ObjectiveTo investigate the association of comprehensive control of multiple metabolic risk factors with the risk of all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease （MASLD） and its quantitative effect. MethodsA retrospective cohort study was conducted based on the data from National Health and Nutrition Examination Survey （NHANES） in 2003—2018. A total of 29 458 participants were enrolled， including 12 528 patients with MASLD and 16 930 non-MASLD controls. The control status of nine risk factors was assessed， i.e.， hypertension， diabetes， liver fibrosis （assessed by fibrosis-4 index ［FIB-4］）， aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio， serum albumin， renal function （assessed by serum creatinine）， systemic inflammation （assessed by neutrophil count）， smoking， and physical activity. According to the status of comprehensive risk factor control， the patients with MASLD were further divided into low-control group with 1 107 patients， moderate-control group with 7 042 patients， and high-control group with 4 379 patients. A total of 397 participants were enrolled in the external validation cohort， among whom there were 266 participants with MASLD and 131 participants without MASLD. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test was used for comparison of categorical data between groups. The Cox proportional hazards model incorporating complex sampling weights for NHANES data were used to investigate the association between the degree of risk factor control and all-cause mortality， and the Kaplan-Meier curve， the log-rank test， restricted mean survival time （RMST）， and population attributable fraction （PAF） were used for further assessment. The robustness of the findings was validated in an independent clinical cohort （n=397）. ResultsThe cohort study based on the NHANES database showed that during the median follow-up time of 6.7 years， 1 171 deaths occurred among the 12 528 patients with MASLD. There was a significant reduction in mortality risk with the increase in the number of risk factors controlled （trend test： χ²=65.06， P<0.001）. Compared with the low-control group， the mortality risk decreased successively in the moderate-control group （hazard ratio ［HR］=0.59， 95% confidence interval ［CI］： 0.51 — 0.69） and the high-control group （HR=0.36， 95%CI： 0.27 — 0.48）， and the mortality risk was reduced by 22% for each additional risk factor controlled （HR=0.78， 95%CI： 0.74 — 0.82）. The PAF analysis showed that AST/ALT ratio control （PAF=19.2%） and physical activity （PAF=18.9%） were the largest contributors. The survival analysis of the sub-cohort constructed based on nearest neighbor matching （with a maximum follow-up time of 13.3 years） showed that there was a significant difference in cumulative survival rate between the MASLD groups with different control levels and the non-MASLD group （P<0.001）. The RMST analysis further quantified the survival benefit of each group， and the high-control group had the longest 10-year RMST （9.88 years）， which was superior to that of the non-MASLD group （9.43 years）， the moderate-control group （9.33 years）， and the low-control group （7.96 years）. The multivariable-adjusted model analysis of the complete cohort showed that compared with the non-MASLD population， the MASLD patients in the low-control group had a significant increase in mortality risk， the moderate-control group had a comparable mortality risk， and the high-control group had a significantly lower mortality risk. The subgroup analysis showed a significant protective effect of comprehensive control in both male and female individuals （P<0.05）， and the interaction analysis suggested a potentially stronger protective effect in female individuals （P_{for interaction}=0.031）. The protective effect was statistically significant in patients aged ≥60 years （P<0.05）. There was a significant difference in protective effect across the groups stratified based on waist circumference （P<0.05）， but there was no significant interaction between groups （P_{for interaction}=0.821）. In the external validation cohort， among the 397 participants， there were 72 cases of all-cause mortality （18.1%）. The survival analysis showed a significant gradient increase in the survival rate of MASLD patients with the increase in the level of control （P=0.022）. The RMST analysis showed that the moderate- and high-control groups had a better RMST than the non-MASLD group at 5 years （4.47 years vs 4.56 years vs 4.40 years）， with a more significant survival advantage at 10 years （8.67 years vs 8.95 years vs 8.44 years）. The Cox regression analysis showed that， with the low-control MASLD group as the reference， there was a significant reduction in mortality risk in the moderate-control group （HR=0.41， 95%CI： 0.21 — 0.81） and the high-control group （HR=0.32， 95%CI： 0.14 — 0.71）； with the non-MASLD population as the reference， there was a significant increase in mortality risk in the low-control group （HR=2.02， 95%CI： 1.03 — 3.95）， with a comparable mortality risk in the moderate-control group （HR=0.83， 95%CI： 0.48 — 1.44） and the high-control group （HR=0.66， 95%CI： 0.30 — 1.38）， and the point estimates of the effects were highly consistent with the main study. ConclusionAmong MASLD patients， better control of metabolic risk factors is associated with a lower mortality risk. Achieving optimal control can eliminate the excess mortality risk associated with MASLD， thereby helping patients achieve a better survival prognosis than the general population.

As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

Objective: To explore the current status and influencing factors of eating behaviors in adolescents, so as to provide a theoretical foundation for health promotion education among adolescents. Methods: Based on the database from Survey of Chinese Family Health Index (2021), by a random number table method, 1 065 teenagers were selected from the provincial capitals of 22 provinces and 5 autonomous regions in China, as well as 4 municipalities directly under the central government. A general characteristic questionnaire, Patient Health Questionnaire-9 (PHQ-9), Short Form of the Family Health Scale (FHS-SF), 10-item Short Version of the Big Five Personality(BFP-10), Content-based Media Exposure Scale (CM-E) and Sakata Eating Behavior Scale Short Form(EBS-SF) were used to collect information. Multivariate stepwise linear regression analysis was employed to identify and analyze related factors of eating behaviors among adolescents. Receiver operating characteristic was used to validate the predictive ability of the EBS-SF score for overweight and obesity among adolescents. Results: The average scores of BFI-10,C-ME, FHS-SF, PHQ-9 and EBS-SF were (33.08±4.64)(19.20±4.55)(38.48±6.65)(6.09±5.63)(16.75±4.36), respectively. Multivariate linear regression showed that family type (other types), agreeableness, conscientiousness, family health and depression were the main related factors of EBS-SF scores among adolescents( B =2.61,-0.42,0.20,-0.11,0.23, P <0.05).The analysis of receiver operating characteristic curve showed that the EBS-SF scores had a good ability in predicting obesity among male adolescents ( AUC= 0.73, P <0.01). Conclusions Family type, big five personality, family health,depression are the related factors of eating behaviors among adolescents. EBS-SF scores are predictive of obesity in adolescents, which would provide a new perspective for promoting healthy eating habits among adolescents.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

OBJECTIVE: To explore the mechanism by which the extract of Semen Ziziphi Spinosae extract promotes bone growth in mice by modulation of the expression of miR-34a-5p in brain tissue. METHODS: Mice were assigned to four experimental groups:a normal control group, a drug administration group (receiving 0.320 mg·g^-1 body weight of Semen Ziziphi Spinosae extract via intragastric administration), a positive control group (receiving 0.013 mg·g^-1 body weight of jujube seed saponin via intragastric administration), and a combination group administration with Semen Ziziphi Spinosae extract plus a 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist (intragastric administration of Semen Ziziphi Spinosae extract combined with intracerebroventricular injection of 8 μg P-MPPF per mice for the final three days of the experiment). Following a 20-day administration period, the effects of the interventions on bone growth, serum growth hormone (GH) levels, and 5-HT2AR expression in brain tissue were evaluated. MicroRNAs (miRNAs) that were differentially expressed in the brain tissues of mice exhibiting bone growth induced by Semen Ziziphi Spinosae extract, as compared to those in normal mice, were identified using a gene chip approach. The interaction between miR-34a-5p and 5-HT2AR was subsequently validated through quantitative reverse transcription polymerase chainreaction (RT-qPCR) and dual-luciferase reporter gene assays. Subsequently, by utilizing the miR-34a-5p inhibitor group and mimics group, along with the normal control group, the drug administration group, the positive control group, and the drug administration combined with miR-34a-5p inhibitor group, the variations in 5-HT2AR expression in mouse brain tissue across all groups were examined, and the binding activity of 5-hydroxytryptamine (5-HT) to the 5-hydroxytryptamine 1A receptor (5-HT1AR) in mice was assessed. RESULTS: The body lengths of the normal control group and the drug administration group were(8.9±0.3) and(10.4±0.4) cm;femur lengths were (8.5±0.3) and (9.1±0.5) mm;tibia lengths were (10.7±0.3) and (11.2±0.4) mm, respectively. The contents of GH levels were (58.6±8.2) and (72.9±6.1) ng·ml-1;and the contents of 5-HT2AR were (32.0±5.0) and (21.9± 5.5) ng·ml-1, respectively. Compared with the normal control group, the drug administration group promoted the growth of body length, femur, and tibia in mice, and increased GH secretion, showing statistically significant differences (P<0.05). Additionally, it significantly reduced the content of 5-HT2AR in brain tissue, with statistical significance (P<0.01). The gene chip analysis identified a total of 16 differentially expressed miRNAs, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics analysis predicted that the up-regulated miR-34a-5p could regulate the expression of 5-HT2AR, a prediction that was confirmed through a dual-luciferase reporter gene assay, demonstrating a direct regulatory interaction between the two. Furthermore, in vivo experiments in mice revealed that overexpression and silencing of miR-34a-5p resulted in corresponding changes in the expression levels of 5-HT2AR in brain tissues/cells, as well as in the binding activity between 5-HT and 5-HT1AR. CONCLUSION The Semen Ziziphi Spinosae extract promotes animal bone growth by enhancing miR-34a-5p expression in brain tissue, downregulating the expression level of 5-HT2AR, improving the binding activity between 5-HT and 5-HT1AR, and extending slow-wave sleep duration, thereby stimulating GH secretion.
Animals ; MicroRNAs/metabolism* ; Mice ; Male ; Brain/metabolism* ; Ziziphus/chemistry* ; Bone Development/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Plant Extracts/pharmacology*