SWI and CTP fusion model based on sparse representation method to predict cerebral infarction trend.

Objective: SWI image signal is related to venous reflux disorder and perfusion defect. Computed tomography perfusion (CTP) contains perfusion information in space and time. There is a complementary basis between them to affect the prognosis of cerebral infarction. Methods: Sixty-six patients included in the retrospective study were designated as the training set. Effective perfusion indicator features and imaging radiomic features of the peri-infarction area on Susceptibility weighted imaging (SWI) and CTP modality images were extracted from each case. Thirty-three patients from the prospectively included group were designated as the test set of the machine learning model based on a sparse representation method. The predicted results were compared with the DWI results of the patients' 7-10 days review to assess the validity and accuracy of the prediction. Results: The AUC of the SWI + CTP integrated model was 0.952, the ACC was 0.909, the SEN was 0.889, and the SPE was 0.933. The prediction performance is the highest. Compared with the value of AUC: the SWI model is 0.874, inferior to the performance of the SWI + CTP model, and the CTP model is 0.715. Conclusion: The prediction efficiency of the changing trend of infarction volume is further improved by the correlation between the combination of the two image features.

Spatial landscape of malignant pleural and peritoneal mesothelioma tumor immune microenvironment.

Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence (mIF) analyses on tissue microarrays (n=3) from malignant peritoneal (MPeM, n=25) and pleural (MPM, n=88) mesothelioma patients. Our study aimed to elucidate spatial distributions of key immune cell populations and their association with LAG3, BAP1, NF2, and MTAP, with MTAP serving as a CDKN2A/B surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types with MM patient prognosis and clinical characteristics. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared to MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared to those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma (https://mesotheliomaspatialatlas.streamlit.app/), containing mIF and hematoxylin and eosin (H&E) images.

DHA dietary intervention caused different hippocampal lipid and protein profile in ApoE-/- and C57BL/6J mice.

BACKGROUND: Changes in protein and lipid levels may occur in the Alzheimer's disease brain, and DHA can have beneficial effects on it. To investigate the impact of DHA dietary intervention on brain protein and lipid profile in ApoE-/- mice and C57 mice. METHOD: Three-month-old ApoE-/- mice and C57 mice were randomly divided into two groups respectively, and fed with control diet and DHA-fortified diet for five months. Cortical TC, HDL-C and LDL-C levels and cholesterol metabolism-related protein expression were measured by ELISA or immunohistochemistry methods. Hippocampus were collected for proteomic and lipidomics analysis by LC-MS/MS and differential proteins and lipid metabolites were screened and further analyzed by GO functional annotation and KEGG pathway enrichment analysis. RESULTS: DHA intervention decreased cortical TC level in both C57 and ApoE-/- mice (P < 0.05), but caused different change of cortical HDL-C, LDL-C level and LDL-C/HDL-C ratio in C57 and ApoE-/- mice (P < 0.05). Discrepant cortical and hippocampal LDLR, ABCG1, Lox1 and SORT1 protein expression was found between C57 and ApoE-/- mice (P < 0.05), and DHA treatment caused different changes of these proteins in C57 and ApoE-/- mice (P < 0.05). Differential hippocampal proteins and lipids profile were found in C57 and ApoE-/- mice before and after DHA treatment, which were mainly involved in vesicular transport and phospholipid metabolic pathways. CONCLUSION: ApoE genetic defect caused abnormal cholesterol metabolism, and affected protein and lipid profile, as well as discrepant response of hippocampal protein and lipids profile in the brain of mice given DHA fortified diet intervention.

Metabolic and Microbial Dysregulation in Preterm Infants with Neonatal Respiratory Distress Syndrome: An Early Developmental Perspective.

Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.

Suboptimal diet quality is associated with the incidence of type 2 diabetes mellitus in middle-aged and older populations in China: evidence from a population-based cross-sectional study.

The association between dietary quality and type 2 diabetes mellitus (T2DM) based on the Chinese Dietary Balance Index (DBI-16) is seldom reported. We hypothesized that poor dietary quality might increase the risk of T2DM in the middle-aged and older populations. A total of 1816 individuals (≥50 years) were included in the study. Demographic characteristics and dietary intake data were collected. Logistic regression and restricted cubic spline (RCS) analyses were conducted to explore the association between DBI-16 indexes and the risk of T2DM. The insufficient intake of vegetables and dairy might decrease the risk of T2DM (ORVegetable = 0.77, 95% CI = 0.60-0.97; ORDairy = 0.58, 95% CI = 0.35-0.96), but the individuals with insufficient intake of fruit were more likely to have a higher risk of T2DM (ORfruit = 2.26, 95% CI = 1.69-3.06). Compared with the subjects with the lowest quartile of Low Bound Score (LBS) or Diet Quality Distance (DQD), the individuals with Q2 and Q3 level of LBS (ORQ2 = 1.40, 95% CI = 1.03-1.90, P = .033; ORQ3 = 1.52, 95% CI = 1.11-2.08, P < .01) or DQD (ORQ2 = 1.45, 95% CI = 1.06-1.99, P = .021; ORQ3 = 1.64, 95% CI = 1.20-2.24, P < .01) showed increased risk of T2DM with a nonlinear association observed by RCS analysis. We concluded that imbalanced dietary intake, especially insufficient daily fruit intake, might predict an increased risk of T2DM in the middle-aged and elderly Chinese.

STaRNet: A spatio-temporal and Riemannian network for high-performance motor imagery decoding.

Brain-computer interfaces (BCIs), representing a transformative form of human-computer interaction, empower users to interact directly with external environments through brain signals. In response to the demands for high accuracy, robustness, and end-to-end capabilities within BCIs based on motor imagery (MI), this paper introduces STaRNet, a novel model that integrates multi-scale spatio-temporal convolutional neural networks (CNNs) with Riemannian geometry. Initially, STaRNet integrates a multi-scale spatio-temporal feature extraction module that captures both global and local features, facilitating the construction of Riemannian manifolds from these comprehensive spatio-temporal features. Subsequently, a matrix logarithm operation transforms the manifold-based features into the tangent space, followed by a dense layer for classification. Without preprocessing, STaRNet surpasses state-of-the-art (SOTA) models by achieving an average decoding accuracy of 83.29% and a kappa value of 0.777 on the BCI Competition IV 2a dataset, and 95.45% accuracy with a kappa value of 0.939 on the High Gamma Dataset. Additionally, a comparative analysis between STaRNet and several SOTA models, focusing on the most challenging subjects from both datasets, highlights exceptional robustness of STaRNet. Finally, the visualizations of learned frequency bands demonstrate that temporal convolutions have learned MI-related frequency bands, and the t-SNE analyses of features across multiple layers of STaRNet exhibit strong feature extraction capabilities. We believe that the accurate, robust, and end-to-end capabilities of the STaRNet will facilitate the advancement of BCIs.

Effect of blood flow-restrictive resistance training on metabolic disorder and body composition in older adults with type 2 diabetes: a randomized controlled study.

Introduction: To explore whether blood flow-restrictive resistance exercise (BFRE) can be used as an alternative strategy to moderate-intensity resistance training (RT) to improve metabolic disorder and body composition in older adults with type 2 diabetes (T2DM). Methods: This is a single-blind, randomized, controlled trial. Ninety-eight older adults with T2DM were randomly divided into three groups: BFRE group (n = 34), RT group (n = 31) and control group (n = 33). Two exercise groups received supervised collective training for a period of six months, each lasting 50 min, three times a week. The primary outcomes included fasting plasma glucose (FPG), Glycosylated hemoglobin (HbA1c), blood lipids, blood pressure, and body composition. The secondary outcome was muscle performance. Results: After six months of intervention, the FPG, HbA1c, blood lipids, diastolic blood pressure, body composition, and muscle performance of the two exercise groups were significantly improved relative to the control group and baseline measurements (P < 0.05). There was no significant increase in lean mass between the two exercise groups compared to the control group and baseline (p > 0.05). There was no significant decrease in systolic blood pressure between the two exercise groups compared to the control group (p > 0.05), but it was significantly lower than their baseline (P < 0.05). There was no significant difference in all indicators between the two exercise groups at the baseline, third and sixth months of intervention (p > 0.05). Discussion: BFRE can safely and effectively improve the metabolic disorder and body composition of older adults with T2DM. For elderly exercise beginners, BFRE can be used as an alternative strategy to moderate-intensity resistance training. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357.

Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19.

BACKGROUND: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events. RESULTS: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported. CONCLUSIONS: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).

Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS-STING Pathway.

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.

Dynamics of green macroalgal micro-propagules and the influencing factors in the southern Yellow Sea, China.

Micro-propagules (banks of microscopic forms) play important roles in the expansion of green tides, which are spreading on eutrophic coasts worldwide. In particular, large-scale green tides (Yellow Sea Green Tide, YSGTs) have persisted in the Yellow Sea for over 15 years, but the dynamics and functions of micro-propagules in their development remain unclear. In the present study, year-round field surveys were conducted to identify the reservoirs and investigate the persistence mechanisms and associated biotic and abiotic factors driving the temporal and spatial variations of micro-propagules. Micro-propagules in the southern Yellow Sea (SYS) showed evident spatial heterogeneity in terms of seasonal patterns and major influencing factors. Offshore of the SYS, the micro-propagule population underwent ephemeral expansion along with a large-scale bloom of floating Ulva algae in late spring and early summer. The Subei Shoal, particularly the sediments in the central raft region, had the highest micro-propagule abundance (MA) and was a major reservoir. The pronounced seasonal variation of MA in the Subei Shoal was primarily associated with the attached Ulva algae on Neopyropia aquaculture rafts. Vast aquaculture rafts provided essential substrates for micro-propagules to complete their life cycle and replenish the seed bank, thereby sustaining persistent YSGTs. It implied that habitat modification has pronounced ecological impacts on this intertidal muddy flat. The unique environmental conditions (enriched nutrients, esp. nitrate, favourable seawater temperatures in spring, and strong tidal mixing) facilitated the abundance, seasonal variation and recruitment of micro-propagules in the Subei Shoal. Given the current mitigation measures implemented in the raft region, further research is required to monitor and investigate the physiological and ecological responses of micro-propagule populations to the complex hydrobiological, geochemical, and physical matrices.

Losses of low-germinating, slow-growing species prevent grassland composition recovery from nutrient amendment.

Nutrient enrichment often alters the biomass and species composition of plant communities, but the extent to which these changes are reversible after the cessation of nutrient addition is not well-understood. Our 22-year experiment (15 years for nutrient addition and 7 years for recovery), conducted in an alpine meadow, showed that soil nitrogen concentration and pH recovered rapidly after cessation of nutrient addition. However, this was not accompanied by a full recovery of plant community composition. An incomplete recovery in plant diversity and a directional shift in species composition from grass dominance to forb dominance were observed 7 years after the nutrient addition ended. Strikingy, the historically dominant sedges with low germination rate and slow growth rate and nitrogen-fixing legumes with low germination rate were unable to re-establish after nutrient addition ceased. By contrast, rapid recovery of aboveground biomass was observed after nutrient cessation as the increase in forb biomass only partially compensated for the decline in grass biomass. These results indicate that anthropogenic nutrient input can have long-lasting effects on the structure, but not the soil chemistry and plant biomass, of grassland communities, and that the recovery of soil chemical properties and plant biomass does not necessarily guarantee the restoration of plant community structure. These findings have important implications for the management and recovery of grassland communities, many of which are experiencing alterations in resource input.

CBX7C⋠PHC2 interaction facilitates PRC1 assembly and modulates its phase separation properties.

CBX7 is a key component of PRC1 complex. Cbx7C is an uncharacterized Cbx7 splicing isoform specifically expressed in mouse embryonic stem cells (mESCs). We demonstrate that CBX7C functions as an epigenetic repressor at the classic PRC1 targets in mESCs, and its preferential interaction to PHC2 facilitates PRC1 assembly. Both Cbx7C and Phc2 are significantly upregulated during cell differentiation, and knockdown of Cbx7C abolishes the differentiation of mESCs to embryoid bodies. Interestingly, CBX7C⋅PHC2 interaction at low levels efficiently undergoes the formation of functional Polycomb bodies with high mobility, whereas the coordination of the two factors at high doses results in the formation of large, low-mobility, chromatin-free aggregates. Overall, these findings uncover the unique roles and molecular basis of the CBX7C⋅PHC2 interaction in PRC1 assembly on chromatin and Pc body formation and open a new avenue of controlling PRC1 activities via modulation of its phase separation properties.

Modulating PCGF4/BMI1 Stability Is an Efficient Metastasis-Regulatory Strategy Used by Distinct Subtypes of Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm prone to metastasis. Whether cancer-associated fibroblasts (CAFs) affect the metastasis of ICC is unclear. Herein, ICC patient-derived CAF lines and related cancerous cell lines were established and the effects of CAFs on the tumor progressive properties of the ICC cancerous cells were analyzed. CAFs could be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-sequencing analyses of ICC cancerous cell lines identified polycomb group ring finger 4 (PCGF4; alias BMI1) as a potential metastasis regulator. The changes of PCGF4 levels in ICC cells mirrored the restraining or promoting effects of CAFs on ICC migration. Immunohistochemical analyses on the ICC tissue microarrays indicated that PCGF4 was negatively correlated with overall survival of ICC. The promoting effects of PCGF4 on cell migration, drug resistance activity, and stemness properties were confirmed. Mechanistically, cancer-restraining CAFs triggered the proteasome-dependent degradation of PCGF4, whereas cancer-promoting CAFs enhanced the stability of PCGF4 via activating the IL-6/phosphorylated STAT3 pathway. In summary, the current data identified the role of CAFs in ICC metastasis and revealed a new mechanism of the CAFs on ICC progression in which PCGF4 acted as the key effector by both categories of CAFs. These findings shed light on developing comprehensive therapeutic strategies for ICC.

Mendelian randomization suggests a causal relationship between gut microbiota and nonalcoholic fatty liver disease in humans.

Targeting the gut microbiota is an emerging strategy to treat nonalcoholic fatty liver disease (NAFLD). Nonetheless, the causal relationship between specific gut microbiota and NAFLD remains unclear. We first obtained genome-wide association study statistics on gut microbiota and NAFLD from publicly available databases. We then performed the Mendelian randomization (MR) analysis to determine the potential causal relationship between the gut microbiota and NAFLD by 5 different methods, and conducted a series of sensitivity analyses to validate the robustness of the MR analysis results. Furthermore, we investigated the direction of causality by bidirectional MR analysis. For 211 gut microbiota, 2 MR methods confirmed that phylum Tenericutes, class Deltaproteobacteria and class Mollicutes were significantly associated with the risk of NAFLD. Heterogeneity (P > .05) and pleiotropy (P > .05) analyses validated the robustness of the MR results. There was no causal effect of NAFLD on these bacterial taxa in the reverse MR analysis. We identified specific gut microbiota with causal effects on NAFLD through gene prediction, which may provide useful guidance for targeting the gut microbiota to intervene and treat NAFLD.

Flexible Composite Electrolyte Membranes with Fast Ion Transport Channels for Solid-State Lithium Batteries.

Numerous endeavors have been dedicated to the development of composite polymer electrolyte (CPE) membranes for all-solid-state batteries (SSBs). However, insufficient ionic conductivity and mechanical properties still pose great challenges in practical applications. In this study, a flexible composite electrolyte membrane (FCPE) with fast ion transport channels was prepared using a phase conversion process combined with in situ polymerization. The polyvinylidene fluoride-hexafluoro propylene (PVDF-HFP) polymer matrix incorporated with lithium lanthanum zirconate (LLZTO) formed a 3D net-like structure, and the in situ polymerized polyvinyl ethylene carbonate (PVEC) enhanced the interface connection. This 3D network, with multiple rapid pathways for Li+ that effectively control Li+ flux, led to uniform lithium deposition. Moreover, the symmetrical lithium cells that used FCPE exhibited high stability after 1200 h of cycling at 0.1 mA cm-2. Specifically, all-solid-state lithium batteries coupled with LiFePO4 cathodes can stably cycle for over 100 cycles at room temperature with high Coulombic efficiencies. Furthermore, after 100 cycles, the infrared spectrum shows that the structure of FCPE remains stable. This work demonstrates a novel insight for designing a flexible composite electrolyte for highly safe SSBs.

Impact of obesity on outcomes of rotator cuff repair: A systematic review and meta-analysis.

BACKGROUND: To synthesize the existing evidence on the association between obesity and rotator cuff repair outcomes such as pain, shoulder function, range of motion, and complications. METHODS: We searched PubMed, EMBASE, and Scopus databases for relevant observational studies (cohort and case-control) and randomized controlled trials (RCTs). The target population in the included studies comprised adults who had undergone rotator cuff repair procedures. The outcomes of interest were functional outcomes (such as range of motion), pain scores, patient-reported outcome measures, and complication rates (such as re-repair and readmission rates). We applied random-effects models and calculated pooled effect sizes reported as standardized mean differences (SMDs) or relative risks (RRs) with 95% confidence intervals. RESULTS: We analysed data from 11 studies. In most, the follow-up periods ranged from 12 to 60 months. Obese individuals experienced greater pain (SMD 0.30; 95% CI, 0.10, 0.50) and lower shoulder function (SMD -0.33; 95% CI, -0.54, -0.12) than other individuals in the long-term post-operative follow-up. Obese individuals also had higher risks of complications (RR 1.48; 95% CI, 1.11, 1.98) and readmission (RR 1.35; 95% CI, 1.27, 1.43), but a similar likelihood of re-repair (RR, 1.27; 95% CI, 0.82, 1.95) than non-obese/normal BMI individuals. While the forward flexion and external rotation functions were comparable, obese individuals displayed less internal rotation function than other individuals (SMD -0.59; 95% CI, -0.87, -0.30). CONCLUSION: Obesity was associated with unfavourable outcomes after rotator cuff surgery, including increased pain, reduced shoulder function, high risks of complications, and readmission. These findings emphasize the importance of addressing obesity-related factors to improve post-operative outcomes.

Enhanced Survival with Lymphadenectomy in Early-Stage Metachronous Second Primary Lung Cancer: A Retrospective Analysis.

INTRODUCTION: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer (MSPLC) remains poorly understood. This retrospective study aimed to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. METHODS: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score-matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score-matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% in the non-lymphadenectomy group (HR: 0.76; 95% confidence interval 0.64-0.90; p = 0.002). CONCLUSION: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggest the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, emerging as a significant health issue on a global scale. Berberine exhibits potential for treating NAFLD, but clinical evidence remains inconclusive. This meta-analysis was conducted to assess the efficacy and safety of berberine for treating NAFLD. METHODS: This study was registered with PROSPERO (No. CRD42023462338). Identification of randomized controlled trials (RCTs) involved searching 6 databases covering the period from their initiation to 9 September 2023. The primary outcomes comprised liver function markers such as glutamyl transpeptidase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), lipid indices including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI). Review Manager 5.4 and STATA 17.0 were applied for analysis. RESULTS: Among 10 RCTs involving 811 patients, berberine demonstrated significant reductions in various parameters: ALT (standardized mean difference (SMD) = - 0.72), 95% confidence interval (Cl) [- 1.01, - 0.44], P < 0.00001), AST (SMD = - 0.79, 95% CI [- 1.17, - 0.40], P < 0.0001), GGT (SMD = - 0.62, 95% CI [- 0.95, - 0.29], P = 0.0002), TG (SMD = - 0.59, 95% CI [- 0.86, - 0.31], P < 0.0001), TC(SMD = - 0.74, 95% CI [- 1.00, - 0.49], P < 0.00001), LDL-C (SMD = - 0.53, 95% CI [- 0.88, - 0.18], P = 0.003), HDL-C (SMD = - 0.51, 95% CI [- 0.12, 1.15], P = 0.11), HOMA-IR (SMD = - 1.56, 95% CI [- 2.54, - 0.58], P = 0.002), and BMI (SMD = - 0.58, 95% CI [- 0.77, - 0.38], P < 0.00001). Importantly, Berberine exhibited a favorable safety profile, with only mild gastrointestinal adverse events reported. CONCLUSION: This meta-analysis demonstrates berberine's efficacy in improving liver enzymes, lipid profile, and insulin sensitivity in NAFLD patients. These results indicate that berberine shows promise as an adjunct therapy for NAFLD. Trial registration The protocol was registered with PROSPERO (No. CRD42023462338). Registered on September 27, 2023.

Cross-Platform Comparison of Highly Sensitive Immunoassays for Inflammatory Markers in a COVID-19 Cohort.

A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing Ab pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on human serum samples from the National Institutes of Health IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. First, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Second, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Third, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.