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Abstract GPUs are increasingly playing vital roles in the modern technology industry. Improving the GPU performance involves optimizing its architectural design and fine-tuning its software code. However, to achieve this, engineers must investigate codes from as many GPU-related applications as possible to identify code portions that need fine-tuning. Moreover, this effort requires engineers to have good domain knowledge, and their work is made more arduous because the source codes of applications are normally confidential. To this end, we introduce ShaderAnalyzer, a solution leveraging graph mining and machine learning to analyze GPU-executed low-level machine codes and identify their fine-tuning opportunities. Our approach includes representing machine code with graph structure and subsequently identifying frequently occurring substructures within the codes. Optimizing the execution of these substructures can enhance the overall performance of the GPU. In addition, our model leverages these frequent patterns to further facilitate engineers’ tasks by selecting representative patterns to predict and investigate low-efficiency ones. We conduct comprehensive experiments to evaluate the performance of our solution, and the results have been validated by our industry partners. ShaderAnalyzer is an end-to-end framework that helps engineers identify code segments with the highest potential for performance gains after fine-tuning and offers valuable insights for hardware architects in future products design.

Abstract Backgound People with diabetes are much more likely to develop acute kidney injury (AKI) than people without diabetes. Low 25-hydroxy-vitamin D [25(OH)D] concentrations increased the risk of AKI in specific populations. Few studies have explored the relationship between the 25(OH)D level and AKI in patients with diabetes. We conducted this study to investigate the relationship between the plasma level of 25(OH)D and the risk of AKI in patients with diabetes, and to evaluate whether the 25(OH)D level could be a good prognostic marker for AKI progression. Methods A total of 347 patients with diabetes were retrospectively reviewed. The primary endpoint was the first event of AKI. The secondary endpoint is need-of-dialysis. AKI patients were further followed up for 6 months with the composite endpoint of end-stage renal disease (ESRD) or all-cause death. Kaplan–Meier survival analysis and Cox proportional hazards models were used. Results During a median follow-up of 12 weeks (12.3 ± 6.7), 105 incident AKI were identified. The middle and high tertiles of baseline 25(OH)D levels were associated with a significantly decreased risk of AKI and dialysis compared to the low tertile group (HR = 0.25, 95% CI 0.14–0.46; HR = 0.24, 95% CI 0.13–0.44, respectively, for AKI; HR = 0.15; 95% CI 0.05–0.46; HR = 0.12; 95% CI 0.03–0.42, respectively, for dialysis). Sensitivity analysis revealed similar trends after excluding participants without history of CKD. Furthermore, AKI patients with 25(OH)D deficiency were associated with a higher risk for ESRD or all-cause death (HR, 4.24; 95% CI, 1.80 to 9.97, P

Abstract Background As the global elderly population rises, providing quality care for older adults is increasingly challenging. Rehabilitation technicians are crucial in this effort. Their knowledge and attitudes significantly impact care quality and their willingness to work with the elderly. While many studies have examined healthcare professionals’ attitudes toward older adults, few focus on rehabilitation students. This study assesses Chinese rehabilitation students’ knowledge of aging, attitudes toward older individuals, willingness to care for them, and the factors influencing these aspects. Methods A sample of 890 rehabilitation students from three colleges and universities in southwestern China was investigated with a self-administered questionnaire, which included socio-demographic information, the Palmore Facts on Aging Quiz, the Kogan’s Attitude towards Older People Scale and the Chinese Version of the Interpersonal Reactivity Index. Data analyses were conducted using SPSS version 25.0. Descriptive statistics were used to illustrate the demographic characteristics of the respondents. The frequency and percentage of responses was calculated. Means and standard deviations were computed for general knowledge of aging, attitudes toward older people, and empathy. Independent t-tests and one-way ANOVA assessed differences in FAQ, KAOP, and IRI-C scores between groups. Pearson’s correlation examined correlations among general knowledge of aging, attitudes toward older people and empathy ability. Chi-square or Fisher’s exact tests compared willingness to engage in geriatric rehabilitation across different respondent characteristics. Hierarchical multiple regression analysis explored the independent effect of different variables on attitudes toward older people. Results The Chinese rehabilitation students from three colleges and universities in southwestern China displayed a relatively low level of knowledge about aging, but a generally positive attitude towards older people. Females had significantly more positive attitudes toward older people than males(p

Glucose-like peptide-1 (GLP-1) is a vital hormone in the intestines that regulates glucose metabolism. Although pancreatic-derived factor (PANDER) overexpression is known to suppress GLP-1, the underlying mechanisms are unclear. Our study aims to uncover how PANDER influences GLP-1 synthesis and secretion. We established a PANDER overexpression model in STC-1 intestinal cells, confirming its inhibitory effect on GLP-1 secretion. This effect was reversed in PANDER-knockout cells. Additionally, a negative correlation between PANDER and GLP-1 was observed in patients with a history of gestational diabetes. Subsequently, through whole transcriptome gene sequencing in PANDER-overexpressed STC-1 cells, we discovered that the activation of IL-6 and its related STAT3 signaling pathway was significantly inhibited, and this finding was validated by Western blotting and quantitative reverse transcription PCR. Finally, rescue experiments confirmed that the IL-6-related STAT3/Akt/GSK3β/β-catenin signaling pathway mediates the negative regulatory effect of PANDER on GLP-1. Taken together, our data identify IL-6 as a bridge connecting PANDER and GLP-1 in the STC-1 cells, demonstrating potential therapeutic targets for diabetes treatment by targeting the PANDER–IL-6–GLP-1 axis.

Abstract The cell transition from an inflammatory phase to a subsequent proliferative phase is crucial for wound healing, yet the driving mechanism remains unclear. By profiling lncRNA expression changes during human skin wound healing and screening lncRNA functions, we identify SNHG26 as a pivotal regulator in keratinocyte progenitors underpinning this phase transition. Snhg26-deficient mice exhibit impaired wound repair characterized by delayed re-epithelization accompanied by exacerbated inflammation. Single-cell transcriptome analysis combined with gain-of-function and loss-of-function of SNHG26 in vitro and ex vivo reveals its specific role in facilitating inflammatory-to-proliferative state transition of keratinocyte progenitors. A mechanistic study unravels that SNHG26 interacts with and relocates the transcription factor ILF2 from inflammatory genomic loci, such as JUN, IL6, IL8, and CCL20, to the genomic locus of LAMB3. Collectively, our findings suggest that lncRNAs play cardinal roles in expediting tissue repair and regeneration and may constitute an invaluable reservoir of therapeutic targets in reparative medicine.

Abstract Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged

Abstract Purpose The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN). Methods Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR

Abstract With climate change and anthropic influence on the coastal ecosystems, mangrove ecosystems are disappearing at an alarming rate. Accordingly, it becomes important to track, study, record and store the mangrove microbial community considering their ecological importance and potential for biotechnological applications. Here, we provide information on mangrove fungal community composition and diversity in mangrove ecosystems with different plant species and from various locations differing in relation to anthropic influences. We describe twelve newly assembled genomes, including four chromosomal-level genomes of fungal isolates from the mangrove ecosystems coupled with functional annotations. We envisage that these data will be of value for future studies including comparative genome analysis and large-scale temporal and/or spatial research to elucidate the potential mechanisms by which mangrove fungal communities assemble and evolve. We further anticipate that the genomes represent valuable resources for bioprospecting related to industrial or clinical uses.

In Internet of Vehicles (IoV), the security-threat information of various traffic elements can be exploited by hackers to attack vehicles, resulting in accidents, privacy leakage. Consequently, it is necessary to establish security-threat assessment architectures to evaluate risks of traffic elements by managing and sharing security-threat information. Unfortunately, most assessment architectures process data in a centralized manner, causing delays in query services. To address this issue, in this paper, a Hierarchical Blockchain-enabled Security threat Assessment Architecture (HBSAA) is proposed, utilizing edge chains and global chains to share data. In addition, data virtualization technology is introduced to manage multi-source heterogeneous data, and a metadata association model based on attribute graph is designed to deal with complex data relationships. In order to provide high-speed query service, the ant colony optimization of key nodes is designed, and the HBSAA prototype is also developed and the performance is tested. Experimental results on the large-scale vulnerabilities data gathered from NVD demonstrate that the HBSAA not only shields data heterogeneity, but also reduces service response time.

Abstract Due to the repeated changes in the COVID-19 pandemic, we live in an era of various uncertainties that raise future anxiety and behavioral addiction problems. According to the Protection Motivation Theory (PMT), the present study attempted to explore the impact of COVID-19 intolerance of uncertainty (COVID-19 IU) on internet addiction (IA) among college students and the mediating role of future anxiety (FA) by constructing a mediating model. A questionnaire survey was conducted on 679 Chinese college students and PROCESS 3.5 was utilized to test the hypotheses. The results indicated that the COVID-19 IU was significantly positively correlated with IA and FA, and FA was significantly positively correlated with IA. COVID-19 IU had a significant positive predictive effect on IA; FA played a complementary partial mediating role between COVID-19 IU and IA. The results supported the PMT, which not only enriched our understanding of FA under uncertain life circumstances, but also deepened our understanding of the potential mechanisms of the effects of IA. Finally, discussions and suggestions were presented based on the results.

Abstract Adding nanoparticles can significantly improve the tribological properties of lubricants. However, there is a lack of understanding regarding the influence of nanoparticle shape on lubrication performance. In this work, the influence of diamond nanoparticles (DNPs) on the tribological properties of lubricants is investigated through friction experiments. Additionally, the friction characteristics of lubricants regarding ellipsoidal particle shape are investigated using molecular dynamics (MD) simulations. The results show that DNPs can drastically lower the lubricant's friction coefficient μ from 0.21 to 0.117. The shearing process reveals that as the aspect ratio (α) of the nanoparticles approaches 1.0, the friction performance improves, and wear on the wall diminishes. At the same time, the shape of the nanoparticles tends to be spherical. When 0.85 ≤ α ≤ 1.0, rolling is ellipsoidal particles' main form of motion, and the friction force changes according to a periodic sinusoidal law. In the range of 0.80 ≤ α < 0.85, ellipsoidal particles primarily exhibit sliding as the dominant movement mode. As α decreases within this range, the friction force progressively increases. The friction coefficient μ calculated through MD simulation is 0.128, which is consistent with the experimental data.

Telemedicine (TM) is a new medical service model in which computer, communication, and medical technologies and equipment are used to provide “face-to-face” communication between medical personnel and patients through the integrated transmission of data, voice, images, and video. This model has been increasingly applied to the management of patients with sleep disorders, including those with obstructive sleep apnea syndrome (OSAS). TM technology plays an important role in condition monitoring, treatment compliance, and management of OSAS cases. Herein, we review the concept of TM, its application to OSAS, and the related effects and present relevant application suggestions and strategies, which may provide concepts and references for OSAS-related TM development and application.

Heterogeneous catalyst-mediated sulfate radical-based advanced oxidation processes (SR-AOPs) showed excellent performance during antibiotics degradation. Spinel was a promising catalyst for SR-AOPs, but the secondary contamination due to metal ions leaching needed to be addressed. And the destruction of catalyst structure could lead to the reduction of catalytic activity and the difficulty of recovery. Thus, a novel nitrogen-doped carbon (NC)-supported CoFe2O4 (CoFe2O4@NC) was synthesized as the activator of PMS for sulfadiazine (SDZ) degradation under low Co leaching conditions. The consequences indicated that the CoFe2O4@NC/PMS system exhibited higher PMS decomposition efficiency and reaction stoichiometry efficiency than the bare CoFe2O4/PMS systems (CoFe2O4-180 and CoFe2O4-800), which in turn demonstrated a better SDZ removal performance. Under the condition of CoFe2O4@NC dosage 0.1 g/L, PMS concentration 0.5 mM, solution pH 6.8 and temperature 25°C, SDZ (20 mg/L) was almost completely degraded within 60 min. XPS analysis showed that the NC not only protected and stabilized CoFe2O4, but also provided additional active sites for PMS activation. During SDZ degradation, SO4•−, HO•, •O2− and 1O2 were involved in the reaction, among which SO4• and HO• made the main contribution. Meanwhile, CoFe2O4@NC could be recovered by magnetic separation, and showed great stability (Co leaching 0.852 mg/L) and reusability. In the fifth cycle experiment, 85.02 % SDZ degradation was obtained. Based on the detected intermediates (12 intermediates were identified) and DFT calculations, possible degradation pathways for SDZ in CoFe2O4@NC/PMS were proposed. The condensed dual descriptor indicated that the N7, N11, and C15 atoms on SDZ molecule were the main sites of electrophilic attack, which was consistent with the detected intermediates. The degradation of SDZ involved hydroxylation of NH2, cleavage of S−N and extrusion of SO2. This study explored the improvements made in NC support material to catalytic performance and resistance to dissolution of spinel, providing new insights for subsequent researches.

Abstract Background Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high‐risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively. Methods In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the β‐value of the corresponding regression coefficient. A predictive risk‐scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21‐involved risk with the established R‐ISS and R2‐ISS models. Results Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p

Abstract Background Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance. Methods We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis. Result Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo. Conclusions Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC.

Abstract Background The interplay between exosomes and the tumor microenvironment (TME) remains unclear. We investigated the influence of exosomes on the TME in hepatocellular carcinoma (HCC), focusing on their mRNA expression profile. Methods mRNA expression profiles of exosomes were obtained from exoRBase. RNA sequencing data from HCC patients’ tumors were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An exosome mRNA-related risk score model of prognostic value was established. The patients in the two databases were divided into high- and low-risk groups based on the median risk score value, and used to validate one another. Functional enrichment analysis was performed based on a differential gene prognosis model (DGPM). CIBERSORT was used to assess the abundance of immune cells in the TME. The correlation between the expression levels of immune checkpoint-related genes and DGPM was analyzed alongside the prediction value to drug sensitivity. Results A prognostic exosome mRNA-related 4-gene signature (DYNC1H1, PRKDC, CCDC88A, and ADAMTS5) was constructed and validated. A prognostic nomogram had prognostic ability for HCC. The genes for this model are involved in extracellular matrix, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. Expression of genes here had a positive correlation with immune cell infiltration in the TME. Conclusions Our study results demonstrate that an exosome mRNA-related risk model can be established in HCC, highlighting the functional significance of the molecules in prognosis and risk stratification.

To evaluate the correlation between the water absorption characteristics of dried chrysanthemums and their structure, water activity (Aw), and storage temperature, two types of powdered chrysanthemums ("Xiaohuangju" and "Gongjuwang") were analyzed through SEM, FTIR, and XPS. The results indicated that the surface of the powdered chrysanthemums was rough and contained a large number of indentations and cavities. In comparison to "Xiaohuangju", "Gongjuwang" powder had smaller particle sizes and more hydrophilic groups on the surface, such as -OH, O-C-O, etc. To examine the water adsorption behavior of two varieties of powdered chrysanthemums, the static gravimetric method was employed at 20, 30, and 40 ℃ and a range of Aw values from 0.112 to 0.976. Model fitting and thermodynamic analysis were conducted to gain insight into the water adsorption mechanism. An increase in water activity (Aw) resulted in a rise in the equilibrium water content (Xe) of powdered chrysanthemums, conversely, the higher the temperature, the lower the Xe values at the equivalent Aw levels. The fitting results demonstrated that the Peleg model was the most suitable model for depicting the water adsorption isotherms. Results from the thermodynamic analysis suggested that the net isosteric heat of adsorption (qst) decreased when the equilibrium water content (Xe) increased, and the qst values of "Xiaohuangju" and "Gongjuwang" powder remained steady in the presence of Xe values greater than 0.14 g/g and 0.24 g/g, respectively. The monolayer water content (Xm) of "Xiaohuangju" at 20, 30, and 40 ℃ were 0.0690, 0.0525, and 0.0505 g/g (d. b), respectively, while those of "Gongjuwang" were 0.0645, 0.0591 and 0.0584 g/g (d. b). When the temperature and water content increased, the effective pore size (rp) of "Xiaohuangju" powder increased, exhibiting mesoporous characteristics when Xe>0.09 g/g (d. b). Conversely, the internal pores of “Gongjuwang” powder shifted from micropore to mesopore only when Xe>0.11 g/g (d. b). The results of the study can be employed as a guide for improving the drying process of chrysanthemums and determining the most suitable storage conditions.

Objectives: Recent mpox outbreaks highlight diverse transmission modes, with sexual behavior prominent in China's IIb strain. Nevertheless, despite HPV being a common sexually transmitted pathogen, there is a paucity of research into its coexistence and genotype distribution within this patients population. Methods: We conducted a study at the Third People's Hospital of Shenzhen from May to September 2023. We collected information on mpox patients, including their sociodemographic and clinical characteristics. Anal swabs were collected for HPV genotyping. Results: Among 73 MSM mpox cases, HIV positivity was 56.2 % (41/73) and HPV positivity 80.4 % (41/51). Multiple HPV infections were prevalent (56.9 %, 29/51), especially among HIV-positive (93 %, 27/29). HPV16 (29.3 %, 12/41) was the most common high-risk genotype, followed by HPV59 (26.8 %, 10/41), HPV42 (19.5 %, 8/41), HPV6 (14.6 %, 6/41), and HPV54 (14.6 %, 6/41). HPV infection was significantly associated with HIV infection (p = 0.001). Additionally, HIV infection (p = 0.001) and PCR-detected positive sites for mpox (p = 0.047) were associated with high-risk HPV infection. Conclusions: In this study, most of the mpox patients were found to be infected with HPV, mostly with high-risk types and multiple infections. Therefore, it is strongly recommended that mpox-infected individuals intensify HPV-related screening, prevention, and treatment measures.

Metformin, or 1,1-dimethylbiguanide, is a hypoglycemic drug that lowers blood glucose by reducing glycogen synthesis and increasing glucose uptake in peripheral tissues. Six diets with iso-nitrogenous and iso-lipid compositions were prepared, including a positive control (20 % carbohydrate, PC) and a negative control (30 % carbohydrate, T0). The experimental diets contained 0.2 % (T2), 0.4 % (T4), 0.6 % (T6), and 0.8 % (T8) metformin based on the negative control diet. A total of 540 hybrid groupers, with consistent size and health conditions, were randomly assigned to six groups. Each group contained 30 fish, with three replicates per group, and they were fed for eight weeks. The high-carbohydrate diet reduced weight gain, digestive enzyme activities and specific growth rates (P>0.05), while significantly increasing hepatosomatic indices (P

This study aimed to investigate the effect of artemisinin supplementation to high cottonseed meal (CSM) diet on the growth, lipid metabolism and intestinal microbiota of golden pompano (Trachinotus ovatus). Five diets were formulated, including the control (CM, with CSM replacing 16 % of fishmeal) and experimental groups (CA0, CA2, CA4, and CA8, with CSM replacing 36 % of fishmeal and supplemented with 0 %, 0.20 %, 0.40 %, and 0.80 % of artemisinin, respectively). 375 fishes (initial weight 22.45 ± 0.07 g) were randomized into five groups of triplicates each and fed in tanks for 8 weeks. Results indicated that 0.8 % artemisinin improved final weight, weight gain rate and specific growth rate, reduced the serum lipid levels under the condition of 36 % fishmeal replaced with CSM. In the liver, artemisinin supplementation alleviated hepatocyte vacuolization and lipid deposition induced by the high level CSM replacement fishmeal diet, reduced the activity of lipogenesis-related enzymes and increased lipolysis-related enzyme activity. In the intestine, supplementation with 0.8 % artemisinin significantly increased the activities of intestinal digestive enzymes. Supplementation with 0.8 % artemisinin significantly increased the diversity and stability of the intestinal microbiota of the golden pompano, while also reducing the abundance of potentially harmful Vibrio associated with high CSM levels. In conclusion, 0.8 % artemisinin supplementation mitigated the negative effects of high CSM diets on growth, lipid metabolism, and liver health in golden pompano by enhancing lipid metabolism, intestinal digestive enzyme activity, and modulating intestinal microbiota.

Objective The aim of this study was to investigate the characteristics and related functional pathways of the gut microbiota in patients with IgA nephropathy (IgAN) through metagenomic sequencing technology.Methods We enrolled individuals with primary IgAN, including patients with normal and abnormal renal function. Additionally, we recruited healthy volunteers as the healthy control group. Stool samples were collected, and species and functional annotation were performed through fecal metagenome sequencing. We employed linear discriminant analysis effect size (LEfSe) analysis to identify significantly different bacterial microbiota and functional pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to annotate microbiota functions, and redundancy analysis (RDA) was performed to analyze the factors affecting the composition and distribution of the gut microbiota.Results LEfSe analysis revealed differences in the gut microbiota between IgAN patients and healthy controls. The characteristic microorganisms in the IgAN group were classified as Escherichia coli, with a significantly greater abundance than that in the healthy control group (p

ABSTRACTH6N6 avian influenza viruses (AIVs) have been widely detected in wild birds, poultry, and even mammals. Recently, H6N6 viruses were reported to be involved in the generation of H5 and H7 subtype viruses. To investigate the emergence, evolutionary pattern, and potential for an epidemic of H6N6 viruses, the complete genomes of 198 H6N6 viruses were analyzed, including 168 H6N6 viruses deposited in the NCBI and GISAID databases from inception to January 2019 and 30 isolates collected from China between November 2014 and January 2019. Using phylogenetic analysis, the 198 strains of H6N6 viruses were identified as 98 genotypes. Molecular clock analysis indicated that the evolution of H6N6 viruses in China was constant and not interrupted by selective pressure. Notably, the laboratory isolates reassorted with six subtype viruses: H6N2, H5N6, H7N9, H5N2, H4N2, and H6N8, resulting in nine novel H6N6 reassortment events. These results suggested that H6N6 viruses can act as an intermediary in the evolution of H5N6, H6N6, and H7N9 viruses. Animal experiments demonstrated that the 10 representative H6N6 viruses showed low pathogenicity in chickens and were capable of infecting mice without prior adaptation. Our findings suggest that H6N6 viruses play an important role in the evolution of AIVs, and it is necessary to continuously monitor and evaluate the potential epidemic of the H6N6 subtype viruses.

Objectives This study aims to develop and validate a prediction model in-hospital mortality in critically ill patients with sepsis-associated acute kidney injury (SA-AKI) based on machine learning algorithms.Methods Patients who met the criteria for inclusion were identified in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and divided according to the validation (n = 2440) and development (n = 9756, 80%) queues. Ensemble stepwise feature selection method was used to screen for effective features. The prediction models of short-term mortality were developed by seven machine learning algorithms. Ten-fold cross-validation was used to verify the performance of the algorithm in the development queue. The area under the receiver operating characteristic curve (ROC-AUC) was used to evaluate the differentiation accuracy and performance of the prediction model in the validation queue. The best-performing model was interpreted by Shapley additive explanations (SHAP).Results A total of 12,196 patients were enrolled in this study. Eleven variables were finally chosen to develop the prediction model. The AUC of the random forest (RF) model was the highest value both in the Ten-fold cross-validation and evaluation (AUC: 0.798, 95% CI: 0.774–0.821). According to the SHAP plots, old age, low Glasgow Coma Scale (GCS) score, high AKI stage, reduced urine output, high Simplified Acute Physiology Score (SAPS II), high respiratory rate, low temperature, low absolute lymphocyte count, high creatinine level, dysnatremia, and low body mass index (BMI) increased the risk of poor prognosis.Conclusions The RF model developed in this study is a good predictor of in-hospital mortality for patients with SA-AKI in the intensive care unit (ICU), which may have potential applications in mortality prediction.

The integration of digitalization in higher education is a key to increasing the number of students getting access to education in the developing world. Inspired by the fast digitalization in higher education institutes and the lack of relevant empirical studies about the impact of this rapid digitalization on the learning behavior of students, we investigated: how does digital competence, along with personal innovativeness and attitudes toward digital learning, affect the learning behavior of students in China? This study also aims to examine the moderating role of the level of digitization at higher educational institutions between students’ personality traits and their learning behavior. For this purpose, cross sectional data were collected from 1,569 Chinese students through purposive and random sampling through a face-to-face survey. The data were analyzed using the partially least square structural equation model. The findings indicate that digital competence (β = .688, p

IntroductionThe mental health (MH) of college students has long been a crucial concern for families, educational institutions, and society. Extensive research has demonstrated the influential role of exercise motivation in shaping MH. However, further investigation is warranted to ascertain which types of exercise motivation may have more influence on the MH of college students. The present study examined the direct effects of five distinct types of exercise motivation, namely health motivation (HM), appearance motivation (APM), fun motivation (FM), ability motivation (ABM), and social motivation (SM) on MH. Additionally, the study explored the potential mediating role of physical exercise (PE) in these relationships.MethodsAn cross-sectional study design was employed. A total of 433 Chinese college students participated in the study and completed our questionnaires, which included the Exercise motivation scale (EM scale), the Physical exercise scale (PE scale), and the Mental health scale (MH scale).ResultsThe findings revealed a significant and positive relationship between all five categories of exercise motivation and the MH of college students. Specifically, FM was found to have the most pronounced impact on MH, followed by HM, ABM, SM, and APM, in descending order of influence. Furthermore, the impacts of HM, FM, ABM, and SM on MH were found to be partially mediated by PE. However, the association between APM and MH was entirely mediated by PE.DiscussionThe present study contributes to enhancing the comprehension of the underlying mechanisms behind different exercise motivations in relation to PE and MH. Additionally, it offers practical implications for developing intervention strategies for improving the MH of college students.

Background: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission. Objectives: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML. Design: This was a retrospective study. Methods: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction. Results: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8–98.7) and 90.5% (95% CI: 81.3–95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction ( p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients. Conclusion: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

BackgroundTelehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. ObjectiveThe primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician’s perspective. MethodsA telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform’s registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. ResultsOver a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. ConclusionsThis study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.

Abstract Background Continuous and noninvasive hemoglobin (Hb) monitoring during surgery is essential for anesthesiologists to make transfusions decisions. The aim of this study was to investigate the feasibility and accuracy of noninvasive and continuous Hb monitoring using transesophageal descending aortic photoplethysmography (dPPG) in porcine model. Methods Nineteen landrace pigs, aged 3 to 5 months and weighing 30 to 50 kg, were enrolled in this study. A homemade oximetry sensor, including red (660 nm) and infrared (940 nm) lights, was placed in the esophagus for dPPG signal detection to pair with the corresponding reference Hb values (Hbi−STAT) measured by blood gas analysis. The decrease and increase changes in Hb concentration were achieved by hemodilution and transfusion. Metrics, including alternating current (AC), direct current (DC), and AC/DC for both red and infrared light were extracted from the dPPG signal. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting the Hb “trigger threshold” of transfusion (Hb 100 g/L). Agreement and trending ability between Hb measured by dPPG (HbdPPG) and by blood gas analysis were analyzed by Bland-Altman method and polar plot graph. Error grid analysis was also performed to evaluate clinical significance of HbdPPG measurement. Results The dPPG signal was successfully detected in all of the enrolled experimental pigs, without the occurrence of a continuous loss of dPPG signal for 2 min during the entire measurement. A total of 376 pairs of dPPG signal and Hbi−STAT were acquired. ACred/DCred and ACinf/DCinf had moderate correlations with Hbi−STAT, and the correlation coefficients were 0.790 and 0.782, respectively. The areas under the ROC curve for ACred/DCred and ACinf/DCinf in predicting Hbi−STAT < 60 g/L were 0.85 and 0.75, in predicting Hbi−STAT > 100 g/L were 0.90 and 0.83, respectively. Bland-Altman analysis and polar plot showed a small bias (1.69 g/L) but a wide limit of agreement (-26.02–29.40 g/L) and a poor trend ability between HbdPPG and Hbi−STAT. Clinical significance analysis showed that 82% of the data lay within the Zone A, 18% within the Zone B, and 0% within the Zone C. Conclusion It is feasible to establish a noninvasive and continuous Hb monitoring by transesophageal dPPG signal. The ACred/DCred extracted from the dPPG signal could provide a sensitive prediction of the Hb threshold for transfusion. The Hb concentration measured by dPPG signal has a moderate correlation with that measured by blood gas analysis. This animal study may provide an experimental basis for the development of bedside HbdPPG monitoring in the future.

Abstract Inhibition of epigenetic regulators by small molecules is an attractive strategy for cancer treatment. Recently, we characterised the role of lysine methyltransferase 9 (KMT9) in prostate, lung, and colon cancer. Our observation that the enzymatic activity was required for tumour cell proliferation identified KMT9 as a potential therapeutic target. Here, we report the development of a potent and selective KMT9 inhibitor (compound 4, KMI169) with cellular activity through structure-based drug design. KMI169 functions as a bi-substrate inhibitor targeting the SAM and substrate binding pockets of KMT9 and exhibits high potency, selectivity, and cellular target engagement. KMT9 inhibition selectively downregulates target genes involved in cell cycle regulation and impairs proliferation of tumours cells including castration- and enzalutamide-resistant prostate cancer cells. KMI169 represents a valuable tool to probe cellular KMT9 functions and paves the way for the development of clinical candidate inhibitors as therapeutic options to treat malignancies such as therapy-resistant prostate cancer.

Voltage sag is one of the reasons that hinders the high-quality and efficient development of high-tech manufacturing users. Custom power device (CPD) is one of the effective ways to solve voltage sag. The reason why most high-tech manufacturing users are hesitant to invest CPD is that the economic benefits of CPD are vague. To solve this problem, a new premium power service (PPS) for CPD based on trial-purchase model is proposed. By trialing CPD, users can choose to purchase or cancel the devices after trialing, so as to improve the enthusiasm of users to invest premium power and ensure the smooth progress of PPS. According to the operation process of the proposed service, an optimization model of service scheme is established with the goal of maximizing the interests of power utility and user, to optimize the return ratio of users’ mitigation benefits and the length of trial service. The revenue distribution model based on Game theory (Nash negotiation) is established to obtain the revenue distribution strategies of power utility and devices company respectively. The feasibility of proposed service is verified by a semiconductor user in China. The trial-purchase premium power service could be replicable and applicable, which provides a new choice both for power utility and users.

Abstract Background Gestational diabetes mellitus (GDM) affects the metabolism of both the mother and fetus during and after pregnancy. Genetic factors are important in the pathogenesis of GDM, and associations vary by ethnicity. However, related studies about the relationship between the susceptibility genes and glucose traits remain limited in China. This study aimed to identify genes associated with GDM susceptibility in Chinese Han women and validate those findings using clinical data during pregnancy and postpartum period. Methods A genome-wide association study (GWAS) of 398 Chinese Han women (199 each with and without GDM) was conducted and associations between single nucleotide polymorphisms (SNPs) and glucose metabolism were identified by searching public databases. Relationships between filtered differential SNPs and glucose metabolism were verified using clinical data during pregnancy. The GDM group were followed up postpartum to evaluate the progression of glucose metabolism. Results We identified five novel SNPs with genome-wide significant associations with GDM: rs62069863 in TRPV3 gene and rs2232016 in PRMT6 gene were positive correlated with 1 h plasma glucose (1hPG) and 2 h plasma glucose (2hPG), rs1112718 in HHEX/EXOC6 gene and rs10460009 in LPIN2 gene were positive associated with fasting plasma glucose, 1hPG and 2hPG, rs927316 in GLIS3 gene was negative correlated with 2hPG. Of the 166 GDM women followed up postpartum, rs62069863 in TRPV3 gene was positively associated with fasting insulin, homoeostasis model assessment of insulin resistance. Conclusions The variants of rs62069863 in TRPV3 gene, rs2232016 in PRMT6 gene, rs1112718 in HHEX/EXOC6 gene, rs927316 in GLIS3 gene, and rs10460009 in LPIN2 gene were newly-identified susceptibility loci for GDM in the Chinese Han population. TRPV3 was associated with worse insulin resistance postpartum. Trial registration This study was registered in the Chinese Clinical Trial Registry. Trial registration number: ChiCTR2100043762. Date of first registration: 28/02/2021.

BackgroundThe immune response to hepatitis B vaccine may be influenced by numerous factors, and patients with non/low response re-exposed to hepatitis B virus remain susceptible. Thus, a better understanding of the underlying mechanisms of non/low immune response in infants born to Hepatitis B surface antigen (HBsAg)-positive mothers is essential.Methods100 infants born to HBsAg-positive mothers from 2015 to 2020 were enrolled in the study, further divided into the non/low response group (n=13) and the moderate strong response group (n=87) based on the quantification of hepatitis B surface antibody at 12 months of age. The differential expression of 48 immune-related cytokines in the two groups was compared and analyzed in detail. The key cytokines were further identified and clinically predictive models were developed.ResultsWe found that 13 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group, compared with the moderate strong response group at birth. In addition, 9 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group at 12 months of age. Furthermore, we found that IL-5 and HGF were promising predictors for predicting the immunization response to hepatitis B vaccine in infants, and the combination of the two cytokines showed the best predictive efficiency, with an area under the curve (AUC) value of 0.844.ConclusionThe present study provides a theoretical basis on cytokines for developing and implementing effective immunotherapies against non/low immune response in infants born to HBsAg-positive mothers.

Abstract Background Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. Methods Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). Results A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49–0.78; P

Financial inclusion enables greater access to financial resources and facilitates green energy investments, thus emerging as a potential avenue to mitigate pollution. However, the relationship between financial inclusion and environmental impact is complex, with arguments both for and against its positive effects. This study aims to examine the impact of financial inclusion and digital financial inclusion on air quality in thirteen selected Asian countries. The dependent variables used in this study was the Air Quality Index (AQI). The independent variables were financial inclusion, digital financial inclusion, population growth, net trade of goods and services and gross domestic product (GDP). The findings showed that the proxies of financial inclusion had mix effects on air quality, while a higher level of digital financial inclusion led to a better air quality in Asian countries. This study also revealed that population growth and GDP may somehow affect the air quality of Asian countries as well. These results suggest that Asian countries with lower level of financial inclusion and digital financial inclusion need to improve their citizen’s access to financial resources. Several policies shall be implemented to enhance the level of financial inclusion and the air quality.

Rationale & Objective: The Kidney Failure Risk Equations have been proven to perform well in multinational databases, whereas validation in Asian populations is lacking. This study sought to externally validate the equations in a community-based chronic kidney disease cohort in China. Study Design: A retrospective cohort study. Setting & Participants: Patients with and estimated glomerular filtration rate (eGFR)

Abstract Temozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition of resistance limits its therapeutic potential. The human kinome is an undisputable source of druggable targets, still, current knowledge remains confined to a limited fraction of it, with a multitude of under‐investigated proteins yet to be characterized. Here, following a kinome‐wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as a modulator of TMZ resistance in GBM. Validation of PANK4 across various TMZ‐resistant GBM cell models, patient‐derived GBM cell lines, tissue samples, as well as in vivo studies, corroborates the potential translational significance of these findings. Moreover, PANK4 expression is induced during TMZ treatment, and its expression is associated with a worse clinical outcome. Furthermore, a Tandem Mass Tag (TMT)‐based quantitative proteomic approach, reveals that PANK4 abrogation leads to a significant downregulation of a host of proteins with central roles in cellular detoxification and cellular response to oxidative stress. More specifically, as cells undergo genotoxic stress during TMZ exposure, PANK4 depletion represents a crucial event that can lead to accumulation of intracellular reactive oxygen species (ROS) and subsequent cell death. Collectively, a previously unreported role for PANK4 in mediating therapeutic resistance to TMZ in GBM is unveiled.

BackgroundObservational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure.MethodsEmploying genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings.ResultsAccording to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71–0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08–1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02–1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03–1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00–1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02–1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09–1.28, p

Precise traffic prediction is crucial in the domain of intelligent transportation. However, the task of accurately predicting traffic has struggled to keep pace with escalating application demands. One of the main reasons for this difficulty is the neglect of the dependence of surrounding spatial data on traffic information. In this study, we introduce a novel framework that incorporates the surrounding spatial data from the road network into the analysis of existing sensor graphs. We delve into an innovative method for traffic prediction by employing a heterogeneous graph that integrates the surrounding spatial information from the road network. The method is based on the common observation that traffic conditions are closely associated with surrounding spatial information, which can be analyzed utilizing heterogeneous graphs. Consequently, we propose a new framework, the heterogeneous attentive spatial–temporal network (HASTN). This framework constructs a heterogeneous graph that merges road networks with surrounding geographic features and employs attention mechanisms to learn traffic patterns. Our method achieves promising results on public datasets as well as a dataset we proposed. Additionally, we employ spatial information to analyze the impact of road traffic patterns on attention. This research offers a fresh perspective on addressing traffic prediction problems by integrating spatial information.

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.

Abstract Background Impairment of cerebral autoregulation (CA) has been observed in patients undergoing cardiopulmonary bypass (CPB), but little is known about its risks and associations with outcomes. The cerebral oximetry index (COx), which is a moving linear correlation coefficient between regional cerebral oxygen saturation (rScO2) and mean blood pressure (MAP), may reflect CA function. When COx approaches 1, it implies that CA is damaged, whereas the CA is functional when the COx value approaches 0. The objective of this study was to analyze the incidence and risks of impaired CA, based on COx assessment, in patients undergoing total aortic arch replacement under systemic moderate hypothermia and circulatory arrest of the lower body (MHCA). We also evaluated the association between impaired CA and patient outcomes. Methods One hundred and fifty-four adult patients who underwent total aortic arch replacement with stented elephant trunk implantation under MHCA at our hospital were retrospectively analyzed. Patients were defined as having new-onset impaired CA if pre-CPB COx 0.3. Pre- and intraoperative factors were tested for independent association with impaired CA. Postoperative outcomes were compared between patients with normal and impaired CA. Results In our 154 patients, 46(29.9%) developed new-onset impaired CA after CPB. Multivariable analysis revealed a prolonged low rScO2 (rScO2

Abstract Background Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21. Methods This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care. Results When cut-off values of free beta subunit of human chorionic gonadotropin (free β-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively. Conclusions The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.

Abstract Background The aim of this study was to determine the prevalence of high-risk human papillomavirus (HR-HPV) and the correlation between multiple infections and cervical lesions. Methods The current study involved population-based sample of 20,059 women who underwent cervical screening for 15 HR-HPV genotypes with ThinPrep cytologic test (TCT) results. The correlation between multiple HPV genotype infections and cervical lesions was also determined. The odds ratios (ORs) were calculated to assess co-infection patterns for each genotype with 15 other genotypes and the additive statistical interactions were evaluated. Results There was a bimodal pattern among multiple HPV infections, with a peak in the younger group and a second peak in the elderly group. Indeed, most multiple HPV genotypes exhibited a bimodal pattern. The most common HPV type in patients with high-grade squamous intraepithelial lesions (HSILs) was HPV-16, followed by HPV-52, HPV-58, and HPV-33. The most frequent HPV type in patients with cervical cancer was HPV-16, followed by HPV-58 and HPV-33. Women with multiple infections were at a increased risk of low-grade squamous intraepithelial lesions [LSIL] (OR = 2.01; 95% CI 1.38–2.93) and HSIL (OR 2.28; 95% CI 1.36–3.81) when compared to women with single infections. patients with cervical cancer had the higher percentage of multiple HPV infections. Based on the data herein, we suggest that HPV-33 and HPV-58 may also be high-risk HPV types worthy of increased surveillance and follow-up. Conclusion: Our findings suggested that the association between multiple HPV infections and HSIL and LSIL are stronger compared to single HPV infections. There may be some specific combinations that synergistically affected the risk of HSIL and LSIL.

Abstract In this paper, a new reverse half-discrete Mulholland-type inequality with the nonhomogeneous kernel of the form h ( v ( x ) ln n ) $h(v(x)\ln n)$ and the best possible constant factor is obtained by using the weight functions and the technique of real analysis. The equivalent reverses are considered. As corollaries, we deduce some new equivalent reverse inequalities with the homogeneous kernel of the form k λ ( v ( x ) , ln n ) $k_{\lambda }(v(x),\ln n)$ . A few particular cases are provided. Our new reverse half-discrete Mulholland-type inequality which has a nonhomogeneous kernel is more general than in the previous homogeneous kernel work. The harmonized integration will have more applications.

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice.

This study is to explore underlying mechanism of skin wound healing by snakehead fish soup using rat and cell models. We assessed skin wound changes after administering wild and farmed snakehead fish soup intragastrically, then using CCK-8 and scratch tests to evaluate cell proliferation and migration, last assessed vessel tubule formation by HUVEC cells. The results showed that the skin wound healing rates of rats after 14 days of intragastrical administration of farmed and wild snakehead fish soup were 52.71% and 57.76%, respectively, which were substantially greater than the control group (39.84%). With the administration of the soups, the collagen tissue on the skin wound was more homogenous and thicker, and type I collagen was denser. Additionally, interleukin-6 level in rat serum during wound healing was significantly lower, while cyclin-D1 and fibroblast growth factor-2 levels were higher. Furthermore, the soups (particularly at 50 μg/mL) significantly increased the proliferation and migration rates of both the HACAT and NIH3T3 cells, and considerably promoted the tubule formation of HUVEC cells. The findings confirm that the soup can promote skin wound healing and the underlying mechanism involves multiple roles including anti-inflammation, cell proliferation, vessel tubule formation, and collagen expression.

Platelet-derived growth factor B (PDGFB), as an important cellular growth factor, is widely involved in the regulation of cellular events such as cell growth, proliferation, and differentiation. Although important, the expression characteristics and biological functions in the mammalian reproductive system remain poorly understood. In this study, the PDGFB gene of Tibetan sheep was cloned by RT-PCR, and its molecular characteristics were analyzed. Subsequently, the expression of the PDGFB gene in the testes and epididymides (caput, corpus, and cauda) of Tibetan sheep at different developmental stages (3 months, 1 year, and 3 years) was examined by qRT-PCR and immunofluorescence staining. A bioinformatic analysis of the cloned sequences revealed that the CDS region of the Tibetan sheep PDGFB gene is 726 bp in length and encodes 241 amino acids with high homology to other mammals, particularly goats and antelopes. With the increase in age, PDGFB expression showed an overall trend of first decreasing and then increasing in the testis and epididymis tissues of Tibetan sheep, and the PDGFB mRNA expression at 3 months of age was extremely significantly higher than that at 1 and 3 years of age (p < 0.05). The PDGFB protein is mainly distributed in testicular red blood cells and Leydig cells in Tibetan sheep at all stages of development, as well as red blood cells in the blood vessel, principal cells, and the pseudostratified columnar ciliated epithelial cells of each epididymal duct epithelium. In addition, PDGFB protein expression was also detected in the spermatocytes of the 3-month-old group, spermatids of the 1-year-old group, spermatozoa and interstitial cells of the 3-year-old group, and loose connective tissue in the epididymal duct space in each developmental period. The above results suggest that the PDGFB gene, as an evolutionarily conserved gene, may play multiple roles in the development and functional maintenance of testicular cells (such as red blood cells, Leydig cells, and germ cells) and epididymal cells (such as red blood cells, principal cells, and ciliated epithelial cells) during testicular and epididymal development, which lays a foundation for the further exploration of the mechanisms by which the PDGFB gene influences spermatogenesis in Tibetan sheep.

Objective The optimal repair method for bursal‐side partial‐thickness rotator cuff tears (PTRCTs) involving >50% of the thickness remains a controversial topic. The study was aimed to compare the functional and magnetic resonance imaging (MRI) outcomes after in situ repair or tear completion before repair of bursal‐side PTRCTs. Methods A retrospective clinical study was conducted involving 58 patients who underwent in situ repair or tear completion before repair of bursal‐side PTRCTs between January 2019 and December 2020. These patients were divided into two groups: the in situ repair group and the tear completion before repair group. Functional assessment consisted of active range of motion (ROM), visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, and Constant–Murley score. The percentages of patients in each group achieving the minimal clinical important difference (MCID) of the functional scores were determined. The healing status of the rotator cuff was assessed by postoperative MRI. Results There were no statistically significant differences between the two groups in terms of demographic data. The mean follow‐up period was 14.53 ± 2.64 months in the in situ repair group and 15.40 ± 2.66 months in the tear completion before repair group. At the final follow‐up, the forward elevation, external rotation, and internal rotation improved significantly in both groups. The VAS, ASES score, and Constant–Murley score improved significantly in the in situ repair group (5.17 ± 2.00 points to 0.11 ± 0.41 points, p = 0.001; 44.04 ± 17.40 points to 95.47 ± 4.32 points, p = 0.001; 49.50 ± 14.38 points to 93.50 ± 3.49 points, p = 0.001) and in the tear completion before repair group (5.43 ± 3.32 points to 0.03 ± 0.18 points, p = 0.001; 41.50 ± 19.59 points to 95.94 ± 2.68 points, p = 0.001; 47.54 ± 17.13 points to 93.97 ± 2.61 points, p = 0.001). Postoperative MRI revealed that the re‐tear rate was 7.1% (2/28) in the in situ repair group and 3.3% (1/30) in the tear completion before repair group. No significant differences were observed in terms of the functional scores, the percentages of patients achieving the MCID of the functional scores, and the re‐tear rate between the two groups (p > 0.05). Conclusions Both in situ repair and tear completion before repair yielded satisfactory clinical outcomes for patients with bursal‐side PTRCTs. No significant differences were observed in the functional and MRI outcomes between the two groups.

This research investigated the new concept of urban agriculture in the new stage and its patterns based on four practical cases of urban agriculture in Guangzhou: Huacheng Farm Park in Tianhe, Happy Farmland in Haizhu, an urban Jintian in Huangpu, and Amy's Rice Town in Conghua. The results show the following: First, after experiencing the four stages of the independent stage in the urban-rural isolation period, output stage in the rural-support urban period, compensatory stage in the urban-feeding rural period, and modern agriculture stage in the urban-rural integration period, the new stage of urban-rural, high-quality integrated urban agriculture indicates the four new characteristics of new functions, new technologies, new mechanisms, and new forms. Second, based on the concepts of the four new characteristics of urban agriculture in the new stage, the development of urban agriculture in Guangzhou can be summarized by the four basic patterns of stereoscopic agriculture (new form), leisure agriculture (new function), rural complex (new technology), and shared agriculture (new mechanism) distributed from the central to outside region. Stereoscopic agriculture, which is basically located in the CBD, combines agriculture and commercial functions, focusing on new technologies such as e-commerce operations and technological displays, emphasizing the characteristics of commercial operations in the mechanism, and manifesting itself as an intensive three-dimensional construction. Leisure agriculture, essentially located in the urban central area, is the combination of agriculture and the daily recreation function of citizens. It applies park landscape construction and artistic creation techniques, revealing the characteristics of the farming experience and providing leisure parks for citizens. The rural complex is basically located in the inner suburban area and combines agricultural production with scientific research activities. It comprehensively uses new technologies of farmland consolidation and agricultural production and is characterized by science, technology, and agriculture shaped as independent islands. In the outer suburbs, shared agriculture combines traditional agricultural production with the rural tourism experience, in addition to using new agricultural technologies for farmland preparation and production. It also emphasizes using new Internet of Things technologies, highlighting the new mechanism of shared participation, and is designed as standardized farmland. Third, the innovative experience of Guangzhou's urban agriculture development mainly includes strengthening the transformation of agricultural resources and the value of multiple functions; diversified innovation and integration forms; pattern innovation, new technologies, and artificial intelligence to enhance the development of urban agriculture; the combined mechanism of "government, enterprise, and university"; and institutional guarantees to facilitate the implementation of urban agriculture projects. The development of urban agriculture in the new stage of urban-rural integration in Guangzhou provides experience and lessons for other cities.

Abstract Aim We aimed to assess the association between the use of Glucagon-like peptide-1 receptor agonists and the risk of 12 respiratory diseases in patients with type 2 diabetes, obesity, or overweight. Method The PubMed (MEDLINE), EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched from the establishment of the database to December 24, 2022. Dichotomous outcomes were analyzed using RR and 95% CI calculated from fixed-effects models. Results Twenty-eight RCTs were ultimately included for analysis, involving a total of 77,485 participants. Compared to controls, patients with GLP-1RAs have a 14% lower risk of respiratory disease (RR 0.86, 95% CI 0.81–0.93 p