CDK5-USP30 signaling pathway regulates MAVS-mediated inflammation via suppressing mitophagy in MPTP/MPP+ PD model.

The discovery of MPTP, an industrial chemical and contaminant of illicit narcotics, which causes parkinsonism in humans, non-human primates and rodents, has led to environmental pollutants exposure being convicted as key candidate in Parkinson's disease (PD) pathogenesis. Though MPTP-induced mitochondrial dysfunction and neuroinflammation are mainly responsible for the causative issue of MPTP neurotoxicity, the underlying mechanism involved remains unclear. Here, we reveal a novel signaling mechanism of CDK5-USP30-MAVS regulating MPTP/MPP+ induced PD. MPP+ (the toxic metabolite of MPTP) treatment not only led to the increased protein levels of USP30 but also to mitophagy inhibition, mitochondrial dysfunction, and MAVS-mediated inflammation in BV2 microglial cells. Both mitophagy stimulation (Urolithin A administration) and USP30 knockdown relieved MAVS-mediated inflammation via restoring mitophagy and mitochondrial function in MPP+-induced cell model. Notably, MPTP/MPP+-induced CDK5 activation regulated USP30 phosphorylation at serine 216 to stabilize USP30. Moreover, CDK5-USP30 pathway promoted MAVS-mediated inflammation in MPTP/MPP+-induced PD model. Inhibition of CDK5 not only had a protective effect on MPP+-induced cell model of PD via suppressing the upregulation of USP30 and the activation of MAVS inflammation pathway in vitro, but also prevented neurodegeneration in vivo and alleviated movement impairment in MPTP mouse model of PD. Overall, our study reveal that CDK5 blocks mitophagy through phosphorylating USP30 and activates MAVS inflammation pathway in MPTP/MPP+-induced PD model, which suggests that CDK5-USP30-MAVS signaling pathway represents a valuable treatment strategy for PD induced by environmental neurotoxic pollutants in relation to MPTP.

Chinese Healthcare Workers' Knowledge, Attitudes, and Practices in Diabetic Kidney Management: A Multi-Centered Cross-Sectional Study.

Background: Given the importance of diabetic kidney disease (DKD) management, this study aims to explore the knowledge, attitudes, and practices in disease management demonstrated by healthcare workers from the nephrology department. Materials and Methods: This study is a multi-centered cross-sectional study, and adopts snowball sampling, with 530 healthcare workers being recruited to complete a questionnaire covering areas such as demographic characteristics, knowledge, attitude, and practices (KAP) of DKD management. This data was analyzed using descriptive statistics and binary logistics analysis. Results: In this study, 530 healthcare workers were studied, including 94 doctors and 436 nurses. The participants were mainly from general tertiary hospitals in 14 provinces. For Chinese nurse, the results indicate that both poor knowledge level (Odds Ratio (OR) =0.63, 95% Confidence Interval (CI): 0.42-0.94) and having experience in further medical training in nephrology (OR=1.92, 95% CI: 1.20-3.08) are associated with the practice levels. For Chinese doctors, having not experience in further medical training in nephrology (OR=0.36, 95% CI: 0.15-0.83) are associated with their practice levels. Conclusion: In summary, Chinese doctors and nurses in this study showed positive attitudes towards DKD management, but their knowledge and practical skills were lacking. This underscores a notable gap in achieving optimal DKD care. Notably, nurses' knowledge influenced their management practices, and additional nephrology training correlated with better engagement. To improve patient care, enhancing nephrology healthcare professional training and addressing knowledge-practice disparities are recommended.

Long Propagating Polaritonic Heat Transfer: Shaping Radiation to Conduction.

Surface phonon polaritons (SPhPs) originate from the coupling of mid-IR photons and optical phonons, generating evanescent waves along the polar dielectric surface. The emergence of SPhPs gives rise to a phase of quantum matter that facilitates long-range energy transfer (100s µm-scale). Albeit of the recent experimental progress to observe the enhanced thermal conductivity of polar dielectric nanostructures mediated by SPhPs, the potential mechanism to present the high thermal conductivity beyond the Landauer limit has not been addressed. Here, we revisit the comprehensive theoretical framework to unify the distinct pictures of two heat transfer mechanisms by conduction and radiation. We first designed our experimental platform to distinguish contributions of two distinct fundamental modes of SPhPs, resulting in far-field radiation and long propagating conduction, respectively, by tuning the configuration of a nanostructured heat channel integrated into the thermometer. We could effectively control the transmission of long-propagating SPhPs to influence the apparent thermal conductivity of the nanostructure. This study reveals the high thermal conductance of 1.63 nW/K by a fast SPhP mode comparable to that by classical phonons, with measurements showing apparent conductivity values of up to 2 W/m·K at 515 K. The origin of the enhanced thermal conductivity was exploited by observing the interference of dispersive evanescent waves by double heat channels. Furthermore, our experimental observations of length-dependent thermal conductance by SPhPs are in good agreement with the revisited Landauer formula to illustrate a polaritonic mode of heat conduction, considering the dispersive nature of radiation not limited to the physical boundaries of a solid object yet directionally guided along the surface.

Restricted responses of AcMYB68 and AcERF74/75 enhanced waterlogging tolerance in kiwifruit.

Most of kiwifruit cultivars (e.g. Actinidia chinensis cv. Donghong, "DH") were sensitive to waterlogging, thus, waterlogging resistant rootstocks (e.g. Actinidia valvata Dunn, "Dunn") were widely used for kiwifruit industry. Those different species provided ideal materials to understand the waterlogging responses in kiwifruit. Compared to the weaken growth and root activities in "DH", "Dunn" maintained the relative high root activities under the prolonged waterlogging. Based on comparative analysis, transcript levels of pyruvate decarboxylase (PDCs) and alcohol dehydrogenase (ADHs) showed significantly difference between these two species. Both PDCs and ADHs had been significantly increased by waterlogging in "DH", while they were only limitedly triggered by 2 days stress and subsided during the prolonged waterlogging in "Dunn". Thus, 19 differentially expressed transcript factors (DETFs) had been isolated using weighted gene co-expression network analysis combined with transcriptomics and transcript levels of PDCs and ADHs in waterlogged "DH". Among these DETFs, dual luciferase and electrophoretic mobility shift assays indicated AcMYB68 could bind to and trigger the activity of AcPDC2 promoter. The stable over-expression of AcMYB68 significantly up-regulated the transcript levels of PDCs but inhibited the plant growth, especially the roots. Moreover, the enzyme activities of PDC in 35S::AcMYB68 were significantly enhanced during the waterlogging response than that in wild type plants. Most interestingly, comparative analysis indicated that the expression patterns of AcMYB68 and the previously characterized AcERF74/75 (the direct regulator on ADHs) either showed no responses (AcMYB68 and AcERF74) or very limited response (AcERF75) in "Dunn". Taken together, the restricted responses of AcMYB68 and AcERF74/75 in "Dunn" endow its waterlogging tolerance.

The Role of Left Ventricular Pressure-strain Loop in Evaluating Myocardial Work in Patients with Type 2 Diabetes.

Objective: To quantitatively analyze the myocardial work of patients with type 2 diabetes (T2D) by use of the pressure-strain loop and to investigate the clinical factors that affect myocardial work in the left ventricle. Methods: We analyzed data from 50 control patients and 180 case patients, with 70 cases in group A (T2D only), 40 cases in group B (T2D + high blood pressure), 33 cases in group C (T2D + coronary heart disease), and 37 cases in group D (T2D + high blood pressure + coronary heart disease). Each patient received conventional ultrasonography and 2-dimensional speckle-tracking echocardiography, and the pressure-strain loop technique was applied to measure the left ventricular myocardial work parameters to compare the control and case groups. Results: Systolic blood pressure was dramatically higher in groups B and D than in the control group and in groups A and C. N-terminal pro-brain natriuretic peptide was markedly higher in group D than in the control group, and the disease duration was markedly higher in groups C and D than in group A. The left ventricular global longitudinal strain of the epicardium (LVGLSepi) was substantially lower in groups B, C, and D than in the control group. The LVGLSepi of groups C and D was significantly lower than group A, and the LVGLSepi of group D was significantly lower than group B. The LVGLS, LVGLS of the endocardium, global work index, and global constructive work progressively reduced among the control and case groups. LVGLS strongly correlated with global work index (r = -0.886; P < .001) and global constructive work (r = -0.880; P < .001). Body mass index, duration of diabetes, and glycated hemoglobin A1c independently associated with global work index (Body mass index: P = .04; duration of diabetes: P < .001; glycated hemoglobin A1c: P = .02) . In addition to the above three indicators, systolic blood pressure independently associated with global constructive work (systolic blood pressure: P = .04). Conclusion: Pressure-strain loop technology can quantitatively, accurately, and sensitively monitor the variations in left ventricular myocardial contractile function of patients with T2D and detect subclinical cardiac injury at an early disease stage.

CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1).

Δ9-tetrahydrocannabinol (THC) is the psychoactive constituent of cannabis. It is cleared predominantly via metabolism. Metabolism to 11-OH-THC by cytochrome P450 (CYP) 2C9 has been proposed as the main clearance pathway of THC, with the estimated fraction metabolized (fm) about 70%. The remaining clearance pathways are not well established, and it is unknown how THC is eliminated in individuals with reduced CYP2C9 activity. The goal of this study was to systematically identify the CYP enzymes contributing to THC clearance and characterize the metabolites formed. Further, this study aimed to characterize the impact of liver fatty acid binding protein (FABP1) on THC metabolism by human CYPs. THC was metabolized to at least four different metabolites including 11-OH-THC in human liver microsomes (HLMs) and with recombinant CYPs. 11-OH-THC was formed by recombinant CYP2C9 (Km,u = 0.77 nM, kcat = 12 min-1) and by recombinant CYP2C19 (Km,u = 2.2 nM, kcat = 14 min-1). The other three major metabolites were likely hydroxylations in the cyclohexenyl ring and were formed mainly by recombinant CYP3A4/5 (Km,u > 10 nM). HLM experiments confirmed the contributions of CYP2C9, CYP2C19 and CYP3A to THC metabolism. The presence of FABP1 and THC binding to FABP1 altered THC metabolism by recombinant CYPs and HLMs in an enzyme and metabolite specific manner. This suggests that FABP1 may interact with CYP enzymes and alter the fm by CYPs towards THC metabolism. In conclusion, this study is the first to systematically establish the metabolic profile of THC by human CYPs and characterize how FABP1 binding alters CYP mediated THC metabolism.

Factors Impacting One-year Follow-up Visit Adherence after Bariatric Surgery in West China: A Mixed Methods Study.

PURPOSE: Quality follow-up (FU) is crucial after bariatric surgery. However, poor adherence after surgery is prevalent. This research aimed to explore the factors related to FU adherence after bariatric surgery in West China. MATERIALS AND METHODS: This study used a sequential explanatory mixed-methods research design. Participants (n = 177) were identified from the West China Hospital. Demographic information, disease profile, treatment information, and post-surgery FU information were obtained from the bariatric surgery database of the Division of Gastrointestinal Surgery of the West China Hospital. The survey data were analyzed using logistic regression. Semi-structured interviews with participants (n = 10) who had low adherence were conducted. The recording was transcribed verbatim and entered into qualitative data analysis software. Qualitative data were analyzed using a content analysis approach. RESULTS: Multiple logistic regression revealed that living in Chengdu (OR, 2.308), being employed (OR, 2.532), non-smoking (OR, 2.805), and having less than five years of obesity (OR, 2.480) were positive predictors of FU adherence within one year. Semi-structured interviews suggested that factors related to adherence to FU were lack of motivation, lack of opportunity, insufficient ability, and beliefs regarding consequences. CONCLUSION: Factors impacting one-year FU visit adherence after bariatric surgery include not only demographic and disease-related factors but also social and family factors. These results will provide evidence to support healthcare professionals in developing personalized postoperative FU management strategies.

Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

Revealing the structural changes of lignin in Chinese quince (Chaenomeles sinensis) fruit as it matures.

Chinese quince fruits (Chaenomeles sinensis) contain substantial amounts of lignin; however, the exact structure of lignin remains to be investigated. In this study, milled wood lignins (Milled wood lignin (MWL)-1, MWL-2, MWL-3, MWL-4, MWL-5, and MWL-6) were extracted from fruits harvested once a month from May to October 2019 to investigate their structural evolution during fruit growth. The samples were characterized via High-performance anion exchange chromatography (HPAEC), Fourier transform-infrared spectroscopy (FT-IR), gel permeation chromatography (GPC), thermogravimetric (TGA), pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and NMR (2D-heteronuclear single quantum coherence (HSQC) and 31P). The MWL samples in all fruit growth stages were GS-type lignin and lignin core undergoing minimal alterations during fruit development. The predominant linkage in the lignin structure was ß-O-4', followed by ß-ß' and ß-5'. Galactose and glucose were the main monosaccharides associated with MWL. In MWL-6, the lignin exhibited the highest homogeneity and thermal stability. As the fruit matured, a gradual increase in the ß-O-4' proportion and the ratio of S/G was observed. The results provide comprehensive characterization of the cell wall lignin of quince fruit as it matures. This study could inspire innovative applications of quince fruit lignin and provide the optimal harvest time for lignin utilization.

Comparative efficacy of Chinese herbal injections in patients with cardiogenic shock (CS): a systematic review and Bayesian network meta-analysis of randomized controlled trials.

Background: Cardiogenic shock (CS) is the primary cause of death in patients suffering acute myocardial infarction. As an emerging and efficacious therapeutic approach, Chinese herbal injections (CHIs) are gaining significant popularity in China. However, the optimal CHIs for treating CS remain uncertain. Method: We searched eight databases from inception to 30 September 2023. Subsequently, we conducted the Bayesian network meta-analysis (NMA). Interventions were ranked based on the surface under the cumulative ranking curve (SUCRA) probability values. To compare the effects of CHIs on two distinct outcomes, a clustering analysis was performed. Furthermore, the quality of the studies was assessed. Results: For the study, we included 43 RCTs, encompassing 2,707 participants. The study evaluated six herbal injections, namely, Shenfu injection (SF), Shengmai injection (SM), Shenmai injection (Sm), Danshen injection (DS), Huangqi injection (HQ), and Xinmailong injection (XML). The analysis findings suggested that Sm (MD = -1.05, 95% CI: -2.10, -0.09) and SF (MD = -0.81, 95% CI: -1.40, -0.25) showed better efficacy compared to Western medicine (WM) alone in reducing in-hospital mortality. The SUCRA values revealed that Sm + WM ranked first in terms of in-hospital mortality, cardiac index (CI), and hourly urine output but second in improving left ventricular ejection fraction (LVEF) and mean arterial pressure (MAP). SF + WM, however, had the greatest impact on raising the clinical effective rate. In MAP, SM + WM came out on top. Moreover, in terms of safety, only 14 studies (31.8%), including five types of CHIs: SF, Sm, SM, HQ, and XML, observed adverse drug reactions. Conclusion: To summarize, this analysis discovered that, in terms of patients suffering from CS, CHIs + WM yielded significantly greater advantages than WM alone. Based on in-hospital mortality and the remaining outcomes, Sm performed excellently among all the involved CHIs. Systematic Review Registration: https:// www.Crd.york.ac.uk/prospero/, identifier: CRD42022347053.

KFDAE: CircRNA-Disease Associations Prediction Based on Kernel Fusion and Deep Auto-Encoder.

CircRNA has been proved to play an important role in the diseases diagnosis and treatment. Considering that the wet-lab is time-consuming and expensive, computational methods are viable alternative in these years. However, the number of circRNA-disease associations (CDAs) that can be verified is relatively few, and some methods do not take full advantage of dependencies between attributes. To solve these problems, this paper proposes a novel method based on Kernel Fusion and Deep Auto-encoder (KFDAE) to predict the potential associations between circRNAs and diseases. Firstly, KFDAE uses a non-linear method to fuse the circRNA similarity kernels and disease similarity kernels. Then the vectors are connected to make the positive and negative sample sets, and these data are send to deep auto-encoder to reduce dimension and extract features. Finally, three-layer deep feedforward neural network is used to learn features and gain the prediction score. The experimental results show that compared with existing methods, KFDAE achieves the best performance. In addition, the results of case studies prove the effectiveness and practical significance of KFDAE, which means KFDAE is able to capture more comprehensive information and generate credible candidate for subsequent wet-lab.

Efficacy and safety of a panthenol-enriched mask for individuals with distinct impaired skin barrier subtypes.

BACKGROUND: The protection for different skin types with impaired skin barrier in the market is insufficient. AIM: To evaluate the efficacy and safety of a panthenol-enriched mask (La Roche-Posay Mask Pro) in addressing various skin barrier impairment subgroups, including dry sensitive, oily sensitive, and oily acne skin. METHODS: A total of 177 participants were enrolled in the study and divided into three subgroups based on their skin type. Participants used the mask following the specified protocol, with measurements taken for skin hydration, transepidermal water loss (TEWL), sebum content, and skin redness-factors that are directly influenced by skin barrier function. Assessments were conducted at baseline and after 1 day (tested 15 min post-application), 7 days, and 14 days of application using Sebumeter, Tewameter, Corneometer, Mexameter, and VISIA. RESULTS: Results showed significant improvements in skin parameters across all subgroups. In the dry sensitive skin subgroup, the mask increased skin hydration, sebum content, and reduced redness. For the oily sensitive skin subgroup, the mask regulated sebum production and improved skin hydration. In the oily acne skin subgroup, the mask reduced sebum content, redness, TEWL, and post-inflammatory erythema and hyperpigmentation. Tolerance was excellent for all skin types, with no adverse reactions observed. CONCLUSIONS: This study highlights the efficacy and safety of the panthenol-enriched LRP Mask Pro for individuals with distinct skin barrier impairment subgroups. The mask's versatile formulation and proven efficacy make it a valuable skincare product for addressing various skin concerns and achieving healthier, more balanced skin.

TH17 cell: a double-edged sword in the development of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory disease of the gastrointestinal tract, and its pathogenesis has not been fully understood. Extensive dysregulation of the intestinal mucosal immune system is critical in the development and progression of IBD. T helper (Th) 17 cells have the characteristics of plasticity. They can transdifferentiate into subpopulations with different functions in response to different factors in the surrounding environment, thus taking on different roles in regulating the intestinal immune responses. In this review, we will focus on the plasticity of Th17 cells as well as the function of Th17 cells and their related cytokines in IBD. We will summarize their pathogenic and protective roles in IBD under different conditions, respectively, hoping to further deepen the understanding of the pathological mechanisms underlying IBD and provide insights for future treatment.

Multiple diffusive behaviors of the random walk in inhomogeneous environments.

Anomalous diffusive behaviors are observed in highly inhomogeneous but relatively stable environments such as intracellular media and are increasingly attracting attention. In this paper we develop a coupled continuous-time random walk model in which the waiting time is power-law coupled with the local environmental diffusion coefficient. We provide two forms of the waiting time density, namely, a heavy-tailed density and an exponential density. For different waiting time densities, anomalous diffusions with the diffusion exponent between 0 and 2 and Brownian yet non-Gaussian diffusion can be realized within the present model. The diffusive behaviors are analyzed and discussed by deriving the mean-squared displacement and probability density function. In addition we derive the effective jump length density corresponding to the decoupled form to help distinguish the diffusion types. Our model unifies two kinds of anomalous diffusive behavior with different characteristics in the same inhomogeneous environment into a theoretical framework. The model interprets the random motion of particles in a complex inhomogeneous environment and reproduces the experimental results of different biological and physical systems.

Nasal Administration of bFGF-Loaded Nanoliposomes Attenuates Neuronal Injury and Cognitive Deficits in Mice with Vascular Dementia Induced by Repeated Cerebral Ischemia‒Reperfusion.

Introduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.

Machine learning improves the prediction of significant fibrosis in Asian patients with metabolic dysfunction-associated steatotic liver disease - The Gut and Obesity in Asia (GO-ASIA) Study.

BACKGROUND: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non-alcoholic fatty liver disease (NAFLD/MASLD). AIMS: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients. METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria). RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p < 0.001, each). ML models showed 7%-12% better discrimination than FIB-4 to detect SF. Optimised random forest (RF) yielded best NPV/F1 in overall set (0.947/0.754), test set (0.798/0.588) and validation set (0.852/0.559), as compared to FIB4 in overall set (0.744/0.499), test set (0.722/0.456), and validation set (0.806/0.507). Compared to FIB-4, RF could pick 10 times more patients with SF, reduce unnecessary referrals by 28%, and prevent missed referrals by 78%. Age, AST, ALT fasting plasma glucose, and platelet count were top features determining the SF. Sequential use of SAFE < 140 and FIB4 < 1.2 (when SAFE > 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set). CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.

Emulsifiable oil-formulated Beauveria bassiana competes with imidacloprid for seasonal control of cereal aphids in Zhejiang, China.

BACKGROUND: Alternatives to neonicotinoids against cereal aphids are needed to mitigate aphid resistance and non-target effects. The emulsifiable oil formulations of two Beauveria bassiana strains, namely Bb registered as a mycoinsecticide and TBb overexpressing an endogenous virulence factor, were tested for seasonal control of cereal aphids at the elongating (April 7) to milk ripening (May 12) stages of winter wheat crop in Yuhang, Zhejiang. Each of three field trials consisted of blank control and the treatments (three randomized 100-m2 plots per capita) of each fungal strain sprayed biweekly at rates of 1.0 × 1013 and 1.5 × 1013 conidia ha-1 and 10% imidacloprid WP sprayed biweekly at a label rate. RESULTS: Tiller infestation percentage and aphid density in the 5-week field trials after the first spray were reduced to 18.7-22.4% and 9.1-12.4 aphids per tiller in the fungal treatments, and 12.8-25.3% and 2.8-20.9 aphids per tiller in the chemical treatment, contrasting with 49.2-60.3% and 37.1-108.5 aphids per tiller in the control. Percent control efficacies (±SD) computed with weekly aphid densities over the period averaged 84.0 ± 1.6 and 85.3 ± 1.8 versus 78.0 ± 4.0 and 79.9 ± 3.2 in the high-rate versus low-rate treatments of Bb and TBb, respectively, and 84.5 ± 7.8 in the chemical treatment. Imidacloprid showed faster kill action but more variable efficacy than the fungal treatments throughout the trials. CONCLUSION: Either Bb or TBb formulation competes with imidacloprid in reducing percent infestation and aphid density. The overall efficacy was significantly higher in the treatments of TBb than of Bb. © 2024 Society of Chemical Industry.

Concurrent chemoradiotherapy versus radiotherapy alone in older patients with stage II nasopharyngeal carcinoma after intensity-modulated radiotherapy: A propensity score-matched cohort study.

BACKGROUND AND PURPOSE: Whether concurrent chemoradiotherapy (CCRT) benefits the older (age ≥ 60 years) patients with stage II nasopharyngeal carcinoma (NPC) has not been determined. This study aimed to compare the outcomes and toxicities of CCRT with Intensity-Modulated Radiotherapy (IMRT) alone in older patients with stage II NPC. MATERIALS AND METHODS: Between January 2010 and December 2017, 220 older (age ≥ 60 years) patients with stage II NPC were analyzed. A pair of 53 patients were matched between the CCRT group and RT group by using propensity score matching (PSM) in terms of age, sex, pathological type, T and N stage, ACE-27 scores, CRP, LDH and Hb. Cancer-specific survival (CSS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) were analysed by the Kaplan-Meier method and log-rank test. Multivariate analysis was performed to assess the prognostic risk factors by using a Cox's proportional hazards regression model. Treatment toxicities were clarified and compared between the two groups by using the χ2 test. RESULTS: The median follow-up time of the whole cohort was 82.0 months (range, 11-151 months). PSM analysis indicated that compared with the RT group, significantly higher 5-year CSS (98.1 % vs. 83.0 %, P = 0.02), PFS (98.1 % vs. 79.2 %, P = 0.01) and DMFS (100.0 % vs. 92.4 %, P = 0.04) were observed in the CCRT group. Multivariate analysis showed that CCRT was an independent prognostic factor predicting CSS (HR, 0.34; 95 % CI, 0.15-0.79; P = 0.01), PFS (HR, 0.48; 95 % CI, 0.25-0.93; P = 0.03), and LRRFS (HR, 0.36; 95 % CI, 0.14-0.90; P = 0.03), and a higher ACE-27 score predicted a worse CSS. Patients in the CCRT group experienced higher frequencies of the acute toxicities than patients in the RT group. Late complications were comparable between the two groups. CONCLUSION: CCRT significantly improved the survival benefits for the older patients with stage II NPC compared with IMRT alone without adding late complications, whereas increased some of the treatment-associated acute toxicities.

Machine-learning model comprising five clinical indices and liver stiffness measurement can accurately identify MASLD-related liver fibrosis.

BACKGROUND & AIMS: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B-related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD)-related fibrosis diagnosis and establish a machine-learning (ML) model to improve the diagnostic performance. METHODS: A total of 946 biopsy-proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). RESULTS: The AUROCs of aMAP versus fibrosis-4 index (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut-off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB-4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM-plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM-plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM-plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). CONCLUSIONS: The aMAP score is capable of diagnosing MASLD-related fibrosis. The LSM-plus model could accurately identify MASLD-related cirrhosis and advanced fibrosis.