Development and validation of HBV surveillance models using big data and machine learning.

BACKGROUND: The construction of a robust healthcare information system is fundamental to enhancing countries' capabilities in the surveillance and control of hepatitis B virus (HBV). Making use of China's rapidly expanding primary healthcare system, this innovative approach using big data and machine learning (ML) could help towards the World Health Organization's (WHO) HBV infection elimination goals of reaching 90% diagnosis and treatment rates by 2030. We aimed to develop and validate HBV detection models using routine clinical data to improve the detection of HBV and support the development of effective interventions to mitigate the impact of this disease in China. METHODS: Relevant data records extracted from the Family Medicine Clinic of the University of Hong Kong-Shenzhen Hospital's Hospital Information System were structuralized using state-of-the-art Natural Language Processing techniques. Several ML models have been used to develop HBV risk assessment models. The performance of the ML model was then interpreted using the Shapley value (SHAP) and validated using cohort data randomly divided at a ratio of 2:1 using a five-fold cross-validation framework. RESULTS: The patterns of physical complaints of patients with and without HBV infection were identified by processing 158,988 clinic attendance records. After removing cases without any clinical parameters from the derivation sample (n = 105,992), 27,392 cases were analysed using six modelling methods. A simplified model for HBV using patients' physical complaints and parameters was developed with good discrimination (AUC = 0.78) and calibration (goodness of fit test p-value >0.05). CONCLUSIONS: Suspected case detection models of HBV, showing potential for clinical deployment, have been developed to improve HBV surveillance in primary care setting in China. (Word count: 264).

This study has developed a suspected case detection model for HBV, which can facilitate early identification and treatment of HBV in the primary care setting in China, contributing towards the achievement of WHO's elimination goals of HBV infections.We utilized the state-of-art natural language processing techniques to structure the data records, leading to the development of a robust healthcare information system which enhances the surveillance and control of HBV in China.

D-Xylose Blocks the Broad Negative Regulation of XylR on Lipid Metabolism and Affects Multiple Physiological Characteristics in Mycobacteria.

D-xylose is the most abundant fermentable pentose, which usually represents an architectural component of the bacterial cell wall. However, its regulatory function and the involved signaling pathway in bacteria remain largely unclear. Here, we show that D-xylose can act as a signaling molecule to regulate the lipid metabolism and affect multiple physiological characteristics in mycobacteria. D-xylose directly interacts with XylR and inhibits its DNA-binding ability, thus blocking XylR-mediated repression. The xylose inhibitor, XylR, plays a global regulatory role and affects the expression of 166 mycobacterial genes that are involved in lipid synthesis and metabolism. Furthermore, we show that the xylose-dependent gene regulation of XylR affects the multiple physiological characteristics of Mycobacterium smegmatis, including bacterial size, colony phenotype, biofilm formation, cell aggregation, and antibiotic resistance. Finally, we found that XylR inhibited the survival of Mycobacterium bovis BCG in the host. Our findings provide novel insights into the molecular mechanism of lipid metabolism regulation and its correlation with bacterial physiological phenotypes.

Crebanine induces ROS-dependent apoptosis in human hepatocellular carcinoma cells via the AKT/FoxO3a signaling pathway.

Background: Hepatocellular carcinoma (HCC), as an aggressive cancer with a high mortality rate, needs high-efficiency and low-toxicity drug therapy. Natural products have great potential as candidate lead compounds for the development of new HCC drugs. Crebanine is an isoquinoline alkaloid derived from Stephania with various potential pharmacological effects such as anti-cancer. However, the molecular mechanism underlying crebanine-induced liver cancer cells apoptosis has not been reported. Here, we investigated the effect of crebanine on HCC and identified a potential mechanism of action. Methods: In this paper, we intend to detect the toxic effects of crebanine on hepatocellular carcinoma HepG2 cells through a series of in vitro experiments, including detecting the effects of crebanine on the proliferation of HepG2 cells using the CCK8 method and plate cloning assay, observing the growth status and morphological changes of crebanine on HepG2 cells by inverted microscopy; and using the Transwell method to determine the the effect of crebanine on the migration and invasion ability of HepG2 cells; using Hoechst 33258 assay to stain cancer cells, thus observing the effect of crebanine on the morphology of HepG2 apoptotic cells, and detecting the apoptotic state and level of HepG2 cells by flow cytometry; using ROS kit and JC-1 assay kit to detect the changes of reactive oxygen species and mitochondrial membrane potential of HepG2 The immunofluorescence assay was taken to verify whether crebanine had an effect on the expression of p-FoxO3a in cancer cells; the Wetern blot assay was also used to examine the effect of crebanine on proteins related to the mitochondrial apoptotic pathway and its effect on the regulation of the relative protein expression of AKT/FoxO3a axis; after this, NAC and AKT inhibitor LY294002 were used to cells were pretreated with NAC and AKT inhibitor LY294002, respectively, in order to further validate the inhibitory effect of crebanine. Results: It was shown that crebanine effectively inhibited the growth and capacity of HepG2 cells migration and invasion in a dose-dependent manner. Furthermore, the effect of crebanine on the morphology of HepG2 cells was observed through microscopy. Meanwhile, crebanine induced apoptosis by causing reactive oxygen species (ROS) burst and mitochondrial membrane potential (MMP) disrupt. We found that crebanine could down-regulate Bcl-2 and up-regulate Bax, cleaved-PARP, cleaved-caspase-3 and cleaved-caspase-9, but these effects were overturned by ROS inhibitor N-acetylcysteine (NAC). Crebanine also down-regulated p-AKT and p-FoxO3a, and the PI3K inhibitor LY294002 significantly enhances this effect. We also found that the expression of AKT/FoxO3a signaling pathway was ROS-dependent. As shown by Western blots, NAC could partially attenuate the inhibitory effect of crebanine on AKT and FoxO3a phosphorylation. Conclusion: Based on our results, our results suggest that crebanine, as a compound with potential anticancer activity, has significant cytotoxic effects on hepatocellular carcinoma,and it likely induces apoptosis via ROS in the mitochondrial pathway and simultaneously affects the biological function of HCC via the ROS-AKT-FoxO3a signaling axis.

NIX protein enhances antioxidant capacity of and reduces the apoptosis induced by HSP90 inhibitor luminespib/NVP-AUY922 in PC12 cells.

Pheochromocytomas and paragangliomas (PCPGs) are catecholamine-producing neuroendocrine tumors. Accumulating evidences indicate that the blockade of antioxidative pathways might be a novel therapeutic approach to the treatment of PCPG. NIX has been confirmed to play a key role in maintaining redox homeostasis in tumors, while the function of NIX in PCPG remains unclear. In this study, the analyses of the disease-free survival (DFS) showed that high NIX protein level is related to poor prognosis in patients of PCPG. Consistent with this, high level of NIX protein upregulates the level of p-NF-κB and promotes the migration of PC12 cells. In NIX-over-expressing PC12 cells, the level of reactive oxygen species (ROS) is decreased while trolox-equivalent antioxidant capacity (TEAC) increased. But in NIX-silencing cells, ROS level is increased, while TEAC reversely reduced, consequently antioxidase and phase II enzymes of NRF2 signaling were activated, and elevated endoplasmic reticulum (ER) stress was observed. Additionally, the apoptosis induced by luminespib/NVP-AUY922, an inhibitor of heat shock protein 90 (HSP90, a cellular stress response factor), was enhanced in NIX-silencing cells but reduced in the NIX-over-expressing cells. All of these results indicated that high NIX protein level enhances antioxidant capacity of PC12 cells and reduces the apoptosis caused by cell stress, such as induced by luminespib/NVP-AUY922. Therefore, luminespib/NVP-AUY922 might be effective only for PCPG with low NIX level, while targeting NIX could be a further supplement to the therapeutic treatment strategy for PCPG patients with high NIX protein level.

Chemical properties and antioxidant activity of exopolysaccharides fractions from mycelial culture of Inonotus obliquus in a ground corn stover medium.

The medicinal mushroom Inonotus obliquus has been a folk remedy for a long time in East-European and Asian countries. We first reported the enhancement in production and antioxidant activity of exopolysaccharides by I. obliquus culture under lignocellulose decomposition. In this study, the two different sources of exopolysaccharides from the control medium and the lignocellulose (corn stover) containing medium by I. obliquus in submerged fermentation were fractionated and purified by chromatography. The exopolysaccharides from the corn stover-containing medium presented significantly stronger hydroxyl and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity than the control. Three fractions from the control medium and the corn stover-containing medium were isolated respectively. The fraction of DEPL3 from the corn stover-containing medium with the highest protein content (38.3%), mannose content (49.6%), and the lowest molecular weight (29 kDa) had the highest antioxidant activity with the lowest IC50 values. In conclusion, lignocellulose decomposition changed the chemical characterisation and significantly enhanced the antioxidant activity of exopolysaccharide fractions.