on the tracking accuracy for each locomotive; at the same time, the stability of the closed-loop system is verified based on Lyapunov stability theory. Finally, the effectiveness of the proposed algorithm in terms of its tracking accuracy and anti-saturation performance is verified experimentally.

BackgroundThis study aimed to explore the distribution of intestinal and pharyngeal microbiota on the first day of life in preterm infants and compare the composition of microbiota in infants delivered by cesarean section or vaginally.MethodsThis study included 44 late preterm infants with a gestational age of 34–36 + 6 weeks. Stool and throat swab samples were collected from the preterm infants on the first day of life. The infants were divided into cesarean section and vaginal delivery groups. Illumina NovaSeq high-throughput sequencing technology was used to sequence the V3-V4 hypervariable region of the 16S rRNA gene of all bacteria in the samples. Venn diagram was used to identify shared operational taxonomic units (OTUs) in the intestines and pharynges. Microbial analysis was conducted at the phylum and genus levels, and α and β diversity comparisons were performed.Results(1) Gestational age may have significantly affected the microbial colonization of the intestines and pharynges of preterm infants on the first day after birth (p ≤ 0.001). (2) More OTUs were detected in the pharynx than in the intestines, both have a total of 819 shared OTUs. Proteobacteria, Firmicutes, and Bacteroidota were the dominant phyla in both. At the genus level, Streptococcus had a lower relative abundance in stool samples (0.5%) compared to throat samples (0.5% vs. 22.2%, p = 0.003). 3) The relative abundance of Streptococcus in pharyngeal samples was 26.2% in the cesarean section group much higher than the 3.8% in the vaginal delivery group (p = 0.01).ConclusionThe early postnatal period is a critical time for the establishment of an infant's microbiota. Gestational age at birth may influence microbial colonization, while birth weight, gender, and mode of delivery do not. The intestinal and pharyngeal microbiota composition of preterm infants on the first day after birth showed high similarity, but larger samples are needed for further validation.

Disinfection by-products (DBPs) generated from water treatment have serious adverse effects on human health and natural ecosystems. However, research on the mutagenicity of DBPs with different chemical structures is still limited. In the present study, we compared the mutagenicity of 8 typical DBPs in human-hamster hybrid (AL) cells and clarified the mechanisms involved. Our data displayed that the rank order for mutagenicity was as follows: iodoacetamide (IAcAm) > iodoacetonitrile (IAN) > iodoacetic acid (IAA) > bromoacetamide (BAcAm) ≈ bromoacetonitrile (BAN) > bromoacetic acid (BAA), which was confirmed by DNA double strand breaks and oxidative DNA damage. In contrast, bromoform (TBM) and iodoform (TIM) had minimal mutagenicity. The mutation spectrum analysis further revealed that IAN, IAcAm, and IAA could induce multilocus deletions in mammalian cells. Interestingly, nitrogenous DBPs (N-DBPs) and IAA were found to cause varying degrees of iron overload and lipid peroxidation, which was mediated by the activation of the Nrf2/HO-1 signaling pathway. Moreover, the presence of deferoxamine (DFO), an iron ion inhibitor, effectively reduced γ-H2AX and 8-OHdG induced by N-DBPs and IAA. These results indicated that the variations in genotoxicity among DBPs with different structures were associated with their ability to disrupt iron homeostasis. This study provided new insights into the mechanisms underlying the structure-dependent toxicity of DBPs and established a foundation for a more comprehensive understanding and intervention of the health risks associated with DBPs.

BackgroundRecent studies have confirmed that metabolites and immunocyte phenotype may be associated with the risk of lymphoma. However, the bidirectional causality between metabolites, immunocyte phenotype, disease risk, and whether immunity is an intermediate mediator between metabolism and lymphoma causality is still unclear.ObjectiveTo elucidate the causal relationship between metabolites, immune cell phenotypes, and lymphomas, we used two-sample Mendelian randomization (MR) and two-step MR analysis.MethodsApplying large-scale genome-wide association studies (GWAS) pooled data, we selected 1400 metabolites and 731 immunocyte phenotypes with eight lymphoma subtypes for two-sample bi-directional MR analysis. In addition, we used two-step MR to quantify the proportion of metabolite effects on lymphomas mediated by immunocyte phenotype.ResultsThis study yielded a bidirectional causal relationship between 17 metabolites and lymphoma and a bidirectional causal relationship between 12 immunocyte phenotypes and lymphoma. In addition, we found causal associations between metabolites and lymphomas, three groups of which were mediated by immunocyte phenotypes. Among them, CD27 on plasmablast/plasma cell (PB/PC) was a mediator of the positive association of arginine to glutamate ratio with chronic lymphocytic leukemia, with a mediator ratio of 14.60% (95% CI=1.29-28.00%, P=3.17 × 10-2). Natural killer (NK) cells as a percentage of all lymphocytes(NK %lymphocyte) was a mediator of the negative association of X-18922(unknown metabolite) levels with diffuse large B-cell lymphoma, with a mediation proportion of -8.940% (95% CI=-0.063-(-17.800) %, P=4.84 × 10-2). CD25 on IgD- CD24- B cell was the mediator of the positive association between X-24531(unknown metabolite) levels and diffuse large B-cell lymphoma, with a mediation proportion of 13.200% (95% CI=-0.156-26.200%, P=4.73 × 10-2).ConclusionIn the present study, we identified a causal relationship between metabolites and lymphoma, in which immunocyte phenotypes as mediators are involved in only a minor part. The mediators by which most metabolites affect the risk of lymphoma development remain unclear and require further exploration in the future.

Resumo Objetivo Avaliar os efeitos do modelo de enfermagem de Newman na qualidade de vida e recuperação muscular do assoalho pélvico em pacientes com disfunção do assoalho pélvico pós-parto. Métodos Oitenta e oito pacientes com disfunção do assoalho pélvico pós-parto tratadas de janeiro a abril de 2023 foram divididas em grupo Observação e Controle (n=44) por meio de tabela de números aleatórios. O grupo Controle recebeu enfermagem de rotina e o grupo Observação recebeu cuidados de enfermagem de Newman. A qualidade de vida foi avaliada pelo Short Form-36 Health Status Questionnaire. A função do assoalho pélvico foi avaliada por meio do Pelvic Floor Impact Questionnaire-7 (PFIQ7) e da Pelvic Organ Prolapse Quantification (POPQ). Resultados Após a intervenção, as pontuações de aspectos físico, emocional, capacidade funcional, social e motor do grupo Observação foram superiores às do grupo Controle (P

IntroductionThus far, the impact of kaolin mining activities on the surrounding native plants and rhizosphere microecology has not been fully understood.MethodsIn this study, we used 16S rRNA high-throughput sequencing to examine the impact of kaolin mining on the rhizosphere bacterial communities and functions of three local plant species: Conyza bonariensis, Artemisia annua, and Dodonaea viscosa.ResultsThe results showed that kaolin mining significantly reduced the diversity of rhizosphere bacteria in these plants, as indicated by the Shannon, Simpson, Chao1, and observed species indices (p

Habitat quality (HQ) serves as a pivotal metric for assessing biodiversity and ecosystem health, with alterations in land use driven by human activities posing direct implications on HQ and ecological sustainability within river basins. Prior research on HQ has predominantly centered on historical land use changes, neglecting the comprehensive consideration of future land use transformations and ecological zoning strategies’ influence on HQ. Consequently, this investigation simulates potential land use shifts in the Min River Basin across various future scenarios, leveraging the integration of PLUS and InVEST models, quantitatively dissects HQ’s responsiveness to these changes and delves into the spatial differentiation dynamics underlying these responses, while also exploring the drivers behind such differentiation. Synergizing with the Human Footprint Index (HFI), the study devises a rational ecological zoning plan tailored to the region and outlines targeted control measures for each zone. The results of the study showed that: 1) the east-central part of the Min River Basin was subject to a greater degree of human interference, and the trend of interconversion between grassland, forest land, and cropland was relatively significant, with construction land mainly originating from the transfer of cropland; 2) from 2000 to 2020, average HQ scores for priority protected zones, priority recovery zones, and appropriate development zones stood at 0.9372, 0.2697, and 0.6098, respectively, accompanied by a rise in the proportion of low and moderate HQ areas to 15% and 17%; (3) DEM and Slope were the main drivers affecting HQ, and their explanatory power reached 0.519 and 0.426, respectively; (4) in comparison to a natural development scenario (ND), the planning protection scenario (PP) offers greater promise for ecological preservation and sustainable development within the Min River Basin. The research results can provide technical support for the ecological restoration of land resources and the development and protection of national land space in watershed areas.

Root rot is one of the common diseases of Lycium barbarum. Pathogens can cause devastating disasters to plants after infecting host plants. This study investigated the effect of arbuscular mycorrhizal fungi (AMF) Rhizophagus intraradices inoculation on phenylpropane metabolism in L. barbarum and evaluated its resistance to root rot. The experiment was set up with AMF inoculation treatments (inoculated or not) and root rot pathogen-Fusarium solani inoculation treatments (inoculated or not). The results showed that AMF was able to form a symbiosis with the root system of L. barbarum, thereby promoting plant growth significantly and increasing plants’ resistance to disease stress. The plant height of AMF-colonized L. barbarum increased by 24.83% compared to non-inoculated diseased plants. After inoculation with AMF, the plant defense response induced by pathogen infection was stronger. When the enzyme activity of the leaves reached the maximum after the onset of mycorrhizal L. barbarum, phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, and 4-coumaric acid-CoA ligase increased by 3.67%, 31.47%, and 13.61%, respectively, compared with the non-inoculated diseased plants. The products related to the lignin pathway and flavonoid pathway downstream of phenylpropane metabolism such as lignin and flavonoids were also significantly increased by 141.65% and 44.61% compared to nonmycorrhizal diseased plants. The activities of chitinase and β-1,3-glucanase increased by 36.00% and 57.96%, respectively. The contents of salicylic acid and jasmonic acid were also 17.7% and 31.63% higher than those of nonmycorrhizal plants in the early stage of plant growth, respectively. The results indicated that AMF significantly promoted plant growth and enhanced disease resistance by increasing enzyme activities and the production of lignin and flavonoids.

AimsThis study addresses the essential need for updated information on the burden of lip and oral cavity cancer (LOC) in China for informed healthcare planning. We aim to estimate the temporal trends and the attributable burdens of selected risk factors of LOC in China (1990–2021), and to predict the possible trends (2022–2031).Subject and methodsAnalysis was conducted using data from the Global Burden of Disease study (GBD) 2021, encompassing six key metrics: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute number and age-standardized rates, alongside 95% uncertainty intervals, were computed. Forecasting of disease burden from 2022 to 2031 was performed using an autoregressive integrated moving average (ARIMA) model.ResultsOver the observed period (1990–2021), there were notable increases in the number of deaths (142.2%), incidence (283.7%), prevalence (438.0%), DALYs (109.2%), YLDs (341.2%), and YLLs (105.1%). Age-standardized rates demonstrated notable changes, showing decreases and increases of −5.8, 57.3, 143.7, −8.9%, 85.8%, and − 10.7% in the respective metrics. The substantial majority of LOC burden was observed among individuals aged 40–79 years, and LOC may exhibit a higher burden among males in China. From 2022 to 2031, the age-standardized rate of incidence, prevalence, and YLDs of LOC showed upward trends; while mortality, DALYs, and YLLs showed downward trends, and their estimated values were predicted to change to 2.72, 10.47, 1.11, 1.10, 28.52, and 27.43 per 100,000 in 2031, respectively. Notably, tobacco and high alcohol use emerged as predominant risk factors contributing to the burden of LOC.ConclusionBetween 1990 and 2021, the disability burden from LOC in China increased, while the death burden decreased, and projections suggest these trends will persist over the next decade. A significant portion of this disease burden to modifiable risk factors, specifically tobacco use and excessive alcohol consumption, predominantly affecting males and individuals aged 40–79 years. Attention to these areas is essential for implementing targeted interventions and reducing the impact of LOC in China.

3D printing forming quality control is a research hotspot and difficulty. The traditional approach is either to optimize the printing material properties, to optimize the printing device structure, or to control the printing process, for achieving the purpose of precision printing. In fact, in the 3D printing control system (3DPCS), control and measurement signals are transmitted through open communication network, inevitably leads to communication and transmission delays, which can adversely affect the 3DPCS dynamics and even cause instability, not to mention guarantee precision printing. For such a time-delay system, this paper presents an open issue, i.e. the stability analysis and stabilization control problem of the 3DPCS, in order to serve the improvement of the printing accuracy. First, the 3DPCS framework and dynamic model with time-varying delay are proposed. Second, the delay-dependent stability and stabilization conditions of the 3DPCS are derived by constructing the augmented Lyapunov–Krasovskii functional (LKF) and by using the relaxed mixed convex combination technologies, after which less conservative conditions are obtained by introducing a free weighting matrix to improve the accuracy. Thus, the corresponding controller gain is further obtained. Finally, the 3DPCS example and a well-known numerical example are carried out. Simulation results show that the upper bound of acceptable time delay of systems are larger, and the controller designed based on the stabilization condition can ensure the stable operation of the 3DPCS. Both aspects demonstrate the advantages of the proposed approach.

Abstract The Aral Sea, located in Central Asia, has undergone significant reduction in surface area owing to the combined impacts of climate change and human activities. This reduction has led to a regional ecological crisis and profound repercussions on ecosystem services. Investigating the spatiotemporal variations and synergistic trade-offs of ESs in the Aral Sea basin is crucial for fostering the integrated development of the region’s socioeconomic ecology. This study utilizes the Future Land-Use Simulation and InVEST models to analyze future land-use scenarios, integrating CMIP6 projections to assess the quality of four key ecosystem services: water production, soil conservation, carbon storage, and habitat quality over two timeframes: the historical period (1995–2020) and the projected future (2021–2100). Employing Spearman correlation, the study explores the trade-offs and synergies among these ecosystem services. Findings reveal that the primary forms of land-use change in the Aral Sea basin are the reduction in water area (− 49.59%) and the rapid expansion of urban areas (+ 504.65%). Temporally, habitat quality exhibits a declining trend, while carbon storage shows an increasing trend, and water production and soil retention fluctuate initially decreasing and then increasing. Spatially, water production and carbon storage demonstrate an increasing trend from the northwest to the southeast. Habitat quality exhibits a higher spatial pattern in the southeast and south, contrasting with lower spatial patterns in the north and west. Low-level soil conservation is predominantly distributed in the northwest, while medium to low-level soil conservation is prevalent in the east of the basin. The trade-off and synergy analysis indicates that between 1995 and 2020, a trade-off relationship existed between carbon storage and habitat quality and water production, whereas synergies were observed between soil conservation and carbon storage, water production and habitat quality, and soil conservation. The correlation between water production and soil conservation emerges as the strongest, whereas the correlation between carbon storage and habitat quality appears to be the weakest. The dynamic spatiotemporal changes, trade-offs, and collaborative relationships of ESs constitute major aspects of ecosystem service research, holding substantial implications for the effective management of the regional ecological environment.

Abstract Background RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. Methods The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. Results The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. Conclusion Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

Abstract Parental experiences can affect the phenotypic plasticity of offspring. In locusts, the population density that adults experience regulates the number and hatching synchrony of their eggs, contributing to locust outbreaks. However, the pathway of signal transmission from parents to offspring remains unclear. Here, we find that transcription factor Forkhead box protein N1 (FOXN1) responds to high population density and activates the polypyrimidine tract-binding protein 1 (Ptbp1) in locusts. FOXN1–PTBP1 serves as an upstream regulator of miR-276, a miRNA to control egg-hatching synchrony. PTBP1 boosts the nucleo-cytoplasmic transport of pre-miR-276 in a “CU motif”-dependent manner, by collaborating with the primary exportin protein exportin 5 (XPO5). Enhanced nuclear export of pre-miR-276 elevates miR-276 expression in terminal oocytes, where FOXN1 activates Ptbp1 and leads to egg-hatching synchrony in response to high population density. Additionally, PTBP1-prompted nuclear export of pre-miR-276 is conserved in insects, implying a ubiquitous mechanism to mediate transgenerational effects.

Abstract In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.

Abstract Aberrant signaling pathway activity is a hallmark of tumorigenesis and progression, which has guided targeted inhibitor design for over 30 years. Yet, adaptive resistance mechanisms, induced by rapid, context-specific signaling network rewiring, continue to challenge therapeutic efficacy. Leveraging progress in proteomic technologies and network-based methodologies, we introduce Virtual Enrichment-based Signaling Protein-activity Analysis (VESPA)—an algorithm designed to elucidate mechanisms of cell response and adaptation to drug perturbations—and use it to analyze 7-point phosphoproteomic time series from colorectal cancer cells treated with clinically-relevant inhibitors and control media. Interrogating tumor-specific enzyme/substrate interactions accurately infers kinase and phosphatase activity, based on their substrate phosphorylation state, effectively accounting for signal crosstalk and sparse phosphoproteome coverage. The analysis elucidates time-dependent signaling pathway response to each drug perturbation and, more importantly, cell adaptive response and rewiring, experimentally confirmed by CRISPR knock-out assays, suggesting broad applicability to cancer and other diseases.

Abstract Background Goji (Lycium barbarum) is an important economic crop that is widely cultivated in Northwest China and is known as superfood. Goji plants are often affected by powdery mildew (Arthrocladiella mougeotii) in the field, resulting in considerable reduction in production and serious economic losses. The long-term reliance on agricultural chemicals to control powdery mildew not only leads to environmental pollution, but also causes excessive residues to accumulate in fruits, endangering human health. The plant epicuticular wax is the first physical barrier between land plants and the atmospheric environment, and plays an important role in the interactions of plants with pathogenic microorganisms. However, the relationship between epicuticular wax and powdery mildew resistance in goji plants is not well understood. Results The leaf epicuticular wax crystals of ‘Ningqi I’ goji were dense and small, and the wax load was 121.74 μg/cm2, which was 3.36 times greater than that of ‘Huangguo’ goji. The ratio of alcohol components in ‘Ningqi I’ goji was 121.18% greater than that in ‘Huangguo’ goji. The incidence rate and disease index of ‘Ningqi I’ goji inoculated with powdery mildew were significantly lower than those inoculated ‘Huangguo’ goji, showing high resistance and moderate susceptibility, respectively. After mechanical wax removal, the disease indices of the two goji varieties increased significantly, indicating extreme susceptibility. Seventeen differential expression genes showing significantly greater expression in ‘Ningqi’ goji leaves than in ‘Huangguo’ goji leaves were enriched in genes involved in fatty acid elongation and the wax biosynthesis pathway. The FAR activity and relative expression levels of LbaFAR and LbaWSD1 in ‘Ningqi I’ goji were significantly greater than those in ‘Huangguo’ goji. The relative expression levels of these genes significantly increased in the overexpression tobacco lines FAR-OE and WSD1-OE, and the wax load were augmented by 46.10% and 22.23%, respectively. Conclusions The increased expression of the LbaFAR and LbaWSD1 genes in ‘Ningqi I’ leaves led to increased FAR and WSD1 activity, increasing the wax load and alcohol content of the epicuticular of leaves, and improving leaf glossiness, resulting in strengthened resistance to powdery mildew. Therefore, the production of leaf epicuticular wax mediated by the LbaFAR and LbaWSD1 genes could be the main reason for the difference in powdery mildew resistance between the two goji varieties, which can provide a theoretical basis for the selection of resistant varieties to control goji powdery mildew. Graphical Abstract

Abstract Background Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. Methods Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. Results Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. Conclusions This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. Trial registration ISRCTN65203415.

Objective Evaluation of urban rail transit service quality based on passenger demand not only promotes service quality improvement and enhances passenger satisfaction with travel, but also contributes to economic and social benefits of urban rail transit operating enterprises. Method The QFD (quality function deployment) theory is introduced to obtain passenger demand data, which are identified, classified, filtered and refined into evaluation indicators. A quality evaluation index system for urban rail transit service based on passenger demand is constructed. Using AHP (analytic hierarchy process) and entropy weight method to calculate the weight of each indicator combination, and using a cloud model to obtain the comprehensive evaluation results of urban rail transit service quality. The IPA (importance-performance analysis) is introduced to conduct in-depth research on the evaluation results, further exploring the priority of the impact of each evaluation indicator on the overall service quality. Taking the first phase of the Kunming Metro project as an example, based on actual survey data, the final service quality evaluation results of the line are obtained through cloud model and analyzed using IPA. Result & Conclusion The service quality evaluation results of the first phase of Kunming Metro project are relatively satisfactory, consistent with the actual research conclusion of the project, demonstrating the effectiveness of the urban rail transit service quality evaluation method based on passenger demand. After conducting IPA analysis on the evaluation results of this example, specific strategies for improving the service quality of the first phase of Kunming Metro project are proposed: coordinating interchange, increasing the frequency of departure, and timely adjusting ventilation based on weather conditions.

Abstract Objectives This study aims to construct and apply a training course system which was scientific and comprehensive to foster the core competence of infectious disease specialist nurses. Design A two-round Delphi consultation survey was carried out to collect feedback from experts on constructing the training course system of core competence for infectious disease specialist nurses. Besides, a non-randomized controlled experimental study was adopted to check the application effect of the courses. Methods This study adopted a series of methods including group discussion, theoretical analysis and Delphi consultation to draft the training course content of core competence of infectious disease specialist nurses. Twenty-one Chinese experts were invited to participate in the Delphi consultation from November 2021 to December 2021. From October 2022 to January 2023, a total of 105 infectious disease specialist nurses from two training bases were selected by the convenience sampling method, of which the nurses in one training base were the control group and the nurses in the other training base were the observation group. The observation group was trained by the constructed core competence training course. Questionnaire evaluation was used to compare the core competence of infectious disease specialist nurses and the training effect. Results The experts, regarded as the authorities on the subject, were highly motivated in this study. Besides, they reached a consensus on the results. The final training course system of core competence for infectious disease specialist nurses focused on 5 competence modules and was composed of 12 categories of courses with 66 classes and corresponding objectives. The core competence scores of the observation group were significantly higher than those in the control group after training (P

Abstract Background Traumatic brain injury (TBI) is a common condition in veterinary medicine that is difficult to manage.Veterinary regenerative therapy based on adipose mesenchymal stem cells seem to be an effective strategy for the treatment of traumatic brain injury. In this study, we evaluated therapeutic efficacy of canine Adipose-derived mesenchymal stem cells (AD-MSCs)in a rat TBI model, in terms of improved nerve function and anti-neuroinflammation. Results Canine AD-MSCs promoted neural functional recovery, reduced neuronal apoptosis, and inhibited the activation of microglia and astrocytes in TBI rats. According to the results in vivo, we further investigated the regulatory mechanism of AD-MSCs on activated microglia by co-culture in vitro. Finally, we found that canine AD-MSCs promoted their polarization to the M2 phenotype, and inhibited their polarization to the M1 phenotype. What’s more, AD-MSCs could reduce the migration, proliferation and Inflammatory cytokines of activated microglia, which is able to inhibit inflammation in the central system. Conclusions Collectively, the present study demonstrates that transplantation of canine AD-MSCs can promote functional recovery in TBI rats via inhibition of neuronal apoptosis, glial cell activation and central system inflammation, thus providing a theoretical basis for canine AD-MSCs therapy for TBI in veterinary clinic.

Abstract Aims This study was designed to develop a biosafety incident response competence scale and evaluate its validity and reliability among clinical nurses. Design This study employed a sequential approach, comprising four phases: (1) the establishment of a multidimensional conceptual model, (2) the preliminary selection of the items, (3) further exploration and psychometric testing of the items, (4) the application of the scale among clinical nurses. Methods The biosafety incident response competence conceptual model was developed through literature review and the Delphi method. A total of 1,712 clinical nurses participated in the preliminary items selection, while 1,027 clinical nurses were involved in the further psychometric testing from July 2023 to August 2023. The item analysis, exploratory factor analysis and confirmatory factor analysis were conducted to evaluate the construct validity. Reliability was measured using Cronbach’s alpha, split-half reliability, and test-retest reliability, while validity analysis included content validity, structural validity, convergent validity, and discriminant validity. From September to November 2023, we conducted a survey using the established scale with a total of 4338 valid questionnaires collected. T-test and variance analysis was employed to determine potential variations in biosafety incident response competence based on participants characteristics. Results The final scale is composed of 4 factors and 29 items, including monitoring and warning abilities, nursing disposal abilities, biosafety knowledge preparedness, and infection protection abilities. The explanatory variance of the 4 factors was 75.100%. The Cronbach’s alpha, split-half reliability and test-retest reliability were 0.974, 0.945 and 0.840 respectively. The Scale-level content validity index was 0.866. The Average Variance Extracted of the 4 factors was larger than 0.5, the Construct Reliability was larger than 0.7, and the Heterotrait-Monotrait ratio were less than 0.9. There were significant differences in the scores of response competence among nurses of different ages, working years, titles, positions, departments, marital status and participation in biosafety training (all P

Abstract Background Although previous studies have found that parenting style significantly predicts emotional and behavioral problems (EBPs) among Chinese adolescents, the mechanism between different parenting styles and EBPs requires in-depth investigation. In our study, we aimed to investigate the mediating effect of resilience, a positive psychological characteristic, between parenting style and EBPs among Chinese adolescents. Methods In this cross-sectional study, we used a multistage stratified cluster random sampling method to collect data in Shenyang, Liaoning Province from November to December 2019. Self-developed questionnaires were distributed to 1028 adolescents aged 10–18. Finally, the study consisted of 895 participants. The bootstrap method was used to investigate the role of resilience as a mediator in the relationship between different parenting styles and EBPs from a positive psychology perspective. Results The mean score of EBPs was 12.71 (SD = 5.77). After controlling for variables such as gender, age, left-behind children, family type and family income, resilience partially played a mediating role in the associations of paternal rejection (a × b = 0.051 BCa95%CI:0.023,0.080), maternal rejection (a × b = 0.055 BCa95%CI: 0.024, 0.086), paternal emotional warmth (a × b = -0.139 BCa95%CI: -0.182, -0.099) and maternal emotional warmth (a × b = -0.140 BCa95%CI: -0.182, -0.102), with EBPs. The effect sizes were11.28%, 11.51%, 40.76%, and 38.78%, respectively. Conclusions Resilience could partially mediate the relationship between parenting style and EBPs, highlighting that parents should adopt a positive parenting style and that resilience improvement could be effective in reducing EBPs among Chinese adolescents.