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Abstract Background BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was first reported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades. Case presentation We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements. CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until the last follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement categories. Conclusions Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The application of FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rare clinical scenarios.

Abstract DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.

As the rate of population aging accelerates, the prevalence of stroke among the older population continues to rise. Elderly stroke patients have a high prevalence of neurological impairment, severe clinical manifestations, many associated comorbidities, unfavorable prognosis, prolonged rehabilitation duration, and need extended caregiver support. Elderly stroke patients have challenges in accessing necessary long-term care services due to several circumstances, resulting in notable issues in long-term care. This paper examines the clinical features of elderly stroke patients and presents an overview of long-term care both domestically and internationally. It discusses the current issues surrounding long-term care in our country, focusing on three different forms of care. The paper proposes countermeasures to address these problems, considering the roles of the government, society, medical professionals, institutions, families, and individuals. The aim is to offer guidance for enhancing the quality of long-term care.

The blood–brain barrier is known to consist of a variety of cells and complex inter-cellular junctions that protect the vulnerable brain from neurotoxic compounds; however, it also complicates the pharmacological treatment of central nervous system disorders as most drugs are unable to penetrate the blood–brain barrier on the basis of their own structural properties. This dramatically diminished the therapeutic effect of the drug and compromised its biosafety. In response, a number of drugs are often delivered to brain lesions in invasive ways that bypass the obstruction of the blood–brain barrier, such as subdural administration, intrathecal administration, and convection-enhanced delivery. Nevertheless, these intrusive strategies introduce the risk of brain injury, limiting their clinical application. In recent years, the intensive development of nanomaterials science and the interdisciplinary convergence of medical engineering have brought light to the penetration of the blood–brain barrier for brain-targeted drugs. In this paper, we extensively discuss the limitations of the blood–brain barrier on drug delivery and non-invasive brain-targeted strategies such as nanomedicine and blood–brain barrier disruption. In the meantime, we analyze their strengths and limitations and provide outlooks on the further development of brain-targeted drug delivery systems.

Abstract Background Hypertension is one of the most common chronic diseases with a low control rate globally. The effect of communication skills training contributing to hypertension control remains uncertain. The aim of the present study was to assess the effectiveness of an educational intervention based on the Calgary-Cambridge guide in improving hypertensive management. Methods A cluster randomized controlled trial enrolled 27 general practitioners (GPs) and 540 uncontrolled hypertensive patients attending 6 community health centers in Chengdu, China. GPs allocated to the intervention group were trained by an online communication course and two face-to-face workshops based on Calgary-Cambridge guides. The primary outcome was blood pressure (BP) control rates and reductions in systolic and diastolic BP from baseline to 3 months. The secondary outcome was changes in GPs’ communication skills after one month, patients’ knowledge and satisfaction after 3 months. Bivariate analysis and the regression model assessed whether the health provider training improved outcomes. Results After the communication training, the BP control rate was significantly higher (57.2% vs. 37.4%, p

Abstract Background Cox‐Maze procedure is currently the gold standard treatment for atrial fibrillation (AF). However, data on the effectiveness of the Cox‐Maze procedure after concomitant mitral valve surgery (MVS) are not well established. The aim of this study was to assess the safety and efficacy of Cox-Maze procedure versus no-maze procedure n in AF patients undergoing mitral valve surgery through a systematic review of the literature and meta‐analysis. Methods A systematic search on PubMed/MEDLINE, EMBASE, and Cochrane Central Register of Clinical Trials (Cochrane Library, Issue 02, 2017) databases were performed using three databases from their inception to March 2023, identifying all relevant randomized controlled trials (RCTs) comparing Cox-Maze procedure versus no procedure in AF patients undergoing mitral valve surgery. Data were extracted and analyzed according to predefined clinical endpoints. Results Nine RCTs meeting the inclusion criteria were included in this systematic review with 663 patients in total (341 concomitant Cox‐Maze with MVS and 322 MVS alone). Across all studies with included AF patients undergoing MV surgery, the concomitant Cox‐Maze procedure was associated with significantly higher sinus rhythm rate at discharge, 6 months, and 12 months follow‐up when compared with the no-Maze group. Results indicated that there was no significant difference between the Cox‐Maze and no-Maze groups in terms of 1 year all-cause mortality, pacemaker implantation, stroke, and thromboembolism. Conclusions Our systematic review suggested that RCTs have demonstrated the addition of the Cox‐Maze procedure for AF leads to a significantly higher rate of sinus rhythm in mitral valve surgical patients, with no increase in the rates of mortality, pacemaker implantation, stroke, and thromboembolism.

Abstract Internet of Things has become a common paradigm for various domains. To meet a user’s complex requirement, we should compose multiple IoT devices (IoT services) to provide comprehensive services to the user. However, these services usually coexist, which is likely to lead to conflicts. Moreover, each user may have different kinds of needs. Suppose that in a smart home there are more than one person, a conflict may occur when they request the same service in this environment. Actually, even though they request different IoT services, among which if there exists function impact or QoS impact, a conflict could still occur. In this paper, we propose to employ high-level Petri nets to detect conflicts among IoT services. We first model the formal methods for conflict policies. Then, we present a Petri nets-based mechanism for modeling and detecting conflicts. Finally, we expand the previous model and use high-level Petri nets for handling fuzzy IoT conflict policies modeling and reasoning. The experimental results show that the proposed approach performs well in accuracy.

Prunasin and amygdalin are important factors that influence the kernel taste of apricots, however, the regulatory mechanisms underlying this are unclear. In this study, we analyzed the phenotype and transcriptome of kernels during development in Prunus sibirica (bitter kernels) and Prunus armeniaca × Prunus sibirica (kernel consumption apricot, sweet kernels). Prunasin and amygdalin content was significantly higher in bitter kernels compared with that in sweet kernels. Prunasin content exhibited a decreasing trend in both bitter and sweet kernels. The fastest decline was observed in bitter and sweet kernels during S3–S4 (82.21%) and S2–S3 (59.65%), respectively. The amygdalin content in the bitter kernels exhibited the fastest increase between 45–60 d after flowering, and reached a peak at 6.22% on 60 d after flowering. In contrast, the peak in sweet kernels occurred at 60 d after flowering, with a much lower content of 0.18%. Transcriptome analysis revealed 6,942 differentially expressed genes (DEGs), with a subset of 38 DEGs specifically enriched in the cyanoamino acid metabolic pathway. Among these, the ten candidate genes, including CYP79, CYP71, UGT1, AH, and PH, were identified as crucial in regulating prunasin and amygdalin metabolism. Furthermore, a weighted gene co-expression network analysis (WGCNA) unveiled two modules that exhibited significant correlation with prunasin and amygdalin content. Five DEGs were located at the center of the co-expression network, and were identified as hub genes, with four positively regulating prunasin content and one negatively regulating amygdalin content. Our results provide novel insights into the molecular-level regulation of the apricot kernel taste.

Parking lot lane detection is a critical component of automated driving technology, requiring high accuracy, speed, and ease of deployment. In this study, we aimed to develop a comprehensive dataset of parking lane lines and construct an innovative parking lot recognition model. The model, named the Point Angle Instance Network (PAINet), effectively clusters each key point by embedding angle information, thus enhancing the stability and training efficiency. Additionally, we have developed an information collection module to address the issue of fault detection of the guidance arrow in parking lot environments. The performance of the model was tested and evaluated using the created parking lane dataset, and promising results were obtained. The model achieved an F1 score of 85.48%, an FPS of 164, and a GFLOPs of 4.1 in the task of parking lot lane detection in a surround-view situation. These results indicate the accuracy, practicality, and real-time performance of the model, highlighting its potential for use in automated driving systems.

Abstract Purification of ethylene (C2H4) as the most extensive and output chemical, from complex multi-components is of great significance but highly challenging. Herein we demonstrate that precise pore structure tuning by controlling the network hydrogen bonds in two highly-related porous coordination networks can shift the efficient C2H4 separation function from C2H2/C2H4/C2H6 ternary mixture to CO2/C2H2/C2H4/C2H6 quaternary mixture system. Single-crystal X-ray diffraction revealed that the different amino groups on the triazolate ligands resulted in the change of the hydrogen bonding in the host network, which led to changes in the pore shape and pore chemistry. Gas adsorption isotherms, adsorption kinetics and gas-loaded crystal structure analysis indicated that the coordination network Zn-fa-atz (2) weakened the affinity for three C2 hydrocarbons synchronously including C2H4 but enhanced the CO2 adsorption due to the optimized CO2-host interaction and the faster CO2 diffusion, leading to effective C2H4 production from the CO2/C2H2/C2H4/C2H6 mixture in one step based on the experimental and simulated breakthrough data. Moreover, it can be shaped into spherical pellets with maintained porosity and separation performance.

Abstract Background The widespread utilization of chest High-resolution Computed Tomography (HRCT) has prompted detection of pulmonary ground-glass nodules (GGNs) in otherwise asymptomatic individuals. We aimed to establish a simple clinical risk score model for assessing GGNs based on HRCT. Methods We retrospectively analyzed 574 GGNs in 574 patients undergoing HOOK-WIRE puncture and pulmonary nodule surgery from January 2014 to November 2018. Clinical characteristics and imaging features of the GGNs were assessed. We analyzed the differences between malignant and benign nodules using binary logistic regression analysis and constructed a simple risk score model, the VBV Score, for predicting the malignancy status of GGNs. Then, we validated this model via other 1200 GGNs in 1041 patients collected from three independent clinical centers in 2022. Results For the exploratory phase of this study, out of the 574 GGNs, 481 were malignant and 93 were benign. Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. Then, we derived a VBV Score = vacuole sign + air bronchogram + intra-nodular vessel sign, to predict the malignancy of GGNs, with a sensitivity, specificity, and accuracy of 95.6%, 80.6%, and 93.2%, respectively. We also validated it on other 1200 GGNs, with a sensitivity, specificity, and accuracy of 96.0%, 82.6%, and 95.0%, respectively. Conclusions Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. VBV Score showed good sensitivity, specificity, and accuracy for differentiating benign and malignant pulmonary GGNs.

AbstractBlasting excavation is frequently used in myriads of hydraulic tunnels in Southwest China. To evaluate the effects of blasting parameters on the stability of tunnels and reveal reasonable blasting parameters, a field test on blasting parameters is carried out in typical sections of a diversion tunnel at a large hydropower project in Southwest China. Two different charging methods are designed. The multiple monitoring techniques, i.e. blasting vibration test (point), wave velocity test (line), three-dimensional laser scanning (plane), and microseismic monitoring (volume), combined with corresponding criteria are adopted to evaluate the effects of two different blasting parameters on construction safety. Multiple monitoring results well reflect the disturbance of blasting excavation on rock mass. In addition, the effects on rock damage and deformation of two different blasting parameters have some differences. The blasting parameters with less charge in the cut and breaking holes and more charge in the perimeter hole contribute to reducing rock mass damage and deformation. Therefore, the more reasonable blasting scheme is revealed. Present study will provide a new thought for the evaluation and optimization of blasting parameters in hydraulic tunnels.

Abstract Vegetation restoration in dryland regions may be a powerful way to control desertification and promote local habitat recovery. In these artificial revegetation systems, ecosystem processes and functioning are strongly determined by nitrogen (N) availability, while soil inorganic N (SIN) is the major available N form and is absorbed as a main N source for plants. However, SIN dynamics, their influencing factors, and their relative importance to the ecosystem of these N‐limited systems are not well understood. A field investigation was conducted to examine the monthly variations in SIN and its response to planting age and vegetation type in a typical artificial sand‐fixing system in northwestern China. The SIN content in topsoil (0–20 cm) during the growing season ranged from 7.10 to 95.65 mg kg−1, with a mean value of 27.14 mg kg−1. Soil nitrate N had a dominant role in determining SIN monthly dynamics, which showed a fluctuating trend with two peak values in early July and late August. SIN showed a significant increasing trend with the planting age of sand‐fixing vegetation, and it was highest for Nitraria sphaerocarpa (55.66 ± 5.76 mg kg−1), followed by Haloxylon ammodendron (29.81 ± 3.47 mg kg−1) and interspace (11.39 ± 1.13 mg kg−1). SIN displayed a hump‐shaped relationship with air temperature (R2 = 0.96, p

Abstract Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non‐invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)‐coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte‐derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte‐derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury.

BackgroundHearing loss and tinnitus have been linked to mild cognitive impairment (MCI); however, the evidence is constrained by ethical and temporal constraints, and few prospective studies have definitively established causation. This study aims to utilize Mendelian randomization (MR) and cross-sectional studies to validate and analyze this association.MethodsThis study employs a two-step approach. Initially, the genetic data of the European population from the Genome-wide association studies (GWAS) database is utilized to establish the causal relationship between hearing loss and cognitive impairment through Mendelian randomization using the inverse variance weighted (IVW) method. This is achieved by identifying strongly correlated single nucleotide polymorphisms (SNPs), eliminating linkage disequilibrium, and excluding weak instrumental variables. In the second step, 363 elderly individuals from 10 communities in Qingdao, China are assessed and examined using methods questionnaire survey and pure tone audiology (PTA). Logistic regression and multiple linear regression were used to analyze the risk factors of MCI in the elderly and to calculate the cutoff values.ResultsMendelian randomization studies have shown that hearing loss is a risk factor for MCI in European populations, with a risk ratio of hearing loss to MCI loss of 1. 23. The findings of this cross-sectional study indicate that age, tinnitus, and hearing loss emerged as significant risk factors for MCI in univariate logistic regression analysis. Furthermore, multivariate logistic regression analysis identified hearing loss and tinnitus as potential risk factors for MCI. Consistent results were observed in multiple linear regression analysis, revealing that hearing loss and age significantly influenced the development of MCI. Additionally, a notable finding was that the likelihood of MCI occurrence increased by 9% when the hearing threshold exceeded 20 decibels.ConclusionThis study provides evidence from genomic and epidemiological investigations indicating that hearing loss may serve as a risk factor for cognitive impairment. While our epidemiological study has found both hearing loss and tinnitus as potential risk factors for cognitive decline, additional research is required to establish a causal relationship, particularly given that tinnitus can manifest as a symptom of various underlying medical conditions.

Music performance anxiety (MPA) is recognized as a distinct emotional behavior rather than merely a motor control disorder and is influenced by specific conditioning experiences. This study investigates the interrelationships between MPA, self-efficacy, and future career expectations among music students within the Chinese context. The participants of this study were 340 high school students majoring in music education and performance, drawn from three music schools in China. Data were collected using several questionnaires: the MPA Inventory for Adolescents (MPAI-A), the Self-Efficacy Formative Questionnaire, and the Career Futures Inventory (CFI). The findings indicate that MPA is negatively associated with self-efficacy and future career expectations. Additionally, self-efficacy acts as a partial moderator between MPA and career expectations, suggesting that enhancing the self-efficacy of music students can boost their future career aspirations and mitigate the adverse effects of MPA. This research explores the complex relationships among MPA, self-efficacy, and future career expectations, emphasizing the importance of curriculum and pedagogical strategies in music schools. Music students with high levels of self-efficacy may exhibit more confidence and stable performances before audiences. According to the panel regression analysis, self-efficacy significantly positively influences career expectations. An appropriate educational environment and supportive pedagogical approaches to MPA can foster the early career development of musicians.

Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.

Abstract Molecular engineering of drug delivering platforms to provide collaborative biological effects with loaded drugs is of great medical significance. Herein, cannabinoid receptor 1 (CB1)‐ and reactive oxygen species (ROS)‐targeting electrosprayed microspheres (MSs) are fabricated by loading with the CB1 agonist arachidonoyl 2′‐chloroethylamide (ACEA) and producing ROS in a photoresponsive manner. The synergistic anti‐tumor effects of ACEA and ROS released from the MSs are assessed. ACEA inhibits epidermal growth factor receptor signaling and altered tumor microenvironment (TME) by activating CB1 to induce tumor cell death. The MSs are composed of glycidyl methacrylate‐conjugated xanthan gum (XGMA) and Fe3+, which form dual molecular networks based on a Fe3+‐(COO−)3 network and a C═C addition reaction network. Interestingly, the Fe3+‐(COO−)3 network can be disassembled instantly under the conditions of lactate sodium and ultraviolet exposure, and the disassembly is accompanied by massive ROS production, which directly injures tumor cells. Meanwhile, the transition of dual networks to a single network boosts the ACEA release. Together, the activities of the ACEA and MSs promote immunogenic tumor cell death and create a tumor‐suppressive TME by increasing M1‐like tumor‐associated macrophages and CD8+ T cells. In summation, this study demonstrates strong prospects of improving anti‐tumor effects of drug delivering platforms through molecular design.

Summary: 18F-FDG PET/MRI shows potential efficacy in the diagnosis of bladder cancer (BLCA). However, the performance of 18F-FDG PET/MRI in staging and neoadjuvant therapy (NAT) response evaluation for BLCA patients remains elusive. Here, we conduct this study to evaluate the performance of 18F-FDG PET/MRI and its derived parameters for tumor staging and NAT response prediction in BLCA. Forty BLCA patients were retrospectively enrolled to evaluate the performance of 18F-FDG PET/MRI in staging and NAT response prediction in BLCA. The feasibility of using 18F-FDG PET/MRI-related parameters for tumor staging and NAT response evaluation was also analyzed. In conclusion, 18F-FDG PET/MRI is found to show good performance in the BLCA staging and NAT response prediction. Moreover, ΔSUVmean is an efficacious candidate parameter for NAT response prediction. This study highlights that 18F-FDG PET/MRI is a promising imaging approach in the clinical diagnosis and treatment for BLCA.

IntroductionBacillus velezensis occurs extensively in the soil environment. It produces a range of antimicrobial compounds that play an important role in the field of biological control. However, during the actual application process it is often affected by factors such as the medium formulation and fermentation conditions, and therefore biocontrol measures often do not achieve their expected outcomes.MethodsIn this study, the B. velezensis BHZ-29 strain was used as the research object. The carbon and nitrogen sources, and inorganic salts that affect the number of viable bacteria and antibacterial potency of B. velezensis BHZ-29, were screened by a single factor test. A Plackett–Burman design experiment was conducted to determine the significant factors affecting the number of viable bacteria and antibacterial potency, and a Box–Behnken design experiment was used to obtain the optimal growth of B. velezensis BHZ-29. The medium formula that produced the highest number of viable bacteria and most antibacterial substances was determined. The initial pH, temperature, amount of inoculant, liquid volume, shaking speed, and culture time were determined by a single factor test. The factors that had a significant influence on the number of viable bacteria of B. velezensis BHZ-29 were selected by an orthogonal test. A Box–Behnken design experiment was conducted to obtain the optimal fermentation conditions, and highest number of viable bacteria and antibacterial titer.ResultsMolasses, peptone, and magnesium sulfate had significant effects on the viable count and antibacterial titer of B. velezensis BHZ-29. The viable count of B. velezensis BHZ-29 increased from 7.83 × 109 to 2.17 × 1010 CFU/mL, and the antibacterial titer increased from 111.67 to 153.13 mm/mL when the optimal media were used. The optimal fermentation conditions for B. velezensis BHZ-29 were as follows: temperature 25.57°C, pH 7.23, culture time 95.90 h, rotation speed 160 rpm, amount of inoculant 2%, and liquid volume 100 ml. After the optimization of fermentation conditions, the number of viable bacteria increased to 3.39 × 1010 CFU/mL, and the bacteriostatic titer increased to 158.85 mm/ml.The plant height and leaf number of cotton plants treated with BHZ-29 fermentation broth were higher than those of cotton inoculated with Verticillium dahliae. The number of bacteria was 1.15 × 107 CFU/g, and the number of fungi was 1.60 × 105 spores/g. The disease index of the cotton seedlings treated with the optimized fermentation broth was 2.2, and a control effect of 93.8% was achieved. B. velezensis BHZ-29 could reduce the disease index of cotton Verticillium wilt and had a controlling effect on the disease. The best effect was achieved in the treatment group with an inoculation concentration of 2 × 108 CFU/ml, the disease index was 14.50, and a control effect of 84.18% was achieved.DiscussionThe fermentation process parameters of the number of viable bacteria and antibacterial titer by strain B. velezensis BHZ-29 were optimized to lay a foundation for the practical production and application of strain B. velezensis BHZ-29 in agriculture.

BackgroundIt has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related.MethodsWe performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found.ResultsLachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05–1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88–0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90–0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94–1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83–0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73–1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified.ConclusionThis Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut–brain axis in migraine as well as possible targets for treatment interventions.

BackgroundCell transplants as a treatment for Parkinson’s disease have been studied for decades, and stem cells may be the most promising cell sources for this treatment. We aimed to investigate whether stem cell transplantation contributes to the cure for Parkinson’s disease and the factors that may influence the efficacy for this therapy.MethodsPubMed, Embase, Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and ChinaInfo were thoroughly searched to find controlled trials or randomized controlled trials performing stem cell transplantation in patients with Parkinson’s disease. The pooled effects were analyzed to evaluate the weighted mean difference (WMD) with 95% confidence intervals.ResultsNine articles were identified including 129 individuals. Stem cell transplantation was an effective treatment for Parkinson’s disease (WMD = −14.86; 95% CI: −16.62 to −13.10; p

Amygdalus species have considerable ecological and economic value, however, the phylogenetic relationships among Amygdalus remain controversy. In this study, we sequenced and assembled the chloroplast (cp) genomes of five Amygdalus species: Prunus communis, P. mongolica, P. pedunculata, P. triloba, and P. mira. We then conducted comparative genomic analyses and constructed their phylogenetic relationships. The genome length ranged from 157,870 to 158,451 bp, and 131 genes were annotated (86 protein-coding genes, 37 tRNAs, and 8 rRNAs). Additionally, 49–57 simple sequence repeats were detected, with most in the large single-copy region and with AT base preferences. Comparative genomic analyses revealed high similarities in structure, order, and gene content. However, we identified four highly divergent sequences: trnR-UCU-atpA, nbdhC-trnV-UAC, ycf4-cemA, and rpl32-trnL-UAG. The phylogenomic relationship analysis suggested that the Amygdalus species were grouped together, in which P. pedunculata, P. triloba, and Prunus tangutica were categorized into a branch, P. mongolica and Prunus davidiana were clustered a branch. This study provides an improved understanding of the genetic relationships among the Amygdalus and provides a basis for the development and utilization of Amygdalus resources.

Abstract The molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided the immune system with the signal to detect and eliminate the infected or cancerous cells. In the context of cancer, owing to the crucial immune-regulatory roles played by MHC-I molecules, the abnormal modulation of MHC-I expression and function could be hijacked by tumor cells to escape the immune surveillance and attack, thereby promoting tumoral progression and impairing the efficacy of cancer immunotherapy. Here we reviewed and discussed the recent studies and discoveries related to the MHC-I molecules and their multidirectional functions in the development of cancer, mainly focusing on the interactions between MHC-I and the multiple participators in the tumor microenvironment and highlighting the significance of targeting MHC-I for optimizing the efficacy of cancer immunotherapy and a deeper understanding of the dynamic nature and functioning mechanism of MHC-I in cancer.

Abstract This study aimed to investigate the frequency and features of diffuse alveolar hemorrhage (DAH) in Chinese patients with systemic lupus erythematosus (SLE) and evaluate the association of DAH with the features. A total of 943 patients with SLE were categorized into two groups: 896 patients without DAH and 47 patients with DAH. The demographic data, clinical and laboratory findings, and SLE disease activity index 2000 of all patients were statistically analyzed. The DAH frequency in patients with SLE was 4.98%, and the mortality rate of DAH was 42.55%. The clinical features with statistical differences between the two groups were analyzed by multivariate logistic regression, and the results suggested that shorter disease duration [odds ratio (OR): 0.972, 95% confidence interval (CI) 0.946, 0.998], younger age (OR: 0.867, 95% CI 0.764, 0.984), moderate (OR: 25.949, 95% CI 3.316, 203.065) or severe (OR: 24.904, 95% CI 2.675, 231.859) anemia, abnormally elevated levels of urine protein (OR: 10.839, 95% CI 1.351, 86.938) and serum creatinine (OR: 14.534, 95% CI 5.012, 42.142), interstitial lung disease (OR: 6.569, 95% CI 2.053, 21.021), and infection (OR: 8.890, 95% CI 3.580, 22.077) were independent risk factors for the occurrence of DAH in patients with SLE. Moderate or severe anemia was highly suggestive of DAH.

Abstract Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.

Exosomes are nanoscale membrane-enclosed extracellular vesicles secreted by various cells, which have enormous potential as disease biomarkers for clinical application. However, the isolation and detection of exosomes remain enormous challenges, which limits their further application. Herein, inspired by immunomagnetic beads, a magnetic nanoparticle conjugated aptamer was repurposed for the effective capture and detection of exosomes. The magnetic nanoparticles, composed of Fe3O4 synthesized by the hydrothermal method as the core and coupled with gold nanoparticles (Fe3O4@Au), provide a large specific surface area, making the resulting composite material an effective platform for exosome capture. Furthermore, the elution of captured exosomes with 1.0 M NaCl made downstream analysis of exosomes possible. The preliminary clinical application value of the composite in exosome analyses of serum from healthy individuals and patients with Alzheimer's disease (AD) has also been verified, which could provide a promising platform for biomedical and clinical diagnosis.

Abstract High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Abstract Diagnosis of aneurysm and possibility of aneurysm rupture are crucial for avoiding brain hemorrhage. In this work, blood stream inside internal carotid arteries (ICAs) are simulated in diverse working conditions to disclose the importance of hemodynamic factors on the rupture of aneurysm. The main attention of this study is to investigate the role of hemodynamic on the aneurysm rupture. Statistical and computational methods are applied to investigate coiling porosity and blood hematocrit in 9 specific real ICA geometries. Response surface model (RSM) develops 25 runs to investigate all features of selected geometrical parameters and treatment factors. Computational fluid dynamic is used for the simulation of the blood stream in the selected aneurysms. The effects of sac section area and mean radius of parent vessel on blood hemodynamics are fully investigated. Hemodynamic factors are examined and compared at the peak systolic time instant, including pressure distributions, and velocity. Achieved results indicate that the increasing sac section area (from 36.6 to 75.4 mm2) results in 20% pressure reduction on the sac wall.

Plant dyes have the advantages of green environmental protection and high safety, but due to the shortage of resources, high cost and low color fastness, the industrial application of plant dyes is limited. Baiyi people have the traditional custom of plant dyeing in Heqing, Yunnan Province, and there are rich local dye plant resources and traditional dyeing technology. In order to investigate, record and study Baiyi people plant dyeing and related traditional knowledge, expand plant dye resources and promote the development and utilization of plant dyes, this study conducted ethnobotanical investigation on plant dyeing and related traditional knowledge of Baiyi people in Liuhe Yi Township, Heqing County, Dali Prefecture. From September 2019 to March 2020, 288 informants were interviewed by semi-structured interviews from four villages in Liuhe Yi Township, Heqing County, Dali Prefecture; local dye plants were investigated by field research; traditional plant dyeing crafts were recorded by participatory observation; traditional knowledge of plant dyeing was analysed through quantitative analysis (f value, CIIs value, ICF value). The results are as follows: (1) The Baiyi people use 11 species of dye plants in Heqing, belonging to 10 families and 11 genera. (2) People of different regions, ages and genders have different cognitions of traditional knowledge of plant dyeing. (3) The use frequency and cultural importance index of Viburnum cylindricum and Buddleja officinalis are higher, and the cognition of Baiyi people is highly consistent on dye plants of blue. (4) Baiyi people often use dye plants to dye their own traditional cloth (folk cloth made from Gerbera delavayi). This research reveals that Baiyi people have a relatively complete knowledge system of traditional plant dyeing in Heqing, but it has gradually lost with the development of the times. This study provides scientific clues for the exploitation of dye plant resources and the research of traditional plant dyeing technology, promotes the industrial application of dye plants of minority, and has a great significance and application value for the economic development in minority areas.

Abstract Background Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of excessive reactive oxygen species (ROS) plays an important role in the development and progression of the disease. Glucocorticoids are the first-line medications for patients with PNS, but their clinical use is hampered by dose-dependent side effects. Herein, we accelerated the rate of conversion from Ce4+ to Ce3+ by doping Zr4+ in ceria-zirconia nanomedicines to treat the PNS rat model by removal of ROS. Results The engineered Ce0.7Zr0.3O2 (7CZ) nanomedicines significantly improved the ROS scavenging ability of podocytes at a very low dose, enabling effective inhibition of podocyte apoptosis and actin cytoskeleton depolymerization induced by adriamycin (ADR). Accordingly, podocyte injury was effectively alleviated in rat models of ADR-induced nephrotic syndrome, as confirmed by serum tests and renal tissue staining. Moreover, the mRNA sequencing assay revealed the protective molecular signaling pathways of 7CZ nanomedicines in podocytes. Conclusion 7CZ nanomedicines were highly effective in protecting against ADR-induced podocyte injury in vitro and in vivo at a very low concentration. Graphical Abstract

Ni/Ni3Al heterogeneous multilayer structures are widely used in aerospace manufacturing because of their unique coherent interfaces and excellent mechanical properties. Revealing the deformation mechanisms of interfacial structures is of great significance for microstructural design and their engineering applications. Thus, this work aims to establish the connection between the evolution of an interfacial misfit dislocation (IMD) network and tensile deformation mechanisms of Ni/Ni3Al multilayer structures. It is shown that the decomposition of IMD networks dominates the deformation of Ni/Ni3Al multilayer structures, which exhibits distinct effects on crystallographic orientation and layer thickness. Specifically, the Ni/Ni3Al (100) multilayer structure achieves its maximum yield strength of 5.28 GPa at the layer thickness of 3.19 nm. As a comparison, the (110) case has a maximum yield strength of 4.35 GPa as the layer thickness is 3.01 nm. However, the yield strength of the (111) one seems irrelevant to layer thickness, which fluctuates between 10.89 and 11.81 GPa. These findings can provide new insights into a deep understanding of the evolution and deformation of the IMD network of Ni/Ni3Al multilayer structures.

In this paper, N-vinylpyrrolidone was copolymerized with acrylic acid and itaconic acid by free radical polymerization, and a series of polyacrylic acid-co-itaconic acid-co-N-vinylpyrrolidone (PAIN) dispersants with different pyrrolidone ligand contents were synthesized and characterized. Then, the cobalt blue nano-pigment slurry (20 wt%) was prepared through a water-based grinding method, and the optimum grinding technology was explored and determined as follows: PAIN2 as a dispersant, a dispersant dosage of 10 wt%, and a grinding time of 480 min. According to this optimum grinding technology, the prepared pigment slurry had a significantly decreased agglomeration, the D90 of which was 82 nm, and separately increased to 130 nm and 150 nm after heat storage for 3 and 7 days, exhibiting excellent heat storage stability. Additionally, its TSI value was also the lowest (1.9%), indicating good dispersion stability. The QCM and adorption capacity measuring results showed PAIN2 had a larger adsorption capacity, and the formed adsorption layer had a higher rigidity and was not easy to fall off. This was caused by both the interaction of carboxyl groups and the pyrrolidone ligand (strong coordination interaction) in PAIN2 with cobalt blue. The XPS and FT–IR measurements further proved the above-mentioned adsorption mechanism.

This study investigated the corrosion resistance and mechanical properties of Mg-2Zn-0.46Y-0.5Nd (wt.%) alloy plates and screws with fluorinated coatings and atomic layer deposition (ALD)-derived zirconia (ZrO2) coatings in vitro under physiological stress conditions. Synthetic polyurethane hemimandible replicas were split and fixed as the following three groups of magnesium alloy plates and screws: no additional surface coating treatment (Group A), with fluorinated coatings (Group B), and with duplex fluorinated and ALD-derived 100 nm ZrO2 coatings (Group C). A circulating stress of 1–10 N was applied to the distal bone segment, and a 4-week simulated body fluid immersion test was employed to study the remaining material volume and the mechanical properties of the different groups. Compared with Group A and Group B, the degradation rate of magnesium alloy plates and screws’ head regions was significantly slowed down under the protection of duplex MgF2/ZrO2 coatings (p < 0.01). There was no significant difference in the degradation rate of the screw shaft region between groups (p = 0.077). In contrast to fluoride coatings, duplex MgF2/ZrO2 coatings maintained the mechanical strength of magnesium alloy plates and screws after a 14 day in vitro SBF immersion test. We conclude that duplex MgF2/ZrO2 coatings exhibited a certain protective effect on the Mg alloy plates and screws under physiological stress conditions.

Abstract Whether tectonic strain from the early stage India‐Asia collision has synchronously affected the far‐field margin of the Tibetan Plateau is crucial for understanding plateau deformation and growth processes. However, direct evidence for early far‐field deformation remains scarce. Utilizing illite K‐Ar dating of three fault gouge samples, we established the faulting history of the Leibo fault zone (LFZ) at the southeastern margin of the Tibetan Plateau (SEMTP). Consistent authigenic illite ages of 52 ± 2, 54 ± 12 and 55 ± 6 Ma suggest the reactivated thrust faulting of the LFZ in the Early Cenozoic. Positioned ∼700 km east of the collisional boundary and at the intersection of three blocks with distinct lithospheric rheology in strength/viscosity, this event suggests a quasi‐synchronous far‐field tectonic response in the SEMTP to the India‐Asia collision.

BackgroundNo consistent conclusion has been reached regarding the attentional bias characteristics of adolescents with major depressive disorders (MDD), and unexamined co-occurring anxiety distress may contribute to this inconsistency.MethodsWe enrolled 50 MDD adolescents with anxiety distress, 47 MDD adolescents without anxiety distress and 48 healthy adolescents. We measured attentional bias using a point-probe paradigm during a negative-neutral emotional face task. Reaction time, correct response rate and attentional bias value were measured.ResultsMDD adolescents did not show a negative attentional bias; MDD adolescents with anxiety distress exhibited longer reaction time for negative and neutral stimuli, lower correct response rate for negative stimuli. Hamilton Anxiety Scale scores were positively correlated with reaction time, negatively correlated with correct response rate, and not significantly correlated with attentional bias value.LimitationsThe cross-sectional design hinders causal attribution, and positive emotional faces were not included in our paradigm.ConclusionNegative attentional bias is not a stable cognitive trait in adolescents with MDD, and avoidance or difficulty in disengaging attention from negative emotional stimuli may be the attentional bias characteristic of MDD adolescents with anxiety distress.

Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.

As a new type of carbon material, graphene quantum dots (GQDs) show potential application value in chemical catalysis, biomedicine, optoelectronics, energy and other related fields because of its stronger quantum confinement effect and edge effect. Therefore, the preparation and application of GQDs have become one of the hotspots in the research of graphene-based materials. From the published references on the synthesis and applications of GQDs, it can been seen that the difference of raw materials is still one of the important factors which affects the size, functional groups, fluorescence properties, and yields of GQDs, in addition the methods. In order to reduce the preparation cost and develop efficient and green methods to obtain GQDs, this review emphasized the differences in size and fluorescence properties of GQDs prepared by different raw materials such as graphite, coal, coke, as well as organic small molecules and biomass, and the reasons for the differences. Specifically, the advantages and disadvantages of different raw materials related preparation methods of GQDs are compared. Finally, an outlook on the possible solutions to the existing problems and the future research directions on preparation methods of GQDs with high yield and quality is proposed.

Internal short circuits because of deformation or melting down of separators have been recognized as a root cause for many thermal runaway (TR) events of high-energy-density (HED) lithium-ion batteries (LIBs). Ceramic coating of the polyolefin separators is a promising strategy but generally hinders ionic conduction. In this study, we demonstrate that co-coating the separators with boehmite ceramics and Li1.5Al0.5Ti1.5(PO4)3 (LATP) solid-state electrolytes could markedly improve the safety of LIBs while mitigating detrimental effects on electrochemical performance. We assembled HED (~350 Wh/kg) lithium-ion pouch cells with nickel-rich Li(Ni0.9CoxMn0.1-x)O2 cathodes, silicon-based/graphite blended anodes, and co-coated separators of varying thicknesses. It is found that LATP reacts with the organic liquid electrolytes and lithium to generate a robust solid-electrolyte-interface-filled LATP layer during the formation, which can prevent the thermal deformation of separators. During the thermal abusive tests, the battery's TR failure thresholds raised from 146.2 to 162.0 °C. Correspondingly, the direct failure cause of the cell TR hurdled the separator malfunction to the thermochemical reactions of the nickel-rich cathodes. Additionally, pouch cells exhibited impressive electrochemical performance, maintaining a capacity retention of 87.99% after 500 cycles at 1C.

Abstract The increasing demands in augmented somatosensory have promoted quantitative sensing to be an emerging need for athletic training/performance evaluation and physical rehabilitation. Neurons for the somatosensory system in the human body can capture the information of movements in time but only qualitatively. This work presents an electronic Exo-neuron (EEN) that can spread throughout the limbs for realizing augmented somatosensory by recording both muscular activity and joint motion quantitatively without site constraints or drift instability, even in strenuous activities. Simply based on low-cost liquid metal and clinically used adhesive elastomer, the EEN could be easily fabricated in large areas for limbs. It is thin (~120 μm), soft, stretchable (>500%), and conformal and further shows wide applications in sports, rehabilitation, health care, and entertainment.

Abstract Aim The aim of this study is to examine the incidence and risk factors for intimate partner violence (IPV) among patients with gynaecological cancer. Design A cross‐sectional study design was employed. Methods Patients with gynaecological cancer were recruited from a tertiary hospital in Shandong, China. Eligible patients completed a survey including questions regarding their demographic and cancer‐related characteristics, IPV experience and dyadic coping. Results A total of 429 patients were surveyed, 31% of them reported previous experiences with IPV, and negotiation was the most common type reported. The following variables were associated with IPV: a husband, wife and child/children family structure; a husband, wife, child/children and parent‐in‐law family structure; an annual household income ≥¥50,000 ($7207); and a similar or greater income earned by the patient than by her partner. Patient or Public Contribution IPV in patients with gynaecological cancer is investigated in this study.

Developing a meniscus substitute mimicking the anisotropic mechanics (higher circumferential tensile modulus and lower compressive modulus) of native tissue remains a great challenge. In this work, based on the pendant group structure-dependent H-bonding strengthening mechanism, two kinds of amide-based H-bonding crosslinked hydrogels with distinct mechanical behaviors, that is, the flexible poly(N-acryloyl glycinamide) (PNAGA) and the ultra-stiff poly(N-acryloylsemicarbazide) (PNASC) hydrogels are employed to construct the biomimetic meniscus substitute. To this end, a gel microparticle-based self-thickening strategy is first proposed to fabricate PNASC (GMP-PNASC) high-modulus hydrogels skeleton by extrusion printing technology in mimicking the collagen fibers in native meniscus to resist the circumferential tensile stress. Then, the PNAGA hydrogel is infused into the PNASC skeleton to replicate the proteoglycan, providing a lower compressive modulus. By regulating the structural features at the interior and peripheral regions, the GMP-PNASC/PNAGA hydrogel meniscus scaffold with the higher tensile modulus (87.28 ± 6.06 MPa) and lower compressive modulus (2.11 ± 0.28 MPa) can be constructed. In vivo outcome at 12 weeks post-implantation of rabbit's medial meniscectomy model confirms the effects of GMP-PNASC/PNAGA meniscus scaffold on alleviating the wear of articular cartilage and ameliorating the development of osteoarthritis (OA).

Abstract Background Exposure to persistent bullying victimization across multiple periods results in a high risk of worse consequences. Although amples studies support the association between bullying victimization and symptoms of anxiety and depression, whether mental health literacy can serve as a moderator on this relationship remains unknown. Therefore, the aim of this study was to examine the patterns of bullying victimization across the life course, and disentangle the moderating effect of mental health literacy between bullying victimization patterns and symptoms of anxiety and depression in Chinese college students. Methods A total of 4036 college students were enrolled by cluster sampling from November 2020 to January 2021. Bullying victimization, mental health literacy, and symptoms of anxiety and depression were measured by self-report validated questionnaires. A latent class analysis was applied to identify bullying patterns. The PROCESS program was conducted to analyze whether mental health literacy moderates the link between bullying victimization patterns and symptoms of anxiety and depression. Results Three latent patterns of bullying victimization were identified as follows: persistent bullying pattern (6.2%), moderate bullying pattern (10.5%), and low bullying pattern (83.3%). Logisitic regression analysis of anxiety and depressive symptoms indicated that compared with low bullying pattern, persistent bullying pattern had the highest risk. Specifically, mental health literacy moderated the association between bullying victimization pattern and anxiety symptoms (B = -0.039, P

Ventilation problems are critical in tunnel engineering, and the loss of air volume in ventilation ducts is generally estimated using empirical methods. The air volume calculation makes it difficult to meet the accuracy requirements, resulting in resource waste or insufficient air supply. In this study, the forced ventilation system of the tunnel under construction was investigated based on the computational fluid dynamics method. The mechanism of air leakage on airflow distribution and pollutant transport in the tunnel is determined. Air leakage reduces the distribution peak of pollutants and effectively accelerates the emission of harmful gases. However, this effect decreases with distance from the air duct inlet. Through the calculation results of nearly one hundred models, it is found that the air leakage of the duct can be fitted by logarithmic function and verified by empirical equation. The matching degree between the fitting function of the model and the empirical equation depends on the length of the tunnel. On this basis, the calculation formula of effective air volume near the working face is derived. This study can be applied to the ventilation engineering of the tunnel under construction and provide a theoretical basis for the calculation of the effective air supply.

Identifying genetic markers of economically valuable traits has practical benefits for the meat goat industry. To better understand the genomic variations influencing body conformation traits, a genome-wide association study was performed on Tashi goats, an indigenous Chinese goat breed. A total of 155 Tashi goats were phenotyped for eight body conformation traits: body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Then, 100 Tashi goats were randomly selected for whole-genome sequencing and genotyped. We obtained 1676.4 Gb of raw data with an average sequencing depth of 6.2X. Clean reads were aligned to the ARS1.2 reference genome, and 11,257,923 single nucleotide polymorphisms (SNPs) were identified. The structure analysis showed that these Tashi goats were almost not genetically related. The 109, 20, 52, 14, 62, 51, 70, and 7 SNPs were significantly associated with body height, body length, chest depth, chest width, chest girth, rump width, rump height, and cannon bone circumference. Within the ±500 kb region of significant SNPs, 183 genes were annotated. The most significantly enriched KEGG pathway was “olfactory transduction”, and the most significantly enriched gene ontology (GO) terms were “cellular process”, “cellular anatomical entity”, and “molecular transducer activity”. Interestingly, we found several SNPs on chromosomes 10 and 11 that have been identified multiple times for all eight body conformation traits located in two fragments (114 kb and 1.03 Mb). In chr.10:25988403-26102739, the six SNPs were tightly linked, the TACTAG genotype was the highest at 91.8%, and the FNTB (Farnesyltransferase, CAAX Box Beta) and CHURC1 (Churchill Domain Containing 1) genes were located. In chr.11:88216493-89250659, ten SNPs were identified with several dependent linkage disequilibrium (LD) blocks, and seven related genes were annotated, but no significant SNP was located in them. Our results provide valuable biological information for improving growth performance with practical applications for genomic selection in goats.

Abstract Monolayer molybdenum disulfide (ML-MoS2) is an emergent two-dimensional (2D) semiconductor holding potential for flexible integrated circuits (ICs). The most important demands for the application of such ML-MoS2 ICs are low power consumption and high performance. However, these are currently challenging to satisfy due to limitations in the material quality and device fabrication technology. In this work, we develop an ultra-thin high-κ dielectric/metal gate fabrication technique for the realization of thin film transistors based on high-quality wafer scale ML-MoS2 on both rigid and flexible substrates. The rigid devices can be operated in the deep-subthreshold regime with low power consumption and show negligible hysteresis, sharp subthreshold slope, high current density, and ultra-low leakage currents. Moreover, we realize fully functional large-scale flexible ICs operating at voltages below 1 V. Our process could represent a key step towards using energy-efficient flexible ML-MoS2 ICs in portable, wearable, and implantable electronics.

Abstract Size-controlled polymer nanodomes (PNDs) benefit a broad cross-section of existing and emerging technologies. Condensed droplet polymerization (CDP) is a vacuum-based synthesis technology that produces PNDs from monomer precursors in a single step. However, the effect of synthesis and processing conditions on the PND size distribution remains elusive. Towards size distribution control, we report the effect of substrate temperature, on which monomer droplets condense, on the size distribution of PNDs. We take a reductionist approach and operate the CDP under batch mode to match the conditions commonly used in condensation research. Notably, despite the rich knowledge base in dropwise condensation, the behavior of nonpolar liquids like a common monomer, i.e., 2-hydroxyethyl methacrylate (HEMA), is not well understood. We bridge that gap by demonstrating that dropwise condensation of HEMA follows a two-stage growth process. Early-stage growth is dominated by drop nucleation and growth, giving rise to relatively uniform sizes with a lognormal distribution, whereas late-stage growth is dominated by the combined effect of drop coalescence and renucleation, leading to a bimodal size distribution. This new framework for understanding the PND size distribution enables an unprecedented population of PNDs. Their controlled size distribution has the potential to enable programmable properties for emergent materials.