Organic nanoparticles incorporated starch/carboxymethylcellulose multifunctional coating film for efficient preservation of perishable products.

Most of postharvest agricultural produces are perishable due to microorganisms infections and physiological change. Herein, one kind of multifunctional coating film of SC-ECCNPs was developed by incorporating organic nanoparticles of ECCNPs into starch/carboxymethylcellulose (SC) to prolong shelf life of food with excellent performances. The SC-ECCNPs coating was prepared with starch and sodium carboxymethylcellulose as film substrate (SC) to incorporate with organic nanoparticles of ECCNPs formed by integrating epigallocatechin-3-gallate (EGCG), cysteine (Cys), and cinnamaldehyde (CA). The incorporation of ECCNPs improves the UV-resistance and physical properties of SC-ECCNPs coating and also endows it with excellent antioxidative and broad-spectrum antibacterial activity. The application possibilities of SC-ECCNPs coating were explored with strawberries and oranges as samples, validating that the SC-ECCNPs coating can prolong the shelf life of fruits at room temperature. The biosafety of the coating was further confirmed with hemolysis and MTT experiments. The SC-ECCNPs coating film was prepared with natural substrates via a simple and green method. The investigation provides an instructive way for developing advanced packaging materials with high performances.

Red-Light Triggered H-Abstraction Photoinitiators for the Efficient Oxygen-Independent Therapy of Hypoxic Tumors.

The clinical application of photodynamic therapy (PDT) is limited by oxygen-dependence and side effects caused by photosensitizer residues. Photoinitiators based on the H-abstraction reaction can address these challenges because they can generate alkyl radical-killing cells independently of oxygen and undergo rapid bleaching following H-abstraction. Nonetheless, the development of photoinitiators for PDT has been impeded by the absence of effective design strategies. Herein, we have developed aryl-ketone substituted cyanine (ACy-R), the first red-light triggered H-abstraction photoinitiators for hypoxic cancer therapy. These ACy-R molecules inherited the near-infrared absorption of cyanine dye, and aryl-ketone modification imparted H-abstraction capability. Experimental and quantum calculations revealed that modifying the electron-withdrawing groups of the aryl (e.g., ACy-5F) improved the contribution of the O atom to the photon excitation process promoting intersystem crossing and H-abstraction ability. Particularly, ACy-5F rapidly penetrated cells and enriched in the endoplasmic reticulum. Even under severe hypoxia, ACy-5F initiated red-light induced H-abstraction with intracellular biomolecules, inducing necroptosis and ferroptosis. Moreover, ACy-5F was degraded after H-abstraction, thus avoiding the side effects of long-term phototoxicity after therapy. This study not only provides a crucial molecular tool for hypoxic tumors therapy, but also presents a promising strategy for the development of multifunctional photosensitizers and photoinitiators.

Regioselective and enantioselective propargylic hydroxylations catalyzed by P450tol monooxygenases.

Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which's an important synthetic intermediate of antifungal drug Ravuconazole.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Bidirectional transitions of sarcopenia states in older adults: The longitudinal evidence from CHARLS.

BACKGROUND: Sarcopenia, the age-related loss of muscle mass and function, brings multiple adverse outcomes including disability and death. Several sarcopenia consensuses have newly introduced the premorbid concept of possible sarcopenia and recommended early lifestyle interventions. Bidirectional transitions of premorbid states have been revealed in several chronic diseases yet not clarified in sarcopenia. This study aims to investigate the underlying transition patterns of sarcopenia states. METHODS: The study utilized three waves of data from a nationally representative survey, the China Health and Retirement Longitudinal Study (CHARLS), and included community-dwelling individuals aged 60 years and older with at least two sarcopenia states assessments based on the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019) between 2011 and 2015. The estimated transition intensity and probability between non-sarcopenia, possible sarcopenia, sarcopenia, and death were investigated using multi-stage Markov (MSM) models. RESULTS: The study comprised 4395 individuals (49.2% female, median age 67 years) with a total of 10 778 records of sarcopenia state assessment, and the mean follow-up period was 3.29 years. A total of 24.5% of individuals with a current state of possible sarcopenia returned to non-sarcopenia, 60.3% remained possible sarcopenia, 6.7% progressed to sarcopenia, and 8.5% died by the next follow-up. The transition intensity of recovery to non-sarcopenia (0.252, 95% CI 0.231-0.275) was 2.8 times greater than the deterioration to sarcopenia (0.090, 95% CI 0.080-0.100) for individuals with possible sarcopenia. For individuals with possible sarcopenia, the estimated probabilities of recovering to non-sarcopenia, progressing to sarcopenia, and transitioning to death within a 1-year observation were 0.181, 0.066, and 0.035, respectively. For individuals with sarcopenia, the estimated probabilities of recovering to non-sarcopenia, recovering to possible sarcopenia, and transitioning to death within 1-year observation were 0.016, 0.125, and 0.075, respectively. In covariables analysis, age, sex, body mass index, physical function impairment, smoking, hypertension, and diabetes are important factors influencing bidirectional transitions. CONCLUSIONS: The findings highlight the bidirectional transitions of sarcopenia states among older adults and reveal a notable proportion of possible sarcopenia show potential for recovery in the natural course. Screening and intensifying interventions based on risk factors may facilitate a recovery transition.

Modified Zhizhu Pill improves the loperamide-induced slow transit constipation via gut microbiota and neurotransmitters in microbiota-gut-brain axis.

BACKGROUND: Slow-transmission constipation is a type of intractable constipation with unknown etiology and unclear pathogenesis. OBJECTIVE: The intention of this study was to evaluate the therapeutic effect and possible mechanism of Modified Zhizhu Pills on loperamide-induced slow transit constipation. METHODS: The effects of the Modified Zhizhu Pill were evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. Fecal parameters (fecal count, fecal water content, and fecal hardness) were measured in constipated rats. The substance, target, and pathway basis of the Modified Zhizhu Pill on constipation was investigated using network pharmacology. The microflora in rats was determined. Serum neurotransmitters (acetylcholine and 5-hydroxytryptamine) were measured in rats and their relationship with the gut microbiota was assessed. RESULTS: Modified Zhizhu Pill increased the number of bowel movements and fecal water content, and decreased fecal hardness and transit time. Network pharmacological analysis showed that Modified Zhizhu Pill can target multiple constipation-related targets and pathways through multiple potential active ingredients. Modified Zhizhu Pill alleviated loperamide-induced microbiota dysbiosis. Modified Zhizhu Pill increased serum 5-hydroxytryptamine and acetylcholine. The increase in serum 5-hydroxytryptamine and acetylcholine was associated with rat gut microbiota. CONCLUSION: These results suggest that Modified Zhizhu Pill may increase intestinal motility and ultimately relieve constipation by improving microecological dysbiosis and neurotransmission.

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer.

OBJECTIVES: The study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. METHODS: Differentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. RESULTS: Upregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. CONCLUSIONS: ECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

A Difluoromethylation Reagent: Access to Difluoromethyl Arenes through Palladium Catalysis.

A new radical difluoromethylation was developed by using inexpensive and readily available difluoroacetic anhydride and N-phenyl-4-methylbenzenesulfonamide for the first time. The reaction of arylboronic acids with the new difluoromethylation reagent, N-phenyl-N-tosyldifluoroacetamide, proceeded smoothly in the presence of palladium catalyst to provide difluoromethylarenes in satisfactory to excellent yields. The electronic property (electron-donating or electron-withdrawing) of the substituent linked to the aromatic ring did not considerably influence the reactivity of arylboronic acid. Various groups, including the synthetically useful functional groups Cl, CN, and NO2, were tolerated well under the current reaction conditions.

Spatiotemporal patterns of leaf nutrients of wild apples in a wild fruit forest plot in the Ili Valley, China.

Malus sieversii, commonly known as wild apples, represents a Tertiary relict plant species and serves as the progenitor of globally cultivated apple varieties. Unfortunately, wild apple populations are facing significant degradation in localized areas due to a myriad of factors. To gain a comprehensive understanding of the nutrient status and spatiotemporal variations of M. sieversii, green leaves were collected in May and July, and the fallen leaves were collected in October. The concentrations of leaf nitrogen (N), phosphorus (P), and potassium (K) were measured, and the stoichiometric ratios as well as nutrient resorption efficiencies were calculated. The study also explored the relative contributions of soil, topographic, and biotic factors to the variation in nutrient traits. The results indicate that as the growing period progressed, the concentrations of N and P in the leaves significantly decreased (P < 0.05), and the concentration of K in October was significantly lower than in May and July. Throughout plant growth, leaf N-P and N-K exhibited hyperallometric relationships, while P-K showed an isometric relationship. Resorption efficiency followed the order of N < P < K (P < 0.05), with all three ratios being less than 1; this indicates that the order of nutrient limitation is K > P > N. The resorption efficiencies were mainly regulated by nutrient concentrations in fallen leaves. A robust spatial dependence was observed in leaf nutrient concentrations during all periods (70.1-97.9% for structural variation), highlighting that structural variation, rather than random factors, dominated the spatial variation. Nutrient resorption efficiencies (NRE, PRE, and KRE) displayed moderate structural variation (30.2-66.8%). The spatial patterns of nutrient traits varied across growth periods, indicating they are influenced by multifactorial elements (in which, soil property showed the highest influence). In conclusion, wild apples manifested differentiated spatiotemporal variability and influencing factors across various leaf nutrient traits. These results provide crucial insights into the spatiotemporal patterns and influencing factors of leaf nutrient traits of M. sieversii at the permanent plot scale for the first time. This work is of great significance for the ecosystem restoration and sustainable management of degrading wild fruit forests.

The Biosynthesis Pattern and Transcriptome Analysis of Sapindus saponaria Oil.

The Sapindus saponaria (soapberry) kernel is rich in oil that has antibacterial, anti-inflammatory, and antioxidant properties, promotes cell proliferation, cell migration, and stimulates skin wound-healing effects. S. saponaria oil has excellent lubricating properties and is a high-quality raw material for biodiesel and premium lubricants, showing great potential in industrial and medical applications. Metabolite and transcriptome analysis revealed patterns of oil accumulation and composition and differentially expressed genes (DEGs) during seed development. Morphological observations of soapberry fruits at different developmental stages were conducted, and the oil content and fatty acid composition of the kernels were determined. Transcriptome sequencing was performed on kernels at 70, 100, and 130 days after flowering (DAF). The oil content of soapberry kernels was lowest at 60 DAF (5%) and peaked at 130 DAF (31%). Following soapberry fruit-ripening, the primary fatty acids in the kernels were C18:1 (oleic acid) and C18:3 (linolenic acid), accounting for an average proportion of 62% and 18%, respectively. The average contents of unsaturated fatty acids and saturated fatty acids in the kernel were 86% and 14%, respectively. Through the dynamic changes in fatty acid composition and DEGs analysis of soapberry kernels, FATA, KCR1, ECR, FAD2 and FAD3 were identified as candidate genes contributing to a high proportion of C18:1 and C18:3, while DGAT3 emerged as a key candidate gene for TAG biosynthesis. The combined analysis of transcriptome and metabolism unveiled the molecular mechanism of oil accumulation, leading to the creation of a metabolic pathway pattern diagram for oil biosynthesis in S. saponaria kernels. The study of soapberry fruit development, kernel oil accumulation, and the molecular mechanism of oil biosynthesis holds great significance in increasing oil yield and improving oil quality.

Schistosomiasis transmission in Zimbabwe: Modelling based on machine learning.

Zimbabwe, located in Southern Africa, faces a significant public health challenge due to schistosomiasis. We investigated this issue with emphasis on risk prediction of schistosomiasis for the entire population. To this end, we reviewed available data on schistosomiasis in Zimbabwe from a literature search covering the 1980-2022 period considering the potential impact of 26 environmental and socioeconomic variables obtained from public sources. We studied the population requiring praziquantel with regard to whether or not mass drug administration (MDA) had been regularly applied. Three machine-learning algorithms were tested for their ability to predict the prevalence of schistosomiasis in Zimbabwe based on the mean absolute error (MAE), the root mean squared error (RMSE) and the coefficient of determination (R2). The findings revealed different roles of the 26 factors with respect to transmission and there were particular variations between Schistosoma haematobium and S. mansoni infections. We found that the top-five correlation factors, such as the past (rather than current) time, unsettled MDA implementation, constrained economy, high rainfall during the warmest season, and high annual precipitation were closely associated with higher S. haematobium prevalence, while lower elevation, high rainfall during the warmest season, steeper slope, past (rather than current) time, and higher minimum temperature in the coldest month were rather related to higher S. mansoni prevalence. The random forest (RF) algorithm was considered as the formal best model construction method, with MAE = 0.108; RMSE = 0.143; and R2 = 0.517 for S. haematobium, and with the corresponding figures for S. mansoni being 0.053; 0.082; and 0.458. Based on this optimal model, the current total schistosomiasis prevalence in Zimbabwe under MDA implementation was 19.8%, with that of S. haematobium at 13.8% and that of S. mansoni at 7.1%, requiring annual MDA based on a population of 3,003,928. Without MDA, the current total schistosomiasis prevalence would be 23.2%, that of S. haematobium 17.1% and that of S. mansoni prevalence at 7.4%, requiring annual MDA based on a population of 3,521,466. The study reveals that MDA alone is insufficient for schistosomiasis elimination, especially that due to S. mansoni. This study predicts a moderate prevalence of schistosomiasis in Zimbabwe, with its elimination requiring comprehensive control measures beyond the currently used strategies, including health education, snail control, population surveillance and environmental management.

The heterogeneous impact of population mobility on the influent characteristics of wastewater treatment facilities.

Improving the resilience of wastewater treatment facilities (WWTFs) has never been more important with rising risks of disasters under climate change. Beyond physical damages, non-physical shocks induced by disasters warrant attention. Human mobility is a vital mediator in transferring the stresses from extreme events into tangible challenges for urban sewage systems by reshaping influent characteristics. However, the impact path remains inadequately explored. Leveraging the stay-at-home orders during the COVID-19 pandemic as a natural experiment, this study aims to quantify and interpret the heterogeneous impacts of mobility reduction on the influent characteristics of WWTFs with different socio-economic, infrastructural, and climatic conditions. To achieve this goal, we developed a research framework integrating causal inference and interpretable machine learning techniques. Based on the empirical data from China, we find that 79.1% of the studied WWTFs, typically located in cities with well-developed drainage infrastructures and low per capita water usage, exhibited resilience against drastic mobility reduction. In contrast, 20.9% of the studied WWTFs displayed significant variations in influent characteristics. Large-capacity WWTFs in subtropical regions encountered challenges with low-load operations, and small-capacity facilities in suburban areas grappled with nutrient imbalances. This study provides valuable insights to equip WWTFs in anticipating and adapting potential variations in influent characteristics triggered by mobility reduction.

Nonparametric receiver operating characteristic curve analysis with an imperfect gold standard.

This article addresses the challenge of estimating receiver operating characteristic (ROC) curves and the areas under these curves (AUC) in the context of an imperfect gold standard, a common issue in diagnostic accuracy studies. We delve into the nonparametric identification and estimation of ROC curves and AUCs when the reference standard for disease status is prone to error. Our approach hinges on the known or estimable accuracy of this imperfect reference standard and the conditional independent assumption, under which we demonstrate the identifiability of ROC curves and propose a nonparametric estimation method. In cases where the accuracy of the imperfect reference standard remains unknown, we establish that while ROC curves are unidentifiable, the sign of the difference between two AUCs is identifiable. This insight leads us to develop a hypothesis-testing method for assessing the relative superiority of AUCs. Compared to the existing methods, the proposed methods are nonparametric so that they do not rely on the parametric model assumptions. In addition, they are applicable to both the ROC/AUC analysis of continuous biomarkers and the AUC analysis of ordinal biomarkers. Our theoretical results and simulation studies validate the proposed methods, which we further illustrate through application in two real-world diagnostic studies.

Assessment of the influence of levees along Yangtze River on Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

BACKGROUND: Oncomelania hupensis is the exclusive intermediate host of Schistosoma japonicum in China. Snail control is an essential component of schistosomiasis elimination programme. With 70 years of continuous efforts, the range of O. hupensis had reduced significantly, but slowed down in last decades. A large number of levees against flooding were constructed along Yangtze River and its affiliated lakes in the middle and lower reaches, which influenced the hydrology and ecology in the alluvial plains. The purpose of this study was to assess the impact of levees on the distribution of O. hupensis in the middle and lower reaches of the Yangtze River. METHODS: The snail habitats were digitalised by hand-held GPS system. The years for discovery and elimination of snail habitats were extracted from historical records. The accumulated snail-infested range for each habitat was calculated on the basis of annual reports. The current distribution of O. hupensis was determined by systematic and environmental sampling. The geographical distribution of levees was obtained from satellite imagery. To assess the impact of levees, the data pertaining to O. hupensis were divided into two parts: inside and outside the Yangtze River. Joinpoint regression was utilised to divide the study time span and further characterise the regression in each period. The 5-year-period moving averages of eliminated area infested by snails were calculated for the habitats inside and outside Yangtze River. The moving routes of corresponding geographical median centres were simulated in ArcGIS. Hotspot analysis was used to determine the areas with statistical significance clustering of O. hupensis density. RESULTS: Three periods were identified according to Joinpoint regression both inside and outside Yangtze River. The area infested by O. hupensis increased in the first two periods. It decreased rapidly outside Yangtze River year over year after 1970, while that inside the Yangtze River did not change significantly. Furthermore, the latter was significantly higher than the former. It was observed that the present density of O. hupensis inside Yangtze River was lower than outside the Yangtze River. The median centre for eliminated ranges inside Yangtze River wavered between the east (lower reach) and the west (middle reach). In contrast, the median centre for eliminated ranges continuously moved from the east to the west. CONCLUSIONS: Our findings indicated that the levees had a considerable negative impact on the distribution of O. hupensis outside Yangtze River. Some hotspots observed in the irrigation areas need a sluice system at the inlet of branch for snail control. The major distribution of O. hupensis located in Hubei might be caused by severe waterlogging. The intensive surveillance should be implemented there. The biggest two freshwater lakes, the major endemic regions historically, were identified as cold spots. The long-term impact of Three Gorges Dam on the distribution of O. hupensis in the lakes should be monitored and evaluated.

Effects of functional defects in the NMD pathway on rice phenotype and transcriptome.

Nonsense-mediated mRNA decay (NMD) is an important RNA quality control pathway. It aids in degrading harmful erroneous mRNA, thereby preserving a stable and healthy internal environment. In this study, we employed CRISPR/Cas9 and amiRNA technology to generate knock out or knock down mutants of realted genes in the rice NMD pathway. Through transcriptome sequencing and observing phenotype changes, the study explored the impact of NMD pathway defects on rice gene expression and alternative splicing. The results suggest that even partial defects will induce phenotypic changes such as plant height and pollen vitality to different degrees, showing necessity of NMD factors. Gene expression analysis reveals that most differentially expressed genes are upregulated in the mutants, with ko-upf1-like and kd-upf1 defects having a more significant impact than kd-upf2 and kd-upf3. Specifically, NMD pathway defects result in increased expression levels of rice defense response-related genes and decreased expression levels of secondary metabolism-related genes, with a wider range of affected genes observed in 60-day-old senescence mutants. Transcript analysis indicates that different NMD related genes defects alter hundreds of alternative splicing events, mostly enriched in genes involving alternative splicing regulatory pathways. Approximately half of these events are shared among different mutants, and a substantial number of affected transcripts show NMD target features. NMD could affect both the transcript abundance and their splicing subtypes to regulate the defense response and early-senescence associated pathways, which plays a vital role in rice growth and reproduction.

Mazabraud's syndrome in female patients: Two case reports.

BACKGROUND: Mazabraud's syndrome (MS) is a rare and slowly progressive benign disease characterized by the concurrent presence of fibrous dysplasia of bone and intramuscular myxoma, and is thought to be associated with mutations of the GNAS gene. To date, only about 100 cases of MS have been reported in the literature, but its standard treatment strategy remains unclear. CASE SUMMARY: We report two cases of MS in young women who underwent different treatments based on their symptoms and disease manifestations. The first patient, aged 37, received internal fixation and intravenous bisphosphonate for a pathological fracture of the right femoral neck, excision of a right vastus medialis myxoma was subsequently performed for pain control, and asymptomatic psoas myxomas were monitored without surgery. Genetic testing confirmed a GNAS gene mutation in this patient. The second patient, aged 24, underwent right vastus intermedius muscle myxoma resection, and conservative treatment for fibrous dysplasia of the ilium. These patients were followed-up for 17 months and 3 years, respectively, and are now in a stable condition. CONCLUSION: Various treatments have been selected for MS patients who suffer different symptoms. The main treatment for myxomas is surgical resection, while fibrous dysplasia is selectively treated if the patient experiences pathological fracture or severe pain. However, given the documented instances of malignant transformation of fibrous dysplasia in individuals with MS, close follow-up is necessary.

Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Aflatoxin B1 decreased flesh flavor and inhibited muscle development in grass carp (Ctenopharyngodon idella).

In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp (Ctenopharyngodon idella) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 µg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle (P < 0.05). The contents of free amino acid decreased gradually (P < 0.05) as dietary AFB1 increased in the muscle of grass carp. The levels of reactive oxygen species, malonaldehyde and protein carbonyl (PC) were increased (P < 0.05) with the dietary AFB1 increased. The levels of antioxidant enzyme (glutathione peroxidase, glutathione, glutathione reductase, total antioxidant capacity, anti-superoxide anion, and anti-hydroxyl radical) were decreased (P < 0.05) with the dietary AFB1 increased. In addition, dietary AFB1 decreased the content of collagen, and downregulated the mRNA and protein levels of transforming growth factor-ß (TGF-ß)/Smads signaling pathway in grass carp muscle (P < 0.05). The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle (P < 0.05). Furthermore, the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were increased (P < 0.05), and the protein levels of phosphorylate-38 mitogen-activated protein kinase (p-p38MAPK), phosphorylate-c-Jun N-terminal kinase, urokinase-type plasminogen activator (uPA), MMP-2 and MMP-9 were upregulated (P < 0.05), but collagen Ⅰ, laminin ß1 and fibronectin were downregulated (P < 0.05) with the dietary AFB1 increased in the muscle of grass carp. Based on the results of this study, we can draw the following conclusion: dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix (ECM) signaling pathway in grass carp. Moreover, the recommended safe limit of AFB1 in feed is no more than 26.77 µg/kg diet according to the PC levels in grass carp muscle.