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In a targeted double-scoring procedure for performance assessments that are used for licensure and certification purposes, a subset of responses receives an independent second rating if the first rating falls into a preidentified critical score range (CSR) where an additional rating would lead to considerably more reliable pass-fail decisions. This study evaluates the CSRs using two approaches--one based on imputation of missing scores and the other based on statistical decision theory--using data from the Performance Assessment for School Leaders (PASL). Results from the evaluation indicate that the currently used CSRs are effective.

Sensitivity analysis, a statistical method crucial for validating inferences across disciplines, quantifies the conditions that could alter conclusions (Razavi et al., 2021). One line of work is rooted in linear models and foregrounds the sensitivity of inferences to the strength of omitted variables (Cinelli & Hazlett, 2019; Frank, 2000). A more recent approach is rooted in the potential outcomes framework for causal inference and foregrounds how hypothetical changes in a sample would alter an inference if such cases were otherwise observed (Frank et al., 2008, 2013; Frank & Min, 2007; Xu et al., 2019). One sensitivity measure is the "Impact Threshold of a Confounding Variable," or ITCV, which generates statements about the correlation of an omitted, confounding variable with both a predictor of interest and the outcome (Frank, 2000). The ITCV index can be calculated for any linear model. The "Robustness of an Inference to Replacement," RIR, assesses how replacing a certain percentage of cases with counterfactuals of zero treatment effect could nullify an inference (Frank et al., 2013). The RIR index is more general than the ITCV index.

The prevalence of collaborative learning in online virtual environments is on the rise. It is vital to investigate the effect of emotional interaction on the learning engagement of students. The university students who participated in 16 h of online collaborative learning responded to an anonymous survey. The instruments included Collaborative Learning Emotional Interaction Scale, Loneliness Scale, Positive and Negative Rumination Scale, and Learning Engagement Scale. The mediating and moderating roles of variables were tested. Both positive and negative emotional interactions in online collaborative learning positively predicted learning engagement. Positive emotional interaction can inversely predict loneliness, while negative emotional interaction has a positive effect on loneliness. Loneliness inversely predicts learning engagement. In the low level of positive rumination, loneliness has a significant inhibitory effect on learning engagement, and the effect is much greater than that in the high level of positive rumination. In online collaborative learning, loneliness mediates the effect of learners' emotional interaction on learning engagement. The level of positive rumination moderated the connection between loneliness and learning engagement, the second part of the mediation model. We can begin by increasing learners' positive rumination and reducing the detrimental impact of negative emotional interaction and isolation on learning engagement in online collaborative learning.

Mobile technologies are widely used in education, both as standalone tools and in conjunction with other applications. The WeChat-based app Rain Classroom is one such application. Rain Classroom includes learning activities not only during class but also before and after class. Previous research has suggested strong demand for WeChat-based apps that can facilitate learning. However, relevant studies have not empirically evaluated the effect of Rain Classroom on English learning performance. This study examined the effects of using Rain Classroom for English learning. A total of 152 students were divided into control and experimental groups, each with 76 students. The experimental group had significantly better English reading, writing and listening scores than the control group did. The effects of the perceived features of Rain Classroom and learner satisfaction on learning performance were also investigated. Both factors had a significant positive influence on learning performance. The Rain Classroom has been proven to be an effective English learning tool. On the basis of the study findings, relevant implications are offered.

Based on 52 studies with samples mostly from English-speaking countries, the current study used Bayesian network meta-analysis to investigate the intervention effectiveness of different reading comprehension strategy combinations on reading comprehension among students with reading difficulties in 3rd through 12th grade. We focused on commonly researched strategies: main idea, inference, text structure, retell, prediction, self-monitoring, and graphic organizers. Results showed (1) instruction of more strategies did not necessarily have stronger effects on reading comprehension; (2) there was no single reading comprehension strategy that produced the strongest effect; (3) main idea, text structure, and retell, taught together as the primary strategies, seemed the most effective; and (4) the effects of strategies only held when background knowledge instruction was included. These findings suggest strategy instruction among students with reading difficulties follows an ingredient-interaction model--that is, no single strategy works the best. It is not "the more we teach, the better outcomes to expect." Instead, different strategy combinations may produce different effects on reading comprehension. Main idea, text structure, and retell together may best optimize the cognitive load during reading comprehension. Background knowledge instruction should be combined with strategy instruction to facilitate knowledge retrieval as to reduce the cognitive load of using strategies.

Abstract Background Older subjects have a higher risk for vertebral compression fracture. Maintaining a higher bone mineral density (BMD) at this age can protect individuals from osteoporosis-related events. Body mass index (BMI) has been found to have a robust association with BMD. However, excessive BMI is detrimental to bone health and may cause systemic disorders. Therefore, the present study aimed to determine the association between BMI and BMD, and identify a reasonable BMI range. Methods A total of 961 participants were recruited from community-dwelling residents between August 2021 and May 2022. A weighted multivariate linear regression model was applied to identify the relationship between BMI and BMD. Meanwhile, subgroup stratified analysis by BMI quartile and gender was also performed. A non-linear relationship and threshold value were determined based on the smooth curve fittings and threshold effects analysis model. Results A robust relationship was found between BMI and BMD, which remained significant in subgroups stratified by gender and BMI quartile. The BMI inflection point values in lumbar BMD and femoral neck BMD were 25.2 kg/m2 and 27.3 kg/m2, respectively. For individuals with BMI 25.2 kg/m2, an increase in BMI was associated with a decrease in lumbar BMD. For subjects with BMI

Abstract Background Morphometric analysis of the psoas major muscle has shown utility in predicting postoperative morbidity in various surgical fields, but its usefulness in predicting complications in elderly patients undergoing multilevel lumbar fusion surgery has not been studied. The study aimed to investigate if psoas major parameters are independent risk factors of early postoperative complication among elderly patients. Methods Patients who underwent multilevel lumbar fusion for degenerative lumbar spinal stenosis (DLSS) were included. The psoas major was measured at the lumbar 3/4 intervertebral disc level in three ways on computed tomography image: psoas muscle mass index, mean muscle attenuation, and morphologic change of the psoas major. Early complications were graded using the Clavien-Dindo classification system and the Comprehensive complication index (CCI). A CCI ≥ 26.2 indicated severe complications. Logistic regression was performed to identify independent risk factors. Results This retrospective study reviewed 108 patients (mean age 70.9 years, female to male ratio 1.8:1). Complications were observed in 72.2% of patients, with allogeneic blood transfusion being the most frequent (66.7%), followed by wound infection, acute heart failure (2.8% each). Severe complications occurred in 13.9% of patients. After multivariable regression analysis, those in the lowest psoas muscle attenuation tertile had higher odds of experiencing early postoperative complications (OR: 3.327, 95% CI 1.134–9.763, p = 0.029) and severe complications (OR: 6.964, 95% CI 1.928–25.160, p = 0.003). Conclusion The psoas muscle attenuation can be used as a predictor of early postoperative complications in elderly patients undergoing multilevel lumbar fusion surgery for DLSS.

Abstract Background This is a retrospective cohort study from a single center of Chest Medical District of Nanjing Brain Hospital Affiliated to Nanjing Medical University, Jiangsu Province, China. It was aim to evaluate the diagnostic value of radial endobronchial ultrasound (R-EBUS) combination with rapid on-site evaluation (ROSE) guided transbronchial lung biopsy (TBLB) for peripheral pulmonary lesions in patients with emphysema. Methods All 170 patients who underwent PPLs with emphysema received an R-EBUS examination with or without the ROSE procedure, and the diagnostic yield, safety, and possible factors influencing diagnosis were analyzed between the two groups by the SPSS 25.0 software. Results The pooled and benign diagnostic yields were not different in the two groups (P = 0.224, 0.924), but the diagnostic yield of malignant PPLs was significantly higher in the group with ROSE than the group without ROSE (P = 0.042). The sensitivity of ROSE was 79.10%, the specificity, 91.67%, the positive predictive value, 98.15%, and the negative predictive value, 84.62%. The diagnostic accuracy, was 95.52%. In the group of R-EBUS + ROSE, the procedural time and the number of times of biopsy or brushing were both significantly reduced (all P

Abstract At present, social networks have become an indispensable medium in people's daily life and work. However, concerns about personal privacy leakage and identity information theft have also emerged. Therefore, a communication network system based on network slicing is constructed to strengthen the protection of communication network privacy. The chameleon hash algorithm is used to optimize attribute-based encryption and enhance the privacy protection of communication networks. On the basis of optimizing the combination of attribute encryption and homomorphic encryption,, a communication network privacy protection method using homomorphic encryption for network slicing and attribute is designed. The results show that the designed network energy consumption is low, the average energy consumption calculation is reduced by 8.69%, and the average energy consumption calculation is reduced by 14.3%. During data transmission, the throughput of the designed network can reach about 700 Mbps at each stage, which has a high efficiency.. The above results demonstrate that the designed communication network provides effective privacy protection. Encrypted data can be decrypted and tracked in the event of any security incident. This is to protect user privacy and provide strong technical support for communication network security.

Abstract This study aims to illustrate epidemiology of comorbid CVD in the real-world clinical setting of patients with psoriasis in China. We used data of adult patients with psoriasis who were registered in the register of China National Clinical Center for Skin and Immune Diseases between August 2020 and September 2021. Psoriasis was clinically diagnosed following the national guidelines. Univariate and multivariate logistic regression models were used to examine the factors associated with comorbid CVD in patients with psoriasis. Of the 11,560 psoriasis patients (age ≥ 18 years, mean age 41.87 years, 64.88% males), 236 were ascertained with CVD, with the overall prevalence being 2.62%. Multivariate logistic regression analysis suggested that the odds ratio (95% confidence interval) of CVD in psoriasis patients was 2.27 (2.03–2.54) for older age (per 10-year increment), 0.65 (0.48–0.90) for female, 2.07 (1.39–3.06) for obesity (BMI ≥ 28 vs.

Abstract Copy number variation (CNV) tends to occur in genetically enriched regions and is likely associated with a number of complex diseases such as skin aging. In this study, we investigated the genome-wide CNVs in 20 wrinkled skin cases (WSC) of Xiang pigs and 63 controls, and identified 7893 copy number variable regions (CNVRs). We estimated the F-statistic (Fst) at each locus and identified that 93 case-controls stratified CNVRs (Fst > = 0.15) overlapped with 87 known genes. Functional enrichment analysis showed that most of these genes were predominantly enriched in pathways and terms related to the extracellular matrix. Finally, we found that some CNVs were predicted to have high effects on genes such as VCAN, TIMP1 and FOXO1 through transcriptional amplification, transcript ablation and so on. Most of the genes overlapped with those CNVRs have been reported to be related to aging in human or animals. The copy numbers presented the positive correlations with the transcript level of the genes in skins between the cases and controls. Our results suggested that those 22 CNVRs, including 19 CNV losses and 3 CNV gains, were putatively associated with the skin wrinkle of Xiang pigs.

Abstract Background In the past few decades, researchers have made promising progress, including the development of immune checkpoint inhibitors (ICIs) in the therapy of bladder cancer (BLCA). Existing studies mainly focus on single immune checkpoint inhibitors but lack relevant studies on the gene expression profiles of multiple immune checkpoints. Methods RNA-sequencing profiling data and clinical information of BLCA patients and normal human bladder samples were acquired from the Cancer Genome Atlas and Gene Expression Omnibus databases and analyzed to identify different expression profiles of immune checkpoint genes (ICGs) after consensus clustering analysis. Based on the 526 intersecting differentially expressed genes, the LASSO Cox regression analysis was utilized to construct the ICG signature. Results According to the expression of ICGs, BLCA patients were divided into three subtypes with different phenotypic and mechanistic characteristics. Furthermore, the developed ICG signature were independent predictors of outcome in BLCA patients, and was correlated with the immune infiltration, the expression of ICGs and chemotherapeutic effect. Conclusions This study systematically and comprehensively analyzed the expression profile of immune checkpoint genes, and established the ICG signature to investigate the differences in ICGs expression and tumor immune microenvironment, which will help risk stratification and accelerate precision medicine. Finally, we identified KRT23 as the most critical model gene, and highlighted KRT23 as a potential target to enhance immunotherapy against BLCA.

Abstract Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (

Abstract Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

Abstract Background Mitochondrial tRNA (mt-tRNA) variants have been found to cause disease. Post-transcriptional queuosine (Q) modifications of mt-tRNA can promote efficient mitochondrial mRNA translation. Q modifications of mt-tRNAAsn have recently been identified. Here, the therapeutic effectiveness of queuine was investigated in cells from patients with mt-tRNAAsn variants. Methods Six patients (from four families) carrying mt-tRNAAsn variants were included in the study. Queuine levels were quantified by mass spectrometry. Clinical, genetic, histochemical, biochemical, and molecular analysis was performed on muscle tissues and lymphoblastoid cell lines (LCLs) from patients to investigate the pathogenicity of the novel m.5708 C > T variant. The use of queuine in mitigating mitochondrial dysfunction resulting from the mt-tRNAAsn variants was evaluated. Results The variants included the m.5701 delA, m.5708 C > T, m.5709 C > T, and m.5698 G > A variants in mt-tRNAAsn. The pathogenicity of the novel m.5708 C > T variant was confirmed, as demonstrated by a decreased steady-state level of mt-tRNAAsn, mtDNA-encoded protein levels, oxygen consumption rate (OCR), and the respiratory complex activity. Notably, the serum queuine level was significantly reduced in these patients and in vitro queuine supplementation was found to restore the reductions in mitochondrial protein activities, mitochondrial membrane potential, OCR, and increases in reactive oxygen species. Conclusions The study not only confirmed the pathogenicity of the m.5708 C > T variant but also explored the therapeutic potential of queuine in individuals with mt-tRNAAsn variants. The recognition of the novel m.5708 C > T variant’s pathogenic nature contributes to our comprehension of mitochondrial disorders. Furthermore, the results emphasize queuine supplementation as a promising approach to enhance the stability of mt-tRNAAsn and rescue mitochondrial dysfunction caused by mt-tRNAAsn variants, indicating potential implications for the development of targeted therapies for patients with mt-tRNAAsn variants.

Abstract Background The prognostic value of the pretreatment prognostic nutritional index (PNI) for gynaecological malignancies remain unclear. This meta-analysis aimed to explore the predictive significance of the PNI for gynaecological tumours. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to January 30, 2024, to identify relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations of the PNI with overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in patients with gynaecological tumours. We examined the correlation of the PNI with clinicopathological parameters of patients with gynaecological carcinoma by utilizing pooled odds ratios (ORs) and 95% CIs. Results A total of 28 articles involving 9,428 patients were included in the meta-analysis. The results revealed that a low PNI significantly predicted worse OS (HR = 1.60, 95% CI: 1.39–1.84, P

Abstract Background Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15–39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. Methods Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation. Results Between 1990 and 2021, the worldwide prevalence of migraine among 15–39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35–39 age group. Notably, female rates consistently exceeded male rates across all age categories. Conclusion The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine.

Abstract Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C → T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria.

Abstract Background The hyperinflammatory condition and lymphoproliferation due to Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) affect the detection of lymphomas by 18F-FDG PET/CT. We aimed to improve the diagnostic capabilities of 18F-FDG PET/CT by combining laboratory parameters. Methods This retrospective study involved 46 patients diagnosed with EBV-positive HLH, who underwent 18F-FDG PET/CT before beginning chemotherapy within a 4-year timeframe. These patients were categorized into two groups: EBV-associated HLH (EBV-HLH) (n = 31) and EBV-positive lymphoma-associated HLH (EBV + LA-HLH) (n = 15). We employed multivariable logistic regression and regression tree analysis to develop diagnostic models and assessed their efficacy in diagnosis and prognosis. Results A nomogram combining the SUVmax ratio, copies of plasma EBV-DNA, and IFN-γ reached 100% sensitivity and 81.8% specificity, with an AUC of 0.926 (95%CI, 0.779–0.988). Importantly, this nomogram also demonstrated predictive power for mortality in EBV-HLH patients, with a hazard ratio of 4.2 (95%CI, 1.1–16.5). The high-risk EBV-HLH patients identified by the nomogram had a similarly unfavorable prognosis as patients with lymphoma. Conclusions The study found that while 18F-FDG PET/CT alone has limitations in differentiating between lymphoma and EBV-HLH in patients with active EBV infection, the integration of a nomogram significantly improves the diagnostic accuracy and also exhibits a strong association with prognostic outcomes.

Abstract The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body’s immune potential, providing an eutherapeutic strategy for the treatment of OC.

Abstract Background Tubal mesosalpinx cysts are paratubal cysts, that account for approximately 10% of adnexal masses, and the presence of these cysts combined with adnexal torsion is a rare acute abdominal condition, with few cases reported in the literature. We reported two cases of adolescent tubal mesosalpinx cysts combined with adnexal torsion and reviewed the literature to help improve the diagnosis of the disease. Case reports The first patient was an 11-year-old girl with left lower abdominal pain for 5 days and fever with nausea and vomiting for 3 days, who was found to have a cystic pelvic mass on preoperative imaging and was diagnosed intraoperatively and postoperatively on pathology as having a left tubal mesosalpinx cyst combined with adnexal torsion. The second patient was a 13-year-old girl with right lower abdominal pain for 16 h and a palpable mass in the lower and middle abdomen on examination, which was hard and tender to palpate. Preoperative imaging revealed a large cystic mass in the right adnexal region, and intraoperative and postoperative pathology revealed a right tubal mesosalpinx cyst combined with adnexal torsion. Conclusions Tubal mesosalpinx cysts combined with adnexal torsion are rare causes of acute lower abdominal pain. Early diagnosis and timely surgery are necessary to ensure ovarian and tubal function. Accurate preoperative imaging diagnosis is challenging, and MRI is a beneficial supplement to ultrasound and CT examinations, providing more objective imaging information and reducing the incidence of adverse outcomes.

Abstract Accurately assigning standardized diagnosis and procedure codes from clinical text is crucial for healthcare applications. However, this remains challenging due to the complexity of medical language. This paper proposes a novel model that incorporates extreme multi-label classification tasks to enhance International Classification of Diseases (ICD) coding. The model utilizes deformable convolutional neural networks to fuse representations from hidden layer outputs of pre-trained language models and external medical knowledge embeddings fused using a multimodal approach to provide rich semantic encodings for each code. A probabilistic label tree is constructed based on the hierarchical structure existing in ICD labels to incorporate ontological relationships between ICD codes and enable structured output prediction. Experiments on medical code prediction on the MIMIC-III database demonstrate competitive performance, highlighting the benefits of this technique for robust clinical code assignment.

Abstract Hailstorms, characterized by their intensity, are often accompanied by strong winds and heavy rain, posing significant destructive potential. Data indicate that the economic losses caused by hail to buildings, particularly solar panels, have been increasing annually. However, research on the hail resistance of photovoltaic panels has predominantly focused on the isolated effects of hail impacts and wind loads, neglecting the coupling effects between wind and hail. In this study, a device was designed to couple both wind and hail. The effects of turbulence, hail size, and velocity on hail impact behavior were systematically studied and quantified. A predictive formula for the peak load of hail impact on structures was established. The results indicate that the impact of turbulence on hail is significant. When turbulence intensity varies with hail velocity, hail impact force increases as turbulence decreases and hail velocity increases. When both turbulence and hail diameter vary, the impact force of smaller hailstones shows less variation with increasing turbulence. According to variance analysis, hail velocity is the most significant factor affecting hail impact, followed by hail diameter and finally turbulence. The regression equation is given by $$F = - 0.624I_{{\text{u}}} + 5116.25D + 7.85V_{hail} - 259.709$$ F = - 0.624 I u + 5116.25 D + 7.85 V hail - 259.709 , where $$F$$ F represents the peak impact force in Newtons (N), $$I_{{\text{u}}}$$ I u denotes the turbulence intensity, $$D$$ D is the hail diameter in meters (m), and $$V_{hail}$$ V hail is the hail velocity in meters per second (m/s).

Abstract Background A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. Methods Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. Results Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14–4.16%), below the literature-defined performance goal of 11% (P

Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Abstract The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p

Abstract Background Selection markers are useful in genetic modification of yeast Pichia pastoris. However, the leakage of the promoter caused undesired expression of selection markers especially those toxic proteins like MazF, halting the cell growth and hampering the genetic manipulation in procaryotic system. In this study, a new counter-selectable marker-based strategy has been established for seamless modification with high efficiency and low toxicity. Results At first, the leaky expression of the enhanced green fluorescent protein (EGFP) as a reporter gene under the control of six inducible promoters of P. pastoris was investigated in two hosts Escherichia coli and P. pastoris, respectively. The results demonstrated that the DAS1 and FDH1 promoters (PDAS1 and PFDH1) had the highest leakage expression activities in procaryotes and eukaryotes, and the DAS2 promoter (PDAS2) was inducible with medium strength but low leakage expression activity, all of which were selected for further investigation. Next, Mirabilis antiviral proteins (MAPs) c21873-1, c21873-1T (truncated form of c21873-1) and c23467 were mined as the new counter-selectable markers, and hygromycin B (Hyg B) resistance gene was used as the positive-selectable marker, respectively. Then, modular plasmids with MAP-target gene-Hyg B cassettes were constructed and used to transform into P. pastoris cells after linearization, and the target genes were integrated into its genome at the BmT1 locus through single-crossover homologous recombination (HR). After counter-selection induced by methanol medium, the markers c21873-1 and c21873-1T were recycled efficiently. But c23467 failed to be recycled due to its toxic effect on the P. pastoris cells. At last, the counter-selectable marker c21873-1 under the tightly regulated PDAS2 enabled the encoding genes of reporter EGFP and tested proteins to be integrated into the target locus and expressed successfully. Conclusions We have developed MAP c21873-1 as a novel counter-selectable marker which could perform efficient gene knock-in by site-directed HR. Upon counter-selection, the marker could be recycled for repeated use, and no undesirable sequences were introduced except for the target gene. This unmarked genetic modification strategy may be extended to other genetic modification including but not limited to gene knock-out and site-directed mutagenesis in future.

Abstract Background Moral distress occurs in daily nursing work and plagues nurses. Improving the level of moral courage is one of the main strategies to reduce moral distress, and low levels of moral courage may lead to nurse burnout, increased turnover, and reduced quality of care. Methods Nine electronic databases in Chinese and English were searched for the level of moral courage among nurses, including PubMed, Web of Science, EMBASE, CINAHL, CNKI, Wan fang, Wei pu, CBM and Cochrane Library, for the period from the date of database creation to April 5, 2023. The Agency for Healthcare Research and Quality (AHRQ) was used to assess the methodological quality of the included studies, followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Meta-analysis and Systematic Reviews of Observational Studies guidelines, and data from the included studies were meta-analyzed in STATA version 15 using a fixed-effects model. Results Seventeen cross-sectional studies of moderate or high quality met the eligibility criteria and involved 7718 nurses, and the Nurses’ Moral Courage Scale (NMCS) was used to measure the self-assessed moral courage level of nurses. Eleven of these studies reported total scores for nurses’ moral courage, and the meta-analysis results showed a pooled mean score of 78.94 (95% CI: 72.17, 85.72); Fourteen studies reported mean entry scores for nurses’ moral courage, and the meta-analysis results showed a pooled mean score of 3.93 (95% CI: 3.64, 4.23). Conclusion The results of the meta-analysis showed that nurses’ moral courage levels were in the medium to high range, among the nurses who seemed to be male, non-nursing managers, high school education, had not experienced ethical issues, and considering resignation had lower levels of moral courage. The results of the meta-analysis may provide some reference for nursing managers and even hospital administrators to develop strategies to optimize nursing quality.

Abstract Background Daye No.3 is a novel cultivar of alfalfa (Medicago sativa L.) that is well suited for cultivation in high-altitude regions such as the Qinghai‒Tibet Plateau owing to its high yield and notable cold resistance. However, the limited availability of transcriptomic information has hindered our investigation into the potential mechanisms of cold tolerance in this cultivar. Consequently, we conducted de novo transcriptome assembly to overcome this limitation. Subsequently, we compared the patterns of gene expression in Daye No. 3 during cold acclimatization and exposure to cold stress at various time points. Results A total of 15 alfalfa samples were included in the transcriptome assembly, resulting in 141.97 Gb of clean bases. A total of 441 DEGs were induced by cold acclimation, while 4525, 5016, and 8056 DEGs were identified at 12 h, 24 h, and 36 h after prolonged cold stress at 4 °C, respectively. The consistency between the RT‒qPCR and transcriptome data confirmed the accuracy and reliability of the transcriptomic data. KEGG enrichment analysis revealed that many genes related to photosynthesis were enriched under cold stress. STEM analysis demonstrated that genes involved in nitrogen metabolism and the TCA cycle were consistently upregulated under cold stress, while genes associated with photosynthesis, particularly antenna protein genes, were downregulated. PPI network analysis revealed that ubiquitination-related ribosomal proteins act as hub genes in response to cold stress. Additionally, the plant hormone signaling pathway was activated under cold stress, suggesting its vital role in the cold stress response of alfalfa. Conclusions Ubiquitination-related ribosomal proteins induced by cold acclimation play a crucial role in early cold signal transduction. As hub genes, these ubiquitination-related ribosomal proteins regulate a multitude of downstream genes in response to cold stress. The upregulation of genes related to nitrogen metabolism and the TCA cycle and the activation of the plant hormone signaling pathway contribute to the enhanced cold tolerance of alfalfa.

Abstract Based on double-compressed sampling, a hyperspectral spectral unmixing algorithm (SU_DCS) is proposed, which could directly complete the endmember extraction and abundance estimation. On the basis of the linear mixed model (LMM), we designed spatial and spectral sampling matrices, obtained spatial and spectral measurement data, and constructed a joint unmixing model containing endmember and abundance information. By using operator separation and Lagrangian multiplier algorithm, the endmember matrix, abundance matrix and remixing image can be quickly obtained by matrix operation. The parameters of the unmixing algorithm, including regularization parameter, convergence threshold and spatial sampling rate, are determined using synthetic simulated hyperspectral data. The proposed algorithm is applied to two kinds of real hyperspectral data, with or without ground truth, in order to verify the effectiveness and reliability of the algorithm. Firstly, we provide the performance of the algorithm on real datasets without ground truth. Compared with algorithm VCA_FCLS and algorithm CPPCA_VCA_FCLS, the endmember spectral curve extracted by the proposed SU_DCS is almost consistent with that obtained by VCA_FCLS, and is more smooth than that of obtained by CPPCA_VCA_FCLS. Additionally, the abundance estimation map estimated by the SU_DCS has consistency with the results obtained by VCA_FCLS. Moreover, the proposed SU_DCS has higher peak signal-to-noise ratio (PSNR) for remixing images with higher computational efficiency. Secondly, we provide the performance of the proposed algorithm on four real datasets with ground truth, including dataset Cuprite, dataset Samson, dataset Jasper and dataset Urban. We provide the results of endmember extraction and abundance estimation from the compressed data under different sampling rate conditions. The extracted endmember maintains good consistency with the true spectral curves, and the estimated abundance map can also maintain good spatial consistency with the ground truth. The comparison results with other four comparative algorithms also indicate that the proposed algorithm can obtain relatively accurate endmembers and abundance information from compressed data, the reliability and validity of the proposed algorithm have been proved. In summary, the main innovation of the proposed algorithm is that it can extract endmembers and estimate abundance with high accuracy from a small amount of measurement data.

Abstract Non-Hermitian physics has emerged as a new paradigm that profoundly changes our understanding of non-equilibrium systems, introducing novel concepts such as exceptional points, spectral topology, and non-Hermitian skin effects (NHSEs). Most existing studies focus on non-Hermitian eigenstates, whereas dynamic properties have been discussed only recently, and the dynamic NHSEs are not yet confirmed in experiments. Here, we report the experimental observation of non-Hermitian skin dynamics using tunable one-dimensional nonreciprocal double-chain mechanical systems with glide-time symmetry. Remarkably, dynamic NHSEs are observed with various behaviors in different dynamic phases, which can be understood via the generalized Brillouin zone and the related concepts. Moreover, the observed dynamic NHSEs, amplifications, bulk unidirectional wave propagation, and boundary wave trapping provide promising ways to manipulate waves in a controllable and robust way. Our findings open a new pathway toward non-Hermitian dynamics, which will fertilize the study of non-equilibrium phases of matter.

Abstract Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton’s tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

Abstract Background Plague is an acute infectious disease caused by the Yersinia pestis. Historically, it has been a major pandemic with high mortality rates, known as the “Black Death” in the 14th century, which resulted in millions of deaths in Europe. With increasing economic prosperity, more and more people are traveling to Xizang. However, this trend also hides significant safety hazards. Currently, there are few recent reports on plague, especially those with imaging manifestations available. In this study, we report the detailed clinical and radiological data of the patient with pneumonic plague in Xizang, China, in 2023. Case presentation We report a case of pneumonic plague in Xizang, which occurred in a herdsman living in an area where dead marmots were found. The patient presented with symptoms such as fever, hemoptysis, dyspnea and coma. Chest computed tomography (CT) scans showed multiple nodules distributed in the central regions of lung lobes, consolidation distributed in secondary pulmonary lobules, and had a gravity-dependent distribution pattern. These imaging findings were consistent with pulmonary hemorrhage and diffuse alveolar damage. Despite emergency treatment, the patient died within 48 h of admission. Through retrospective medical history investigation, laboratory examination and autopsy, the final diagnosis was confirmed as pneumonic plague. Conclusion Pneumonic plague is the most deadly infectious disease, and its pathological features mainly include damage to the alveoli, pulmonary hemorrhage, and pulmonary edema. Corresponding to CT, it manifests as acute and rapidly progressing pneumonia, alveolar damage, and pulmonary hemorrhage. The value of this article lies in the completeness and typicality of the imaging data, vivid hand-drawn illustrations of transmission pathways, and comprehensive literature review, all of which serve to enhance public understanding of plague and play an important warning role.

Background: Osteoporosis is recognized as a skeletal disorder characterized by diminished bone tissue quality and density. Regular physical exercise is widely acknowledged to preserve and enhance bone health, but the detailed molecular mechanisms involved remain unclear. Irisin, a factor derived from muscle during exercise, influences bone and muscle. Since its discovery in 2012, irisin has been found to promote bone growth and reduce bone resorption, establishing a tangible link between muscle exertion and bone health. Consequently, the mechanism by which irisin prevents osteoporosis have attracted significant scientific interest. Aim of the review: This study aims to elucidate the multifaceted relationship between exercise, irisin, and bone health. Focusing on irisin, a muscle-derived factor released during exercise, we seek to understand its role in promoting bone growth and inhibiting resorption. Through a review of current research article on irisin in osteoporosis, Our review provides a deep dive into existing research on influence of irisin in osteoporosis, exploring its interaction with pivotal signaling pathways and its impact on various cell death mechanisms and inflammation. We aim to uncover the molecular underpinnings of how irisin, secreted during exercise, can serve as a therapeutic strategy for osteoporosis. Key scientific concepts of the review: Irisin, secreted during exercise, plays a vital role in bridging muscle function to bone health. It not only promotes bone growth but also inhibits bone resorption. Specifically, Irisin fosters osteoblast proliferation, differentiation, and mineralization predominantly through the ERK, p38, and AMPK signaling pathways. Concurrently, it regulates osteoclast differentiation and maturation via the JNK, Wnt/β-catenin and RANKL/RANK/OPG signaling pathways. This review further delves into the profound significance of irisin in osteoporosis and its involvement in diverse cellular death mechanisms, including apoptosis, autophagy, ferroptosis, and pyroptosis.

Employing crystal facets to regulate the catalytic properties in electrocatalytic carbon dioxide reduction reaction (eCO2RR) has been well demonstrated on electrocatalysts containing single metals but rarely explored for bimetallic systems. Here, we synthesize ZnSn(OH)6 (ZSO) microcrystals (MCs) with distinct facets and investigate the facet effects in eCO2RR. Electrochemical studies and in situ Fourier Transform Infrared Spectroscopy (in situ-FTIR) reveal that ZSO MCs produce mainly C1 products of HCOOH and CO. The {111} facet of the ZSO MCS exhibits higher selectivity and faradaic efficiency (FE) than that of the {100} facet over a wide range of potentials (−0.9 V ∼ −1.3 V versus RHE). Density Functional Theory (DFT) calculations elucidate that the {111} facet is favorable to the adsorption/activation of CO2 molecules, the formation of intermediate in the rate-determining step, and the desorption of C1 products of CO and HCOOH molecules.

Abstract Introduction Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. Methods This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008–December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. Results Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients’ mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87–61.78), 14.08 (95% CI 3.04–65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08–0.54) and 0.07 (95% CI 0.006–0.78), respectively. Conclusions Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals’ care and outcomes.

In recent years, ammonia (NH3) has received widespread attention as a fuel for internal combustion engines.Ammonia combustion produces a large amount of water, but incomplete combustion of ammonia may cause corrosion to engine piston components in medium to high temperature environments with water present.In this work, taking 4032 aluminum alloy piston material as the research object, the corrosion behavior in a 25%(mass fraction) ammonia solution was analyzed at a constant temperature of 200 ℃, and the corrosion weight loss, corrosion product morphology and corrosion electrochemical properties of aluminum alloys were explored emphatically at different time scales.Results showed that the corrosion rate of 4032 aluminum alloy in medium to high temperature ammonia environment exhibited a trend of first increasing and then decreasing with the prolongation of soaking time, and the corrosion products were mainly Al(OH)3.With the extension of soaking time, the corrosion potential Ecorr and polarization resistance Rp of 4032 aluminum alloy increased gradually, while the corrosion current density Jcorr decreased gradually, which further analyzed the corrosion mechanism.

Fe(II) is of great importance in iron-based advanced oxidation processes. However, traditional methods to maintain Fe(II) concentration, such as the addition of chelating agents or reducing agents, may lead to an increase in chemical oxygen demand of secondary pollution. Therefore, in this study, iron sulfides, namely ferrous sulfide (FeS), pyrite (FeS2), and sulfidated nanoscale zero-valent iron (S-nZVI), were applied for not only the regeneration of Fe(II) but also the direct dissolution of Fe(II). Nanoscale calcium peroxide (nCaO2) was synthesized and used as the oxidant. The removal of 1,2-dichloroethane (1,2-DCA) were significantly promoted from 8.8 to 98.2, 79.2, and 80.8% with the aid of FeS, FeS2, and S-nZVI within 180 min, respectively. The dominant reactive oxygen species were demonstrated and their steady-state concentrations were quantified. Besides, the dechlorination of 1,2-DCA reached 90.4, 69.5, and 83.9% in nCaO2/Fe(III) systems coupled with FeS, FeS2, and S-nZVI, respectively. All three systems had high tolerance to the complex water conditions, of which FeS-enhanced nCaO2/Fe(III) system displayed the best performance, which could be recommended to put into practice for the remediation of 1,2-DCA contaminated groundwater. HIGHLIGHTS FeS, FeS2, and S-nZVI were applied for the enhancement of nCaO2/Fe(III) system.; The advantages of nCaO2 toward commercial CaO2 were elucidated.; The dominant ROS and their steady-state concentrations were determined.; The effect of complex solution matrixes on the performance of enhanced systems was investigated.; The universality on the removal of other typical contaminants was inspected.;

Abstract Background Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death in neonatal piglets, which has brought huge economic losses to the pork industry worldwide since its first discovery in the early 1970s in Europe. Passive immunization with neutralizing antibodies against PEDV is an effective prevention measure. To date, there are no effective therapeutic drugs to treat the PEDV infection. Results We conducted a screening of specific nanobodies against the S1 protein from a phage display library obtained from immunized alpacas. Through competitive binding to antigenic epitopes, we selected instead of chose nanobodies with high affinity and constructed a multivalent tandem. These nanobodies were shown to inhibit PEDV infectivity by the neutralization assay. The antiviral capacity of nanobody was found to display a dose-dependent pattern, as demonstrated by IFA, TCID50, and qRT-PCR analyses. Notably, biparatopic nanobody SF-B exhibited superior antiviral activity. Nanobodies exhibited low cytotoxicity and high stability even under harsh temperature and pH conditions, demonstrating their potential practical applicability to animals. Conclusions Nanobodies exhibit remarkable biological properties and antiviral effects, rendering them a promising candidate for the development of anti-PEDV drugs.

Abstract Identifying individuals poised to gain from immune checkpoint inhibitor (ICI) therapies is a pivotal element in the realm of tailored healthcare. The expression level of Programmed Death Ligand 1 (PD-L1) has been linked to the response to ICI therapy, but its assessment typically requires substantial tumor tissue, which can be challenging to obtain. In contrast, blood samples are more feasible for clinical application. A number of promising peripheral biomarkers have been proposed to overcome this hurdle. This research aims to evaluate the prognostic utility of the albumin-to-lactate dehydrogenase ratio (LAR), the Pan-immune-inflammation Value (PIV), and the Prognostic Nutritional Index (PNI) in predicting the response to ICI therapy in individuals with advanced non-small cell lung cancer (NSCLC). Furthermore, the study seeks to construct a predictive nomogram that includes these markers to facilitate the selection of patients with a higher likelihood of benefiting from ICI therapy. A research initiative scrutinized the treatment records of 157 advanced NSCLC patients who received ICI therapy across two Jiangxi medical centers. The cohort from Jiangxi Provincial People’s Hospital (comprising 108 patients) was utilized for the training dataset, while the contingent from Jiangxi Cancer Hospital (49 patients) served for validation purposes. Stratification was based on established LAR, PIV, and PNI benchmarks to explore associations with DCR and ORR metrics. Factorial influences on ICI treatment success were discerned through univariate and multivariate Cox regression analysis. Subsequently, a Nomogram was devised to forecast outcomes, its precision gauged by ROC and calibration curves, DCA analysis, and cross-institutional validation. In the training group, the optimal threshold values for LAR, PIV, and PNI were identified as 5.205, 297.49, and 44.6, respectively. Based on these thresholds, LAR, PIV, and PNI were categorized into high (≥ Cut-off) and low (

Abstract Tumor-draining lymph nodes (TDLNs) are usually the first station of tumor metastasis in lung cancer. TDLNs+ have distinct pathomorphologic and tumor microenvironment (TME)-compositional patterns, which still need to be thoroughly investigated in lung adenocarcinoma (LUAD). Here, we enrolled 312 LUAD patients with TDLNs+ from our institution between 2015 and 2019. 3DHISTECH was used to scan all of the TDLNs+. Based on morphologic features, TDLNs+ patterns were classified as polarized-type or scattered-type, and TME-compositional patterns were classified as colloid-type, necrosis-type, specific-type, and common-type. Multivariate analysis revealed an increased risk of early recurrence associated with scattered-type (HR 2.37, 95% CI: 1.06–5.28), colloid-type (HR 1.95, 95% CI: 1.03–3.67), and necrosis-type (HR 2.21, 95% CI: 1.13–4.89). NanoString transcriptional analysis revealed an immunosuppression and vascular invasion hallmark in scattered and necrosis patterns and an immunoactivated hallmark in polarized and common patterns. According to imaging mass cytometry (IMC), the scattered and necrosis patterns revealed that germinal centers (GC) were compromised, GCB cell and T cell proliferation were deficient, tumor cells had the potential for proliferation, and the immune attack may be weaker. In this study, we present evidence that LUAD patients have distinct patterns and immune hallmarks of TDLNs+ related to their prognosis.

Catastrophe theory was used to establish a safety assessment model to reduce the reliance on subjective judgments in evaluation of timber-framed heritage buildings. This study was conducted in three phases. Initially, a comprehensive evaluation index system was established from the perspective of foundation. It consisted of eight aspects and 25 safety evaluation indicators using superstructure load-bearing elements, maintenance structures, and their interconnections in timber-framed heritage buildings. The 25 safety evaluation indicators included foundation, base, stone piers, columns, beams, lintels (beams, pads, and other bending components), bracket sets, arches, maintenance walls, beam-brace connections, and roof structures. The bottom-level indicators in the index system were dimensionless. The second phase employed typical catastrophe models (cusp, swallowtail, and butterfly) for normalization, resulting in calculated catastrophe scales and evaluation levels. The case study of the Buddha Hall of Zhihua Temple, Beijing, was applied in the final phase. It was found that the catastrophe scales method solved the subjectivity issues in determining weights. Additionally, the calculations were found to be concise and reliable, providing accurate results. The model can be used as a theoretical reference for the future safety assessment of timber-framed heritage buildings.

Abstract The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

Abstract Chimeric antigen receptor (CAR) T-cell therapy has achieved substantial clinical outcomes for tumors, especially for hematological malignancies. However, extending the duration of remission, reduction of relapse for hematological malignancies and improvement of the anti-tumor efficacy for solid tumors are challenges for CAR-T cells immunotherapy. Besides the endeavors to enhance the functionality of CAR-T cell per se, optimization of the infusion and delivery strategies facilitates the breakthrough of the hurdles that limited the efficacy of this cancer immunotherapy. Here, we summarized the infusion and delivery strategies of CAR-T cell therapies under pre-clinical study, clinical trials and on-market status, through which the improvements of safety and efficacy for hematological and solid tumors were analyzed. Of note, novel infusion and delivery strategies, including local-regional infusion, biomaterials bearing the CAR-T cells and multiple infusion technique, overcome many limitations of CAR-T cell therapy. This review provides hints to determine infusion and delivery strategies of CAR-T cell cancer immunotherapy to maximize clinical benefits.