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Abstract Traumatic dental injuries (TDIs) of teeth occur frequently in children and adolescents. TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion, subluxation, extrusive luxation, intrusive luxation, lateral luxation, and avulsion. In these TDIs, management of injured soft tissue, mainly periodontal ligament, and dental pulp, is crucial in maintaining the function and longevity of the injured teeth. Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth, mobility, direction of displacement, distance of displacement, and whether there are alveolar fractures. In avulsion, the maturation stage of the permanent tooth, the out-socket time, storage media/condition of the avulsed tooth, and management of the PDL should also be considered. Especially, in this review, we have subdivided the immature tooth into the adolescent tooth (Nolla stage 9) and the very young tooth (Nolla stage 8 and below). This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation, diagnostic process, management plan decision, follow-up, and orthodontic treatment for tooth luxation and avulsion injuries.

Abstract Background Complicated crown-root fractures are a type of tooth fracture that involves the enamel, dentin, and cementum and accompanied by pulp exposure. The treatment of a complicated crown-root fracture is always challenging due to the difficulties in achieving a hermetic seal and a stable restoration with a fracture level close to the crestale bone level. This study aimed to evaluate and compare the efficacy of single-visit and multi-visit approaches for fragment reattachment in complicated crown-root fractures of anterior teeth. Methods Two cohort consist of 10 adolescent patients in each group at both genders, who suffered from permanent anterior tooth complicated crown-root fracture were included. Fragment reattachment with root canal treatment was performed with either single or multiple-visit approach. Single visit fragment attachement combined with root cannel therapy was conducted in single-visit approach group immediately after injury. Fragment attachment, root cananel therapy and post resoration were performed during three times ‘ clinical visit in multi-visit approach group. Results All the patients in both groups achieved satisfactory aesthetic results one year after fragment reattachment. Patients who underwent a multi-visit approach had a significantly shorter operative duration, less intra-operative pain and fatigue, slightly better periodontal health at an early stage, and a decreased incidence of temporomandibular joint disorders compared to those who underwent a single-visit approach. However, multiple visits approach may increase the risk of fragment detachment postoperatively. Conclusion Fragment reattachment a reliable but temporary technique for adolescent patients who have suffered from complicated crown-root fractures. Multi-visit approach showed similar effecacy to single-visit approach but with slightly less complications. The choose of these two merhos should depend on the specific patient situation and patient compliance. Trial registration This prospective cohort study was retrospectively registered in Chinese Clinical Trial Registry (ChiCTR2300076811) on 19/10/2023.

Abstract Fusarium oxysporum (Schl.) f.sp. melonis, which causes muskmelon wilt disease, is a destructive filamentous fungal pathogen, attracting more attention to the search for effective fungicides against this pathogen. In particular, Silver nanoparticles (AgNPs) have strong antimicrobial properties and they are not easy to develop drug resistance, which provides new ideas for the prevention and control of muskmelon Fusarium wilt (MFW). This paper studied the effects of AgNPs on the growth and development of muskmelon, the control efficacy on Fusarium wilt of muskmelon and the antifungal mechanism of AgNPs to F. oxysporum. The results showed that AgNPs could inhibit the growth of F. oxysporum on the PDA and in the PDB medium at 100–200 mg/L and the low concentration of 25 mg/L AgNPs could promote the seed germination and growth of muskmelon seedlings and reduce the incidence of muskmelon Fusarium wilt. Further studies on the antifungal mechanism showed that AgNPs could impair the development, damage cell structure, and interrupt cellular metabolism pathways of this fungus. TEM observation revealed that AgNPs treatment led to damage to the cell wall and membrane and accumulation of vacuoles and vessels, causing the leakage of intracellular contents. AgNPs treatment significantly hampered the growth of mycelia in the PDB medium, even causing a decrease in biomass. Biochemical properties showed that AgNPs treatment stimulated the generation of reactive oxygen species (ROS) in 6 h, subsequently producing malondialdehyde (MDA) and increasing protective enzyme activity. After 6 h, the protective enzyme activity decreased. These results indicated that AgNPs destroy the cell structure and affect the metabolisms, eventually leading to the death of fungus.

Abstract To investigate whether sepsis-induced neuroinflammation of medulla visceral zone (MVZ) predominates the systemic inflammation through cholinergic anti-inflammatory pathway (CAP), and to explore the effect of central anti-inflammation on systemic inflammation. 112 adult Sprague–Dawley male rats were randomly divided into sepsis experimental group (n = 56) and neuroinflammation experimental group (n = 56). The two experimental groups were individually randomly divided into control group (n = 8), model group (n = 16), central anti-inflammatory group (n = 16) and vagus transection group (n = 16). Rats in two control groups were administered with saline at the dose of 6 mL/kg intraperitoneally or with 25 μL artificial cerebrospinal fluid injected into forth ventricle once a day for 3 days. Rats in two model groups were administered with Lipopolysaccharide (LPS) at the dose of 6 mg/kg intraperitoneally or with 25 μg/25 μL LPS injected into forth ventricle once a day for 3 days. Rats in two central anti-inflammatory groups were fed with 10 mg/mL minocycline sucrose solution as the only water source for 4 days prior to be treated as the model groups of their own, and feeding style was continued until the end of the experiment. Rats in the two vagus transection groups were undergone right vagotomy and 7 days of adaptive feeding prior to be treated as the same as those in the central anti-inflammatory group of their own. The Murine Sepsis Score (MSS), mortality rate and heat rate variability (HRV) were recorded during the last 3 days of intervention. Then the rats were sacrificed and blood samples were collected for ELISA analysis to detect the serum level of inflammatory cytokines such as TNF-α, IL-6, and IL-10. The expression of TNF-α and IL-6 in medulla oblongata were analyzed by Western blot. The correlation and regression analysis among the expression levels of cytokines in medulla oblongata, HRV indexes and serum inflammatory cytokines were performed. The mortality rate and MSS of the sepsis model group and the MVZ’s neuroinflammation model group were significantly higher than those of their own control group, and the central anti-inflammation reduced the mortality rate and MSS scores of the two model groups, while the right vagotomy abolished the effect of central anti-inflammatory. In the sepsis model group and the MVZ’s neuroinflammation model group, the levels of TNF-α, IL-6, and other cytokines in serum and MVZ were significantly increased, and HRV indexes (SDNN, RMSSD, LF, HF, LF/HF) were significantly decreased (P = 0.000). Central anti-inflammatory treatment reversed the above changes. However, right vagotomy abolished the central anti-inflammatory effect. Correlation and regression analysis showed that there was a significant linear correlation among the expression of inflammatory factors in MVZ, the indexes of HRV and the levels of serum cytokines. Our study shows that sepsis-induced MVZ’s neuroinflammation exert a powerful influence on the systemic inflammation through CAP in sepsis. Central anti-inflammation effectively improves systemic inflammation through inhibiting MVZ’s neuroinflammation in sepsis. The time domain and frequency domain indexes of HRV can reflect the regulatory effect of CAP and the degree of inflammation of MVZ, which may be potentially used to monitor the condition and treatment effectiveness of sepsis patients.

Abstract α-Actinins play crucial roles in cytoskeletal mechanobiology by acting as force-bearing structural modules that orchestrate and sustain the cytoskeletal framework, serving as pivotal hubs for diverse mechanosensing proteins. The mechanical stability of α-actinin dimer, a determinant of its functional state, remains largely unexplored. Here, we directly quantify the force-dependent lifetimes of homo- and hetero-dimers of human α-actinins, revealing an ultra-high mechanical stability of the dimers associated with > 100 seconds lifetime within 40 pN forces under shear-stretching geometry. Intriguingly, we uncover that the strong dimer stability is arisen from much weaker sub-domain pair interactions, suggesting the existence of distinct dimerized functional states of the dimer, spanning a spectrum of mechanical stability, with the spectrin repeats (SRs) in folded or unfolded conformation. In essence, our study supports a potent mechanism for building strength in biomolecular dimers through weak, multiple sub-domain interactions, and illuminates multifaceted roles of α-actinin dimers in cytoskeletal mechanics and mechanotransduction.

Abstract Objectives To construct and validate multiparametric MR-based radiomic models based on primary tumors for predicting lymph node metastasis (LNM) following neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) patients. Methods A total of 150 LARC patients from two independent centers were enrolled. The training cohort comprised 100 patients from center A. Fifty patients from center B were included in the external validation cohort. Radiomic features were extracted from the manually segmented volume of interests of the primary tumor before and after nCRT. Feature selection was performed using multivariate logistic regression analysis. The clinical risk factors were selected via the least absolute shrinkage and selection operator method. The radiologist’s assessment of LNM was performed. Eight models were constructed using random forest classifiers, including four single-sequence models, three combined-sequence models, and a clinical model. The models’ discriminative performance was assessed via receiver operating characteristic curve analysis quantified by the area under the curve (AUC). Results The AUCs of the radiologist’s assessment, the clinical model, and the single-sequence models ranged from 0.556 to 0.756 in the external validation cohort. Among the single-sequence models, modelpost_DWI exhibited superior predictive power, with an AUC of 0.756 in the external validation set. In combined-sequence models, modelpre_T2_DWI_post had the best diagnostic performance in predicting LNM after nCRT, with a significantly higher AUC (0.831) than those of the clinical model, modelpre_T2_DWI, and the single-sequence models (all p

Abstract Introduction Virtual Patients (VPs) have been shown to improve various aspects of medical learning, however, research has scarcely delved into the specific factors that facilitate the knowledge gain and transfer of knowledge from the classroom to real-world applications. This exploratory study aims to understand the impact of integrating VPs into classroom learning on students’ perceptions of knowledge acquisition and transfer. Methods The study was integrated into an elective course on “Personalized Medicine in Cancer Treatment and Care,” employing a qualitative and quantitative approach. Twenty-two second-year medical undergraduates engaged in a VP session, which included role modeling, practice with various authentic cases, group discussion on feedback, and a plenary session. Student perceptions of their learning were measured through surveys and focus group interviews and analyzed using descriptive statistics and thematic analysis. Results Quantitative data shows that students highly valued the role modeling introduction, scoring it 4.42 out of 5, and acknowledged the practice with VPs in enhancing their subject matter understanding, with an average score of 4.0 out of 5. However, students’ reflections on peer dialogue on feedback received mixed reviews, averaging a score of 3.24 out of 5. Qualitative analysis (of focus-group interviews) unearthed the following four themes: ‘Which steps to take in clinical reasoning’, ‘Challenging their reasoning to enhance deeper understanding’, ‘Transfer of knowledge ‘, and ' Enhance Reasoning through Reflections’. Quantitative and qualitative data are cohered. Conclusion The study demonstrates evidence for the improvement of learning by incorporating VPs with learning activities. This integration enhances students’ perceptions of knowledge acquisition and transfer, thereby potentially elevating students’ preparedness for real-world clinical settings. Key facets like expert role modeling and various authentic case exposures were valued for fostering a deeper understanding and active engagement, though with some mixed responses towards peer feedback discussions. While the preliminary findings are encouraging, the necessity for further research to refine feedback mechanisms and explore a broader spectrum of medical disciplines with larger sample sizes is underscored. This exploration lays a groundwork for future endeavors aimed at optimizing VP-based learning experiences in medical education.

Abstract In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p

Abstract Background The crossbreeding of specialized beef cattle breeds with Chinese indigenous cattle is a common method of genetic improvement. Xia’nan cattle, a crossbreed of Charolais and Nanyang cattle, is China’s first specialized beef cattle breed with independent intellectual property rights. After more than two decades of selective breeding, Xia’nan cattle exhibit a robust physique, good environmental adaptability, good tolerance to coarse feed, and high meat production rates. This study analyzed the population genetic structure, genetic diversity, and genomic variations of Xia’nan cattle using whole-genome sequencing data from 30 Xia’nan cattle and 178 published cattle genomic data. Result The ancestry estimating composition analysis showed that the ancestry proportions for Xia’nan cattle were mainly Charolais with a small amount of Nanyang cattle. Through the genetic diversity studies (nucleotide diversity and linkage disequilibrium decay), we found that the genomic diversity of Xia’nan cattle is higher than that of specialized beef cattle breeds in Europe but lower than that of Chinese native cattle. Then, we used four methods to detect genome candidate regions influencing the excellent traits of Xia’nan cattle. Among the detected results, 42 genes (θπ and CLR) and 131 genes (F ST and XP-EHH) were detected by two different detection strategies. In addition, we found a region in BTA8 with strong selection signals. Finally, we conducted functional annotation on the detected genes and found that these genes may influence body development (NR6A1), meat quality traits (MCCC1), growth traits (WSCD1, TMEM68, MFN1, NCKAP5), and immunity (IL11RA, CNTFR, CCL27, SLAMF1, SLAMF7, NAA35, and GOLM1). Conclusion We elucidated the genomic features and population structure of Xia’nan cattle and detected some selection signals in genomic regions potentially associated with crucial economic traits in Xia’nan cattle. This research provided a basis for further breeding improvements in Xia’nan cattle and served as a reference for genetic enhancements in other crossbreed cattle.

Charcoal, a byproduct of biomass burning, is widely and heterogeneously distributed in fire-affected ecosystems. However, few field studies have been conducted to evaluate the effects of fire-deposited charcoal on the post-fire soil quality. In this study, we aimed to investigate whether charcoal generated during post timber harvest broadcast burning influenced the recovery of individual soil properties and overall soil quality in subtropical forest plantations. Broadcast burning was conducted on experimental Pinus massoniana plantation timber harvest sites in southern China. Surface soils (0–10 cm) were collected in plots established on the burnt sites five years after the disturbance event. Plots were established immediately after burning with three different levels of charcoal input (C0, removal of all visible charcoal; C1, charcoal retained in-situ; C2, charcoal removed from C0 added to C2) and an unburnt control (UB). Thirty-two soil indicators representing soil physical, chemical, and biological properties were determined. The results showed that 11 indicators exhibited significant differences among the treatments, with significantly lower SOM, microbial biomass carbon (MBC), peroxidase (POD) and leucine aminopeptidase (LAP) activities for the C0 and C1 plots than the UB plots (P 0.05). The soil available N, P and exchangeable nutrient contents were not significantly different among the treatments (P > 0.05). Our results indicate that SOM and microbial attributes did not recover five years after the disturbance event and that charcoal appeared to play a positive role in the post-fire soil restoration. Whether the accelerated recovery of soil restoration induced by charcoal might contribute to higher forest productivity needs to be testified in combination with plant growth and performance analysis in the future.

Background: To investigate the long-term corneal stromal remodeling and central stromal thickness (CST) reduction accuracy after small-incision lenticule extraction (SMILE) for high myopia correction. Methods: This prospective study included 30 patients (50 eyes) who had undergone SMILE. Measurements of CST reduction using optical coherence tomography were performed at 1 month, 6 months, 1 year, and 3 years after surgery. Correlations were performed between planned and achieved CST reductions. Results: The study enrolled 50 eyes of 30 patients. The mean spherical equivalent was -9.25±1.52 D(diopters). The postoperative CST increased in the first month after surgery and remained stable for a year. Thereafter, it remained stable during follow-up from 1 to 3 years postoperatively. The predicted CST reduction was 146.4 ± 10.3 μm. The achieved CST reductions at 1 month, 6 months, 1 year, and 3 years after surgery were 135.3 ± 12.1 μm, 130.8 ± 10.6 μm, 125.9 ± 9.4 μm, and 122.2 ± 10.6 μm, respectively. An overestimation of CST reduction was observed three years after surgery. Correlation analysis revealed a strong correlation between planned and achieved CST reductions; however, no correlation was found between CST reductions predicted error and the planned CST reductions. Conclusion: During long-term follow-up, our findings revealed a significant stromal remodeling following SMILE in patients with high myopia. Therefore, clinicians should consider it when screening patients with high myopia for SMILE.

Summary: Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3′ untranslated regions (3′ UTRs), thereby regulating mRNA localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, the precise regulatory mechanisms governing cell-type-specific APA remain unclear. In this study, we uncover PQBP1 as an emerging APA regulator that actively maintains cell-specific APA profiles in neural progenitor cells (NPCs) and delicately manages the equilibrium between NPC proliferation and differentiation. Multi-omics analysis shows that PQBP1 directly interacts with the upstream UGUA elements, impeding the recruitment of the CFIm complex and influencing polyadenylation site selection within genes associated with the cell cycle. Our findings elucidate the molecular mechanism by which PQBP1 orchestrates dynamic APA changes during neurogenesis, providing valuable insights into the precise regulation of cell-type-specific APA and the underlying pathogenic mechanisms in neurodevelopmental disorders.

Axon projection is a spatial- and temporal-specific process in which the growth cone receives environmental signals guiding axons to their final destination. However, the mechanisms underlying changes in axonal projection direction without well-defined landmarks remain elusive. Here, we present evidence showcasing the dynamic nature of axonal projections in Drosophila’s small ventral lateral clock neurons (s-LNvs). Our findings reveal that these axons undergo an initial vertical projection in the early larval stage, followed by a subsequent transition to a horizontal projection in the early-to-mid third instar larvae. The vertical projection of s-LNv axons correlates with mushroom body calyx expansion, while the s-LNv-expressed Down syndrome cell adhesion molecule (Dscam1) interacts with Netrins to regulate the horizontal projection. During a specific temporal window, locally newborn dorsal clock neurons secrete Netrins, facilitating the transition of axonal projection direction in s-LNvs. Our study establishes a compelling in vivo model to probe the mechanisms of axonal projection direction switching in the absence of clear landmarks. These findings underscore the significance of dynamic local microenvironments in the complementary regulation of axonal projection direction transitions.

Background: Our previous studies have demonstrated that the activated Cholinergic Anti-inflammatory Pathway (CAP) effectively suppresses systemic inflammation and immunity in early sepsis. Some parameters of Heart Rate Variability (HRV) could be used to reflect the regulatory activity of CAP. However, in the early stages of severe sepsis of some patients, the inflammatory storm can still result in multiple organs dysfunction and even death, suggesting they lose CAP's modulation ability. Since CAP is part of the vagus nerve and is directly innervated by the Medullary Visceral Zone (MVZ), we can reasonably concluded that pathological changes induced by MVZ's neuroinflammation should be responsible for CAP's dysfunction in modulating systemic inflammation in early sepsis. Methods: We conducted two independent septic experiments, the sepsis model rats were prepared by cecum ligation and puncture (CLP) method. In the first experiment, A total of 64 adult male Sprague-Dawley rats were included. Under the condition of sepsis and CAP's pharmacological activation or blockade, we investigated the MVZ's pathological changes, the functional state of key neurons including catecholaminergic and cholinergic neurons, key genes' expression such as Oligodendrocyte Transcription Factor 2 (Olig-2) mRNA, glial fibrillary acidic protein (GFAP) mRNA, and matrix metalloprotein (MMP) −9 mRNA, and CAP's activities reflected by HRV. The second experiment involved in 56 rats, through central anti-inflammation by feeding with 10 mg/ml minocycline sucrose solution as the only water source, or right vagus transection excepting for central anti-inflammation as a mean of the CAP's functional cancel, we confirmed that the neuroinflammation in MVZ affected systemic inflammation through CAP in sepsis. Results: In the first experiment, cholinergic and catecholaminergic neurons showed significant apoptosis with reduced expressions of TH, but the expression of CHAT remained relatively unaffected in MVZ in sepsis. HRV parameters representing the tone of the vagus nerve, such as SDNN, RMSSD, HF, SD1, and SD2, did not show significant differences among the three Septic Groups, although they all decreased significantly compared to the Control Group. The expressions of GFAP mRNA and MMP-9 mRNA were up-regulated, while the expression of Olig-2 mRNA was down-regulated in the Septic Groups. Intervention of CAP had a significant effect on cholinergic and catecholaminergic neurons' apoptosis, as well as the expressions of TH/CHAT and these key genes, but had little effect on HRV in sepsis. In the second experiment, the levels of TNF-α, IL-6, in serum and MVZ were significantly increased in sepsis. Central anti-inflammatory treatment reversed these changes. However, right vagotomy abolished the central anti-inflammatory effect. Conclusions: Our study uncovered that MVZ's neuroinflammation may play a crucial role in the uncontrolled systemic inflammation through inflammatory demyelination in MVZ, which disrupts CAP's modulation on the systemic inflammation in early sepsis.

Resources and the environment are essential for socioeconomic development. A scientific and reasonable evaluation and forewarning of the resource and environmental carrying capacity (RECC) is of great significance for regional sustainable development. Although great progress has made in existing research on RECC, there is still no consensus on the definition, evaluation and forewarning method for RECC. Therefore, this study introduced the novel concepts of pressure, support and adjustment, proposed a theoretical framework of RECC reflecting the interaction between the above three, constructed a new evaluation index system of RECC, evaluated RECC based on the ratio method, identified important influencing factors using obstacle model, and put forward the hierarchical forewarning method of RECC with the threshold of 1. Finally, a case demonstration in regard to Yichang city, with a prominent ecological and economic status as the location of China’s Three Gorges Project, was conducted. The results revealed that: 1) The average pressure, support, and adjustment exhibited overall upward trends. The pressure and adjustment increased from west to east, while the support of central districts was relatively lower. 2) The RECC of Yichang city and counties improved from 2016 to 2021, increasing from west to east, and the differences in the RECC of various counties were remarkable but gradually shrank. 3) The RECC of Yichang city remained at the Non-Alert Level. The number of counties with RECC values at Alert Level II decreased from two to zero, and the number of counties at the Non-Alert Level increased from eight to ten. Xiaoting and Zhijiang, with more RECC values at Alert Level II, should receive more attention. This study is expected to enrich the methodology of RECC evaluation and forewarning, and provide possible implications for economic development and environmental protection planning in Yichang and other cities of the same type.

Abstract Background While mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant challenge in China, research investigating the effectiveness of the September 2017 pilot program to eliminate MTCT of HIV, syphilis, and HBV is limited. Baoan district, which has a higher-than-average rate of hepatitis B infection among pregnant women and strong support from the government, was one of six national pilot districts selected for the program. Therefore, this study aims to assess the progress and implementation of the elimination of MTCT of HBV in Baoan district over a period of 5 years. Methods Data was collected from the national information system for the prevention of MTCT, registration forms, and follow-up forms of pregnant women and their live births from 2018 to 2022. Joinpoint models were used to analyze changing trends over time, calculating annual percentage change (APC) and the corresponding 95% confidence interval (95%CI). Multivariate logistic regression models were used to analyze risk factors for HBV MTCT. Results From 2018 to 2022, the coverage of HBV screening during pregnancy increased from 98.29 to 99.55% (APC = 0.30, P = 0.012). The coverage of HBV early screening within 13 gestational weeks increased from 40.76 to 86.42% (APC = 18.88, P = 0.033). The prevalence of maternal HBV infection declined by an APC of − 3.50 (95% CI -6.28 ~ − 0.63). The coverage of antiviral therapy among high-risk pregnant women increased from 63.59 to 90.04% (APC = 11.90, P = 0.031). Coverage for timely administration of hepatitis B immunoglobulin, hepatitis B birth dose vaccine, and three-dose hepatitis B vaccination remained consistently above 97.50%. The coverage of post-vaccination serological testing (PVST) in high-risk infants was 56.15% (1352/2408), and the MTCT rate of HBV was 0.18%. Mothers with high-school education or below (OR = 3.76, 95% CI 1.04 ~ 13.60, P = 0.04) and hepatitis B e antigen (HBeAg) positivity (OR = 18.89, 95% CI 1.98 ~ 18.50, P = 0.01) had increased MTCT risk. Conclusions The implementation of comprehensive prevention strategies in Baoan district, including screening, treatment, and immunoprophylaxis, has proven effective in maintaining the MTCT of HBV at an extremely low level. However, it remains crucial to raise public awareness, specifically on the importance of improving the coverage of PVST for infants exposed to HBV.

In order to comply with the development trend of the “Brain Project”, China has listed the neural basis for explaining cognitive function as a core pillar, emphasizing the investment of resources and research capabilities into urgent social needs such as early diagnosis and intervention treatment of neurological and psychiatric diseases. The control scheme proposed on the basis of neural computational models can predict changes in brain dynamics induced by neurostimulation, which helps to develop more effective treatment plans for neurological and psychiatric diseases, while reducing the risk of brain damage and secondary injury that may result from direct animal experiments or clinical trials. The paper presents such a theoretical method for modulating brain dynamics based on the concept of pinning control from complex network control theory to suppress spikes generated by neural population networks affected by measurement noise. The main issues to be addressed of the work include: how to select driving nodes (the locations where need to exert neurostimulation) to better ensure the effectiveness of pinning strategies for neural population networks with different topologies? What are relationships among control gain, control energy, coupling strength and the number of driving nodes while ensuring the effectiveness of control strategies? To solve these problems, firstly, based on the Wendling-type neural population model, graph theory and complex network theory are applied to construct neural population networks with “nearest-neighbor”, “scale-free” and “small-world” topologies, respectively. Then, different pinning control strategies are designed to modulate the brain dynamics simulated by the established network models according to the degree distribution, and better strategies are determined through simulation experiments. The local control adopts the output-feedback method based on the fuzzy regulator and cubature Kalman filter algorithm. Finally, the effects of coupling strength and number of driving nodes on control gain amplitude and control energy are studied using analytical and statistical methods. This work provides new ideas for the development of neuromodulation strategies in the treatment of neurological and psychiatric diseases, and is expected to play a potential role in future clinical applications.

Abstract Psoraleae Fructus (PF) is a widely-used herb with diverse pharmacological activities, while its related hepatic injuries have aroused public concerns. In this work, a systematic approach based on RNA sequencing (RNA-seq), high-content screening (HCS) and molecular docking was developed to investigate the potential mechanism and identify major phytochemicals contributed to PF-induced hepatotoxicity. Animal experiments proved oral administration of PF water extracts disturbed lipid metabolism and promoted hepatic injuries by suppressing fatty acid and cholesterol catabolism. RNA-seq combined with KEGG enrichment analysis identified mitochondrial oxidative phosphorylation (OXPHOS) as the potential key pathway. Further experiments validated PF caused mitochondrial structure damage, mtDNA depletion and inhibited expressions of genes engaged in OXPHOS. By detecting mitochondrial membrane potential and mitochondrial superoxide, HCS identified bavachin, isobavachalcone, bakuchiol and psoralidin as most potent mitotoxic compounds in PF. Moreover, molecular docking confirmed the potential binding patterns and strong binding affinity of the critical compounds with mitochondrial respiratory complex. This study unveiled the underlying mechanism and phytochemicals in PF-induced liver injuries from the view of mitochondrial dysfunction.

Abstract Objectives To evaluate the image quality and utility of virtual monoenergetic images (VMI) of dual-layer spectrum computed tomography (DLSCT) in assessing preoperative T-stage for early rectal adenocarcinoma (ERA). Methods This retrospective study included 67 ERA patients (mean age 62 ± 11.1 years) who underwent DLSCT and MR examination. VMI 40–200 keV and poly energetic image (PEI) were reconstructed. The image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and tumor contrast of different energy levels were calculated and compared, respectively. Two radiologists independently assess the image quality of the VMIs and PEI using 5-point scales. The diagnostic accuracies of DLSCT and HR-MRI for ERA T-staging were evaluated and compared. Results The maximum noise was observed at VMI 40 keV, and noise at VMI 40–200 keV in the arterial and venous phases showed no significant difference (all p > 0.05). The highest SNR and CNR were obtained at VMI 40 keV, significantly greater than other energy levels and PEI (all p < 0.05). Tumor contrast was more evident than PEI at 40–100 keV in the arterial phase and at 40 keV in the venous phase (all p < 0.05). When compared with PEI, VMI 40 keV yielded the highest scores for overall image quality, tumor visibility, and tumor margin delineation, especially in the venous phase (p < 0.05). The overall diagnostic accuracy of DLSCT and HR-MRI for T-stage was 65.67 and 71.64% and showed no significant difference (p > 0.05). Conclusions VMI 40 keV improves image quality and accuracy in identifying lesions, providing better diagnostic information for ERA staging. Critical relevance statement Low-keV VMI from DLSCT can improve tumor staging accuracy for early rectal carcinoma, helping guide surgical intervention decisions, and has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC. Keypoints • Compared with PEI, low-keV VIM derived from DLSCT, particularly at the 40 keV, significantly enhanced the objective and subjective image quality of ERA. • Using VMI 40 keV helped increase lesion detectability, leading to improved diagnostic accuracy for ERA. • Low-keV VMI from DLSCT has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC. Graphical Abstract

Patients experiencing severe aortic stenosis with acute decompensation often face elevated surgical aortic valve replacement risks, leading to high postoperative mortality rates. However, for some patients eligible for transcatheter aortic valve implantation (TAVI), computed tomography angiography for assessing the aortic root and coronary artery might be challenging before the TAVI procedure. This case highlights a patient who underwent emergency TAVI guided by coplane view generated using J-tipped wires fluoroscopy without computed tomography evaluation before the TAVI. This approach reduces contrast usage during the TAVI procedure, significantly mitigating the risks of renal injury and heart function deterioration.

Contact interface is essential for the dynamic response of the bolted structures. To accurately predict the dynamic characteristics of bolted joint structures, a fractal extension of the segmented scale model, i.e., the JK model, is proposed in this paper to comprehensively analyze the dynamic contact performance of engineering surfaces and revisit the multi-scale model based on the concept of asperities. The influence of asperity geometry, dimensionless material properties, and the elastic, elastoplastic, and full plastic mechanical models of a single asperity is established considering the asperity–substrate interaction. Then, a segmented scale contact model of rough surfaces is proposed based on the island distribution function in a strict sense. The mechanical contact process of determining rough surfaces is divided into small-scale, medium-scale, and large-scale stages. Moreover, cross-scale boundary conditions, i.e., al1′, al2′, and al3′, are provided through strict mathematical deduction. The results show that the real contact area and contact stiffness are positively correlated with fractal dimension and negatively correlated with fractal roughness. On a small scale, the contact damping decreases with an increase in load. In meso-scale and large-scale stages, the contact damping increases with the load. Finally, the reliability of the proposed model is verified by setting up three groups of modal vibration experiments.

Background: Vancomycin is a first-line drug for the treatment of MRSA infection. However, overuse of vancomycin can cause bacteria to become resistant, forming resistant strains and making infections more difficult to treat. This study aimed to evaluate the efficacy and safety of different antibiotics in the treatment of MRSA infections and to compare them, mainly with vancomycin, to find better vancomycin alternatives. Methods: All studies were obtained from the PubMed and Embase databases from inception to 13 April 2023. The three comprehensive indicators of clinical cure success rate, clinical microbiological success rate, and adverse reactions were evaluated, and the clinical cure success rates of three disease types, complex skin and skin structure infections (cSSSIs), complex skin and soft tissue infections (cSSTIs), and pneumonia, were analyzed in subgroups. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. Results: A total of 38 trials with 6281 patients were included, and 13 drug treatments were evaluated. For MRSA infections, the results of network meta-analysis showed that the clinical success rates of linezolid, the combination of vancomycin and rifampin, and the combination of minocycline and rifampin were better than that of vancomycin (RR 1.71; 95%-CI 1.45–2.02), (RR 2.46; 95%-CI 1.10–5.49) (RR, 2.77; 95%-CI 1.06–7.21). The success rate of clinical microbiological treatment with vancomycin was inferior to that with telavancin (RR 0.74; 95%-CI 0.55–0.99). Linezolid had a higher rate of adverse reactions than teicoplanin (RR 5.35; 95%-CI 1.10–25.98). Subgroup analysis showed that vancomycin had a lower clinical success rate than linezolid in the treatment of MRSA-induced cSSSIs, cSSTIs, and pneumonia (RR 0.59; 95%-CI 0.44–0.80) (RR 0.55; 95%-CI 0.35–0.89) (RR 0.55; 95%-CI 0.32–0.93). Conclusions: This systematic review and NMA provide a new comparison framework for the clinical treatment of MRSA infection. The NMA suggests that linezolid may be the antibiotic of choice for the treatment of MRSA infections, with the ability to improve clinical and microbiological success rates despite its disadvantage in terms of adverse effects. At the same time, the combination of minocycline and rifampicin may be the most effective drug to treat MRSA-induced cSSSIs, tedizolid may be the best drug to treat MRSA-induced cSSTIs, and the combination of vancomycin and rifampicin may be the most effective treatment for MRSA-induced pneumonia. More high-quality studies are still needed in the future to further identify alternatives to vancomycin. Trial registration: PROSPERO registration number CRD42023416788.

Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the “gold standard” for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.

ABSTRACTSaccharomyces cerevisiae (baker’s yeast, budding yeast) is one of the most important model organisms for biological research and is a crucial microorganism in industry. Currently, a huge number of Saccharomyces cerevisiae genome sequences are available at the public domain. However, these genomes are distributed at different websites and a large number of them are released without annotation information. To provide one complete annotated genome data resource, we collected 2,507 Saccharomyces cerevisiae genome assemblies and re-annotated 2,506 assemblies using a custom annotation pipeline, producing a total of 15,407,164 protein-coding gene models. With a custom pipeline, all these gene sequences were clustered into families. A total of 1,506 single-copy genes were selected as marker genes, which were then used to evaluate the genome completeness and base qualities of all assemblies. Pangenomic analyses were performed based on a selected subset of 847 medium-high-quality genomes. Statistical comparisons revealed a number of gene families showing copy number variations among different organism sources. To the authors’ knowledge, this study represents the largest genome annotation project of S. cerevisiae so far, providing rich genomic resources for the future studies of the model organism S. cerevisiae and its relatives.IMPORTANCESaccharomyces cerevisiae (baker’s yeast, budding yeast) is one of the most important model organisms for biological research and is a crucial microorganism in industry. Though a huge number of Saccharomyces cerevisiae genome sequences are available at the public domain, these genomes are distributed at different websites and most are released without annotation, hindering the efficient reuse of these genome resources. Here, we collected 2,507 genomes for Saccharomyces cerevisiae, performed genome annotation, and evaluated the genome qualities. All the obtained data have been deposited at public repositories and are freely accessible to the community. This study represents the largest genome annotation project of S. cerevisiae so far, providing one complete annotated genome data set for S. cerevisiae, an important workhorse for fundamental biology, biotechnology, and industry.

Resistance to chimeric antigen receptor (CAR) T-cell therapy remains a significant challenge in the treatment of solid tumors. This resistance is attributed to various factors, including antigen loss, immunosuppressive tumor microenvironment, and upregulated checkpoint molecules. Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that promotes immune escape in tumors. In this study, we investigated the role of ARID5A (AT-rich interactive domain 5A) in resistance to CAR-T cell therapy. Our findings revealed that ARID5A upregulation in tumor cells induces T cell exhaustion and immune evasion. Mechanistically, ARID5A plays a crucial role in resistance to CAR-T cell therapy by stabilizing IDO1 mRNA, leading to upregulation of IDO1 expression. Elevated IDO1 expression facilitates the conversion of tryptophan to kynurenine, which contributes to CAR-T cell exhaustion. Moreover, kynurenine accumulation within CAR-T cells activates the aryl hydrocarbon receptor (AhR), further exacerbating the exhaustion phenotype. Importantly, we demonstrated that targeting the ARID5A-IDO1-AhR axis using AhR or IDO1 inhibitors effectively alleviated T cell exhaustion induced by ARID5A. These findings suggest that modulating the ARID5A-IDO1-AhR axis may represent a promising therapeutic strategy to overcome CAR T-cell therapy resistance in solid tumors and enhance treatment efficacy.

Abstract Biochar is produced by burning biomass under oxygen‐limited conditions, and it has been widely used as a soil amendment to improve soil functions such as nutrient retention. However, whether the impact of biochar application on soil nitrogen (N) transformation and N2O emission varies with the pyrolysis temperature remains unclear, especially in different forest types in subtropical regions. In this study, a 60‐day laboratory incubation experiment was conducted to evaluate the impact of biochar with different pyrolysis temperatures (300°C [BC300], 500°C [BC500], and 800°C [BC800]) on net N transformation rates and N2O emission in soils collected from Castanopsis kawakamii dominated natural forest (NF) and Chinese fir (Cunninghamia lanceolate, CF) plantation in subtropical China. The results showed that the application of biochar significantly increased soil ammonium (NH4+) content (p

Abstract BRISC (BRCC3 isopeptidase complex) is a deubiquitinating enzyme that has been linked with inflammatory processes, but its role in liver diseases and the underlying mechanism are unknown. Here, we investigated the pathophysiological role of BRISC in acute liver failure using a mice model induced by D-galactosamine (D-GalN) plus lipopolysaccharide (LPS). We found that the expression of BRISC components was dramatically increased in kupffer cells (KCs) upon LPS treatment in vitro or by the injection of LPS in D-GalN-sensitized mice. D-GalN plus LPS-induced liver damage and mortality in global BRISC-null mice were markedly attenuated, which was accompanied by impaired hepatocyte death and hepatic inflammation response. Constantly, treatment with thiolutin, a potent BRISC inhibitor, remarkably alleviated D-GalN/LPS-induced liver injury in mice. By using bone marrow-reconstituted chimeric mice and cell-specific BRISC-deficient mice, we demonstrated that KCs are the key effector cells responsible for protection against D-GalN/LPS-induced liver injury in BRISC-deficient mice. Mechanistically, we found that hepatic and circulating levels of TNF-α, IL-6, MCP-1, and IL-1β, as well as TNF-α- and MCP-1-producing KCs, in BRISC-deleted mice were dramatically decreased as early as 1 h after D-GalN/LPS challenge, which occurred prior to the elevation of the liver injury markers. Moreover, LPS-induced proinflammatory cytokines production in KCs was significantly diminished by BRISC deficiency in vitro, which was accompanied by potently attenuated NF-κB activation. Restoration of NF-κB activation by two small molecular activators of NF-κB p65 effectively reversed the suppression of cytokines production in ABRO1-deficient KCs by LPS. In conclusion, BRISC is required for optimal activation of NF-κB-mediated proinflammatory cytokines production in LPS-treated KCs and contributes to acute liver injury. This study opens the possibility to develop new strategies for the inhibition of KCs-driven inflammation in liver diseases.

Organic matter pores is the most important shale reservoir space in South China, and the types of organic matter influence the formation and evolution process of organic matter pores. In order to achieve in-situ observation of the pore evolution process of single organic matter and reveal the pore evolution process during the pyrolysis of the macerals of the Lower Paleozoic shale, this paper focuses on the low-maturity Upper Ordovician shale from Ohio, USA and the Lower Silurian shale in the eastern Baltic Sea, Europe. By using femtosecond laser, cooling-heating stage, microscope and SEM techniques, the in-situ observation of pore evolution of the single organic matters in shale can be realized, and the pore development process and evolution law of different types of organic matters can be distinguished. The in-situ observation results of pore thermal evolution process of low-maturity "gas-prone" graptolite and "oil-prone" lamalginite show that: (1) The initial temperature of obvious volume change of graptolite is higher than that of lamalginite, which infers that the hydrocarbon generation of graptolite is later than that of lamalginite. (2) Both graptolite and lamalginite generated obvious shrinkage cracks during thermal evolution process, but the scale of shrinkage cracks of graptolite is smaller than that of lamalginite, indicating that the hydrocarbon-generating transformation ratio of graptolite is lower than that of lamalginite. (3) There is an obvious difference between graptolite and lamalginite in the evolution of internal pores: the intrinsical biopores of graptolite were enlarged and some new internal pores were formed during the high temperature stage, but no new internal pores of lamalginite were observed during the whole process of thermal evolution, which infers that "gas-generating window" is the main stage of organic matter pore development. Moreover, the difference in the composition and structure of organic matters may be the main reason for the difference in pore evolution of graptolite and lamalginite.

Abstract Background Omicron variant of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global threat to public health. Numerous asymptomatic and mild cases had been admitted in shelter hospitals to quickly win the fight against Omicron pandemic in Shanghai. However, little is known about influencing factors for deterioration and length of stay (LOS) in hospitals among these non-severe cases. Methods This study included 12,555 non-severe cases with COVID-19 in largest shelter hospital of Shanghai, aiming to explore prognostic factors and build effective models for prediction of LOS. Results Data showed that 75.0% of participants were initially asymptomatic. In addition, 94.6% were discharged within 10 days, only 0.3% with deterioration in hospitals. The multivariate analysis indicated that less comorbidities (OR = 1.792, P = 0.012) and booster vaccination (OR = 0.255, P = 0.015) was associated with the decreased risk of deterioration. Moreover, age (HR = 0.991, P

The effects of MRS, whey protein and blueberry alone, and mixed fermentation on the survival rate of lactic acid bacteria under various freeze-drying conditions were investigated. The surface structure of the freeze-dried powders was also investigated to explore the anti-freezing protection mechanism of mixed whey protein and blueberry fermentation on the bacteria. It was found that the mixed fermentation medium of blueberry and whey protein has a protective effect on the freeze-drying bacteria and is better than the traditional MRS and whey protein medium. The optimal concentration of blueberry juice addition was 9%. The survival rate of the pre-freezing temperature at −80 °C was higher than at −20 °C after the pre-freezing and freeze-drying processes. The freeze-drying thickness of 0.3 cm could improve the survival rate of the bacteria. The Fourier transform infrared spectroscopy results indicated the interaction between the whey protein, anthocyanins, and the surface composition of the lactic acid bacteria.

An extended hybrid method for the analysis of the symmetric structural behavior of segmental tunnel linings is proposed. Their deformations cannot be determined by the traditional hybrid methods when the convergences are close to the serviceability limit states (SLSs). Two real-scale tests are employed for the validation of the proposed method. It involves structural analysis that is based on transfer relations. They represent analytical solutions of the linear theory of thin circular arches, and they contain the symmetric mode of rigid-body displacements. The method is termed hybrid because it is based on two types of input, namely the external loading and experimental data of displacements monitored during the test. It is termed extended because, additionally, the vertical and horizontal convergences are employed to produce more accurate structural deformations than obtained by the traditional hybrid method. The latter is found to be unsuitable for structural analysis after sudden failure has occurred in the vicinity of segmental interfaces. At the respective load steps, the structures were in convergence-related serviceability class C, referring to endangered serviceability. The local failures occurring at these load steps resulted in a rapid increase in the structural deformations and fast attainment of the SLS. If, in convergence-related serviceability class C, local failures at segmental interfaces are detected, the strengthening of the structure is necessary. This cannot be delayed to the attainment of serviceability class D, i.e., to reaching the SLS.

When high-strength steel is heated to high temperatures and then cooled naturally, its ductility decreases. In earthquake-prone areas, it is necessary to evaluate the ultra-low cycle fatigue fracture (ULCF) behavior of high-strength steel structures after a fire if these structures are used continuously. However, the ULCF fracture model of high-strength steel subjected to high temperatures followed by natural cooling has not been deeply studied. In view of this, twelve notched, round bar specimens fabricated from Q460D steel and ER55-G welds were heated to 900 °C followed by natural cooling and then cyclic loading experiments and finite element analyses (FEA) were performed on these specimens. The fracture deformation obtained from the experiments was used in the FEA to calibrate the damage degradation parameter of a Cyclic Void Growth Model (CVGM) of Q460D steel and ER55-G welds under this condition. The calibrated values were 0.30 and 0.20, respectively. The calibrated CVGM was employed to predict the number of cycles and the force and displacement at the fracture moment of the notched round bar specimens. The predicted results aligned closely with the experimental results, indicating that CVGM is effective in predicting the fracture of Q460D steel and ER55-G welds following exposure to 900 °C and subsequent natural cooling.

Abstract Background Hemorrhage is a potential and serious adverse drug reaction, especially for geriatric patients with long-term administration of rivaroxaban. It is essential to establish an effective model for predicting bleeding events, which could improve the safety of rivaroxaban use in clinical practice. Methods The hemorrhage information of 798 geriatric patients (over the age of 70 years) who needed long-term administration of rivaroxaban for anticoagulation therapy was constantly tracked and recorded through a well-established clinical follow-up system. Relying on the 27 collected clinical indicators of these patients, conventional logistic regression analysis, random forest and XGBoost-based machine learning approaches were applied to analyze the hemorrhagic risk factors and establish the corresponding prediction models. Furthermore, the performance of the models was tested and compared by the area under curve (AUC) of the receiver operating characteristic (ROC) curve. Results A total of 112 patients (14.0%) had bleeding adverse events after treatment with rivaroxaban for more than 3 months. Among them, 96 patients had gastrointestinal and intracranial hemorrhage during treatment, which accounted for 83.18% of the total hemorrhagic events. The logistic regression, random forest and XGBoost models were established with AUCs of 0.679, 0.672 and 0.776, respectively. The XGBoost model showed the best predictive performance in terms of discrimination, accuracy and calibration among all the models. Conclusion An XGBoost-based model with good discrimination and accuracy was built to predict the hemorrhage risk of rivaroxaban, which will facilitate individualized treatment for geriatric patients.

BackgroundComplementary to traditional biostatistics, the integration of untargeted urine metabolomic profiling with Machine Learning (ML) has the potential to unveil metabolic profiles crucial for understanding diseases. However, the application of this approach in autism remains underexplored. Our objective was to delve into the metabolic profiles of autism utilizing a comprehensive untargeted metabolomics platform coupled with ML.MethodsUntargeted metabolomics quantification (UHPLC/Q-TOF-MS) was performed for urine analysis. Feature selection was conducted using Lasso regression, and logistic regression, support vector machine, random forest, and extreme gradient boosting were utilized for significance stratification. Pathway enrichment analysis was performed to identify metabolic pathways associated with autismResultsA total of 52 autistic children and 40 typically developing children were enrolled. Lasso regression identified ninety-two urinary metabolites that significantly differed between the two groups. Distinct metabolites, such as prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, were revealed to be associated with autism through the application of four different ML methods (p

Summary: The establishment, proliferation, and differentiation of stem cells are coordinated with organ development and regulated by the signals in the microenvironment. Prior to gonad formation, how primordial germ cells (PGC) differentiate spatiotemporally to coordinate with gonadogenesis is unclear. In adult ovary, drosophila extracellular glypican Dally in germline stem cell (GSC) niche promotes BMP signaling to inhibit germline differentiation. Here we investigated the relation between the fate of PGC and the spatiotemporal pattern of glypican during ovary development. We found that Dally in ovarian soma assisted BMP signaling to prevent PGC from precocious differentiation. Dally’s presence raises the “hurdle” for ecdysone peaks to eventually remove the transcription factor Kr and de-repress pro-differentiation factor, temporally postponing PGC differentiation until GSC niche establishment. The spatiotemporal glypican in somatic matrix assists PGC to integrate the ovarian local BMP and organismal steroid signals that coordinate PGC’s program with organ/body development to maximize reproductive potential.

A central goal of evolutionary developmental biology is to decipher the evolutionary pattern of gene regulatory networks (GRNs) that control embryonic development, and the mechanism underlying GRNs evolution. The Nodal signaling that governs the body axes of deuterostomes exhibits a conserved GRN orchestrated principally by Nodal, Gdf1/3, and Lefty. Here we show that this GRN has been rewired in cephalochordate amphioxus. We found that while the amphioxus Gdf1/3 ortholog exhibited nearly no embryonic expression, its duplicate Gdf1/3-like, linked to Lefty, was zygotically expressed in a similar pattern as Lefty. Consistent with this, while Gdf1/3-like mutants showed defects in axial development, Gdf1/3 mutants did not. Further transgenic analyses showed that the intergenic region between Gdf1/3-like and Lefty could drive reporter gene expression as that of the two genes. These results indicated that Gdf1/3-like has taken over the axial development role of Gdf1/3 in amphioxus, possibly through hijacking Lefty enhancers. We finally demonstrated that, to compensate for the loss of maternal Gdf1/3 expression, Nodal has become an indispensable maternal factor in amphioxus and its maternal mutants caused axial defects as Gdf1/3-like mutants. We therefore demonstrated a case that the evolution of GRNs could be triggered by enhancer hijacking events. This pivotal event has allowed the emergence of a new GRN in extant amphioxus, presumably through a stepwise process. In addition, the co-expression of Gdf1/3-like and Lefty achieved by a shared regulatory region may have provided robustness during body axis formation, which provides a selection-based hypothesis for the phenomena called developmental system drift.

Personality is considered to be a factor affecting athletic performance. However, inconsistency in the research results regarding size and even direction of the relationship. An evaluation of the evidence of the relationship between personality and athletic performance was conducted in order to summarize the evidence available. A systematic literature search was conducted in March 2023. Sport performance and the Big Five personality model were identified in our research. We used PubMed, Web of Science, Embase, Cochrane Library, Wang Fang (Chinese), Wei Pu (Chinese), and CNKI (Chinese) databases for the systematic literature search (Prospero registration number: CRD42022364000), screened 4,300 studies, and found 23 cross-sectional studies eligible for inclusion in this review. The results of this systematic analysis show that, besides neuroticism, openness, conscientiousness, extraversion, and agreeableness are all positively correlated with sports performance. Conscientiousness and extraversion are the two main personalities in team sports. Openness and agreeableness show different results in different sports, and it is not clear to which project they are beneficial. The value of personality as a possible predictor of athletic performance is generally positive. Therefore, professionals such as applied sports psychologists, coaching personnel, athletes, and sports administrators must comprehensively grasp the significance of personality’s role in achieving success in major competitions. Considering these facts, sports practitioners should promote personality screening and personality development programs.

Microbial transglutaminase (TGase) is a protein that is secreted in a mature form and finds wide applications in meat products, tissue scaffold crosslinking, and textile engineering. Streptomyces mobaraensis is the only licensed producer of TGase. However, increasing the production of TGase using metabolic engineering and heterologous expression approaches has encountered challenges in meeting industrial demands. Therefore, it is necessary to identify the regulatory networks involved in TGase biosynthesis to establish a stable and highly efficient TGase cell factory. In this study, we employed a DNA-affinity capture assay and mass spectrometry analysis to discover several transcription factors. Among the candidates, eight were selected and found to impact TGase biosynthesis. Notably, SMDS_4150, an AdpA-family regulator, exhibited a significant influence and was hence named AdpASm. Through electrophoretic mobility shift assays, we determined that AdpASm regulates TGase biosynthesis by directly repressing the transcription of tg and indirectly inhibiting the transcription of SMDS_3961. The latter gene encodes a LytR-family positive regulator of TGase biosynthesis. Additionally, AdpASm exhibited negative regulation of its own transcription. To further enhance TGase production, we combined the overexpression of SMDS_3961 with the repression of SMDS_4150, resulting in a remarkable improvement in TGase titer from 28.67 to 52.0 U/mL, representing an 81.37% increase. This study establishes AdpA as a versatile regulator involved in coordinating enzyme biosynthesis in Streptomyces species. Furthermore, we elucidated a cascaded regulatory network governing TGase production.

Abstract Background To clarify the relationship between the PaO2/FiO2 and 28-day mortality in patients with sepsis. Methods This was a retrospective cohort study regarding MIMIC-IV database. Nineteen thousand two hundred thirty-three patients with sepsis were included in the final analysis. PaO2/FiO2 was exposure variable, 28-day mortality was outcome variable. PaO2/FiO2 was log-transformed as LnPaO2/FiO2. Binary logistic regression was used to explore the independent effects of LnPaO2/FiO2 on 28-day mortality using non-adjusted and multivariate-adjusted models. A generalized additive model (GAM) and smoothed curve fitting was used to investigate the non-linear relationship between LnPaO2/FiO2 and 28-day mortality. A two-piecewise linear model was used to calculate the OR and 95% CI on either side of the inflection point. Results The relationship between LnPaO2/FiO2 and risk of 28-day death in sepsis patients was U-shape. The inflection point of LnPaO2/FiO2 was 5.30 (95%CI: 5.21—5.39), which indicated the inflection point of PaO2/FiO2 was 200.33 mmHg (95%CI: 183.09 mmHg—219.20 mmHg). On the left of inflection point, LnPaO2/FiO2 was negatively correlated with 28-day mortality (OR: 0.37, 95%CI: 0.32—0.43, p

Scene image text segmentation is an important task in computer vision, but the complexity and diversity of backgrounds make it challenging. All supervised image segmentation tasks require paired semantic label data to ensure the accuracy of segmentation, but semantic labels are often difficult to obtain. To solve this problem, we propose an unsupervised scene image text segmentation model based on the image style transfer model cyclic uniform Generation Adversarial network (CycleGAN), which is trained by partial unpaired label data. Text segmentation is achieved by converting a complex background to a simple background. Since the images generated by CycleGAN cannot retain the details of the text content, we also introduced the Atrous spatial Pyramid pool module (ASPP) to obtain the features of the text from multiple scales. The resulting image quality is improved. The proposed method is verified by experiments on a synthetic data set, the IIIT 5k word data set and the MACT data set, which effectively segments the text and preserves the details of the text content.

Leakage in underground structures, especially tunnels, may cause seepage erosion in the surrounding soil, which in turn leads to ground subsidence, posing a great threat to urban safety. The current literature mainly focuses on seepage erosion in the sand but lacks a systematic study on the development process of seepage erosion induced by tunnel leakage in different strata. To investigate the different seepage erosion modes induced by tunnel leakage in different stratum types, a series of reduced-scale model tests were carried out. A coupled fluid–solid numerical model was further established to analyze the fine-scale characteristics of different seepage erosion modes. The results show that (1) the soil seepage erosion modes can be divided into three categories: no soil cave, unstable soil cave, and stable soil cave; (2) the adopted coupled fluid–solid numerical model based on DEM, which takes into account the degradation of clay during seepage erosion, can effectively simulate the erosion process of soil with different seepage erosion modes; (3) the phenomena of the three erosion modes are different in the process of erosion development; and (4) the micro-mechanisms of the three seepage erosion modes are different, which are manifested in the erosion range, soil arching effect, and displacement.

Climate change significantly impacts the livelihoods of farmer households. Particularly vulnerable areas, both economically and environmentally, face significant threats from climate change. This study developed a framework to assess household-level vulnerability to climate change by integrating the Exposure-Sensitivity-Resilience Analysis (ESRA) and Sustainable Livelihoods Analysis (SLA) frameworks. Using Gui-Zhou Province as the study area, the study examined whether livelihood vulnerability differs among various types of farmer households in economically and environmentally vulnerable areas and identified the main factors contributing to vulnerability. Results indicate significant differences in livelihood vulnerability among the three household types, with pure agricultural households (PAH) being the most vulnerable due to high exposure, sensitivity, and low adaptive capacity. Further analysis revealed minor differences in sensitivity but significant differences in adaptive capacity among the three farmer categories. In terms of sensitivity, all three farmer household categories exhibit high sensitivity to water, housing, and agricultural production. Regarding adaptive capacity, significant differences in human and financial capital exist among the three household types, with off-farm households (OFH) possessing the highest adaptive capacity due to their substantial human and financial capital. Further research identified high exposure and low adaptive capacity as the primary causes of livelihood vulnerability, noting no significant difference in the main contributing factors among the three types of farmer households. Common factors contributing to the livelihood vulnerability of farmer households include agricultural cooperatives, labor capacity, temperature changes, drought frequency changes, precipitation changes, agricultural insurance, and losses in agricultural production. Overall, the proposed livelihood vulnerability framework offers guidance for analyzing the vulnerability of farmer households in areas with both economic and environmental vulnerabilities under climate change. Concurrently, tailored measures to reduce farmer households’ livelihood vulnerability should be developed for different household types, considering the local climatic, geographic, and socioeconomic conditions.

Sudden leakage during tunnel construction poses a great threat to the safety of the tunnel. There are relatively few studies on the mechanism of structural collapse induced by tunnel leakage, so it is difficult to propose effective control measures. To solve this problem, a coupled fluid–solid strata analysis model and a nonlinear FEM tunnel model were established based on model test results to analyze the mechanism of tunnel collapse. The following conclusions were drawn: (1) A DEM-based coupled fluid–solid model combined with a nonlinear FEM tunnel model can effectively simulate the physical process of tunnel collapse. (2) The mechanism of tunnel leakage-induced strata response is the continuous destabilization and reappearance of the soil arching effect, which restricts the erosion of the soil and results in macroscopic soil caves, and finally leads to the impact load of the destabilized soil. (3) The process of the tunnel structure collapse is as follows: firstly, a large deformation of the tunnel structure is caused by the redistribution of external loads generated by the earth arching effect; then, due to the multiple impact loads from the destabilization of the soil, plastic hinges are generated at the tunnel joints, and the tunnel collapses.

Hydrothermal geothermal energy, as a widely distributed, large reserve and easily exploitable renewable source, can be used for both power generation and building heating. In this study, a numerical simulation of heat extraction performance is conducted based on monitoring well temperature data in a geothermal field in Xiong’an New Area. The effects of the reinjection temperature, injection flow rate, and reinjection rate on the outlet temperature and the reservoir temperature during a long-term operation are analyzed. The results indicate that the lower reinjection temperature can generate a critical disturbance scope for the thermal reservoir during the exploitation process. The impact scope on the thermal reservoir can reach 210.3 m at a reinjection temperature of 25 °C, which is not conducive to maintaining the outlet temperature of production wells in the long-term. The reinjection rate significantly affects both the horizontal and vertical temperature fields of the thermal reservoir. Under reinjection conditions of 30 °C and 40 kg/s, the horizontal and vertical impact scope of the thermal reservoir are 262.3 and 588.5 m, respectively. The reinjection rate is inversely related to the outlet temperature. A decrease from 100% to 70% in the reinjection rate can increase the outlet temperature by 4.21%. However, a decrease in the reinjection rate will lead to a decline in the groundwater level. Therefore, balancing the variation in outlet temperature and groundwater level is crucial in practical engineering.

China’s urbanization has received as much attention as its economic growth in recent years. While rapid urbanization has promoted modernization and wealth creation, it has also brought many problems and challenges. So, since 2014, the Chinese government has implemented a new urbanization policy nationwide. However, few researchers have examined whether China’s new urbanization policies promote sustainable urbanization. This paper evaluates the sustainable urbanization of 19 urban agglomerations in China using the elastic coefficient. The results indicate a significant increase in the number of cities achieving sustainable urbanization since the implementation of China’s new urbanization policy. The number has risen from 46 in the period of 2010–2015 to 71 in the period of 2015–2021. Considering the impact of the new coronavirus on economy, there would have been even more cities entering sustainable urbanization during the latter period. This indicates that the new urbanization policy has a positive influence on the sustainable urbanization of China’s urban agglomerations. The sustainable urbanization status is not static and changes with different policies that are implemented in different time periods. Therefore, it is important to find useful policies that can guide and enhance the urbanization process in these cities. In addition, cities that have a sustainable urbanization status are not perfect. To address this issue, it is important to categorize and implement targeted policies for cities experiencing both sustainable and non-sustainable urbanization. Changes in a city’s size or urbanization rates are not related to the city’s sustainable urbanization status. A larger city size does not indicate sustainable urbanization, and, similarly, cities with faster urbanization rates do not exhibit a higher level of urbanization sustainability.

To investigate the mechanical behavior and design methodology of column-free QRST (quasi-rectangular segmental tunnel) structures, a theoretical analysis based on prototype experiments and simulation models is conducted. Initially, a prototype experimental investigation is conducted to reveal the structural behavior at the service stage. Subsequently, the ESHR model (Equivalent Stiffness Homogeneous Ring), the BS model (Beam Spring), and the MBS model (Modified Beam Spring) are used to simulate structural behavior. For design purposes, the design methodology is explored based on the ESHR model, followed by a sensitivity analysis of several key load parameters. Based on the experimental results, weak parts of the column-free QRST structure are found to include several joints (Joint 1, Joint 5, Joint 3, and Joint 8), and corresponding optimization measures are proposed. By comparing the test results, the above-mentioned three models demonstrate their applicability in structural simulation, with the ESHR model having sufficient design accuracy. A model-based deformation mechanism analysis found that joints contribute approximately 2/3 of the structural deformation. For the structural design of the column-free QRST using the ESHR model, amplifying the calculated results of structures directly subjected to the service stage by 10% suffices to meet engineering requirements. Based on the test and study, special attention should be paid to the negative bending moment regions at the waists of the structure during both the design and service stages.

Aim: To develop scientific, systematic and clinically applicable nursing-sensitive quality indicators for vaginal birth after cesarean in obstetrics, which provide a theoretical and clinical basis for monitoring and improving the nursing quality of vaginal birth after cesarean in China. Methods: A modified Delphi-consensus technique was used in this study. Based on literature retrieval published between January 2012 and December 2022 and group discussion, the preliminary nursing-sensitive quality indicators were selected using a structural-process-outcome model. Then a questionnaire was designed on the preliminary indicators. The modified Delphi method was used to conduct two rounds of expert consultation among 26 hospitals in China. The survey data of experts’ opinions were collected and analyzed to determine the final nursing-sensitive quality indicators. The importance of indicators, rationality of calculation formula and operability of data collection were analyzed and discussed. Results: A total of 33 nursing-sensitive quality indicators were determined. The indicators were composed of 3-level ones, including 3 first-level indicators (structural, process and outcome indicators), 9 s-level ones and 33 third-level ones. The positive coefficients in the two rounds of expert consultation were 95.56 % and 97.67 %, respectively, and the authoritative coefficients were 0.88 and 0.94. The coefficients of variation ranged from 0.05 to 0.28. Conclusion: The nursing-sensitive quality indicators were successfully developed using the modified Delphi method. The indicators are scientific, systematic and clinically operable, and play an important role in improving the nursing quality for pregnant women with vaginal birth after cesarean.

In order to study the feasibility of strengthening of segmental tunnel linings by using steel–concrete composites (SCC), a three-dimensional (3D) finite element (FE) model is proposed in this paper. The nonlinear mechanical behavior of concrete is described by a plastic-damage model. The nonlinearity, resulting from the interface of the SCC and reinforced concrete (RC) segments, is simulated with the help of a system of springs. The analysis results are compared with those obtained from a full-scale test of a tunnel segment. Their agreement validates the usefulness of the 3D FE model. Numerical re-analysis of the test shows that the interfacial connectors govern both the strengthening effect of SCC and the failure pattern of the strengthened segments. Thus, the force-transmitting capacity of the interfacial connectors should be concerned in design activities. As regards the circular segments, the interfacial connectors refer to both the shearing and the stripping connectors. The composite effect of the SCC and RC segments increases with the increasing number of these connectors. The latter, therefore, results in the increases of the bearing capacities and stiffnesses of the strengthened segments. Those increases become insignificant as the number of these connectors is sufficient to ensure a perfect composite effect of the SCC and RC segments. In addition, the numerical simulations show that using high-performance steel shell (HPS) or/and ultra-high-performance concrete (UHPC) is an effective way to increase the strengthening effect of SCCs.

Abstract Purpose To investigate the factors influencing and long-term effects of manual myotomy (MM) occurring during physiotherapy for congenital muscular torticollis (CMT). Methods We retrospectively collected the clinical data of children with CMT receiving physiotherapy between 2008 and 2018. The children were divided into manual myotomy (MM) and non-manual myotomy (NMM) groups according to whether MM occurred during treatment. We assessed physiotherapy outcomes in children with CMT using craniofacial asymmetry parameters and the Cheng–Tang rating score. By measuring the ear-eye distance, ear-nose distance, eye-mouth distance, ear-mouth distance, half-head circumference, and half-head top at two sides to evaluate craniofacial asymmetry. Based on the Cheng–Tang assessment criteria, we recorded the range of rotation, range of lateral flexion, the status of the contracted muscle, the hardness of the mass, the extent of head tilting during activities and sleeping, the status of daily activities, face size, type of head shape, cranial changes, and subjective head tilting to assess the effectiveness of treatment. Clinical data and outcome indicators (craniofacial asymmetry parameters and Cheng–Tang rating score) were compared. Results The MM group had a significantly higher total Cheng–Tang rating score than the NMM group (P