Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry.

Hepatitis C virus (HCV) infection is tightly connected to the lipid metabolism with lipid droplets (LDs) serving as assembly sites for progeny virions. A previous LD proteome analysis identified annexin A3 (ANXA3) as an important HCV host factor that is enriched at LDs in infected cells and required for HCV morphogenesis. To further characterize ANXA3 function in HCV, we performed proximity labeling using ANXA3-BioID2 as bait in HCV-infected cells. Two of the top proteins identified proximal to ANXA3 during HCV infection were the La-related protein 1 (LARP1) and the ADP ribosylation factor-like protein 8B (ARL8B), both of which have been previously described to act in HCV particle production. In follow-up experiments, ARL8B functioned as a pro-viral HCV host factor without localizing to LDs and thus likely independent of ANXA3. In contrast, LARP1 interacts with HCV core protein in an RNA-dependent manner and is translocated to LDs by core protein. Knockdown of LARP1 decreased HCV spreading without altering HCV RNA replication or viral titers. Unexpectedly, entry of HCV particles and E1/E2-pseudotyped lentiviral particles was reduced by LARP1 depletion, whereas particle production was not altered. Using a recombinant vesicular stomatitis virus (VSV)ΔG entry assay, we showed that LARP1 depletion also decreased entry of VSV with VSV, MERS, and CHIKV glycoproteins. Therefore, our data expand the role of LARP1 as an HCV host factor that is most prominently involved in the early steps of infection, likely contributing to endocytosis of viral particles through the pleiotropic effect LARP1 has on the cellular translatome.

Alternative splicing of BCL-x is controlled by RBM25 binding to a G-quadruplex in BCL-x pre-mRNA.

BCL-x is a master regulator of apoptosis whose pre-mRNA is alternatively spliced into either a long (canonical) anti-apoptotic Bcl-xL isoform, or a short (alternative) pro-apoptotic Bcl-xS isoform. The balance between these two antagonistic isoforms is tightly regulated and overexpression of Bcl-xL has been linked to resistance to chemotherapy in several cancers, whereas overexpression of Bcl-xS is associated to some forms of diabetes and cardiac disorders. The splicing factor RBM25 controls alternative splicing of BCL-x: its overexpression favours the production of Bcl-xS, whereas its downregulation has the opposite effect. Here we show that RBM25 directly and specifically binds to GQ-2, an RNA G-quadruplex (rG4) of BCL-x pre-mRNA that forms at the vicinity of the alternative 5' splice site leading to the alternative Bcl-xS isoform. This RBM25/rG4 interaction is crucial for the production of Bcl-xS and depends on the RE (arginine-glutamate-rich) motif of RBM25, thus defining a new type of rG4-interacting domain. PhenDC3, a benchmark G4 ligand, enhances the binding of RBM25 to the GQ-2 rG4 of BCL-x pre-mRNA, thereby promoting the alternative pro-apoptotic Bcl-xS isoform and triggering apoptosis. Furthermore, the screening of a combinatorial library of 90 putative G4 ligands led to the identification of two original compounds, PhenDH8 and PhenDH9, superior to PhenDC3 in promoting the Bcl-xS isoform and apoptosis. Thus, favouring the interaction between RBM25 and the GQ-2 rG4 of BCL-x pre-mRNA represents a relevant intervention point to re-sensitize cancer cells to chemotherapy.

Triphasic Ni2P-Ni12P5-Ru with Amorphous Interface Engineering Promoted by Co Nano-Surface for Efficient Water Splitting.

This research designs a triphasic Ni2P-Ni12P5-Ru heterostructure with amorphous interface engineering strongly coupled by a cobalt nano-surface (Co@NimPn-Ru) to form a hierarchical 3D interconnected architecture. The Co@NimPn-Ru material promotes unique reactivities toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media. The material delivers an overpotential of 30 mV for HER at 10 mA cm-2 and 320 mV for OER at 50 mA cm-2 in freshwater. The electrolyzer cell derived from Co@NimPn-Ru(+,-) requires a small cell voltage of only 1.43 V in alkaline freshwater or 1.44 V in natural seawater to produce 10 mA cm-2 at a working temperature of 80 °C, along with high performance retention after 76 h. The solar energy-powered electrolyzer system also shows a prospective solar-to-hydrogen conversion efficiency and sufficient durability, confirming its good potential for economic and sustainable hydrogen production. The results are ascribed to the synergistic effects by an exclusive combination of multi-phasic crystalline Ni2P, Ni12P5, and Ru clusters in presence of amorphous phosphate interface attached onto cobalt nano-surface, thereby producing rich exposed active sites with optimized free energy and multi open channels for rapid charge transfer and ion diffusion to promote the reaction kinetics.

Type I arginine methyltransferases are intervention points to unveil the oncogenic Epstein-Barr virus to the immune system.

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome maintenance but is also highly antigenic. Hence, EBV seemingly evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA to the minimal level to ensure its essential function, thereby, at the same time, minimizing immune recognition. Therefore, defining intervention points at which to interfere with GAr-based inhibition of translation is an important step to trigger an immune response against EBV-carrying cancers. The host protein nucleolin (NCL) plays a critical role in this process via a direct interaction with G-quadruplexes (G4) formed in the GAr-encoding sequence of the viral EBNA1 mRNA. Here we show that the C-terminal arginine-glycine-rich (RGG) motif of NCL is crucial for its role in GAr-based inhibition of translation by mediating interaction of NCL with G4 of EBNA1 mRNA. We also show that this interaction depends on the type I arginine methyltransferase family, notably PRMT1 and PRMT3: drugs or small interfering RNA that target these enzymes prevent efficient binding of NCL on G4 of EBNA1 mRNA and relieve GAr-based inhibition of translation and of antigen presentation. Hence, this work defines type I arginine methyltransferases as therapeutic targets to interfere with EBNA1 and EBV immune evasion.

The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA.

Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA translation initiation in order to minimize the production of antigenic peptides for the major histocompatibility (MHC) class I pathway. Here we show that the emerging peptide of the disordered glycine-alanine repeat (GAr) within EBNA1 dislodges the nascent polypeptide-associated complex (NAC) from the ribosome. This results in the recruitment of nucleolin to the GAr-encoding mRNA and suppression of mRNA translation initiation in cis. Suppressing NAC alpha (NACA) expression prevents nucleolin from binding to the GAr mRNA and overcomes GAr-mediated translation inhibition. Taken together, these observations suggest that EBNA1 exploits a nascent protein quality control pathway to regulate its own rate of synthesis that is based on sensing the nascent GAr peptide by NAC followed by the recruitment of nucleolin to the GAr-encoding RNA sequence.

Hepatitis C virus infection restricts human LINE-1 retrotransposition in hepatoma cells.

LINE-1 (L1) retrotransposons are autonomous transposable elements that can affect gene expression and genome integrity. Potential consequences of exogenous viral infections for L1 activity have not been studied to date. Here, we report that hepatitis C virus (HCV) infection causes a significant increase of endogenous L1-encoded ORF1 protein (L1ORF1p) levels and translocation of L1ORF1p to HCV assembly sites at lipid droplets. HCV replication interferes with retrotransposition of engineered L1 reporter elements, which correlates with HCV RNA-induced formation of stress granules and can be partially rescued by knockdown of the stress granule protein G3BP1. Upon HCV infection, L1ORF1p localizes to stress granules, associates with HCV core in an RNA-dependent manner and translocates to lipid droplets. While HCV infection has a negative effect on L1 mobilization, L1ORF1p neither restricts nor promotes HCV infection. In summary, our data demonstrate that HCV infection causes an increase of endogenous L1 protein levels and that the observed restriction of retrotransposition of engineered L1 reporter elements is caused by sequestration of L1ORF1p in HCV-induced stress granules.

Antiblood Cell Adhesion of Mussel-Inspired Chondroitin Sulfate- and Caffeic Acid-Modified Polycarbonate Membranes.

We fabricated a mussel-inspired hemocompatible polycarbonate membrane (PC) modified by the cross-linking of chondroitin sulfate and caffeic acid polymer using CA-CS via a Schiff base and Michael addition reaction and named it CA-CS-PC. The as-fabricated CA-CS-PC membrane shows excellent hydrophilicity with a water contact angle of 0° and a negative surface charge with a zeta potential of -32 mV. The antiadhesion property of the CA-CS-modified PC membrane was investigated by enzyme-linked immunosorbent assay (ELISA), using human plasma protein fibrinogen adsorption studies, and proved to have excellent antiadhesion properties, because of the lower fibrinogen adsorption. In addition, the CA-CS-PC membrane also shows enhanced hemocompatibility. Finally, blood cell attachment tests of the CA-CS-PC membrane were observed by CLSM and SEM, and the obtained results proved that CA-CS-PC effectively resisted cell adhesion, such as platelets and leucocytes. Therefore, this work disclosed a new way to design a simple and versatile modification of the membrane surface by caffeic acid and chondroitin sulfate and apply it for cell adhesion.

The effective Ni(II) removal of red mud modified chitosan from aqueous solution.

This study used red mud modified with chitosan (RM/CS) as a novel adsorbent to remove Ni(II) ions from an aqueous solution. The adsorbent was characterized by the techniques of the BET method, X-ray diffraction (XRD), and scanning electron microscopy (SEM) analysis. According to the findings, the surface area of RM/CS is nearly doubled compared to CS, from 68.6 to 105.7 m2.g-1. The Ni(II) batch adsorption of RM/CS was performed as a function of pH value, contact time, and volume of adsorbent. Three isotherm adsorption models (Langmuir, Freundlich, and Sips) and three kinetic models (the pseudo-first-order, the pseudo-second-order, and the intra-diffusion models) were fitted with the experimental data to calculate the maximum adsorption capacity and to estimate the uptake in nature. The Langmuir monolayer adsorption capacity for Nickel (II) is 31.66 mg.g-1 at a pH of 6.0, with an adsorption time of 180 min and a temperature of 323 K. The Ni(II) adsorption on RM/CS is the exothermic process and is controlled by the intra-diffusion model.

Effective adsorption of Pb(II) ion from aqueous solution onto ZSM-5 zeolite synthesized from Vietnamese bentonite clay.

ZSM-5 zeolite was successfully synthesized from bentonite clay sourced from Lam Dong Province, Vietnam, using the hydrothermal method at 170 °C for 18 h. The synthesized ZSM-5 (SiO2/Al2O3 ratio ~ 34) exhibited a single phase with high crystallinity (91.8%), and a clear and uniform shape. In a detailed examination of the synthesized material's Pb(II) adsorptive capacity, various factors were taken into account, including pH, interaction time, ionic strength, and the amount of adsorbent. Isotherms and kinetics were examined to elucidate the uptake behavior. Study results suggested that Pb(II) ion uptake by ZSM-5 was most appropriately described by the Sips isotherm and intraparticle diffusion kinetic models. The calculated maximum monolayer adsorption capacity according to the Langmuir isotherm model was 48.36 mg/g. Furthermore, the adsorption mechanisms of Pb(II) on ZSM-5 involving electrostatic interactions, ion exchange, and diffusion into pores were demonstrated using the analytical techniques before and after Pb(II) adsorption. These findings demonstrate that ZSM-5 synthesized from bentonite clay exhibits an excellent adsorption capacity for Pb(II), resulting in promising applications for treating drinking water or aqueous industrial waste containing Pb(II) ions.

Kinetic studies of the removal of methylene blue from aqueous solution by biochar derived from jackfruit peel.

Kinetic studies play an instrumental role in determining the most appropriate reaction rate model for industrial-scale applications. This study focuses on the kinetics of methylene blue (MB) adsorption from aqueous solutions by biochar derived from jackfruit peel. Various kinetic models, including pseudo-first-order (PFO), pseudo-second-order (PSO), intra-diffusion, and Elovich models, were applied to study MB adsorption kinetics of jackfruit peel biochar. The experiments were performed with two initial concentrations of MB (24.23 mg/L and 41.42 mg/L) over a span of 240 min. Our findings emphasized that the Elovich model provided the best fit of the experimental data for MB adsorption. When compared to other materials, biochar from jackfruit peel emerges as an eco-friendly adsorbent for dye decolorization, with potential applications in the treatment of environmental pollution.

Crystallization Pathways and Evolution of Morphologies and Structural Defects of α-MnO2 under Air Annealing.

Manganese dioxide nanomaterials have wide applications in many areas from catalysis and Li-ion batteries to gas sensing. Understanding the crystallization pathways, morphologies, and formation of defects in their structure is particularly important but still a challenging issue. Herein, we employed an arsenal of X-ray diffraction (XRD), scanning electron microscopy (SEM), neutron diffraction, positron annihilation spectroscopies, and ab initio calculations to investigate the evolution of the morphology and structure of α-MnO2 nanomaterials prepared via reduction of KMnO4 solution with C2H5OH prior to being annealed in air at 200-600 °C. We explored a novel evolution that α-MnO2 nucleation can be formed even at room temperature and gradually developed to α-MnO2 nanorods at above 500 °C. We also found the existence of H+ or K+ ions in the [1 × 1] tunnels of α-MnO2 and observed the simultaneous presence of Mn and O vacancies in α-MnO2 crystals at low temperatures. Increasing the temperature removed these O vacancies, leaving only the Mn vacancies in the samples.

Green synthesis of microalgae-based carbon dots for decoration of TiO2 nanoparticles in enhancement of organic dye photodegradation.

TiO2 is a well-known semiconductor used widely in the photocatalyst field, but its photocatalytic applications are hampered by a fast electron-hole recombination rate and low visible light absorption due to a wide-band-gap energy. Herein, we present a simple, low cost, and green approach to obtain carbon dots from microalgae, namely microalgae-based carbon dots (MCDs), using an unprecedented microwave-assisted treatment. The MCDs were successfully decorated on the surface of TiO2 nanoparticles. The as-prepared composite exhibited a superior photodegradation of methylene blue, compared with pristine TiO2 (83% and 27%, respectively) under visible light irradiation. The MCDs in TiO2-MCDs serve as electron reservoirs to trap photoinduced electrons and as photosensitizers for the improvement of visible light absorption; both factors play an important role in the improvement of the TiO2 photocatalytic activity. Furthermore, the as-prepared composite photocatalyst also exhibits high photostability and recyclability during the photodegradation of methylene blue. Therefore, this work provides an original approach to the development of environmentally friendly and highly effective photocatalysts for the treatment of various organic pollutants, which can go a long way toward ensuring a safe and sustainable environment.

Classification of Tetanus Severity in Intensive-Care Settings for Low-Income Countries Using Wearable Sensing.

Infectious diseases remain a common problem in low- and middle-income countries, including in Vietnam. Tetanus is a severe infectious disease characterized by muscle spasms and complicated by autonomic nervous system dysfunction in severe cases. Patients require careful monitoring using electrocardiograms (ECGs) to detect deterioration and the onset of autonomic nervous system dysfunction as early as possible. Machine learning analysis of ECG has been shown of extra value in predicting tetanus severity, however any additional ECG signal analysis places a high demand on time-limited hospital staff and requires specialist equipment. Therefore, we present a novel approach to tetanus monitoring from low-cost wearable sensors combined with a deep-learning-based automatic severity detection. This approach can automatically triage tetanus patients and reduce the burden on hospital staff. In this study, we propose a two-dimensional (2D) convolutional neural network with a channel-wise attention mechanism for the binary classification of ECG signals. According to the Ablett classification of tetanus severity, we define grades 1 and 2 as mild tetanus and grades 3 and 4 as severe tetanus. The one-dimensional ECG time series signals are transformed into 2D spectrograms. The 2D attention-based network is designed to extract the features from the input spectrograms. Experiments demonstrate a promising performance for the proposed method in tetanus classification with an F1 score of 0.79 ± 0.03, precision of 0.78 ± 0.08, recall of 0.82 ± 0.05, specificity of 0.85 ± 0.08, accuracy of 0.84 ± 0.04 and AUC of 0.84 ± 0.03.

Decline in hospitalization for childhood asthma in different air pollution regions in Taiwan, 2001-2012.

This study aimed to investigate the trends in childhood asthma hospitalization in regions with differing levels of air pollution in Taiwan, 2001-2012. Joinpoint regression was used to identify significant trend changes. The hospitalization rate varied according to gender, geographic region, and age. The incidence of childhood asthma hospitalization decreased from 127.99 to 76.67 (/100,000 population), with an average annual percentage change of around -4.1%; in the Yilan region, the average air pollution concentrations were 19.92 µg/m3, 39.47 µg/m3, 25.99 ppb, 2.19 ppb, and 11.23 ppb for PM2.5, PM10, O3, SO2, and NO2, respectively, which were lower than Taiwan's average values; however, the childhood asthma hospitalization rate was the highest (179.75/100,000 population). The national trend in childhood asthma hospitalization exhibited a significant decrease. The effects of air pollution on childhood asthma were greater in the higher-level air pollution regions, while less association was observed in the lower-level air pollution regions.

The utility of surrogate markers in predicting HLA alleles associated with adverse drug reactions in Vietnamese.

BACKGROUND: Screening for HLA-A*31:01/HLA-B*15:02, HLA-B*57:01 and HLA-B*58:01 is recommended in selected populations for prevention of carbamazepine, abacavir, and allopurinol-induced severe cutaneous adverse reactions (SCARs). Compared to conventional methods for detection of HLA alleles, PCR using a tag single nucleotide polymorphism (SNP) can be cost-effective, particularly where the surrogate marker SNP is in absolute linkage disequilibrium with the relevant HLA allele. OBJECTIVE: To determine guidelines for prevention of SCARs though predictive screening for the Australian Vietnamese population, the prevalence of four HLA alleles (HLA-A*31:01, HLA-B*15:02, HLA-B*57:01 and HLA-B*58:01) was examined. The utility of surrogate markers, rs2395029 and rs9263726, was investigated to predict for the presence of HLA-B*57:01 and HLA-B*58:01, respectively. METHODS: Genotyping for specific HLA alleles was performed in 152 healthy Vietnamese living in Sydney using validated and established PCR-based methods. SNP genotyping was conducted using restriction-fragment-length-polymorphism analysis. RESULTS: rs2395029 and rs9263726 strongly correlated with HLA-B*57:01 (κ = 1, p < 0.001) and HLA-B*58:01 (Κ = 0.9, p < 0.001) with 100% sensitivity and 100% negative predictive value for predicting the HLA-B*57:01 and HLA-B*58:01 carriers, respectively. A high prevalence of carriers of HLA-A*31:01 (3.29%), HLA-B*15:02 (14.47%), HLA-B*57:01 (6.58%) and HLA-B*58:01 (9.21%) was revealed. Conclusions: Screening is recommended for these alleles in Australian Vietnamese prior to introducing relevant therapies. SNPs, rs2395029 and rs9263726, can be successfully used as surrogate markers for HLA-B*57:01 and HLA-B*58:01 in this population.

Perilipin-2 is critical for efficient lipoprotein and hepatitis C virus particle production.

In hepatocytes, PLIN2 is the major protein coating lipid droplets (LDs), an organelle the hepatitis C virus (HCV) hijacks for virion morphogenesis. We investigated the consequences of PLIN2 deficiency on LDs and on HCV infection. Knockdown of PLIN2 did not affect LD homeostasis, likely due to compensation by PLIN3, but severely impaired HCV particle production. PLIN2-knockdown cells had slightly larger LDs with altered protein composition, enhanced local lipase activity and higher ß-oxidation capacity. Electron micrographs showed that, after PLIN2 knockdown, LDs and HCV-induced vesicular structures were tightly surrounded by ER-derived double-membrane sacs. Strikingly, the LD access for HCV core and NS5A proteins was restricted in PLIN2-deficient cells, which correlated with reduced formation of intracellular HCV particles that were less infectious and of higher density, indicating defects in maturation. PLIN2 depletion also reduced protein levels and secretion of ApoE due to lysosomal degradation, but did not affect the density of ApoE-containing lipoproteins. However, ApoE overexpression in PLIN2-deficient cells did not restore HCV spreading. Thus, PLIN2 expression is required for trafficking of core and NS5A proteins to LDs, and for formation of functional low-density HCV particles prior to ApoE incorporation.This article has an associated First Person interview with the first author of the paper.

Deep learning approaches for sleep disorder prediction in an asthma cohort.

OBJECTIVE: Sleep is a natural activity of humans that affects physical and mental health; therefore, sleep disturbance may lead to fatigue and lower productivity. This study examined 1 million samples included in the Taiwan National Health Insurance Research Database (NHIRD) in order to predict sleep disorder in an asthma cohort from 2002-2010. METHODS: The disease histories of the asthma patients were transferred to sequences and matrices for the prediction of sleep disorder by applying machine learning (ML) algorithms, including K-Nearest Neighbors (KNN), Support Vector Machine (SVM), and Random Forest (RF), and deep learning (DL) models, including Recurrent Neural Network (RNN), Long Short-Term Memory (LSTM), Gated Recurrent Units (GRU), and Convolution Neural Network (CNN). RESULTS: Among 14,818 new asthma subjects in 2002, there were 4469 sleep disorder subjects from 2002 to 2010. The KNN, SVM, and RF algorithms were demonstrated to be successful sleep disorder prediction models, with accuracies of 0.798, 0.793, and 0.813, respectively (AUC: 0.737, 0.690, and 0.719, respectively). The results of the DL models showed the accuracies of the RNN, LSTM, GRU, and CNN to be 0.744, 0.815, 0.782, and 0.951, respectively (AUC: 0.658, 0.750, 0.732, and 0.934, respectively). CONCLUSIONS: The results showed that the CNN model had the best performance for sleep disorder prediction in the asthma cohort.

A colorectal straight-to-test cancer pathway with general-practitioner-guided triage improves attainment of the 28-day diagnosis target and increases outpatient clinic capacity.

AIM: This study investigates whether a straight-to-test (STT) colorectal cancer pathway improves attainment of the National Health Service (NHS) England 28-day Faster Diagnosis Standard and the effect of the pathway on reducing face-to-face outpatient clinic appointments. Patient satisfaction and the safety of a novel general practitioner (GP) led patient triage system regarding suitability for colonoscopy are also evaluated. METHODS: This is an observational study of all patients managed via an STT colorectal cancer pathway between 1 September 2019 and 19 March 2020. Comparison is made with all patients referred on the suspected colorectal cancer pathway prior to implementation of the STT pathway from 1 January 2019 to 30 July 2019. Patient satisfaction with the STT pathway was assessed with a telephone-based questionnaire. RESULTS: Attainment of the 28-day diagnosis target for all suspected colorectal cancer referrals improved following the establishment of the STT pathway (88% vs. 82%, P < 0.0001). From a potential total of 548 outpatient colorectal clinic appointments for patients on the STT pathway, 504 (92%) were avoided. In those eligible for the STT pathway, GP assessment of patients suitable for colonoscopy agreed with that of the colorectal department in 93% of cases. Of the 50 patients who undertook the satisfaction survey, 86% were satisfied or very satisfied with the pathway. No patient suffered adverse events as a result of their STT investigations. CONCLUSION: An STT pathway for suspected colorectal cancer referrals with novel GP-led patient triage safely streamlines patients through the suspected colorectal cancer diagnostic pathway and significantly reduces requirement for face-to-face outpatient clinic attendance. This is achieved with high patient satisfaction.

Liver cancer prediction in a viral hepatitis cohort: A deep learning approach.

Viral hepatitis is the primary cause of liver diseases, among which liver cancer is the leading cause of death from cancer. However, this cancer is often diagnosed in the later stages, which makes treatment difficult or even impossible. This study applied deep learning (DL) models for the early prediction of liver cancer in a hepatitis cohort. In this study, we surveyed 1 million random samples from the National Health Insurance Research Database (NHIRD) to analyze viral hepatitis patients from 2002 to 2010. Then, we used DL models to predict liver cancer cases based on the history of diseases of the hepatitis cohort. Our results revealed the annual prevalence of hepatitis in Taiwan increased from 2002 to 2010, with an average annual percentage change (AAPC) of 5.8% (95% CI: 4.2-7.4). However, young people (aged 16-30 years) exhibited a decreasing trend, with an AAPC of -5.6 (95% CI: -8.1 to -2.9). The results of applying DL models showed that the convolution neural network (CNN) model yielded the best performance in terms of predicting liver cancer cases, with an accuracy of 0.980 (AUC: 0.886). In conclusion, this study showed an increasing trend in the annual prevalence of hepatitis, but a decreasing trend in young people from 2002 to 2010 in Taiwan. The CNN model may be applied to predict liver cancer in a hepatitis cohort with high accuracy.

Model System for the Formation of Tick-Borne Encephalitis Virus Replication Compartments without Viral RNA Replication.

Flavivirus is a positive-sense, single-stranded RNA viral genus, with members causing severe diseases in humans such as tick-borne encephalitis, yellow fever, and dengue fever. Flaviviruses are known to cause remodeling of intracellular membranes into small cavities, where replication of the viral RNA takes place. Nonstructural (NS) proteins are not part of the virus coat and are thought to participate in the formation of these viral replication compartments (RCs). Here, we used tick-borne encephalitis virus (TBEV) as a model for the flaviviruses and developed a stable human cell line in which the expression of NS proteins can be induced without viral RNA replication. The model system described provides a novel and benign tool for studies of the viral components under controlled expression levels. We show that the expression of six NS proteins is sufficient to induce infection-like dilation of the endoplasmic reticulum (ER) and the formation of RC-like membrane invaginations. The NS proteins form a membrane-associated complex in the ER, and electron tomography reveals that the dilated areas of the ER are closely associated with lipid droplets and mitochondria. We propose that the NS proteins drive the remodeling of ER membranes and that viral RNA, RNA replication, viral polymerase, and TBEV structural proteins are not required.IMPORTANCE TBEV infection causes a broad spectrum of symptoms, ranging from mild fever to severe encephalitis. Similar to other flaviviruses, TBEV exploits intracellular membranes to build RCs for viral replication. The viral NS proteins have been suggested to be involved in this process; however, the mechanism of RC formation and the roles of individual NS proteins remain unclear. To study how TBEV induces membrane remodeling, we developed an inducible stable cell system expressing the TBEV NS polyprotein in the absence of viral RNA replication. Using this system, we were able to reproduce RC-like vesicles that resembled the RCs formed in flavivirus-infected cells, in terms of morphology and size. This cell system is a robust tool to facilitate studies of flavivirus RC formation and is an ideal model for the screening of antiviral agents at a lower biosafety level.