TGF-ß downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial-mesenchymal transition of liver progenitor cells.

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

GRIN2A mutation is a novel indicator of stratifying beneficiaries of immune checkpoint inhibitors in multiple cancers.

Glutamate-NMDAR receptors (GRINs) have been reported to influence cancer immunogenicity; however, the relationship between GRIN alterations and the response to immune checkpoint inhibitors (ICIs) has not been determined. This study combined clinical characteristics and mutational profiles from multiple cohorts to form a discovery cohort (n = 901). The aim of this study was to investigate the correlation between the mutation status of the GRIN gene and the response to ICI therapy. Additionally, an independent ICI-treated cohort from the Memorial Sloan Kettering Cancer Center (MSKCC, N = 1513) was used for validation. Furthermore, this study explored the associations between GRIN2A mutations and intrinsic and extrinsic immunity using multiomics analysis. In the discovery cohort, patients with GRIN2A-MUTs had improved clinical outcomes, as indicated by a higher objective response rate (ORR: 36.8% vs 25.8%, P = 0.020), durable clinical benefit (DCB: 55.2% vs 38.7%, P = 0.005), prolonged progression-free survival (PFS: HR = 0.65; 95% CI 0.49 to 0.87; P = 0.003), and increased overall survival (OS: HR = 0.67; 95% CI 0.50 to 0.89; P = 0.006). Similar results were observed in the validation cohort, in which GRIN2A-MUT patients exhibited a significant improvement in overall survival (HR = 0.66; 95% CI = 0.49 to 0.88; P = 0.005; adjusted P = 0.045). Moreover, patients with GRIN2A-MUTs exhibited an increase in tumor mutational burden, high expression of costimulatory molecules, increased activity of antigen-processing machinery, and infiltration of various immune cells. Additionally, gene sets associated with cell cycle regulation and the interferon response were enriched in GRIN2A-mutated tumors. In conclusion, GRIN2A mutation is a novel biomarker associated with a favorable response to ICIs in multiple cancers.

Regional lymph node density-based nomogram predicts prognosis in nasopharyngeal carcinoma patients without distant metastases.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a relatively common type of cancer in Southern China, with local recurrence or distant metastases even after radical treatment; consequently, it is critical to identify the patients at higher risk for these events beforehand. This study aimed to assess the prognostic value of regional lymph node density (RLND) associated nomograms in NPC and to evaluate the utility of nomograms in risk stratification. METHODS: A total of 610 NPC patients without distant metastases (425 in the training and 185 in the validation cohort) were enrolled. The MRI-identified nodal features and clinical characteristics were documented, and the RLND was calculated. Cox analyses were conducted to identify prognostic-associated factors. Nomograms were generated based on the multivariate analysis results. The predictive accuracy and discriminative ability of the nomogram models were determined using the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve; the results were compared with those of the tumor-node-metastasis (TNM) classification. Decision curve analysis (DCA) and C-index were used to assess the prognostic effect and added discriminative ability of RLND. We also estimated the optimal RLND-based nomogram score cut-off values for survival prediction. RESULTS: RLND was an independent predictor of overall survival (OS) and disease-free survival (DFS), with hazard ratios of 1.36 and 1.30, respectively. RLND was utilized in the construction of nomograms, alongside other independent prognostic factors. The RLND-based nomogram models presented a more effective discriminative ability than the TNM classification for predicting OS (C-index, 0.711 vs. 0.680) and DFS (C-index, 0.681 vs. 0.669), with favorable calibration and consistency. The comparison of C-index values between the nomogram models with and without RLND provided substantiation of the crucial role RLND plays in these models. DCA confirmed the satisfactory clinical practicability of RLND. Moreover, the nomograms were used to categorize the patients into three groups (high-, middle-, and low-risk), and the Kaplan-Meier curves showed significant differences in prognosis between them (p < 0.05). These results were verified in the validation cohort. CONCLUSION: RLND stands as a robust prognostic factor in NPC. The RLND-based nomograms excel in predicting survival, surpassing the TNM classification.

Only one of three hydrophobins (Hyd1-3) contributes to conidial hydrophobicity and insect pathogenicity of Metarhizium robertsii.

Class I/II hydrophobins constitute a family of small amphiphilic proteins that mediate cell hydrophobicity and adhesion to host or substrata and have pleiotropic effects in filamentous fungi. Here we report that only class I Hyd1 is essential for conidial hydrophobicity and insect pathogenicity among three hydrophobins (Hyd1-3) characterized in Metarhizium robertsii, an insect-pathogenic fungus. Aerial conidiation levels of three Δhyd1 mutants were much more reduced in 5-day-old cultures than in 7-day-old cultures, which were wettable (hydrophilic), but restored to a wild-type level in 15-day-old cultures. The Δhyd1 mutants were compromised in conidial quality, including significant decreases in hydrophobicity (58%), adhesion to insect cuticle (36%), insect pathogenicity via normal cuticle infection (37%), UVB resistance (20%), and heat tolerance (10%). In contrast, none of all examined phenotypes were affected in the null mutants of hyd2 and hyd3. Intriguingly, micromorphology and integrity of hydrophobin rodlet bundles on conidial coat were not affected in all mutant and wild-type strains, but the rodlet bundles were disordered in the absence of hyd1, suggesting a link of the disorder to the decreased hydrophobicity. Therefore, Hyd1 mediates the fungal hydrophobicity and plays an important role in conidial quality control and insect-pathogenic lifecycle. Class I Hyd2 and class II Hyd3 seem functionally redundant in M. robertsii.

Neural control of cerebral blood flow: scientific basis of scalp acupuncture in treating brain diseases.

Scalp acupuncture (SA), as a modern acupuncture therapy in the treatment of brain diseases, especially for acute ischemic strokes, has accumulated a wealth of experience and tons of success cases, but the current hypothesized mechanisms of SA therapy still seem to lack significant scientific validity, which may not be conducive to its ultimate integration into mainstream medicine. This review explores a novel perspective about the mechanisms of SA in treating brain diseases based on its effects on cerebral blood flow (CBF). To date, abundant evidence has shown that CBF is significantly increased by stimulating specific SA points, areas or nerves innervating the scalp, which parallels the instant or long-term improvement of symptoms of brain diseases. Over time, the neural pathways that improve CBF by stimulating the trigeminal, the facial, and the cervical nerves have also been gradually revealed. In addition, the presence of the core SA points or areas frequently used for brain diseases can be rationally explained by the characteristics of nerve distribution, including nerve overlap or convergence in certain parts of the scalp. But such characteristics also suggest that the role of these SA points or areas is relatively specific and not due to a direct correspondence between the current hypothesized SA points, areas and the functional zones of the cerebral cortex. The above evidence chain indicates that the efficacy of SA in treating brain diseases, especially ischemic strokes, is mostly achieved by stimulating the scalp nerves, especially the trigeminal nerve to improve CBF. Of course, the mechanisms of SA in treating various brain diseases might be multifaceted. However, the authors believe that understanding the neural regulation of SA on CBF not only captures the main aspects of the mechanisms of SA therapy, but also facilitates the elucidation of other mechanisms, which may be of greater significance to further its clinical applications.

5-HT and S100ß values in evaluating severity of cognitive impairment after traumatic brain injury.

INTRODUCTION: The aim of the study was to investigate the relationship between serum serotonin (5-HT) and central nervous system specific protein S100b application value in evaluating the severity of cognitive impairment after traumatic brain injury (TBI). MATERIAL AND METHODS: 102 patients with TBI treated in Jilin Neuropsychiatric Hospital from June 2018 to October 2020 were selected. According to Montreal Cognitive Assessment (MoCA) scale, patients were tested for cognitive function from multiple levels, such as attention, executive function, memory, and language. Patients with cognitive impairment were included into study group ( n = 64), and those without cognitive impairment were assigned to control group ( n = 58). Serum 5-HT and S100b were compared between the two groups with b level. Serum 5-HT and S100b were analyzed by receiver operating characteristic curve (ROC), b application value judging cognitive impairment. RESULTS: Serum 5-HT and S100b levels in the study group were significantly higher than those in the control group ( p < 0.05). In serum 5-HT and S100b, there was a significant negative correlation with a MoCA score ( r = -0.527, r = -0.436; p < 0.05, p < 0.05). Combined detection of serum 5-HT and S100b's area under ROC curve (AUC) was 0.810 (95% CI: 0.742-0.936, p < 0.05), sensitivity was 0.842, and specificity was 0.813. CONCLUSIONS: Serum 5-HT and S100b levels are closely related to the cognitive function of TBI patients. Combined detection is helpful to improve the accuracy of predicting cognitive impairment.

Essential Role of WetA, but No Role of VosA, in Asexual Development, Conidial Maturation and Insect Pathogenicity of Metarhizium robertsii.

Conidial maturation, which is crucial for conidial quality, is controlled by the asexual development activator WetA and the downstream, velvety protein VosA in Aspergillus. Their orthologs have proved functional in conidial quality control of Beauveria bassiana, as seen in Aspergillus, but are functionally unexplored, in Metarhizium robertsii, another hypocrealean insect pathogen. Here, WetA and VosA prove essential and nonessential for M. robertsii's life cycle, respectively. Disruption of wetA increased hyphal sensitivity to oxidative stress and Congo red-induced cell wall stress, but had little impact on radial growth. The ΔwetA mutant was severely compromised in conidiation capacity and conidial quality, which was featured by slower germination, decreased UV resistance, reduced hydrophobicity, and deformed hydrophobin rodlet bundles that were assembled onto conidial coat. The mutant's virulence was greatly attenuated via normal infection due to a blockage of infection-required cellular processes. All examined phenotypes were unaffected for the ΔvosA mutant. Intriguingly, mannitol was much less accumulated in the 7- and 15-day-old cultures of ΔwetA and ΔvosA than of control strains, while accumulated trehalose was not detectable at all, revealing little a link of intracellular polyol accumulation to conidial maturation. Transcriptomic analysis revealed differential regulation of 160 genes (up/down ratio: 72:88) in ΔwetA. These genes were mostly involved in cellular component, biological process, and molecular function but rarely associated with asexual development. Conclusively, WetA plays a relatively conserved role in M. robertsii's spore surface structure, and also a differentiated role in some other cellular processes associated with conidial maturation. VosA is functionally redundant in M. robertsii unlike its ortholog in B. bassiana. IMPORTANCE WetA and VosA regulate conidiation and conidial maturation required for the life cycle of Beauveria bassiana, like they do in Aspergillus, but remain functionally unexplored in Metarhizium robertsii, another hypocrealean pathogen considered to have evolved insect pathogenicity ~130 million years later than B. bassiana. This study reveals a similar role of WetA ortholog in asexual development, conidial maturation, and insect pathogenicity, and also its distinctive role in mediating some other conidial maturation-related cellular events, but has functional redundancy of VosA in M. robertsii. The maturation process vital for conidial quality proves dependent on a role of WetA in spore wall assembly but is independent of its role in intracellular polyol accumulation. Transcriptomic analysis reveals a link of WetA to 160 genes involved in cellular component, biological process, and molecular function. Our study unveils that M. robertsii WetA or VosA is functionally differential or different from those learned in B. bassiana and other ascomycetes.

Phase Transformation from Amorphous RuSx to Ru-RuS2 Hybrid Nanostructure for Efficient Water Splitting in Alkaline Media.

Ruthenium (Ru)-based materials, as a class of efficient hydrogen evolution reaction (HER) catalysts, play an important role in hydrogen generation by electrolysis of water in an alkaline solution for clean hydrogen energy. Hybrid nanostructure (HN) materials, which include two or more components with distinct functionality, show better performance than their individual materials, since HN materials can potentially integrate their advantages and overcome the weaknesses. However, it remains a challenge to construct Ru-based HN materials with desired crystal phases for enhanced HER performances. Herein, a series of new Ru-based HN materials (t-Ru-RuS2, S-Ru-RuS2, and T-Ru-RuS2) through phase engineering of nanomaterials (PEN) and chemical transformation are designed to achieve highly efficient HER properties. Owing to the plentiful formation of heterojunctions and amorphous/crystalline interfaces, the t-Ru-RuS2 HN delivers the most outstanding overpotential of 16 mV and owns a small Tafel slope of 29 mV dec-1 at a current density of 10 mA cm-2, which exceeds commercial Pt/C catalysts (34 mV, 38 mV dec-1). This work shows a new insight for HN and provides alternative opportunities in designing advanced electrocatalysts with low cost for HER in the hydrogen economy.

Research progress on autophagic flux regulation in cataract / 国际眼科杂志(Guoji Yanke Zazhi)

Autophagic flux refers to a series of dynamic process of autophagic bilayer membrane formation, autophagosome formation, autophagolysosomes formation and degradation. The etiology of cataract is complex, including congenital abnormalities in lens development due to genetic mutations, oxidative damage due to aging, abnormalities in glucose metabolism due to diabetes, and proliferation of lens epithelial cells(LECs)stimulated by postoperative inflammatory factor, all of which are associated with the development of cataracts. A growing number of research in recent years have discovered that altering the status of LECs can contribute to the pathophysiological process of cataract by regulating autophagic flux. This review summarized the impacts of autophagic flux regulation on cataract.

Isobaric tags for relative and absolute quantitation quantitative proteomics research of human lens epithelial cells after ultraviolet-B irradiation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of protein expressions in human lens epithelial cells(SRA01/04)undergoing oxidative damage, hoping to provide new protein target for the pathogenesis of age-related cataract(ARC).METHODS: SRA01/04 cells were divided into experimental group and control group. In the experimental group, cells were irradiated with ultraviolet-B(UVB)for 10min to establish the model of oxidative damage, whereas cells in the control group were untreated. Protein expression profile from the two groups was sequenced by isobaric tags for relative and absolute quantitation(iTRAQ). The filtering criteria that fold change &#x0026;#x003E;1.2 and p&#x0026;#x003C;0.05 was used to determine the differentially expressed proteins(DEPs). Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were utilized for functional enrichment analysis of the top 50 DEPs with either up-regulated or down-regulated significance. Furthermore, Pathway commons software was used to establish the protein-protein interaction(PPI)network.RESULTS: Overall, 552 DEPs were screened out. A total of 176 DEPs were up-regulated in the experimental group compared with the control group, including HMGB1 and USP1, while 376 DEPs were down-regulated, including POLR2A and POLR2B. GO and KEGG enrichment analysis indicated that the top 50 DEPs with up-regulated or down-regulated significance were involved in various crucial biological processes and signaling pathways. PPI network revealed that oxidative damage repair(ODR)-related proteins might play a key role in UVB-induced oxidative damage.CONCLUSIONS: The expressions of multiple proteins, especially ODR-related proteins, can be altered in SRA01/04 cells via UVB irradiation. These findings may provide cellular-related insights into the pathogenesis of ARC and into proteins or pathways associated with therapeutic targets.

Roles of BrlA and AbaA in Mediating Asexual and Insect Pathogenic Lifecycles of Metarhizium robertsii

BrlA and AbaA are key activators of the central developmental pathway (CDP) that controls asexual development in Aspergillus but their roles remain insufficiently understood in hypocerealean insect pathogens. Here, regulatory roles of BrlA and AbaA orthologs in Metarhizium robertsii (Clavicipitaceae) were characterized for comparison to those elucidated previously in Beauveria bassiana (Cordycipitaceae) at phenotypic and transcriptomic levels. Time-course transcription profiles of brlA, abaA, and the other CDP activator gene wetA revealed that they were not so sequentially activated in M. robertsii as learned in Aspergillus. Aerial conidiation essential for fungal infection and dispersal, submerged blastospore production mimicking yeast-like budding proliferation in insect hemocoel, and insect pathogenicity via cuticular penetration were all abolished as a consequence of brlA or abaA disruption, which had little impact on normal hyphal growth. The disruptants were severely compromised in virulence via cuticle-bypassing infection (intrahemocoel injection) and differentially impaired in cellular tolerance to oxidative and cell wall-perturbing stresses. The ΔbrlA and ΔabaA mutant shad 255 and 233 dysregulated genes (up/down ratios: 52:203 and 101:122) respectively, including 108 genes co-dysregulated. These counts were small compared with 1513 and 2869 dysregulated genes (up/down ratios: 707:806 and 1513:1356) identified in ΔbrlA and ΔabaA mutants of B. bassiana. Results revealed not only conserved roles for BrlA and AbaA in asexual developmental control but also their indispensable roles in fungal adaptation to the insect-pathogenic lifecycle and host habitats. Intriguingly, BrlA- or AbaA-controlled gene expression networks are largely different between the two insect pathogens, in which similar phenotypes were compromised in the absence of either brlA or abaA.

EGFR-mediated activation of adipose tissue macrophages promotes obesity and insulin resistance.

Obesity and obesity-related health complications are increasing in prevalence. Adipose tissue from obese subjects has low-grade, chronic inflammation, leading to insulin resistance. Adipose tissue macrophages (ATMs) are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. In response to a high fat diet (HFD), ATM numbers initially increase by proliferation of resident macrophages, but subsequent increases also result from infiltration in response to chemotactic signals from inflamed adipose tissue. To elucidate the underlying mechanisms regulating the increases in ATMs and their proinflammatory phenotype, we investigated the role of activation of ATM epidermal growth factor receptor (EGFR). A high fat diet increased expression of EGFR and its ligand amphiregulin in ATMs. Selective deletion of EGFR in ATMs inhibited both resident ATM proliferation and monocyte infiltration into adipose tissue and decreased obesity and development of insulin resistance. Therefore, ATM EGFR activation plays an important role in adipose tissue dysfunction.

Clinical course of patients on maintenance hemodialysis and COVID-19: a retrospective longitudinal study.

Coronavirus Disease 2019 (COVID-19) emerges as a global pandemic and there is a lack of evidence about the clinical course and outcome of patients on maintenance hemodialysis (MHD). Here we conducted a retrospective longitudinal study aimed to analyze the clinical features and outcome of MHD patients hospitalized with COVID-19. Of 3126 inpatients with COVID-19 at 3 Branches of Wuhan Tongji Hospital from Jan 18th to Mar 9th, 2020, 19 patients were undergoing maintenance hemodialysis. Among the 19 MHD patients with COVID-19, 6 patients (31.6%) died, and 13 patients (68.4%) were able to be discharged. Baseline characteristics, clinical courses, laboratory findings, and dynamic trajectories of major laboratory markers were compared between survivors and nonsurvivors. According to our findings, MHD patients with COVID-19 who experienced non-surviving outcome had more elevated CRP, IL6 and procalcitonin as well as fibrinogen levels at various points compared to survivors. Thus the dysregulation of immune response as well as coagulation abnormalities might be highly involved in the pathological process of COVID-19, contributing to the poor prognosis in MHD patients.

Regioselective Construction of Chemically Transformed Phosphide-Metal Nanoheterostructures for Enhanced Hydrogen Evolution Catalysis.

Engineering nanoheterostructures (NHs) plays a key role in exploring novel or enhanced physicochemical properties of nanocrystals. Despite previously reported synthetic methodologies, selective synthesis of NHs to achieve the anticipated composition and interface is still challenging. Herein, we presented a colloidal strategy for the regioselective construction of typical Ag-Co2P NHs with precisely controlled location of Ag nanoparticles (NPs) on unique chemically transformed Co2P nanorods (NRs) by simply changing the ratio of different surfactants. As a proof-of-concept study, the constructed heterointerface-dependent hydrogen evolution reaction (HER) catalysis was demonstrated. The multiple Ag NP-tipped Co2P NRs exhibited the best HER performance, due to their more exposed active sites and the synergistic effect at the interfaces. Our results open up new avenues in rational design and fabrication of NHs with delicate control over the spatial distribution and interfaces between different components.

Peritumoral edema in preoperative magnetic resonance imaging is an independent prognostic factor for hepatocellular carcinoma.

BACKGROUND: Peritumoral edema is an independent prognostic risk factor for malignant tumors. Therefore, assessment of peritumoral edema in preoperative magnetic resonance imaging (MRI) may provide better prognostic information in patients with hepatocellular carcinoma (HCC). AIM: To determine whether peritumoral edema in preoperative MRI is a prognostic factor for HCC. METHODS: A retrospective analysis of 90 patients with HCC confirmed by surgical pathology was performed. All patients' peritumoral edema in preoperative MRI was reviewed by two radiologists. The association of disease recurrence with peritumoral edema and clinicopathological features was assessed using the Cox proportional hazards model. Interobserver agreement for evaluating peritumoral edema was determined using Cohen's κ coefficient. RESULTS: Recurrence and non-recurrence after an average 20.8 month follow-up was 25.6% (23/90) and 74.4% (67/90), respectively. The ratio of peritumoral edema of 90 patients with HCC in preoperative MRI was 35.6% (32/90). In univariate Cox regression analysis, peritumoral edema [hazard ratio (HR) 11.08, P < 0.001], tumor diameter (HR 4.12, P = 0.001), microvascular invasion (HR 2.78, P = 0.020), gender (HR 0.29, P = 0.006), cirrhosis (HR 2.45, P = 0.049), ascites syndrome (HR 2.83, P = 0.022), aspartate aminotransferase(AST)/alanine aminotransferase(ALT) (HR 5.07, P = 0.003) were indicators for HCC recurrence. In multivariate Cox regression analysis, the tumor diameter (HR 2.53, P = 0.032) and peritumoral edema (HR 8.71, P < 0.001) were independent prognostic factors of HCC. The sensitivity, specificity, positive predictive value and negative predictive value of peritumoral edema and tumor diameter were 82.6%&60.9%, 80.6%&77.6%, 59.4%&48.3%, and 93.1%&85.3%, respectively. CONCLUSION: Peritumoral edema in preoperative MRI may be considered as a biomarker of prognostic information for patients with HCC.

Improving generation of H2O2 and •OH at copper hexacyanocobaltate/graphene/ITO composite electrode for degradation of levofloxacin in photo-electro-Fenton process.

In this work, copper hexacyanocobaltate was electro-deposited at amino-graphene-coated indium-tin-oxide glass to form multifunctional heterogeneous catalyst (CuCoG/ITO), which was confirmed by field emission scanning microscope, infrared spectra, X-ray diffraction, and electro-chemistry techniques. A novel heterogeneous photo-electro-Fenton-like system was established using CuCoG/ITO as an air-diffusion electrode, in which hydrogen peroxide (H2O2) and hydroxyl radical (•OH) could be simultaneously generated by air O2 reduction. The productive rate of •OH could reached to 70.5 µmol h-1 at - 0.8 V with 300 W visible light irradiation at pH 7.0, 0.1 M PBS. Levofloxacin could be quickly degraded at CuCoG/ITO during heterogeneous photo-electro-Fenton process in neutral media with a first-order kinetic constant of 0.49 h-1.

Association of liver abnormalities with in-hospital mortality in patients with COVID-19.

BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

Genetic polymorphisms of ATG16L1 and IRGM genes in Malaysian patients with Crohn's disease.

OBJECTIVE: To investigate the association between genetic polymorphisms in ATG16L1 and IRGM genes and the development of Crohn's disease (CD) in Malaysian patients. METHODS: Altogether 335 participants were recruited, including 85 patients with CD and 250 unrelated healthy controls, and their informed consent was obtained. Genomic DNA was extracted via a conventional phenol-chloroform extraction method. Six single nucleotide polymorphisms (SNPs) in ATG16L1 and IRGM genes were genotyped using TaqMan SNP genotyping assays. Associations between SNP and CD were determined using Fisher's exact test, odds ratio, and 95% confidence interval. Statistical power and the Hardy-Weinberg equilibrium were also calculated. RESULTS: Two SNPs (rs2241880 and rs6754677) in the ATG16L1 gene were significantly associated with the onset of CD in the Malaysian population. The A allele and homozygous A/A genotype of the rs2241880 A/G polymorphism were protective against CD in the overall Malaysian and Malay population. The G allele and homozygous G/G genotype of the rs6754677 G/A polymorphism were protective in the Indian population, whereas the homozygous A/A genotype showed a risk of developing CD. The homozygous G/G genotype of IRGM rs11747270 was significantly present in the controls. However, this significance was not observed in a race-stratified analysis. All three ATG16L1 SNPs were associated with inflamed terminal ileum. IRGM rs4958847 and rs11747270 increased the risk of developing arthritis in patients with CD. CONCLUSION: We found a significant association between SNP, which are located in autophagy-related genes, and CD in a Malaysian population.

Ganoderic acid A protects lens epithelial cells from UVB irradiation and delays lens opacity / 中国天然药物

A contributory role of oxidative stress and protection by antioxidant nutrients have been suspected in cataract formation. Ganoderic acid A (GAA), an effective lanostane triterpene, is widely reported as an antioxidant. The aim of this study is to investigate the potential effects of GAA on cataract formation. After lens epithelial cells (LECs) were exposed to UVB radiation for different periods, cell viability, apoptosis-related protein levels, malondialdehyde (MDA) and superoxide dismutase (SOD) activities were monitored. We found that cell viability, the Bcl-2/Bax ratio and SOD activity were increased, while Cleaved caspase-3 levels and MDA activity were decreased compared with those in UVB-impaired LECs after GAA treated. Furthermore, GAA activated PI3K/AKT in UVB-impaired LECs and effectively delayed the occurrence of lens opacity in vitro. In conclusion, these findings demonstrated that GAA exhibited protective functions in SRA01/04 cells and rat lenses against UVB-evoked impairment through elevating cell viability and antioxidant activity, inhibiting cell apoptosis, activating the PI3K/AKT pathway and delaying lens opacity.