Low-grade wind-driven directional flow in anchored droplets.

Low-grade wind with airspeed Vwind < 5 m/s, while distributed far more abundantly, is still challenging to extract because current turbine-based technologies require particular geography (e.g., wide-open land or off-shore regions) with year-round Vwind > 5 m/s to effectively rotate the blades. Here, we report that low-speed airflow can sensitively enable directional flow within nanowire-anchored ionic liquid (IL) drops. Specifically, wind-induced air/liquid friction continuously raises directional leeward fluid transport in the upper portion, whereas three-phase contact line (TCL) pinning blocks further movement of IL. To remove excessive accumulation of IL near TCL, fluid dives, and headwind flow forms in the lower portion, as confirmed by microscope observation. Such stratified circulating flow within single drop can generate voltage output up to ~0.84 V, which we further scale up to ~60 V using drop "wind farms". Our results demonstrate a technology to tap the widespread low-grade wind as a reliable energy resource.

A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo.

Signal transducer and activator of transcription 5 (STAT5) is an attractive therapeutic target, but successful targeting of STAT5 has proved to be difficult. Here we report the development of AK-2292 as a first, potent and selective small-molecule degrader of both STAT5A and STAT5B isoforms. AK-2292 induces degradation of STAT5A/B proteins with an outstanding selectivity over all other STAT proteins and more than 6,000 non-STAT proteins, leading to selective inhibition of STAT5 activity in cells. AK-2292 effectively induces STAT5 depletion in normal mouse tissues and human chronic myeloid leukemia (CML) xenograft tissues and achieves tumor regression in two CML xenograft mouse models at well-tolerated dose schedules. AK-2292 is not only a powerful research tool with which to investigate the biology of STAT5 and the therapeutic potential of selective STAT5 protein depletion and inhibition but also a promising lead compound toward ultimate development of a STAT5-targeted therapy.

Recapitulating familial hypercholesterolemia in a mouse model by knock-in patient-specific LDLR mutation.

Familial hypercholesterolemia (FH) is one of the most prevalent monogenetic disorders leading to cardiovascular disease (CVD) worldwide. Mutations in Ldlr, encoding a membrane-spanning protein, account for the majority of FH cases. No effective and safe clinical treatments are available for FH. Adenine base editor (ABE)-mediated molecular therapy is a promising therapeutic strategy to treat genetic diseases caused by point mutations, with evidence of successful treatment in mouse disease models. However, due to the differences in the genomes between mice and humans, ABE with specific sgRNA, a key gene correction component, cannot be directly used to treat FH patients. Thus, we generated a knock-in mouse model harboring the partial patient-specific fragment and including the Ldlr W490X mutation. LdlrW490X/W490X mice recapitulated cholesterol metabolic disorder and clinical manifestations of atherosclerosis associated with FH patients, including high plasma low-density lipoprotein cholesterol levels and lipid deposition in aortic vessels. Additionally, we showed that the mutant Ldlr gene could be repaired using ABE with the cellular model. Taken together, these results pave the way for ABE-mediated molecular therapy for FH.

Additional Yield of Random Biopsy in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.

Engineered Staphylococcus auricularis Cas9 with high-fidelity.

CRISPR-Cas9 is a versatile gene editing tool with a broad application of basic research and clinical therapeutics. However, the potential impact caused by off-target effects remains a critical bottleneck. The small Cas9 ortholog from Staphylococcus auricularis (SauriCas9) was identified, which recognizes a 5'-NNGG-3' protospacer adjacent motif (PAM), exhibiting high activity for genome editing. Recently, we also reported enhanced-fidelity Staphylococcus aureus Cas9 (efSaCas9), which harbors a single mutation N260D. Protein sequence alignment revealed that SauriCas9 has 62.4% sequence identity with SaCas9. Because SauriCas9 is more flexible in recognizing the target sequence with PAM of 5'-NNGG-3' than SaCas9 of 5'-NNGRRT-3' PAM, we sought to test whether key mutation(N260D) or adjacent residue mutation in efSaCas9 can be appliable to SauriCas9. With this concept, two engineered SauriCas9 variants (SauriCas9-HF1, harboring the N269D mutation; SauriCas9-HF2, harboring the D270N mutation) dramatically improved targeting specificity by targeted deep sequencing and GUIDE-seq. At certain sites, reduced off-target effects (approximately 61.6- and 111.9-fold improvements) of SauriCas9-HF2 compared with wild-type SauriCas9 were observed. Overall, two identified SauriCas9 variants (SauriCas9-HF1 and SauriCas9-HF2) expand the utility of the CRISPR toolkit for research and therapeutic applications.

Role of stress in skin diseases: A neuroendocrine-immune interaction view.

Psychological stress is a crucial factor in the development of many skin diseases, and the stigma caused by skin disorders may further increase the psychological burden, forming a vicious cycle of psychological stress leading to skin diseases. Therefore, understanding the relationship between stress and skin diseases is necessary. The skin, as the vital interface with the external environment, possesses its own complex immune system, and the neuroendocrine system plays a central role in the stress response of the body. Stress-induced alterations in the immune system can also disrupt the delicate balance of immune cells and inflammatory mediators in the skin, leading to immune dysregulation and increased susceptibility to various skin diseases. Stress can also affect the skin barrier function, impair wound healing, and promote the release of pro-inflammatory cytokines, thereby exacerbating existing skin diseases such as psoriasis, atopic dermatitis, acne, and urticaria. In the present review, we explored the intricate relationship between stress and skin diseases from a neuroendocrine-immune interaction perspective. We explored the occurrence and development of skin diseases in the context of stress, the stress models for skin diseases, the impact of stress on skin function and diseases, and relevant epidemiological studies and clinical trials. Understanding the relationship between stress and skin diseases from a neuroendocrine-immune interaction perspective provides a comprehensive framework for targeted interventions and new insights into the diagnosis and treatment of skin diseases.

Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway.

OBJECTIVE AND DESIGN: To elucidate Sirt1's role in gouty arthritis inflammation and its potential mechanisms. MATERIAL: Constructed murine models of gouty arthritis and conducted THP-1 cell experiments. TREATMENT: 1 mg of MSU crystals injected into mice ankle joints for a 72-h intervention. After a 3-h pre-treatment with Sirt1-specific inhibitor (EX527) and agonist (SRT2104), inflammation was induced for 21 h using lipopolysaccharide (LPS) plus MSU crystals. METHODS: We assessed gouty arthritis severity through joint inflammation index, swelling, and hematoxylin and eosin (H&E) staining, and measured CD68 mononuclear macrophages and Sirt1 expression in synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, and Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK/NF-κB/AP-1 and Nrf2/HO-1 pathways proteins. RESULTS: Significant joint swelling, synovial tissue edema, and inflammatory cell infiltration were observed. CD68 mononuclear macrophages and Sirt1 expression were elevated in synovium. Sirt1 activation decreased inflammatory factors, M1 polarization, and ROS generation. Sirt1 activation reduced p38/JNK phosphorylation, thereby inhibiting downstream NF-κB p65/AP-1 and enhancing Nrf2/HO-1, thus suppressing inflammation. CONCLUSIONS: Sirt1 alleviates M1 macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Thus, activating Sirt1 may provide a new therapeutic target for gouty arthritis.

Synthesis of Nonclassical Heteroaryl C-Glycosides via Decarboxylative C-H Glycosylation.

A photoredox-promoted decarboxylative C-H glycosylation for the synthesis of nonclassical heteroaryl C-glycosides is reported. This methodology is characterized by an exceedingly simple reaction system, high diastereoselectivity, and good functional group tolerance. Moreover, the operational procedure is simple, and the gram-scale reaction highlights the practical applicability of this protocol.

Identifying latent subtypes of symptom trajectories in major depressive disorder patients and their predictors.

This study aimed to identify different symptom trajectories based on the severity of depression symptoms within a 2-month follow-up, and to explore predictive factors for different symptom trajectories. Three hundred and ninety-two adults diagnosed with major depressive disorder (MDD) were recruited from two longitudinal cohorts. Patients received antidepressant treatment as usual, and the depression symptoms were evaluated by the 17-item Hamilton depression rating scale (HAMD-17) at baseline, two weeks, and eight weeks. Based on the HAMD-17 scores, different trajectories of symptom change were distinguished by applying Growth Mixture Modeling (GMM). Furthermore, the baseline sociodemographic, clinical, and cognitive characteristics were compared to identify potential predictors for different trajectories. Through GMM, three unique depressive symptom trajectories of MDD patients were identified: (1) mild-severity class with significant improvement (Mild, n = 255); (2) high-severity class with significant improvement (High, n = 39); (3) moderate-severity class with limited improvement (Limited, n = 98). Among the three trajectories, the Mild class had a relatively low level of anxiety symptoms at baseline, whereas the High class had the lowest education level and the worst cognitive performance. Additionally, participants in the Limited class exhibited an early age of onset and experienced a higher level of emotional abuse. MDD patients could be categorised into three distinct latent subtypes through different symptom trajectories in this study, and the characteristics of these subtype patients may inform identifications for trajectory-specific intervention targets.

Preoperative prediction of microsatellite instability status in colorectal cancer based on a multiphasic enhanced CT radiomics nomogram model.

BACKGROUND: To investigate the value of a nomogram model based on the combination of clinical-CT features and multiphasic enhanced CT radiomics for the preoperative prediction of the microsatellite instability (MSI) status in colorectal cancer (CRC) patients. METHODS: A total of 347 patients with a pathological diagnosis of colorectal adenocarcinoma, including 276 microsatellite stabilized (MSS) patients and 71 MSI patients (243 training and 104 testing), were included. Univariate and multivariate regression analyses were used to identify the clinical-CT features of CRC patients linked with MSI status to build a clinical model. Radiomics features were extracted from arterial phase (AP), venous phase (VP), and delayed phase (DP) CT images. Different radiomics models for the single phase and multiphase (three-phase combination) were developed to determine the optimal phase. A nomogram model that combines clinical-CT features and the optimal phasic radscore was also created. RESULTS: Platelet (PLT), systemic immune inflammation index (SII), tumour location, enhancement pattern, and AP contrast ratio (ACR) were independent predictors of MSI status in CRC patients. Among the AP, VP, DP, and three-phase combination models, the three-phase combination model was selected as the best radiomics model. The best MSI prediction efficacy was demonstrated by the nomogram model built from the combination of clinical-CT features and the three-phase combination model, with AUCs of 0.894 and 0.839 in the training and testing datasets, respectively. CONCLUSION: The nomogram model based on the combination of clinical-CT features and three-phase combination radiomics features can be used as an auxiliary tool for the preoperative prediction of the MSI status in CRC patients.

Practical gram-scale synthesis of bicyclol metabolites M2 and M3.

Bicyclol, an innovative hepatoprotective drug, was approved by the Chinese National Medical Products Administration (NMPA) in 2001 to treat Hepatitis B and drug-induced liver injury. Two active metabolites of bicyclol have been identified as M2 and M3. To evaluate the impact on drug safety and efficacy of possible drug-drug interactions (DDIs) associated with these metabolites, a sufficient quantity of these metabolites is required. Herein, we report a concise novel route for the synthesis of M2 and M3 using the Suzuki-Miyaura coupling as the key step. Furthermore, we complete the gram-scale syntheses of M2 and M3.

Inclusion Complexes of Ethanamizuril with ß- and Hydroxypropyl-ß-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study.

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with ß-CD and HP-ß-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both ß-CD and HP-ß-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-ß-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

Tissue-specific patterns of regulatory changes underlying gene expression differences among Ficedula flycatchers and their naturally occurring F1 hybrids.

Changes in interacting cis- and trans-regulatory elements are important candidates for Dobzhansky-Muller hybrid incompatibilities and may contribute to hybrid dysfunction by giving rise to misexpression in hybrids. To gain insight into the molecular mechanisms and determinants of gene expression evolution in natural populations, we analyzed the transcriptome from multiple tissues of two recently diverged Ficedula flycatcher species and their naturally occurring F1 hybrids. Differential gene expression analysis revealed that the extent of differentiation between species and the set of differentially expressed genes varied across tissues. Common to all tissues, a higher proportion of Z-linked genes than autosomal genes showed differential expression, providing evidence for a fast-Z effect. We further found clear signatures of hybrid misexpression in brain, heart, kidney, and liver. However, while testis showed the highest divergence of gene expression among tissues, it showed no clear signature of misexpression in F1 hybrids, even though these hybrids were found to be sterile. It is therefore unlikely that incompatibilities between cis-trans regulatory changes explain the observed sterility. Instead, we found evidence that cis-regulatory changes play a significant role in the evolution of gene expression in testis, which illustrates the tissue-specific nature of cis-regulatory evolution bypassing constraints associated with pleiotropic effects of genes.

Modulation of resting-state functional connectivity in default mode network is associated with the long-term treatment outcome in major depressive disorder.

BACKGROUND: Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD. METHODS: Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD. RESULTS: Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up. CONCLUSION: Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.

Multimodal and Multicolor Anti-counterfeiting Realized in CaCd2Ga2Ge3O12 with a Single Activator of Mn2.

The continuously growing significance of information security and authentication has put forward many new requirements and challenges for modern luminescent materials and anti-counterfeiting technologies. Recently, luminescent materials have attracted much attention in this field owing to their legibility, repeatability, multicolor, and multiple stimuli-responsive nature. In this work, the efficient multicolor and multimodal luminescence material CaCd2Ga2Ge3O12:Mn2+ was successfully designed and synthesized using the strategy of single-doped Mn2+ in a single matrix. Also, we combined the morphology, crystal structure, energy band calculation, luminescence properties, and trap analysis to study the optical data storage capacity of CaCd2Ga2Ge3O12:Mn2+. Interestingly, in the presence of the 254 nm UV lamp, the sample can exhibit a tunable emission color from bule to cyan to yellow by increasing the dopant concentration of Mn2+. Also, under the afterglow and thermoluminescence luminescence modes, it presented strong yellow emission centered at 558 nm. Based on the advantage of multiple tunable luminescence, samples were made into anti-counterfeiting ink and were used to print four optical devices through the screen printing technology. The results show that the material has excellent multicolor anti-counterfeiting properties under the three luminescence modes, which has contributed to the development of many kinds of luminescent anti-counterfeiting materials for security purposes.

Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder.

This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6 months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.

Impact of childhood maltreatment on adult resilience.

BACKGROUND: Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience poor mental health, some traumatized people are grown to be more resilient than others. Few studies have examined the association between childhood maltreatment and adult resilience. This study aimed to determine different relationships between specific types and features of childhood maltreatment with adult resilience among Chinese with Major Depressive Disorder (MDD) and healthy controls (HCs). METHODS: A total of 101 patients with MDD and 116 participants in the healthy control (HC) group from Zhumadian Psychiatric Hospital and its nearby communities were included in this analysis. Childhood maltreatment was assessed retrospectively using Childhood Trauma Questionnaire (CTQ). Adults' resilience was assessed by the Connor-Davidson Resilience Scale (CD-RISC). Generalized linear models were applied between childhood maltreatment (specific types and features) and resilience adjusting for covariates. RESULTS: The total score of CD-RISC and factor scores of strength, optimism, and tenacity in the HC group were higher than those in the MDD group. CTQ total score had a negative association with optimism score among participants in MDD (ß=-0.087, P < 0.001) and HC (ß=-0.074, P = 0.023) groups. Higher emotional neglect (EN) score (ß=-0.169, P = 0.001) and physical neglect (PN) score (ß=-0.153, P = 0.043) were related to a worse optimism score in MDD group. Emotional abuse (EA) score was associated with a worse tenacity score (ß=-0.674, P = 0.031) in MDD group. For participants in HC group, higher EN and PN scores were related to worse resilience scores (tenacity, strength, and optimism). CONCLUSIONS: Patients with MDD showed lower optimism than HCs. Childhood maltreatment, especially childhood negect, independently contributed to optimism, with more severe childhood maltreatment predictive of worse performance of optimism. EA in childhood was also linked to worse tenacity in adult patients with MDD.

The relationship between personality traits and dysfunctional attitudes in individuals with or without major depressive disorder: a case control study.

BACKGROUND: Dysfunctional attitudes, which are characterized by distorted self-cognitions, were considered to be linked to personality traits. It was found that certain personality traits may predict dysfunctional attitudes in patients with major depressive disorder (MDD). Nonetheless, the relationship between personality traits and dysfunctional attitudes remains under-researched. AIMS: The aim of this study is to examine the relationship between specific domains of Sixteen Personality Factor (16PF) and dysfunctional attitudes in Chinese participants with or without MDD. In addition, the present study explores the associations between 16PF and eight subtypes of dysfunctional attitudes, based on the proposed eight-factor structure of the Chinese version of the Dysfunctional Attitude Scale-Form A (C-DAS-A). METHODS: One hundred and sixty-eight participants with MDD and 130 healthy participants were included in the study (Trial Registration Number: ChiCTR1800014591). Personality was assessed using the 16PF Questionnaire. Dysfunctional attitudes were measured through the C-DAS-A. RESULTS: The 16PF dimensions associated with dysfunctional attitudes and the eight subtypes were mainly concentrated in the four anxiety facets including factors C, L, O, and Q4, in both MDD and HC groups. There were significant differences in the 16 PF dimensions that would explain dysfunctional attitudes between the two groups, which were as follows: factors C, G, and O in the MDD group, and factors L and Q4 in the HC group. CONCLUSIONS: Personality traits, especially the anxiety-related personality traits, were distinctly associated with the development of dysfunctional attitudes in people with or without MDD.

Development and validation of machine learning models for nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) had become the most prevalent liver disease worldwide. Early diagnosis could effectively reduce NAFLD-related morbidity and mortality. This study aimed to combine the risk factors to develop and validate a novel model for predicting NAFLD. METHODS: We enrolled 578 participants completing abdominal ultrasound into the training set. The least absolute shrinkage and selection operator (LASSO) regression combined with random forest (RF) was conducted to screen significant predictors for NAFLD risk. Five machine learning models including logistic regression (LR), RF, extreme gradient boosting (XGBoost), gradient boosting machine (GBM), and support vector machine (SVM) were developed. To further improve model performance, we conducted hyperparameter tuning with train function in Python package 'sklearn'. We included 131 participants completing magnetic resonance imaging into the testing set for external validation. RESULTS: There were 329 participants with NAFLD and 249 without in the training set, while 96 with NAFLD and 35 without were in the testing set. Visceral adiposity index, abdominal circumference, body mass index, alanine aminotransferase (ALT), ALT/AST (aspartate aminotransferase), age, high-density lipoprotein cholesterol (HDL-C) and elevated triglyceride (TG) were important predictors for NAFLD risk. The area under curve (AUC) of LR, RF, XGBoost, GBM, SVM were 0.915 [95% confidence interval (CI): 0.886-0.937], 0.907 (95% CI: 0.856-0.938), 0.928 (95% CI: 0.873-0.944), 0.924 (95% CI: 0.875-0.939), and 0.900 (95% CI: 0.883-0.913), respectively. XGBoost model presented the best predictive performance, and its AUC was enhanced to 0.938 (95% CI: 0.870-0.950) with further parameter tuning. CONCLUSIONS: This study developed and validated five novel machine learning models for NAFLD prediction, among which XGBoost presented the best performance and was considered a reliable reference for early identification of high-risk patients with NAFLD in clinical practice.

Effects of self-care programs on the incidence of diabetes among adults with prediabetes: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To verify the effects of self-care programs among adults with prediabetes, to identify the preferable structure components and to summarise the core content components of self-care programs. DESIGN: A systematic review and meta-analysis of randomised controlled trials. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, Wanfang, CNKI, Chinese Biomedical Database and Open Grey were searched for studies published from January 2002 to December, 2021. Meta-analysis was conducted to verify the effects of self-care programs on diabetes incidence. Subgroup analyses based on structure components were performed to contrast the effects. We made a critical analysis to generalise the core elements of content components. The study was reported according to PRISMA statement. RESULTS: Totally, 15 studies were included in systematic review, of which 14 studies were eligible for meta-analysis. The results of meta-analysis showed the incidence of diabetes for prediabetic adults receiving self-care programs was significantly lower than those who received usual care (OR 0.58; 95% CI 0.46 to 0.73). The results of subgroup analyses based on delivery mode, intervention implementer, health education brochures provided, and follow-up duration showed statistically significant reduction in incidence compared with control group (p < .05). However, the differences of these pair-wise comparisons (face-to-face or remote, individual or interdisciplinary team, with or without brochures provided, ≤1 year or >1 year) were not statistically significant (p > .05). Three core content elements were generalised: cognitive education, behaviour guidance and psychological support. CONCLUSIONS: Self-care programs can effectively delay the progression of prediabetes to diabetes. Regardless of the diversified structure components, self-care programs can achieve better effects on the diabetes incidence than usual care, while the optimal structure components still remain unknown. Cognitive education, behaviour guidance and psychological support are core elements for these programs. RELEVANCE TO CLINICAL PRACTICE: More clinical trials with rigorous study design are needed to provide further evidence.