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ObjectivesWe assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients.MethodsA total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis.ResultsWe showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3.ConclusionUsing serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.

According to the results of sensory evaluation performed by experts, 14 black tea samples were divided into two groups based on their aroma quality: high-quality and quality-deficient black tea. Using fast gas chromatography-electronic-nose (GC-E-Nose) and gas chromatography-mass spectrometry (GC-MS) combined with multivariate statistical analysis, discriminant analysis of the two groups were carried out, and the key differential components between these groups were selected. The results showed that 117-dimensional dataset was obtained by the fusion of the GC-E-Nose (44-dimensional) and GC-MS (73-dimensional) data and used to establish a model for accurate classification of the two types of black tea employing orthogonal partial least squares-discriminant analysis (OPLS-DA). The model’s explanatory and predictive capacity (R2Y = 0.976, Q2 = 0.959) were better than those of the model established based on the GC-E-Nose or GC-MS data. Based on variable important in projection (VIP) scores > 1.6 and P < 0.05, eight key aroma components including dimethyl sulfide (B3 and B25), β-ionone (A59), (3E)-4,8-dimethylnon-1,3,7-triene (A20), dihydroactinidiolide (A64), linalool (A17), phenylethyl alcohol (A19), δ-octyl lactone (A41) and γ-nonalatone (A45) were selected, which played an important role in the classification. These results showed that GC-E-Nose combined with GC-MS allows rapid and accurate discrimination between quality-deficient and high-quality black tea, which can be used as a supplement to traditional sensory evaluation, providing technical support for quality control and improvement of black tea.

ObjectiveAlthough glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-β superfamily, its function in liver fibrosis has rarely been studied. Here, we investigated the role of GDNF in hepatic stellate cell (HSC) activation and liver fibrosis in humans and mice.DesignGDNF expression was examined in liver biopsies and sera from patients with liver fibrosis. The functional role of GDNF in liver fibrosis was examined in mice with adenoviral delivery of the GDNF gene, GDNF sgRNA CRISPR/Cas9 and the administration of GDNF-blocking antibodies. GDNF was examined on HSC activation using human and mouse primary HSCs. The binding of activin receptor-like kinase 5 (ALK5) to GDNF was determined using surface plasmon resonance (SPR), molecular docking, mutagenesis and co-immunoprecipitation.ResultsGDNF mRNA and protein levels are significantly upregulated in patients with stage F4 fibrosis. Serum GDNF content correlates positively with α-smooth muscle actin (α-SMA) and Col1A1 mRNA in human fibrotic livers. Mice with overexpressed GDNF display aggravated liver fibrosis, while mice with silenced GDNF expression or signalling inhibition by GDNF-blocking antibodies have reduced fibrosis and HSC activation. GDNF is confined mainly to HSCs and contributes to HSC activation through ALK5 at His39 and Asp76 and through downstream signalling via Smad2/3, but not through GDNF family receptor alpha-1 (GFRα1). GDNF, ALK5 and α-SMA colocalise in human and mouse HSCs, as demonstrated by confocal microscopy.ConclusionsGDNF promotes HSC activation and liver fibrosis through ALK5/Smad signalling. Inhibition of GDNF could be a novel therapeutic strategy to combat liver fibrosis.

To face the increasing requirement for grains as the global population continues to grow, improving both crop yield and quality has become essential. Plant health directly impacts crop quality and yield, making the development of plant health-monitoring technologies essential. Variable sensing technologies for outdoor/indoor farming based on different working principles have emerged as important tools for monitoring plants and their microclimates. These technologies can detect factors such as plant water content, volatile organic compounds (VOCs), and hormones released by plants, as well as environmental conditions like humidity, temperature, wind speed, and light intensity. To achieve comprehensive plant health monitoring for multidimensional assessment, multimodal sensors have been developed. Non-invasive monitoring approaches are also gaining attention, leveraging biocompatible and flexible sensors for plant monitoring without interference with its natural growth. Furthermore, wireless data transmission is crucial for real-time monitoring and efficient farm management. Reliable power supplies for these systems are vital to ensure continuous operation. By combining wearable sensors with intelligent data analysis and remote monitoring, modern agriculture can achieve refined management, resource optimization, and sustainable production, offering innovative solutions to global food security and environmental challenges. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA)-mediated gene regulation contributes to liver pathophysiology, including hepatic stellate cell (HSC) activation and fibrosis progression. Here, we investigated the role of miR-942 in human liver fibrosis. The expression of miR-942, HSC activation markers, transforming growth factor-beta pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI), as well as collagen deposition, were investigated in 100 liver specimens from patients with varying degree of hepatitis B virus (HBV)-related fibrosis. Human primary HSCs and the immortalized cell line (LX2 cells) were used for functional studies. We found that miR-942 expression was upregulated in activated HSCs and correlated inversely with BAMBI expression in liver fibrosis progression. Transforming growth factor beta (TGF-β) and lipopolyssacharide (LPS), two major drivers of liver fibrosis and inflammation, induce miR-942 expression in HSCs via Smad2/3 respective NF-κB/p50 binding to the miR-942 promoter. Mechanistically, the induced miR-942 degrades BAMBI mRNA in HSCs, thereby sensitizing the cells for fibrogenic TGF-β signaling and also partly mediates LPS-induced proinflammatory HSC fate. In conclusion, the TGF-β and LPS-induced miR-942 mediates HSC activation through downregulation of BAMBI in human liver fibrosis. Our study provides new insights on the molecular mechanism of HSC activation and fibrosis.