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ABSTRACT Background Systemic inflammation stands as a pivotal factor tightly interwoven with the progression of COVID‐19. This study endeavors to elucidate the significance of three key inflammatory molecules, that is, heparin‐binding protein (HBP), interleukin‐6 (IL‐6), and C‐reactive protein (CRP), in assessing the severity and prognostic implications of COVID‐19. Methods The demographic, clinical, and laboratory data were retrospectively collected from a cohort of 214 adult patients diagnosed with COVID‐19. Patients were divided into two groups: nonsevere (n = 93; 43.5%) and severe (n = 121; 56.5%). Additionally, based on their organ function, patients were categorized into nonorgan failure (n = 137) and organ failure (n = 77) groups. The levels of inflammation‐related cytokines were then compared among these defined groups. Results The severe group was characterized by a higher proportion of males, older age, and longer hospital stays compared to nonsevere cases. Additionally, severe cases exhibited a higher prevalence of underlying diseases and organ failure. Statistical analysis revealed significantly elevated levels of HBP, IL‐6, and CRP in the severe group. HBP, IL‐6, and CRP were identified as independent risk factors for severe COVID‐19. Furthermore, a combined assessment of these biomarkers demonstrated superior diagnostic sensitivity (85.10%) and specificity (95.70%) for predicting COVID‐19 severity. A positive relationship between elevated HBP, IL‐6, and CRP levels and impaired organ function was also observed. The predictive efficiency significantly increased (hazard ratio = 3.631, log‐rank p = 0.003) when two or more of them were combinedly used. Notably, elevated levels of HBP, IL‐6, and CRP were associated with an increased risk of mortality. Conclusions In conclusion, the combined assessment of HBP, IL‐6, and CRP offers enhanced accuracy and specificity in predicting the severity, organ failure, and mortality risk associated with COVID‐19.

Abstract Background CHF (Congenital hepatic fibrosis) is a rare hereditary disease characterized by periportal fibrosis and ductal plate malformation. Little is known about the clinical presentations and outcome in CHF patients with an extraordinary complication with biliary sepsis. Case summary Our case described a 23-year-old female diagnosed as CHF combined with biliary sepsis. Her blood culture was positive for KP (Klebsiella pneumoniae), and with a high level of CA19-9 (> 1200.00 U/ml, ref: G (p. V1287G) and c.9059T > C (p. L3020P) in PKHD1 gene. After biliary sepsis relieved, her liver function test was normal, and imaging examination results showed no significant difference with the results harvested during her biliary sepsis occurred. Conclusion The diagnosis of CHF complicated with biliary sepsis in the patient was made. Severely biliary sepsis due to KP infection may not inevitably aggravate congential liver abnormality in young patients. Our case provides a good reference for timely treatment of CHF patients with biliary sepsis.

LiNbO _3 (LNO) is currently intensively studied as an important ferroelectric material. In this work, polycrystalline LNO films were prepared through a sputtering technique, and their ferroelectricity-related resistive switching property was investigated using a device structure of PtSi/SiO _2 /LNO/Pt. The device exhibits a volatile resistance switching property at lower positive sweeping voltages and a stable bipolar nonvolatile switching property at higher sweeping voltages. The resistive switching mechanism of the device is discussed based on the domain wall conductivity characteristics of the polycrystalline LNO thin films. The PtSi/SiO _2 /LNO/Pt memristor device has potential applications in memory and artificial neural synapses.

Objectives Fatigue is common in patients with chronic liver disease; however, its pathogenesis is unclear. This study aimed to provide insights into the pathogenesis of chronic liver disease-related fatigue by assessing the relationship between fatigue and the degree of inflammation in chronic liver disease.Design We performed a cross-sectional study of 1374 patients with pathologically proven chronic liver disease diagnosed at the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China.Setting Primary single-centre study.Participants One thousand three hundred and seventy-four patients with liver biopsy-proven chronic liver disease.Interventions The patients were divided into fatigue and non-fatigue groups according to the Chronic Liver Disease Questionnaire. Propensity score matching was used to match the baseline features of the patients in the two groups.Primary and secondary outcome measures Liver steatosis, ballooning, inflammation and fibrosis were measured according to the pathological results of liver biopsy. Fatigue was measured using the Chronic Liver Disease Questionnaire.Results Of the 1374 patients, 262 (19.67%) experienced fatigue. There were 242 and 484 patients with and without fatigue, respectively, who were successfully matched for sex, age and classification of chronic liver disease by propensity score matching. After matching, the fatigue group showed higher liver enzyme levels, inflammation grades and fibrosis stages than the non-fatigue group (p0.05).Conclusion Patients with chronic liver disease were burdened by fatigue, which increased progressively with rising liver inflammation severity in young-aged and middle-aged rather than elderly patients.

Introduction and Objectives: The optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. Patients and Methods: The data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). Results: A total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P

Alternative splicing is dysregulated in hepatocellular carcinoma. Here, the authors investigate the role of the splice variant of Splicing Regulatory Glutamic Acid and Lysine Rich Protein 1 (SREK1) and its upstream regulator, Serine/arginine-rich splicing factor 10 (SRSF10) in sustaining the oncogenic signal.

Abstract Objective Tumor cells could acquire drug resistance through cell autophagy. This study aimed to explore the role of SNHG16 in sorafenib‐resistant HCC cells and its mechanism with miR‐23b‐3p. Methods The sorafenib‐resistant Hep3B cell model was established. The SNHG16 and miR‐23b‐3p gene expressions were determined in normal HCC and sorafenib‐resistant HCC tissues. Detection of the expression of SNHG16 and miR‐23b‐3p and its respective correlation with survival rate were performed. Target genes to SNHG16 and miR‐23b‐3p were predicted, and verified by dual‐fluorescent reporter assay. The effects of SNHG16 and miR‐23b‐3p on SNHG16, miR‐23b‐3p, EGR1 expression, viability, apoptosis as well as LC3II/LC3 expression in Hep3B and Hep3B/So cells were detected by qRT‐PCR, CCK‐8, flow cytometry, and western blot. In in vivo studies, the NOD/SCID mice model was established to explore the effects of Hep3B and Hep3B/So cells with inhibited SNHG16 or miR‐23b‐3p on tumor size, EGR1 expression, and autophagy. Results High SNHG16 expression in HCC‐resistant tissues and low miR‐23b‐3p expression in all HCC tissues were detected, and the two were negatively correlated. Low SNHG16 and high miR‐23b‐3p were related to a high survival rate of HCC patients. Moreover, SNHG16 overexpression promoted Hep3B/So cell viability and autophagy, suppressed apoptosis by inhibiting miR‐23b‐3p expression through up‐regulating EGR1, however, the effect of si‐SNHG16 was opposite. In in vivo studies, miR‐23b‐3p inhibitor suppressed the high sorafenib sensitivity in Hep3B/So cells caused by SNHG16 silencing through promoting viability, autophagy, and suppressing apoptosis. Conclusion SNHG16 promotes Hep3B/So cell viability, autophagy, and inhibits apoptosis to maintain its resistance to sorafenib through regulating the expression of miR‐23b‐3p via sponging EGR1.

A patient with pneumonia had a fever for 2 weeks. After the initial anti-infection treatment failed, he was diagnosed with C. psittaci pneumonia complicated with organizing pneumonia, through next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) and lung biopsy. He was treated with antibiotics and corticosteroids for 2 months.

In this study, molybdenum disulfide (MoS2) film samples were prepared at different temperatures and annealed through magnetron sputtering technology. The surface morphology, crystal structure, bonding structure, and optical properties of the samples were characterized and analyzed. The surface of the MoS2 films prepared by radio frequency magnetron sputtering is tightly coupled and well crystallized, the density of the films decreases, and their voids and grain size increase with the increase in deposition temperature. The higher the deposition temperature is, the more stable the MoS2 films deposited will be, and the 200 °C deposition temperature is an inflection point of the film stability. Annealing temperature affects the structure of the films, which is mainly related to sulfur and the growth mechanism of the films. Further research shows that the optical band gaps of the films deposited at different temperatures range from 0.92 eV to 1.15 eV, showing semiconductor bandgap characteristics. The optical band gap of the films deposited at 200 °C is slightly reduced after annealing in the range of 0.71–0.91 eV. After annealing, the optical band gap of the films decreases because of the two exciton peaks generated by the K point in the Brillouin zone of MoS2. The blue shift of the K point in the Brillouin zone causes a certain change in the optical band gap of the films.

BackgroundAPOBEC3G (A3G) and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized.Methods and findingsIn the present study, we have demonstrated that the regions of APOBEC3F (A3F) that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD) of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required for its functional interaction with full-length A3F are also required for the degradation of the C-CDD of A3F; in contrast, those Vif domains that are uniquely required for functional interaction with A3G are not required for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains required for the degradation of A3F are also required for the degradation of A3C and A3DE. On the other hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminases A3C and A3DE.ConclusionsOur data suggest that distinct regions of A3F and A3G are targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE through similar recognition determinants, which are conserved among Vif molecules from diverse HIV-1 strains. Mapping these determinants may be useful for the design of novel anti-HIV inhibitors.

The amino-terminal region of the Vif molecule in human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV) contains a conserved SLV/Ix4Yx9Y motif that was first described in 1992, but the importance of this motif for Vif function has not yet been examined. Our characterization of the amino acids surrounding this motif in HIV-1 Vif indicated that the region is critical for APOBEC3 suppression. In particular, amino acids K22, K26, Y30, and Y40 were found to be important for the Vif-induced degradation and suppression of cellular APOBEC3G (A3G). However, mutation of these residues had little effect on the Vif-mediated suppression of A3F, A3C, or A3DE, suggesting that these four residues are not important for Vif assembly with the Cul5 E3 ubiquitin ligase or protein folding in general. The LV portion of the Vif SLV/Ix4Yx9Y motif was found to be required for optimal suppression of A3F, A3C, or A3DE. Thus, the SLV/Ix4Yx9Y motif and surrounding amino acids represent an important functional domain in the Vif-mediated defense against APOBEC3. In particular, the positively charged K26 of HIV-1 Vif is invariably conserved within the SLV/Ix4Yx9Y motif of HIV/SIV Vif molecules and was the most critical residue for A3G inactivation. A patch of positively charged and hydrophilic residues (K22x3K26x3Y30x9YRHHY44) and a cluster of hydrophobic residues (V55xIPLx4-5LxΦ2YWxL72) were both involved in A3G binding and inactivation. These structural motifs in HIV-1 Vif represent attractive targets for the development of lead inhibitors to combat HIV infection. [ABSTRACT FROM AUTHOR]