Anti-hsa-miR-59 alleviates premature senescence associated with Hutchinson-Gilford progeria syndrome in mice.

Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature aging disorder without an effective therapeutic regimen. Because of their targetability and influence on gene expression, microRNAs (miRNAs) are attractive therapeutic tools to treat diseases. Here we identified that hsa-miR-59 (miR-59) was markedly upregulated in HGPS patient cells and in multiple tissues of an HGPS mouse model (LmnaG609G/G609G ), which disturbed the interaction between RNAPII and TFIIH, resulting in abnormal expression of cell cycle genes by targeting high-mobility group A family HMGA1 and HMGA2. Functional inhibition of miR-59 alleviated the cellular senescence phenotype of HGPS cells. Treatment with AAV9-mediated anti-miR-59 reduced fibrosis in the quadriceps muscle, heart, and aorta, suppressed epidermal thinning and dermal fat loss, and yielded a 25.5% increase in longevity of LmnaG609G/G609G mice. These results identify a new strategy for the treatment of HGPS and provide insight into the etiology of HGPS disease.

A Liver Stiffness-Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma.

BACKGROUND & AIMS: The existing hepatocellular carcinoma (HCC) risk scores have modest accuracy, and most are specific to chronic hepatitis B infection. In this study, we developed and validated a liver stiffness-based machine learning algorithm (ML) for prediction and risk stratification of HCC in various chronic liver diseases (CLDs). METHODS: MLs were trained for prediction of HCC in 5155 adult patients with various CLDs in Korea and further tested in 2 prospective cohorts from Hong Kong (HK) (N = 2732) and Europe (N = 2384). Model performance was assessed according to Harrell's C-index and time-dependent receiver operating characteristic (ROC) curve. RESULTS: We developed the SMART-HCC score, a liver stiffness-based ML HCC risk score, with liver stiffness measurement ranked as the most important among 9 clinical features. The Harrell's C-index of the SMART-HCC score in HK and Europe validation cohorts were 0.89 (95% confidence interval, 0.85-0.92) and 0.91 (95% confidence interval, 0.87-0.95), respectively. The area under ROC curves of the SMART-HCC score for HCC in 5 years was ≥0.89 in both validation cohorts. The performance of SMART-HCC score was significantly better than existing HCC risk scores including aMAP score, Toronto HCC risk index, and 7 hepatitis B-related risk scores. Using dual cutoffs of 0.043 and 0.080, the annual HCC incidence was 0.09%-0.11% for low-risk group and 2.54%-4.64% for high-risk group in the HK and Europe validation cohorts. CONCLUSIONS: The SMART-HCC score is a useful machine learning-based tool for clinicians to stratify HCC risk in patients with CLDs.

Age and the relative importance of liver-related deaths in nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: It is unclear if the leading causes of death in patients with NAFLD differ by age. We aimed to investigate if the relative importance of liver-related deaths is lower and overshadowed by cardiovascular and cancer-related deaths in the elderly population. APPROACH AND RESULTS: We conducted a territory-wide retrospective cohort study of adult patients with NAFLD between 2000 and 2021 in Hong Kong. The outcomes of interest were all-cause and cause-specific mortality. Age groups at death were studied at 10-year intervals. During 662,471 person-years of follow-up of 30,943 patients with NAFLD, there were 2097 deaths. The top three causes of death were pneumonia, extrahepatic cancer, and cardiovascular diseases. Liver disease was the sixth leading cause of death in patients aged 70-79 and 80-89 years, accounting for 5.1% and 5.9% of deaths, respectively, but only accounted for 3% or fewer of the deaths in the other age groups. Nonetheless, liver disease was the leading cause of death in patients with NAFLD-related cirrhosis, accounting for 36.8% of all deaths. The incidence of liver-related death was higher in men younger than age 70 but higher in women afterwards. The incidence of liver-related death in women increased from 0.62 to 7.14 per 10,000 person-years from age 60-69 to 70-79 years. CONCLUSION: The relative importance of liver-related death increases with age in patients with NAFLD, especially among women. In patients with cirrhosis, liver disease is the leading cause of death.

Duration of type 2 diabetes and liver-related events in nonalcoholic fatty liver disease: A landmark analysis.

BACKGROUND AND AIMS: We aimed to determine the impact of the duration of type 2 diabetes (T2D) on the risk of liver-related events and all-cause mortality in patients with NAFLD. APPROACH AND RESULTS: We conducted a territory-wide cohort study of adult patients with NAFLD diagnosed between January 1, 2000, and July 31, 2021, in Hong Kong. T2D was defined by the use of any antidiabetic agents, laboratory tests, and/or diagnosis codes. The primary endpoint was liver-related events, defined as a composite endpoint of HCC and cirrhotic complications. To conduct a more granular assessment of the duration of T2D, we employed landmark analysis in four different ages of interest (biological age of 40, 50, 60, and 70 years). By multivariable analysis with adjustment of non-liver-related deaths, compared with patients without diabetes at age 60 (incidence rate of liver-related events: 0.70 per 1,000 person-years), the adjusted subdistribution HR (SHR) of liver-related events was 2.51 (95% CI: 1.32-4.77; incidence rate: 2.26 per 1,000 person-years) in patients with T2D duration < 5 years, 3.16 (95% CI: 1.59-6.31; incidence rate: 2.54 per 1,000 person-years) in those with T2D duration of 6-10 years, and 6.20 (95% CI: 2.62-14.65; incidence rate: 4.17 per 1000 person-years) in those with T2D duration more than 10 years. A similar association between the duration of T2D and all-cause mortality was also observed. CONCLUSIONS: Longer duration of T2D is significantly associated with a higher risk of liver-related events and all-cause mortality in patients with NAFLD.

The Role and Mechanism of Ambra1-Mediated Mitophagy in TDCPP-Exposed Mouse Hippocampal Neurons.

Tri(1,3-dichloro-2-propyl)phosphate (TDCPP) is one of the most widely used organophosphorus flame retardants in consumer products. TDCPP has been confirmed to be neurotoxic, but its mechanism has not been clarified and may be related to mitophagy. AMBRA1 can promote neurological autophagy, but whether AMBRA1 is involved in the mechanism of TDCPP-induced neurotoxicity has not been elucidated. In this study, the optimal neuronal damage model was established by exposing mice hippocampal neurons to TDCPP. Furthermore, on the basis of this model, siRNA was used to knock down AMBRA1. Combined with qRT-PCR and Western blot techniques, we identified AMBRA1-mediated mitophagy-induced neuronal damage in vitro mechanism. The experimental results indicated that TDCPP treatment for 24 h led to a decrease in the cell viability of mouse hippocampal neurons, causing neuronal damage. Meanwhile, TDCPP exposure increased autophagy marker proteins p62 and LC3B, and down-regulated mitochondrial DNA ND1 damage and TOMM20 protein, suggesting that TDCPP exposure promoted mitophagy. In addition, TDCPP exposure led to changes in the expression of AMBRA1 and the key factors of mitophagy, FUNDC1, PINK1, and PARKIN, whereas mitophagy was inhibited after knockdown of AMBRA1. The research results indicated that exposure to TDCPP induced neuronal damage and promoted mitophagy. The mechanism may be that AMBRA1 promoted mitophagy in neuronal cells through the PARKIN-dependent/non-dependent pathway. This study revealed the toxic effects of TDCPP on the nervous system and its potential molecular mechanisms, which provided important clues for further understanding the mechanism of action of AMBAR1-mediated mitophagy.

Diagnostic and prognostic performance of the SAFE score in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: The steatosis-associated fibrosis estimator (SAFE) score was developed to detect clinically significant liver fibrosis in patients with NAFLD in the United States. We compare the performance of the SAFE score and other non-invasive tests to diagnose liver fibrosis and to correlate the scores with liver-related outcomes in patients with NAFLD in Hong Kong. METHODS: This was a retrospective cohort study involving two data sets. The first cohort was a biopsy cohort of NAFLD patients (n = 279), and the second was a territory-wide cohort of NAFLD patients (n = 4603) retrieved from a territory-wide electronic healthcare database in Hong Kong. RESULTS: In detecting significant fibrosis, liver stiffness measured by transient elastography had the highest area under the receiver operating characteristic curve (AUROC) (.844), followed by SAFE score (.773). SAFE score had the highest AUROC among blood-based algorithms (.773 vs. .746 for FIB-4, .697 for APRI). Based on cut-off values of SAFE score (0 and 100 points), 854 (18.6%), 1596 (34.6%) and 2153 (46.8%) were in the low-, intermediate- and high-risk groups, respectively, in the territory-wide cohort. Six (.7%), 15 (.9%) and 59 (2.7%) developed liver-related events in those three groups respectively. Among patients who had liver-related events at 5 years, using the high cut-off, SAFE score could predict 84.9% of patients accurately, compared to 40.9% for FIB-4 and 27.2% for APRI. CONCLUSION: The SAFE score performed well and better than other blood-based markers in diagnosing significant fibrosis and predicting liver-related events in Asian patients with NAFLD.

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.

The role of microbial partners in heavy metal metabolism in plants: a review.

Heavy metal pollution threatens plant growth and development as well as ecological stability. Here, we synthesize current research on the interplay between plants and their microbial symbionts under heavy metal stress, highlighting the mechanisms employed by microbes to enhance plant tolerance and resilience. Several key strategies such as bioavailability alteration, chelation, detoxification, induced systemic tolerance, horizontal gene transfer, and methylation and demethylation, are examined, alongside the genetic and molecular basis governing these plant-microbe interactions. However, the complexity of plant-microbe interactions, coupled with our limited understanding of the associated mechanisms, presents challenges in their practical application. Thus, this review underscores the necessity of a more detailed understanding of how plants and microbes interact and the importance of using a combined approach from different scientific fields to maximize the benefits of these microbial processes. By advancing our knowledge of plant-microbe synergies in the metabolism of heavy metals, we can develop more effective bioremediation strategies to combat the contamination of soil by heavy metals.

Microplastic contamination in the agricultural soil-mitigation strategies, heavy metals contamination, and impact on human health: a review.

Microplastic pollution has emerged as a critical global environmental issue due to its widespread distribution, persistence, and potential adverse effects on ecosystems and human health. Although research on microplastic pollution in aquatic environments has gained significant attention. However, a limited literature has summarized the impacts of microplastic pollution the agricultural land and human health. Therefore, In the current review, we have discussed how microplastic(s) affect the microorganisms by ingesting the microplastic present in the soil, alternatively affecting the belowground biotic and abiotic components, which further elucidates the negative effects on the above-ground properties of the crops. In addition, the consumption of these crops in the food chain revealed a potential risk to human health throughout the food chain. Moreover, microplastic pollution has the potential to induce a negative impact on agricultural production and food security by altering the physiochemical properties of the soil, microbial population, nutrient cycling, and plant growth and development. Therefore, we discussed in detail the potential hazards caused by microplastic contamination in the soil and through the consumption of food and water by humans in daily intake. Furthermore, further study is urgently required to comprehend how microplastic pollution negatively affects terrestrial ecosystems, particularly agroecosystems which drastically reduces the productivity of the crops. Our review highlights the urgent need for greater awareness, policy interventions, and technological solutions to address the emerging threat of microplastic pollution in soil and plant systems and mitigation strategies to overcome its potential impacts on human health. Based on existing studies, we have pointed out the research gaps and proposed different directions for future research.

Biochar and saline soil: mitigation strategy by incapacitating the ecological threats to agricultural land.

Soil salinity caused a widespread detrimental issue that hinders productivity in agriculture and ecological sustainability, while waste-derived soil amendments like biochar have drawn attention for their capacity to act as a mitigating agent, by enhancing the physical and chemical features of soil, and contributing to the recovery of agricultural waste resources. However, the information concerning biochar and salinity which affect the physicochemical characteristics of soils, crop physiology, and growth is limited. To investigate whether biochar mitigates the salinity stress on wheat crop seedlings, we grow them with salinity stress (120 mM), and biochar (20 tons ha-1), and its interactive effects. The soil properties of soil organic carbon (SOC), soil organic matter (SOM), dissolved organic carbon (DOC), and soil available phosphorus (SAP) decreased in the saline soil by 36.71%, 46.97%, 26.31%, and 15.00%, while biochar treatment increased SOC, DOC, and SAP contents by 7.42%, 31.57%, and 15.00%, respectively. On the other hand, dissolved organic nitrogen (DON) contents decreased in all the treatments compared to the control. The root growth traits, SPAD values, leaf nitrogen, photosynthetic parameters, antioxidant enzymes, and reactive oxygen species decreased in the saline treatment while increasing in the biochar and interactive treatment. Thus, these activities resulted in higher leaves and root biomass in the biochar treatment alone and interactive treatment of salinity and biochar. According to principal component analysis, redundancy analysis, and the mantel test, using biochar in conjunction with salinity treatment was found to be more effective than salinity treatment alone. The results of this study suggest that biochar can be used as a sustainable agricultural technique and a means of mitigation agent by lowering soil salinity while increasing the biomass of crops.

Biochar improves the physical and nutritional quality of soil and plant function.Salinity stress declined the physiological activities and biomass of the crop.Biochar mitigates the salinity stress in soil and enhances the plant functioning.Exposure to both treatments enhances the antioxidant enzyme activity and biomass.

Glucose input profit soil organic carbon mineralization and nitrogen dynamics in relation to nitrogen amended soils.

Exogenous carbon (C) inputs stimulate soil organic carbon (SOC) decomposition, strongly influencing atmospheric concentrations and climate dynamics. The direction and magnitude of C decomposition depend on the C and nitrogen (N) addition, types and pattern. Despite the importance of decomposition, it remains unclear whether organic C input affects the SOC decomposition under different N-types (Ammonium Nitrate; AN, Urea; U and Ammonium Sulfate; AS). Therefore, we conducted an incubation experiment to assess glucose impact on N-treated soils at various levels (High N; HN: 50 mg/m2, Low N; LN: 05 mg/m2). The glucose input increased SOC mineralization by 38% and 35% under HN and LN, respectively. Moreover, it suppressed the concentration of NO3--N by 35% and NH4+-N by 15% in response to HN and LN soils, respectively. Results indicated higher respiration in Urea-treated soils and elevated net total nitrogen content (TN) in AS-treated soils. AN-amended soil exhibited no notable rise in C mineralization and TN content compared to other N-type soils. Microbial biomass carbon (MBC) was higher in glucose treated soils under LN conditions than control. This could result that high N suppressed microbial N mining and enhancing SOM stability by directing microbes towards accessible C sources. Our results suggest that glucose accelerated SOC mineralization in urea-added soils and TN contents in AS-amended soils, while HN levels suppressed C release and increased TN contents in all soil types except glucose-treated soils. Thus, different N-types and levels play a key role in modulating the stability of SOC over C input.

Unraveling the ecological threads: How invasive alien plants influence soil carbon dynamics.

Invasive alien plants (IAPs) pose significant threats to native ecosystems and biodiversity worldwide. However, the understanding of their precise impact on soil carbon (C) dynamics in invaded ecosystems remains a crucial area of research. This review comprehensively explores the mechanisms through which IAPs influence soil C pools, fluxes, and C budgets, shedding light on their effects and broader consequences. Key mechanisms identified include changes in litter inputs, rates of organic matter decomposition, alterations in soil microbial communities, and shifts in nutrient cycling, all driving the impact of IAPs on soil C dynamics. These mechanisms affect soil C storage, turnover rates, and ecosystem functioning. Moreover, IAPs tend to increase gross primary productivity and net primary productivity leading to the alterations in fluxes and C budgets. The implications of IAP-induced alterations in soil C dynamics are significant and extend to plant-soil interactions, ecosystem structure, and biodiversity. Additionally, they have profound consequences for C sequestration, potentially impacting climate change mitigation. Restoring native plant communities, promoting soil health, and implementing species-specific management are essential measures to significantly mitigate the impacts of IAPs on soil C dynamics. Overall, understanding and mitigating the effects of IAPs on soil C storage, nutrient cycling, and related processes will contribute to the conservation of native biodiversity and complement global C neutrality efforts.

Unveiling Human Values: Analyzing Emotions behind Arguments.

Detecting the underlying human values within arguments is essential across various domains, ranging from social sciences to recent computational approaches. Identifying these values remains a significant challenge due to their vast numbers and implicit usage in discourse. This study explores the potential of emotion analysis as a key feature in improving the detection of human values and information extraction from this field. It aims to gain insights into human behavior by applying intensive analyses of different levels of human values. Additionally, we conduct experiments that integrate extracted emotion features to improve human value detection tasks. This approach holds the potential to provide fresh insights into the complex interactions between emotions and values within discussions, offering a deeper understanding of human behavior and decision making. Uncovering these emotions is crucial for comprehending the characteristics that underlie various values through data-driven analyses. Our experiment results show improvement in the performance of human value detection tasks in many categories.

Clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial.

OBJECTIVE: We aimed to test the hypothesis that automated fibrosis score calculation and electronic reminder messages could increase the detection of advanced liver disease in patients with type 2 diabetes. DESIGN: In this pragmatic randomised controlled trial at five general medical or diabetes clinics in Hong Kong and Malaysia, we randomly assigned patients in a 1:1 ratio to the intervention group with Fibrosis-4 index and aspartate aminotransferase-to-platelet ratio index automatically calculated based on routine blood tests, followed by electronic reminder messages to alert clinicians of abnormal results, or the control group with usual care. The primary outcome was the proportion of patients with increased fibrosis scores who received appropriate care (referred for hepatology care or specific fibrosis assessment) within 1 year. RESULTS: Between May 2020 and Oct 2021, 1379 patients were screened, of whom 533 and 528 were assigned to the intervention and control groups, respectively. A total of 55 out of 165 (33.3%) patients with increased fibrosis scores in the intervention group received appropriate care, compared with 4 of 131 (3.1%) patients in the control group (difference 30.2% (95% CI 22.4% to 38%); p<0.001). Overall, 11 out of 533 (2.1%) patients in the intervention group and 1 out of 528 (0.2%) patients in the control group were confirmed to have advanced liver disease (difference 1.9% (95% CI 0.61% to 3.5%); p=0.006). CONCLUSION: Automated fibrosis score calculation and electronic reminders can increase referral of patients with type 2 diabetes and abnormal fibrosis scores at non-hepatology settings. TRIAL REGISTRATION NUMBER: NCT04241575.

aMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients.

BACKGROUND & AIMS: The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. METHODS: A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. RESULTS: In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). CONCLUSIONS: The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.

3D-Printed Piezoelectric Scaffolds with Shape Memory Polymer for Bone Regeneration.

The application of piezoelectric nanoparticles with shape memory polymer (SMP) to 3D-printed piezoelectric scaffolds for bone defect repair is an attractive research direction. However, there is a significant difference in dielectric constants between the piezoelectric phase and polymer phase, limiting the piezoelectric property. Therefore, novel piezoelectric acrylate epoxidized soybean oil (AESO) scaffolds doped with piezoelectric Ag-TMSPM-pBT (ATP) nanoparticles (AESO-ATP scaffolds) are prepared via digital light procession 3D-printing. The Ag-TMSPM-pBT nanoparticles improve the piezoelectric properties of the AESO scaffolds by TMSPM covalent functionalization and conductive Ag nanoparticles. The AESO scaffolds doped with 10 wt% Ag-TMSPM-pBT nanoparticles (AESO-10ATP scaffolds) exhibit promising piezoelectrical properties, with a piezoelectric coefficient (d33) of 0.9 pC N-1 and an output current of 146.4 nA, which are close to the piezoelectric constants of bone tissue. In addition, these scaffolds exhibit good shape memory function and can quickly recover their original shape under near-infrared (NIR) light irradiation. The results of osteogenesis capability evaluation indicate that the AESO-10ATP scaffolds can promote osteogenic differentiation of BMSCs in vitro and bone defect repair in vivo, indicating the 3D-printed AESO-10ATP piezoelectric scaffolds may have great application potential for bone regeneration.

Angiotensin-converting enzyme inhibitors prevent liver-related events in nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can inhibit liver fibrogenesis in animal models. We aimed to evaluate the impact of ACEI/ARB use on the risk of liver cancer and cirrhosis complications in patients with NAFLD. APPROACH AND RESULTS: We conducted a retrospective, territory-wide cohort study of adult patients with NAFLD diagnosed between January 2000 and December 2014 to allow for at least 5 years of follow-up. ACEI or ARB users were defined as patients who had received ACEI or ARB treatment for at least 6 months. The primary endpoint was liver-related events (LREs), defined as a composite endpoint of liver cancer and cirrhosis complications. We analyzed data from 12,327 NAFLD patients (mean age, 54.2 ± 14.7 years; 6163 men [50.0%]); 6805 received ACEIs, and 2877 received ARBs. After propensity score weighting, ACEI treatment was associated with a lower risk of LREs (weighted subdistribution hazard ratio [SHR], 0.48; 95% CI, 0.35-0.66; p < 0.001), liver cancer (weighted SHR, 0.46; 95% CI, 0.28-0.75; p = 0.002), and cirrhosis complications (weighted SHR, 0.42; 95% CI, 0.27-0.66; p < 0.001), but ARB was not. In subgroup analysis, ACEI treatment was associated with greater reduction in LREs in patients with chronic kidney diseases (CKDs) than those without (CKD-weighted SHR, 0.74; 95% CI, 0.52-0.96; p = 0.036; non-CKD-weighted SHR, 0.15; 95% CI, 0.07-0.33; p < 0.001). CONCLUSIONS: ACEI, rather than ARB, treatment is associated with a lower risk of LREs in NAFLD patients, especially among those with CKD.

A preliminary exploration for co-detecting RNA virus and STR type on capillary electrophoresis in forensic practice.

RNA virus infection such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection shows severe respiratory symptoms on human and could be an obvious individual characteristic for investigations in forensic science. As for biological samples suspected to contain RNA virus in forensic casework, it requires respective detection of viral RNA and human DNA: reverse transcriptase polymerase chain reaction and DNA type (short tandem repeat [STR] analysis). Capillary electrophoresis (CE) has been shown to be a versatile technique and used for a variety of applications, so we preliminarily explored the co-detection of RNA virus and STR type on CE by developing a system of co-detecting SARS-CoV-2 and STR type under ensuring both the efficiency of forensic DNA analysis and safety of the laboratory. This study investigated the development and validation of the system, including N and ORF1ab primer designs, polymerase chain reaction amplification, allelic ladder, CE detection, thermal cycling parameters, concordance, sensitivity, species specificity, precision, and contrived and real SARS-CoV-2 sample studies. Final results showed the system could simultaneously detect SARS-CoV-2 and STR type, further indicating that CE has possibilities in the multi-detection of RNA viruses/STR type to help to prompt individual characteristics (viral infection) and narrow the scope of investigation in forensic science.

Soil nutrient levels regulate the effect of soil microplastic contamination on microbial element metabolism and carbon use efficiency.

Microplastics (MPs) are emerging environmental contaminants in soil ecosystems that disrupt the soil carbon (C) pool. Therefore, the response of microbial metabolism to MP-contaminated soil is crucial for soil-C stabilization. We undertook factorial experiments in a greenhouse with three types of soil microplastics with three levels of soil nutrients and undertook soil physiochemical analyses after 60 days. The present study revealed how the presence of degradable polylactic acid (PLA) and non-degradable polyethylene (PE) MPs affects soil microbial nutrient limitation and C use efficiency (CUE) at varying nutrient concentrations. The presence of PLA in soil with low nutrient levels led to a significant increase (29%) in the activities of nitrogen (N)-acquiring enzymes. In contrast, the presence of MPs had no effect on C- and N-acquiring enzymes. The occurrence of PE caused a 41% reduction in microbial C limitation in high-nutrient soils, and microbial nutrient metabolism was limited by the occurrence of MPs in soils amended with nutrients. A strong positive correlation between microbial C and nutrient limitation in the soil indicates that addressing C limitation followed by amendment of soil with MPs could potentially intensify microbial N limitation in soils with varying nutrients. In comparison, the microbial CUE increased by 10% with the application of degradable MPs (PLA) to soils with a low nutrient status. These findings highlight the significant influence of both degradable PLA and non-degradable PE MPs on soil microbial processes and C dynamics. In conclusion, PLA enhances metabolic efficiency in nutrient-rich soils, potentially aiding C utilization, whereas PE reduces microbial C limitation, offering promise for soil C sequestration strategies. Our findings underscore the importance of considering MPs in soil ecosystem studies and in broader sustainability efforts.

The toxicological effect on pak choi of co-exposure to degradable and non-degradable microplastics with oxytetracycline in the soil.

Microplastics and antibiotics are emerging as ubiquitous contaminants in farmland soil, harming crop quality and yield, and thus threatening global food security and human health. However, few studies have examined the individual and joint effects of degradable and/or non-degradable microplastics and antibiotics on crop plants. This study examined the individual and joint effects of polyethylene (PE) and polylactic acid (PLA) microplastics and the antibiotic oxytetracycline (OTC) on pak choi by measuring its growth, photosynthesis, antioxidant enzyme activity, and metabolite levels. Microplastics and/or oxytetracycline adversely affected root weight, photosynthesis, and antioxidant enzyme (superoxide dismutase, catalase, and ascorbate peroxidase) activities. The levels of leaf metabolites were significantly altered, causing physiological changes. Biosynthesis of plant secondary metabolites and amino acids was altered, and plant hormones pathways were disrupted. Separately and together, OTC, PE, and PLA exerted phytotoxic and antagonistic effects on pak choi. Separately and together with OTC, degradable microplastics altered the soil properties, thus causing more severe impacts on plant performance than non-degradable microplastics. This study elucidates the effects on crop plants of toxicity caused by co-exposure to degradable or non-degradable microplastic and antibiotics contamination and suggests mechanisms.