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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 ([beta] = 0.688, p < 0.01) exerts a robust positive influence on students' learning behavior. The personal innovativeness had a significant impact on learning behavior ([beta] = 0.720, p < 0.01). The study found that the attitude toward digital learning had a significant impact on students' learning behavior ([beta] = 0.573, p < 0.01). The results also indicated that digitalization at higher education institutes moderated positively between student personality traits and their learning behavior. Thus, the enables individuals to cultivate creativity, explore novel concepts, and acquire fresh insights that enhance their intellectual skills. Ultimately, DHEI also cultivates their attitude toward formal as well as informal digital learning, which significantly influences their learning behavior.

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 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 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

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.

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

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 main function of transfer RNAs (tRNAs) is to carry amino acids into the ribosome and synthesize proteins under the guidance of messenger RNAs (mRNAs). In addition to this, it has been observed that tRNAs undergo precise cleavage at specific loci, giving rise to an extensive array of distinct small RNAs, termed tRNA-derived small RNAs (tsRNAs). Existing studies have shown that tsRNAs are widely present across various organisms and comprehensively regulate gene expression, aberrant expression of tsRNAs is inextricably linked to tumorigenesis and development, thus, a systematic understanding of tsRNAs is necessary. This review aims to comprehensively delineate the genesis and expression patterns of tsRNAs, elucidate their diverse functions and emphasize their prospective clinical application as biomarkers and targets for therapy. It is noteworthy that we innovatively address the roles played by tsRNAs in human cancers at the level of the hallmarks of tumorigenesis proposed by Hanahan in anticipation of a broad understanding of tsRNAs and to guide the treatment of tumors.

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

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.

當今公共議題日益複雜，協作治理成為新公共治理思潮下的產物，而教育部為有效推動十二年國教課綱所進行的師資課程教學與評量之跨系統協作，即為一例。在此治理機制中，透過結構性安排、領導、知識互動與社會學習的協作動態，涵育與萌生了制度調適。本研究之目的即在探討跨系統協作之協作動態與隨之而生的調適。在研究方法上，採文件分析與訪談。本研究發現，教育部跨系統協作的運作，在多元行動者參與決定的過程中，涵攝了成員在可含納多元聲音的制度設計下，透過彼此對話、互動與集體行動，開展了領導、知識互動與社會學習。而在協作中的制度設計、領導、知識互動與社會學習也因應情境條件與行動者特質的改變或需求而進行調適。 Today’s public issues are becoming increasingly complex, and collaborative governance has emerged as a product of the new public governance paradigm. The Ministry of Education’s cross-system collaboration in teacher training, curriculum, teaching and assessment for the implementation of the 12-Year Basic Education Curriculum is an example of collaborative governance. Within this governance mechanism, collaborative dynamics and resultant institutional adaptations are nurtured and developed through structural arrangements, leadership, knowledge exchange, and social learning. The purpose of this study is to explore the collaborative dynamics of cross-system cooperation and the adaptations that arise as a result. To gather the necessary data, both document analysis and interviews were employed. The results reveal that the Ministry of Education’s cross-system collaboration involves multiple actors participating in decision-making processes, encompassing members in the institutional design that accommodates diverse voices. Through dialogue, interaction, and collective action, they engage in leadership, knowledge exchange, and social learning. Furthermore, the design of the collaborative system, leadership, knowledge exchange, and social learning within the collaboration are adapted to changing circumstances and the needs and characteristics of the actors involved.

Abstract Background Thymic carcinoma is a rare disease with an incidence of around 0.5 cases per million with a poor prognosis. The aim of this study was to assess patient outcomes with advanced thymic carcinoma receiving first‐line chemotherapy. Methods In our retrospective cohort study, we included patients who underwent treatment for metastatic thymic carcinoma between January 2013 to December 2019 in our hospital. Overall survival, progression‐free survival (PFS), objective response rates (ORR) and chemotherapy regimens were assessed and analyzed. Results A total of 27 patients were retrospectively analyzed. All patients received a platinum (cisplatin or carboplatin) based regimen as first‐line chemotherapy (29.6% received ADOC, 11.1% received PE, 40.7% received CP, 14.8% received CAP). The median PFS on first‐line chemotherapy was 199 days. The response rate was 40.7%. Median overall survival (OS) was 585 days. Positive CD5 staining was associated with better PFS. Conclusion We highlight the critical role of platinum‐based chemotherapy agents as a primary treatment modality in advanced thymic carcinoma, underscoring the efficacy of platinum as a first‐line option for recurrent disease, even in cases previously treated with platinum. Additionally, our findings indicate that CD5 positivity could be associated with improved PFS, suggesting its potential as a prognostic marker.

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.

In recent years, the international community has increasingly focused on the “dual carbon” issue, as human-induced land use changes significantly impact ecosystem structure and carbon cycling. This study analyzes land use changes in the economic zone of the northern Gulf of Guangxi from 1980 to 2020, utilizing the InVEST model to simulate spatiotemporal changes in carbon storage and conducting zoning studies through spatial analysis. The findings reveal that ① forest land and arable land dominate the northern Gulf of Guangxi’s land use, with notable changes observed in forest land, unused land, and construction land areas. Forest land and construction land have increased by 1761.5 km2 and 1001.19 km2, respectively, while unused land has decreased by 1881.18 km2 from 2000 to 2020. ② The total carbon storage values in the northern Gulf of Guangxi in 1980, 2000, and 2020 were, respectively, 504.91 × 106/t, 487.29 × 106/t, and 500.31 × 106/t, with the expansion of construction land and conversion of forest land being the main reasons for the decrease in carbon storage. ③ In the northern Gulf of Guangxi, there is a slight upward trend in total carbon storage values over time. Spatially, higher carbon storage values are observed in mountainous and hilly areas at high altitudes, while the central and southern coastal areas exhibit lower carbon storage values. ④ The local spatial autocorrelation results reveal that Pu Bei County exhibits high–high clustering of carbon storage, while He Pu County undergoes a transition from high–low to low–low clustering, and several other administrative areas in Beihai demonstrates low–low clustering. Due to the imperative of economic development, the expansion of urban construction land encroaches upon ecological land, resulting in a decline in carbon storage. Therefore, in the Northern Gulf of Guangxi, it is essential to implement measures such as reforestation and establish ecological protection areas such as forests, grasslands, and wetlands to develop effective carbon sequestration methods and compensate for the carbon loss caused by the expansion of construction land.

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.

BackgroundThe exploration of personality traits in relation to psychological constructs has become increasingly relevant in understanding the mental health of university students (the emerging adulthood). Studies have focused on how dimensions intersect with various psychological parameters.AimThe study aims to identify distinct personality profiles among university students based on Eysenck’s personality dimensions and investigate how these profiles differ across psychological constructs.MethodA quantitative methodology was utilized, involving 708 university students from Wenzhou and Nanjing in China as participants. The research employed the Eysenck Personality Questionnaire along with other psychological measures. Latent Profile Analysis was applied to categorize the participants into distinct personality profiles.ResultsFour distinct personality profiles emerged: ‘The Reserved Analyst,’ ‘The Social Diplomat,’ ‘The Unconventional Pragmatist,’ and ‘The Impulsive Truth-Teller.’ Significant differences were found among these profiles on various psychological constructs. ‘The Social Diplomat’ exhibited the most adaptive psychological profile, with higher cognitive reappraisal (F = 45.818, p

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 The progression of prostate cancer (PCa) leads to poor prognosis. However, the molecular mechanism of PCa is still not completely clear. This study aimed to elucidate the important role of centromere protein A (CENPA) in PCa. Large numbers of bulk RNA sequencing (RNA‐seq) data and in‐house immunohistochemistry data were used in analysing the expression level of CENPA in PCa and metastatic PCa (MPCa). Single‐cell RNA‐seq data was used to explore the expression status of CENPA in different prostate subpopulations. Enrichment analysis was employed to detect the function of CENPA in PCa. Clinicopathological parameters analysis was utilised in analysing the clinical value of CENPA. The results showed that CENPA was upregulated in PCa (standardised mean difference [SMD] = 0.83, p = 0.001) and MPCa (SMD = 0.61, p = 0.029). CENPA was overexpressed in prostate cancer stem cells (CSCs) with androgen receptor (AR) negative compared to epithelial cells with AR positive. CENPA may influence the development of PCa through affecting cell cycle. Patients with nodal metastasis had higher expression level of CENPA. And patients with high CENPA expression had poor disease‐free survival. Taken together, Overexpression of CENPA may influence the development of PCa by regulating cell cycle and promoting metastasis.

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

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.

In recent years, the “dual carbon” issue has become a major focus of the international community. Changes in land use driven by anthropogenic activities have a profound impact on ecosystem structure and carbon cycling. This study quantitatively assesses the spatiotemporal changes in cropland occupation and supplementation in the Pearl River Delta from 2000 to 2020 using the InVEST model, analyzing the spatial clustering of carbon storage changes caused by variations in cropland area. The PLUS model was employed to simulate land-use patterns and the spatial distribution of carbon storage in four future development scenarios. The results indicate the following: (1) From 2000 to 2020, the net change rate of cropland area in the Pearl River Delta was −0.81%, with a decrease of 16.49 km2 in cropland area, primarily converted to built-up land and forest land. (2) Carbon storage in the Pearl River Delta exhibited a pattern of lower values in the center and higher values in the periphery. The terrestrial ecosystem carbon storage in the Pearl River Delta was 534.62 × 106 t in 2000, 518.60 × 106 t in 2010, and 512.57 × 106 t in 2020, showing an overall decreasing trend. The conversion of cropland and forest land was the main reason for the decline in total regional carbon storage. (3) The area of carbon sequestration lost due to cropland occupation was significantly greater than the area of carbon loss compensated by new cropland, indicating an imbalance in the quality of cropland occupation and supplementation as a crucial factor contributing to regional carbon loss. (4) Under the ecological priority scenario, the expansion of built-up land and the reduction in ecological land such as cropland and forest land were effectively controlled, resulting in the minimal loss of carbon storage. The soil organic carbon pool of cropland is the most active carbon pool in terrestrial ecosystems and has a significant impact on carbon storage. Clarifying the relationship between “cropland protection measures–land use changes–ecosystem carbon storage” will improve cropland protection policies, provide references for regional carbon sequestration enhancement, and support sustainable socio-economic development.

AIM: To describe the clinical and radiologic features of retrolaminar migration silicone oil (SiO) and observe the dynamic position of ventricular oil accumulation in supine and prone. METHODS: For this retrospective study, 29 patients who had a history of SiO injection treatment and underwent unenhanced head computed tomography (CT) were included from January 2019 to October 2022. The patients were divided into migration-positive and negative groups. Clinical history and CT features were compared using Whitney U and Fisher's exact tests. The dynamic position of SiO was observed within the ventricular system in supine and prone. CT images were visually assessed for SiO migration along the retrolaminar involving pathways for vision (optic nerve, chiasm, and tract) and ventricular system. RESULTS: Intraocular SiO migration was found in 5 of the 29 patients (17.24%), with SiO at the optic nerve head (n=1), optic nerve (n=4), optic chiasm (n=1), optic tract (n=1), and within lateral ventricles (n=1). The time interval between SiO injection and CT examination of migration-positive cases was significantly higher than that of migration-negative patients (22.8±16.5mo vs 13.1±2.6mo, P

Abstract Background Prenatal infection has been implicated in the development of neuropsychiatric disorders in children. We hypothesised that exposure to lipopolysaccharide during prenatal development could induce anxiety-like behaviour and sensorineural hearing loss in offspring, as well as disrupt neural differentiation during embryonic neural development. Methods We simulated prenatal infection in FVB mice and mouse embryonic stem cell (ESC) lines, specifically 46C and E14Tg2a, through lipopolysaccharide treatment. Gene expression profiling analyses and behavioural tests were utilized to study the effects of lipopolysaccharide on the offspring and alterations in toll-like receptor (TLR) 2-positive and TLR4-positive cells during neural differentiation in the ESCs. Results Exposure to lipopolysaccharide (25 µg/kg) on gestation day 9 resulted in anxiety-like behaviour specifically in male offspring, while no effects were detected in female offspring. We also found significant increases in the expression of GFAP and CNPase, as well as higher numbers of GFAP + astrocytes and O4+ oligodendrocytes in the prefrontal cortex of male offspring. Furthermore, increased scores for genes related to oligodendrocyte and lipid metabolism, particularly ApoE, were observed in the prefrontal cortex regions. Upon exposure to lipopolysaccharide during the ESC-to-neural stem cell (NSC) transition, Tuj1, Map2, Gfap, O4, and Oligo2 mRNA levels increased in the differentiated neural cells on day 14. In vitro experiments demonstrated that lipopolysaccharide exposure induced inflammatory responses, as evidenced by increased expression of IL1b and ApoB mRNA. Conclusions Our findings suggest that prenatal infection at different stages of neural differentiation may result in distinct disturbances in neural differentiation during ESC—NSC transitions. Furthermore, early prenatal challenges with lipopolysaccharide selectively induce anxiety-like behaviour in male offspring. This behaviour may be attributed to the abnormal differentiation of astrocytes and oligodendrocytes in the brain, potentially mediated by ApoB/E signalling pathways in response to inflammatory stimuli.

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.

Abstract It is long been suggested that one‐carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small‐molecule kenpaullone (KEN) promoted ADAM10 translation via the 5′ untranslated region (5′UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5′UTR‐interacting RNA binding protein (RBP), mediated KEN‐induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5′UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5′UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 “moonlighted” as RBP by binding to GAGGG motif and promoting the 5′UTR‐dependent ADAM10 translation initiation.

Numerous studies have discussed the therapeutic outcomes of using cell therapy or acupuncture to treat peripheral artery disease (PAD). However, there are no long-term studies on the safety and efficacy of transplanting peripheral blood mononuclear cells (PBMNCs) via acupoints to treat PAD. We first reviewed the short-term and long-term clinical results of PAD patients treated with PBMNCs through intramuscular non-acupoint transplantation (control group; n = 45) or intramuscular acupoint transplantation (acupoint group; n = 45) at a single university hospital general medical center between December 2002 and September 2022. Pain intensity (assessed with the verbal rating scale [VRS] score) in the acupoint group was considerably lower than that in the control group at month 1 (mean ± standard deviation [SD]: 1.29 ± 0.96 vs 1.76 ± 0.82; P = 0.016) and month 3 (mean ± SD: 1.27 ± 0.90 vs 1.61 ± 0.86; P = 0.042). We observed significant improvement of VRS score (P < .001 for all) and ankle-brachial index (ABI; P < .001 for all) from baseline in both groups at months 1, 3, 6, 12, 36, and 60. The 10-year cumulative rate of major amputation–free survival (MAFS) was higher in the acupoint group as compared to the control group (81.9%, 95% confidence interval [CI]: 71.3%–94.1% vs 78.5%, 95% CI: 66.7%–92.3%; P = 0.768). Compared with the routine injection method, intramuscular transplantation of PBMNCs via selected acupoints could significantly decrease the short-term pain intensity in patients with PAD, which remains an option for consideration.

BackgroundSince no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy.MethodsThe Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software.ResultsNine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P

Abstract Soil salinization is a growing issue that limits agriculture globally. Understanding the mechanism underlying salt tolerance in halophytic grasses can provide new insights into engineering plant salinity tolerance in glycophytic plants. Seashore paspalum (Paspalum vaginatum Sw.) is a halophytic turfgrass and genomic model system for salt tolerance research in cereals and other grasses. However, the salt tolerance mechanism of this grass largely unknown. To explore the correlation between Na+ accumulation and salt tolerance in different tissues, we utilized two P. vaginatum accessions that exhibit contrasting tolerance to salinity. To accomplish this, we employed various analytical techniques including ICP-MS-based ion analysis, lipidomic profiling analysis, enzyme assays, and integrated transcriptomic and metabolomic analysis. Under high salinity, salt-tolerant P. vaginatum plants exhibited better growth and Na+ uptake compared to salt-sensitive plants. Salt-tolerant plants accumulated heightened Na+ accumulation in their roots, leading to increased production of root-sourced H2O2, which in turn activated the antioxidant systems. In salt-tolerant plants, metabolome profiling revealed tissue-specific metabolic changes, with increased amino acids, phenolic acids, and polyols in roots, and increased amino acids, flavonoids, and alkaloids in leaves. High salinity induced lipidome adaptation in roots, enhancing lipid metabolism in salt-tolerant plants. Moreover, through integrated analysis, the importance of amino acid metabolism in conferring salt tolerance was highlighted. This study significantly enhances our current understanding of salt-tolerant mechanisms in halophyte grass, thereby offering valuable insights for breeding and genetically engineering salt tolerance in glycophytic plants.

ABSTRACTThe emerging pathogen Elizabethkingia anophelis poses severe threats to public health and has caused several outbreaks. The efficacy of antimicrobials is limited due to the pathogen’s innate multi-drug resistance to most antibiotics. Hence, novel approaches to treat E. anophelis infections are urgently needed. This study evaluated the immunogenic and protective effects of the imipenem-induced outer membrane vesicles (iOMVs) of E. anophelis as a vaccine. Mice immunized with iOMVs were completely protected during lethal-dose challenges. Passive immunization with hyperimmune sera and splenocytes conferred protection against lethal pneumonia. iOMVs also induced Th1-, Th2-, and Th17-driven immune responses. Immunization with iOMVs increased IgG1 and IgG2c isotype levels, and the antisera from immunized mice promoted complement-dependent bactericidal and opsonophagocytic activities against E. anophelis C08. Our study suggests that E. anophelis iOMVs are a promising vaccine candidate for preventing and treating E. anophelis infections and provides insights into the use of OMVs in vaccine development against the clinically emergent E. anophelis.IMPORTANCEElizabethkingia anophelis, a Gram-negative pathogen, causes infections such as bacteraemia, pneumonia, and neonatal meningitis. The pathogen resists most antimicrobial classes, making novel approaches urgently needed. In natural settings, Gram-negative bacteria secrete outer membrane vesicles (OMVs) that carry important molecules in the bacterial life cycle. These OMVs are enriched with proteins involved in virulence, survival, and carbohydrate metabolism, making them a promising source for vaccine development against the pathogen. This study investigated the efficacy of imipenem-induced OMVs (iOMVs) as a vaccine candidate against E. anophelis infection in a mouse pneumonia model. Mice immunized with iOMVs were completely protected during lethal-dose challenges. Passive immunization with hyperimmune sera and splenocytes conferred protection against lethal pneumonia. Further investigation is needed to understand the mechanisms underlying the protective effects of iOMV-induced passive immunity, such as the action on specific antibody subclasses or T cell subsets.

The effects of pre-treatments on the drying characteristics, water state, thermal properties, and bulk shrinkage of potato slices during microwave vacuum drying (MVD) were investigated. The pre-treatment included ultrasound in distilled water (USOD-0%), and ultrasound-assisted osmotic dehydration in a 60% sucrose solution (USOD-60%). Results showed that the drying time of potato slices was reduced and the drying rate was increased when USOD-0% was used as a pretreatment, whereas USOD-60% had a negative effect on the drying rate of the samples. The Weibull model was effective in predicting the water changes in potato slices during the drying process. NMR analysis revealed that the relative content of immovable water (M22) increased initially, then decreased for drying, while the transverse relaxation time (T2) and the relative content of free water (M23) decreased consistently. The DSC results indicated that the glass transition temperature (Tg) had an inverse relationship with the water content of the samples, yet had virtually no influence on the volume shrinkage. The sample volumes decreased linearly with the decrease in water content during the initial drying stages. USOD pre-treatment lessened the volume shrinkage of MVD potato slices. Static gravimetry was used to determine the moisture sorption isotherms of MVD potato slices at 30 °C within the aw range of 0.113–0.923. The GAB model accurately fitted the experimental sorption data, which showed sigmoid shape curves for the MVD samples. When aw values exceeded 0.7, the USOD-60% treatment significantly reduce the water sorption capacity of MVD potato slices, while USOD-0% treatment was observed to increase the hygroscopic properties of MVD samples. Compared with the control, USOD-0% pretreatment significantly increased the monolayer water content (X0), sorption surface area (S0), the thickness of sorbed water multilayer (tm), and density of sorbed water (Ds) values of MVD potato slices, while USOD-60% decreased these values.

Abstract Objective Despite the availability of new agents, elderly patients with multiple myeloma (MM) usually present with poor outcomes due to the heterogeneity of disease conditions, especially immune deficiency. Regulatory B cells (Bregs) can be involved in immune defects by exerting immune regulatory functions in MM. In order to provide more evidence‐based practice for the elderly MM, the study established and assessed a stratified therapeutic model with studies on Bregs for Chinese Elderly Multiple Myeloma in 2021 (CEMM2021). Methods In this open‐label, non‐interventional, prospective study in the real world, 159 newly diagnosed MM (NDMM) patients over 65 years old were sequentially recruited and bone marrow aspirates prior to treatment were obtained to detect the ratios of Bregs by flow cytometry. Results Based on the CEMM2021 model, 147 patients had received at least one cycle of induction therapy, including bortezomib/dexamethasone (Bd) (n = 80), lenalidomide/dexamethasone (Rd) (n = 27), Bd with a third agent X (Bd + X) (n = 27), and other regimens (n = 13). The proportions of patients achieving very good partial response or better were comparable among Bd, Bd + X, and Rd groups (41.9% vs. 54.5% vs. 44.0%, p = 0.472). Besides, the progression‐free survival (PFS) and overall survival (OS) were not significantly different among Rd, Bd, and Bd + X groups. Multivariable analysis showed that induction efficacy less than partial response (PR) were poor prognostic factors for PFS, while Revised‐International Staging System (R‐ISS) III and efficacy less than PR were poor prognostic factors for OS. This study also found that the ratios of bone marrow Bregs 4.2 (p = 0.000) were closely correlated with OS in the elderly MM. Conclusions For the elderly NDMM, the CEMM2021 algorithm in our center might provide a valuable reference for the guidance of therapeutic strategies, with the combination of Bregs resulting in an effective and clinically meaningful prediction in contemporary treatment.

Abstract Background Antiretroviral therapy (ART) is currently the most effective way to treat people living with human immunodeficiency virus (PLHs) and reduce HIV transmission. While there are many factors that reduce adherence to ART, PLHs’ knowledge about ART may determine the level of adherence. It is necessary to design and assess an instrument scale that measures the knowledge of antiretroviral therapy among PLHs. Method A cross-sectional study was conducted among PLHs in Honghe Hani and Yi Autonomous Prefecture, China. Both exploratory and confirmatory factor analyses were used to examine the latent factors of antiretroviral therapy knowledge scale. Internal consistency was assessed separately for the scale and its dimensions by estimating Cronbach’s alphas, split-half reliability and Spearman’s correlation coefficient. ANOVAs were used to compare the scores of different dimensions with sociodemographic characteristics. Results Four factors were extracted according to factor loadings. They had high internal consistency reliability (Cronbach’s alpha: 0.70–0.95) and good construct validity (standardized factor loading range: 0.46–0.86) in the scale. Goodness of fit indices indicated that a four-factor solution fit the data at an accepted level (χ2/degree ratio = 1.980, RMSEA = 0.069, GFI = 0.909, CFI = 0.957, NFI = 0.917, TLI = 0.944). ANOVAs indicated that the score was higher among PLHs who were Han, had spouses/partners, were non-famers or migrant workers, initiated ART, and had a high school or above education. Conclusion The psychometric assessment indicated that this ART knowledge scale had accepted internal consistency and discriminant construct validity. It can be used to assess the knowledge of antiretroviral therapy for PLHs.

Abstract Objective Diabetes is a major cause of the progression of acute kidney injury (AKI). Few prediction models have been developed to predict the renal prognosis in diabetic patients with AKI so far. The aim of this study was to develop and validate a predictive model to identify high-risk individuals with non-recovery of renal function at 90 days in diabetic patients with AKI. Methods Demographic data and related laboratory indicators of diabetic patients with AKI in the First Affiliated Hospital of Guangxi Medical University from January 31, 2012 to January 31, 2022 were retrospectively analysed, and patients were followed up to 90 days after AKI diagnosis. Based on the results of Logistic regression, a model predicting the risk of non-recovery of renal function at 90 days in diabetic patients with AKI was developed and internal validated. Consistency index (C-index), calibration curve, and decision curve analysis were used to evaluate the differentiation, accuracy, and clinical utility of the prediction model, respectively. Results A total of 916 diabetic patients with AKI were enrolled, with a male to female ratio of 2.14:1. The rate of non-recovery of renal function at 90 days was 66.8% (612/916). There were 641 in development cohort and 275 in validation cohort (ration of 7:3). In the development cohort, a prediction model was developed based on the results of Logistic regression analysis. The variables included in the model were: diabetes duration (OR = 1.022, 95% CI 1.012–1.032), hypertension (OR = 1.574, 95% CI 1.043–2.377), chronic kidney disease (OR = 2.241, 95% CI 1.399–3.591), platelet (OR = 0.997, 95% CI 0.995–1.000), 25-hydroxyvitamin D3 (OR = 0.966, 95% CI 0.956–0.976), postprandial blood glucose (OR = 1.104, 95% CI 1.032–1.181), discharged serum creatinine (OR = 1.003, 95% CI 1.001–1.005). The C-indices of the prediction model were 0.807 (95% CI 0.738–0.875) and 0.803 (95% CI 0.713–0.893) in the development and validation cohorts, respectively. The calibration curves were all close to the straight line with slope 1. The decision curve analysis showed that in a wide range of threshold probabilities. Conclusion A prediction model was developed to help predict short-term renal prognosis of diabetic patients with AKI, which has been verified to have good differentiation, calibration degree and clinical practicability.

Abstract Background As postmenopausal osteoporotic fractures can cause higher rates of disability and mortality in women; it is essential to analyze the factors associated with primary and recurrent fractures in postmenopausal osteoporosis (PMOP) patients. Methods Retrospective analysis of 2478 PMOP patients aged ≥ 50 years who attended the Shanghai General Hospital from January 2007 to December 2016, including 1239 patients with no fractures and 1239 patients with histories of fractures (1008 in the primary fracture group and 231 in the re-fracture group). All patients' basic clinical data, serum biochemical and bone metabolic markers, bone mineral density (BMD), and other indicators were recorded uniformly. Comparing the differences between the clinical characteristics of patients with primary and recurrent fractures, as well as the differences in the clinical characteristics of patients with primary and recurrent fractures in combination with different diseases, further analyses the risk factors for primary and recurrent fractures in PMOP patients. SPSS.26 was used for statistical analysis. Results Compared to the unfractured group, the fractured group was older and had lower height and bone mineral density (all P

Abstract Background The molecular mechanism of laryngeal squamous cell carcinoma (LSCC) is not completely clear, which leads to poor prognosis and treatment difficulties for LSCC patients. To date, no study has reported the exact expression level of zinc finger protein 71 (ZNF71) and its molecular mechanism in LSCC. Methods In-house immunohistochemistry (IHC) staining (33 LSCC samples and 29 non-LSCC samples) was utilized in analyzing the protein expression level of ZNF71 in LSCC. Gene chips and high-throughput sequencing data collected from multiple public resources (313 LSCC samples and 192 non-LSCC samples) were utilized in analyzing the exact mRNA expression level of ZNF71 in LSCC. Single-cell RNA sequencing (scRNA-seq) data was used to explore the expression status of ZNF71 in different LSCC subpopulations. Enrichment analysis of ZNF71, its positively and differentially co-expressed genes (PDCEGs), and its downstream target genes was employed to detect the potential molecular mechanism of ZNF71 in LSCC. Moreover, we conducted correlation analysis between ZNF71 expression and immune infiltration. Results ZNF71 was downregulated at the protein level (area under the curve [AUC] = 0.93, p < 0.0001) and the mRNA level (AUC = 0.71, p = 0.023) in LSCC tissues. Patients with nodal metastasis had lower protein expression level of ZNF71 than patients without nodal metastasis (p < 0.05), and male LSCC patients had lower mRNA expression level of ZNF71 than female LSCC patients (p < 0.01). ZNF71 was absent in different LSCC subpopulations, including cancer cells, plasma cells, and tumor-infiltrated immune cells, based on scRNA-seq analysis. Enrichment analysis showed that ZNF71 and its PDCEGs may influence the progression of LSCC by regulating downstream target genes of ZNF71. These downstream target genes of ZNF71 were mainly enriched in tight junctions. Moreover, downregulation of ZNF71 may influence the development and even therapy of LSCC by reducing immune infiltration. Conclusion Downregulation of ZNF71 may promote the progression of LSCC by reducing tight junctions and immune infiltration; this requires further study.

Abstract Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex‐biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)‐treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo‐germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo‐germ mice receiving fecal sample from male mice. Sex‐biased gut metabolites in pseudo‐germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex‐biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex‐biased gut microbiota and metabolites could be a potential sex‐targeting therapeutic strategy of CRC.

Southwestern China has the largest geological phosphorus-rich mountain in the world, which is seriously degraded by mining activities. Understanding the trajectory of soil microbial recovery and identifying the driving factors behind such restoration, as well as conducting corresponding predictive simulations, can be instrumental in facilitating ecological rehabilitation. Here, high-throughput sequencing and machine learning-based approaches were employed to investigate restoration chronosequences under four restoration strategies (spontaneous re-vegetation with or without topsoil; artificial re-vegetation with or without the addition of topsoil) in one of the largest and oldest open-pit phosphate mines worldwide. Although soil phosphorus (P) is extremely high here (max = 68.3 mg/g), some phosphate solubilizing bacteria and mycorrhiza fungi remain as the predominant functional types. Soil stoichiometry ratios (C:P and N:P) closely relate to the bacterial variation, but soil P content contributes less to microbial dynamics. Meanwhile, as restoration age increases, denitrifying bacteria and mycorrhizal fungi significantly increased. Significantly, based on partial least squares path analysis, it was found that the restoration strategy is the primary factor that drives soil bacterial and fungal composition as well as functional types through both direct and indirect effects. These indirect effects arise from factors such as soil thickness, moisture, nutrient stoichiometry, pH, and plant composition. Moreover, its indirect effects constitute the main driving force towards microbial diversity and functional variation. Using a hierarchical Bayesian model, scenario analysis reveals that the recovery trajectories of soil microbes are contingent upon changes in restoration stage and treatment strategy; inappropriate plant allocation may impede the recovery of the soil microbial community. This study is helpful for understanding the dynamics of the restoration process in degraded phosphorus-rich ecosystems, and subsequently selecting more reasonable recovery strategies.

The development of severe multidrug-resistant bacterial infections has recently intensified because of the COVID-19 pandemic. According to the guidelines issued by the World Health Organization (WHO), routine antibiotic administration is not recommended for patients with supposed or confirmed mild SARS-CoV-2 infection or pneumonia, unless bacterial infection is clinically suspected. However, recent studies have pointed out that the proportion of non-essential antibiotic use in patients infected with SARS-CoV-2 remains high. Therefore, the silent pandemic of antibiotic resistance remains a pressing issue regardless of the present threats presented by the COVID-19 pandemic. To prevent or delay entry into the postulated post-antibiotic era, the long-term advocacy for the rational use of antibiotics, the optimization of infection control procedures, and the development of new antibacterial agents and vaccines should be underscored as vital practices of the antibacterial toolbox. Recently, the development of vaccines and monoclonal antibodies has gradually received attention following the advancement of biotechnology as well as enhanced drug discovery and development in cancer research. Although decent progress has been made in laboratory-based research and promising results have been obtained following clinical trials of some of these products, challenges still exist in their widespread clinical applications. This article describes the current advantages of antibacterial monoclonal antibodies, the development of associated clinical trials, and some perceived future perspectives and challenges. Further, we anticipate the development of more therapeutic agents to combat drug-resistant bacterial infections as well as to increase the resilience of current or novel agents/strategies.

Abstract Non-motor symptoms of Parkinson’s disease (PD) such as dysautonomia and REM sleep behavior disorder (RBD) are recognized to be important prodromal symptoms that may also indicate clinical subtypes of PD with different pathogenesis. Unbiased clustering analyses showed that subjects with dysautonomia and RBD symptoms, as well as early cognitive dysfunction, have faster progression of the disease. Through analysis of the Parkinson’s Progression Markers Initiative (PPMI) de novo PD cohort, we tested the hypothesis that symptoms of dysautonomia and RBD, which are readily assessed by standard questionnaires in an ambulatory care setting, may help to independently prognosticate disease progression. Although these two symptoms associate closely, dysautonomia symptoms predict severe progression of motor and non-motor symptoms better than RBD symptoms across the 3-year follow-up period. Autonomic system involvement has not received as much attention and may be important to consider for stratification of subjects for clinical trials and for counseling patients.

Artemisinin is an active ingredient extracted from the Chinese medicine Artemisia carvifolia. The experiment investigated the effects of dietary artemisinin on growth performance, intestinal digestive enzyme activity and flora, antioxidant capacity, immune-related gene expression of Coral trout (Plectropomus leopardus). The 450 fish with an initial weight of 9.40 ± 0.04 g were randomly divided into 5 groups of 3 replicates and fed in 500 m3 fiberglass tank for 9 weeks. Five iso-nitrogenous (50% crude protein) and iso-lipidic (10% crude lipid) diets were formulated by supplementing various mass fractions of artemisinin (C0 0% as control; C0.2 0.20%, C0.4 0.40%, C0.8 0.80%, and C1.2 1.20%). The results showed that the C0.2 had the highest weight gain rate (WGR) compared to the others (P