Ca2+-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy upon glucose starvation.

Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to glucose starvation to induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal that connects environmental sensing to the formation of the autophagy initiation complex during glucose starvation. Mechanistically, glucose starvation instigates the release of vacuolar calcium into the cytoplasm, thus triggering the activation of Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances Atg11 interactions with Bmh1/2 bound to the Snf1-Sip1-Snf4 complex, leading to recruitment of vacuolar membrane-localized Snf1 to the PAS and subsequent Atg1 activation, thereby initiating autophagy. We also identified Glc7, a protein phosphatase-1, as a critical regulator of the association between Bmh1/2 and the Snf1 complex. We thus propose that calcium-triggered Atg11-Bmh1/2-Snf1 complex assembly initiates autophagy by controlling Snf1-mediated Atg1 activation in response to glucose starvation.

The essential link: How STAT3 connects tumor metabolism to immunity.

Immunotherapy is a promising and long-lasting tumor treatment method, but it is challenged by the complex metabolism of tumors. To optimize immunotherapy, it is essential to further investigate the key proteins that regulate tumor metabolism and immune response. STAT3 plays a crucial role in regulating tumor dynamic metabolism and affecting immune cell function by responding to various cytokines and growth factors, which can be used as a potential target for immunotherapy. This review focuses on the crosstalk between STAT3 and tumor metabolism (including glucose, lipid, and amino acid metabolism) and its impact on the differentiation and function of immune cells such as T cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), and reveals potential treatment strategies.

Factors influencing death attitudes of medical students: a scoping review.

Aim: To summarize factors influencing death attitudes of medical students, help identify intervention targets, and design precision interventions for improving death attitudes of medical students. Methods: Web of Science, PubMed, Embase, OVID, China National Knowledge Infrastructure, and Wanfang databases were searched. Retrieval time was from January 2012 to September 2023. Studies on factors influencing death attitudes of medical students were included. Results: Thirty-five studies were included in the final review. A total of 28 factors influencing death attitudes of medical students were summarized and divided into three categories comprising personal factors, social factors, and psychological factors. More than 15 studies confirmed that gender, religion, and discussing death with families were factors that influenced medical students' death attitudes. Conclusion: Results indicate that there are many types of factors that influence death attitudes of medical students. It is necessary for universities to implement death education based individual characteristics and guide medical students to cultivate generally optimistic death attitudes and appropriate life values.

Butterfly-tie like MnCO3@Mn3O4 heterostructure enhanced the electrochemical performances of aqueous zinc ion batteries.

Due to the limited exploitation and utilization of fossil energy resources in recent years, it is imperative to explore and develop new energy materials. As an electrode material for batteries, MnCO3 has the advantages of safety, non-toxicity, and wide availability of raw materials. But it also has some disadvantages, such as short cycle period and low conductivity. In order to improve these deficiencies, we designed a MnCO3@Mn3O4 heterostructure material by a simple solvothermal method, which possessed a microstructure of "butterfly-tie". Owing to the introduction of Mn3O4 and the layered structure of "butterfly-tie", MnCO3@Mn3O4 possessed a discharge capacity of 165 mAh/g when the current density was 0.2 A/g and exhibited satisfactory rate performance. The MnCO3@Mn3O4 heterostructure was optimized by density functional theory (DFT), and the deformation charge density was calculated. It was found that the MnCO3@Mn3O4 heterostructure is stable owing to the molecular interaction between the O atoms from MnCO3 and the Mn atoms from Mn3O4 at the interface of heterojunction. Therefore, the MnCO3@Mn3O4 heterostructure material has promising applications as safe and efficient cathode material for energy batteries.

Parameter Estimation in Spectral Resolution Enhancement Based on Forward-Backward Linear Prediction Total Least Square Method.

In a Fourier transform infrared (IR) spectrometer, the Michelson interference signal extrapolation method based on linear prediction is often used to improve spectral resolution. In this method, an autoregressive (AR) model is established for the Michelson interference signal in the spectrometer. Once the AR model parameters are determined, the AR process is predictable. The interference signal can be used to figure out the AR model's parameters. Based on this, the AR model can be used to extrapolate the interference signal to improve the spectral resolution. In this paper, the forward-backward linear prediction total least squares (FB-TLS) method is proposed to estimate the parameters of the AR model. The parameters that are estimated are used to improve the IR spectral resolution. By simulating different order and signal-to-noise ratio situations, the effects of the Burg, the least square, and the FB-TLS parameter estimation methods on spectral resolution enhancement are studied. The simulation results demonstrate that the FB-TLS parameter estimation method can effectively suppress noise and avoid spurious peaks. The experimental results demonstrate that the FB-TLS parameter estimation method is effective for spectral resolution enhancement technology based on linear prediction. When the FB-TLS method is used to enhance NH3 IR spectral resolution from 2 cm-1 to 1 cm-1, the spectral prediction error in the NH3 characteristic band is only 0.21% compared with the measured NH3 spectrum, whose spectral resolution is 1 cm-1.

Clinical features and prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapidly progressive interstitial lung disease in Chinese patients.

OBJECTIVE: The objective of this study is to investigate clinical features and prognostic factors of antimelanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis with rapidly progressive interstitial lung disease (RP-ILD) in Chinese patients. METHODS: Clinical features and prognostic factors of patients with newly diagnosed or recurrent dermatomyositis patients were retrospectively analyzed. All patients were divided into the anti-MDA5-positive or negative dermatomyositis, and with or without RP-ILD groups. Clinical features and prognostic factors were statistically compared among different groups. RESULTS: The serum ferritin (SF) levels (1500.0 [658.80, 1844.0]) and γ-glutamyl transpeptidase (γ-GT) (125.5 [61.0, 232.0] vs. 28 [16.0, 41.0], Z = 5.528; p < .001) were markedly higher, and phosphocreatine myoenzyme (CK) (73.0 [42.0, 201.0] vs. 1333.0 [79.0, 8000.0], Z = -2.739, p = .006), serum albumin level (32.51 ± 5.23 vs. 35.81 ± 5.88, t = -2.542, p = .013), and lymphocyte count (0.80 ± 0.36 vs. 1.45 ± 0.77, t = -4.717, p < .001) were lower than those in anti-MDA5-negative counterparts. Among patients with anti-MDA5 antibody (Ab) with RP-ILD, the SF level (1531.0 [1163.8, 2016.5] vs. 584.9 [564.8, 1042.5], Z = 2.664, p = .008), γ-GT (134.0 [81.0, 204.5] vs. 123.0 [76.0, 189.0], Z = 3.136, p = .002) and positive rate of anti-RO-52 Ab (90.9% vs. 50.0%, χ2 = 7.222, p = .013) were higher and lymphocyte count (0.79 ± 0.38 vs. 1.32 ± 0.74, t = -3.025, p = .029) was lower than those in their counterparts without RP-ILD. The SF level of anti-MDA5 nonsurvivors (1544 [1447.32, 2089.0] vs. 584.9 [515.7, 1500.0], Z = 2.096, p = .030), anti-RO-52 Ab-positive rate ([16/18, 88.9%] vs. [9/16, 56.2%], χ2 = 4.636, p = .031) were higher than those in survivors. Lymphocytopenia was a risk factor for RP-ILD and death of patients with anti-MDA5-positive dermatomyositis. The area under receiver operating characteristic curve was 0.888 (95% confidence interval: 0.756, 1.000; p < .001), the sensitivity was 85.7%, the specificity was 93.8%, and Youden's index was 0.795. CONCLUSIONS: Anti-MDA5-positive dermatomyositis patients are prone to developing RP-ILD. Declined lymphocyte count is a critical risk factor for RP-ILD, probably acting as a simple and effective predictor for Chinese patients with anti-MDA5-positive dermatomyositis.

Characterization of Group B Streptococcus Recovered from Pregnant Women and Newborns Attending in a Hospital in Beijing, China.

Purpose: We investigate the drug resistance, serotype and multilocus sequence typing (MLST) of Group B streptococcus (GBS) strains obtained from pregnant women and neonates in a hospital in Beijing. Patients and Methods: In this cross-sectional study, 1470 eligible pregnant women at a gestational age of 35-37 weeks presented to our department between May 2015 and May 2016 were included. Vaginal and rectal samples from pregnant women together with sampling from neonatal samples were collected to screen GBS. GBS strains were subject to drug resistance and serotype analysis and MLST. Results: GBS strains were isolated from 111 pregnant women (7.6%) and 6 neonates (0.99%) from 606 matched neonates. 102 strains from pregnant women and 3 strains from neonates were included in the drug sensitivity test, serotyping and MLST typing. All these strains were susceptible to ampicillin, penicillin, ceftriaxone, vancomycin, linezolid, and meropenem. Sixty strains (58.8%) showed multi-drug resistance. Serious cross-resistance was seen between erythromycin and clindamycin. There were eight serotypes, and 37 strains (36.3%) showed a serotype of type III serving as the major type. All 102 GBS strains isolated from pregnant samples could be divided into 18 STs types. They belonged to five clonal complexes and five single clones, with the predominant type of ST19/III, ST10/Ib, and ST23/Ia, with CC19 as the most common type. Three GBS strains isolated from neonates covered two serotypes (ie type III and Ia) that were consistent with those of the mothers. Conclusion: Serotype III was the predominant serotype of GBS in this study. The predominant MLST type was ST19, ST10, and ST23, with ST19/III, ST10/Ib, and ST23/Ia serving as the most prevalent and CC19 as the most common clonal complex. GBS strains from neonates were consistent in the clonal complex, serotype, and MLST with these isolated from the mothers.

Hsa_circ_0017956 Acts as miR-758-3p Sponge to Facilitate the Progression of Non-small-Cell Lung Cancer by Regulating FOXP4 Expression.

Accumulating studies have demonstrated the important role of circular RNAs (circRNAs) in the progression of different human tumors, including non-small-cell lung cancer (NSCLC). The purpose of this study was to deeply study the function and mechanism of circ_0017956 in NSCLC. Real-time quantitative polymerase chain reaction (RT-qPCR) was applied to detect the expression of circ_0017956, microRNA-758-3p (miR-758-3p), and Forkhead Box P4 (FOXP4). Western blot was performed to determine the protein levels. Cell proliferation was examined by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Flow cytometry was used to evaluate the apoptosis of NSCLC cells. Transwell assay was applied to detect cell migratory and invasive capacities. The angiogenesis ability was evaluated by tube formation experiment. The target relationship between miR-758-3p and circ_0017956 or FOXP4 was confirmed by dual-luciferase reporter assay. Animal experiment was conducted to assess the effect of circ_0017956 in vivo. Circ_0017956 and FOXP4 were upregulated, while miR-758-3p was downregulated in NSCLC tissues and cells. Silencing of circ_0017956 significantly suppressed cell proliferation, migration, invasion, and angiogenesis, but promoted cell apoptosis in NSCLC cells. Mechanically, circ_0017956 functioned as a sponge for miR-758-3p and miR-758-3p could directly interact with FOXP4. Moreover, silencing of miR-758-3p or overexpression of FOXP4 could overturn the anticancer influence of circ_0017956 interference on NSCLC cells. Besides that, circ_0017956 knockdown hindered tumor growth in vivo. Altogether, circ_0017956 promoted the progression of NSCLC by regulating FOXP4 through sponging miR-758-3p.

Targeting FABP4 in elderly mice rejuvenates liver metabolism and ameliorates aging-associated metabolic disorders.

INTRODUCTION: Aging is characterized by progressive metabolic dyshomeostasis that increases morbidity and mortality. Solutions for optimizing healthy aging are challenged by lacking appropriate biomarkers. Moreover, druggable targets to rejuvenate the aging-associated metabolic phenotypes remain unavailable. METHODS: Proteomics analysis was performed in a cohort of young and elderly adults. Circulating levels of insulin-like growth factor 1 (IGF-1) and fatty acid binding protein 4 (FABP4) were evaluated by ELISA. FABP4 was silenced in elderly mice by adeno-associated virus. Metabolic activities were measured by metabolic cages. Cognitive function was evaluated by Morris water maze. Glucose and lipid metabolism were evaluated by biochemistry assays with blood samples. RNA-seq in mouse liver was performed for transcriptome analysis. RESULTS: Among 9 aging-sensitive proteins shared by both male and female, FABP4 was identified as a reliable aging biomarker in both human and mouse. Silencing FABP4 in elderly mice significantly rejuvenated the aging-associated decline in metabolic activities. FABP4 knockdown reversed the aging-associated metabolic disorders by promoting degradation of cholesterol and fatty acids, while suppressing gluconeogenesis. Transcriptome analysis revealed a restoration of the pro-aging gene reprogramming towards inflammation and metabolic disorders in the liver after FABP4 knockdown. FABP4 overexpression promoted human LO2 cell senescence. Moreover, administration of an FABP4 inhibitor BMS309403 delivered metabolic benefits in elderly mice. CONCLUSION: Our findings demonstrate FABP4 as a reliable aging biomarker as well as a practicable target to improve healthy aging in the elderly.

Planar Chiral Multiple Resonance Thermally Activated Delayed Fluorescence Materials for Efficient Circularly Polarized Electroluminescence.

Chiral boron/nitrogen doped multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters are promising for highly efficient and color-pure circularly polarized organic light-emitting diodes (CP-OLEDs). Herein, we report two pairs of MR-TADF materials (Czp-tBuCzB, Czp-POAB) based on planar chiral paracyclophane with photoluminescence quantum yields of up to 98 %. The enantiomers showed symmetric circularly polarized photoluminescence spectra with dissymmetry factors |gPL | of up to 1.6×10-3 in doped films. Meanwhile, the sky-blue CP-OLEDs with (R/S)-Czp-tBuCzB showed an external quantum efficiency of 32.1 % with the narrowest full-width at half-maximum of 24 nm among the reported CP-OLEDs, while the devices with (R/S)-Czp-POAB displayed the first nearly pure green CP electroluminescence with |gEL | factors at the 10-3 level. These results demonstrate the incorporation of planar chirality into MR-TADF emitter is a reliable strategy for constructing of efficient CP-OLEDs.

Key emergency response technologies for abrupt air pollution accidents in China.

Abrupt air pollution accidents can endanger people's health and destroy the local ecological environment. The appropriate emergency response can minimize the harmful effects of accidents and protect people's lives and property. This paper provides an overview of the key emergency response technologies for abrupt air pollution accidents around the globe with emphasis on the major achievements that China has obtained in recent years. With decades of effort, China has made significant progress in emergency monitoring technologies and equipment, source estimation technologies, pollutant dispersion simulation technologies and others. Many effective domestic emergency monitoring instruments (e.g., portable DOAS/FT-IR systems, portable FID/PID systems, portable GC-MS systems, scanning imaging remote sensing systems, and emergency monitoring vehicles) had been developed which can meet the demands for routine emergency response activities. A monitoring layout technique combining air dispersion simulation, fuzzy comprehensive evaluation, and a post-optimality analysis was proposed to identify the optimal monitoring layout scheme under the constraints of limited monitoring resources. Multiple source estimation technologies, including the forward method and the inversion method, have been established and evaluated under various scenarios. Multi-scale dynamic pollution dispersion simulation systems with high temporal and spatial resolution were further developed. A comprehensive emergency response platform integrating database support, source estimation, monitoring schemes, fast monitoring of pollutants, pollution predictions and risk assessment was developed based on the technical idea of "source identification - model simulation - environmental monitoring" dynamic interactive feedback. It is expected that the emergency response capability for abrupt air pollution accidents will gradually improve in China.

A Lower HCC Incidence in Chronic HBV-Infected Patients Recovered from Acute-on-Chronic Liver Failure: A Prospective Cohort Study.

Background: Activation of chronic hepatitis B virus (HBV) infection is an important cause of acute-on-chronic liver failure (ACLF). However, the effect of HBV-ACLF episode on hepatocellular carcinoma (HCC) occurrence remains largely unknown. Methods: A total of 769 HBV-ACLF patients and 2114 HBV-related chronic liver disease (HBV-CLD) patients diagnosed between August 1998 and December 2011 were enrolled in this prospective cohort study. Of the HBV-CLD patients, 380 received lifetime antiviral treatment with nucleos(t)ide analogues. Propensity score matching was applied to reduce baseline differences between HBV-ACLF and HBV-CLD cohorts. Results: The survival rate of HBV-ACLF patients was 53.6%, 50.3%, 47.8%, and 46.2% at 90-day, 1-year, 5-year, and 10-year, respectively. The cumulative incidence of HCC was lower in HBV-ACLF cohort with 369 eligible patients survived for >90 days than in HBV-CLD cohort with the 380 patients (5.77/1,000 vs. 9.78/1,000 person-years, p = 0.0497). HBV-ACLF episode decreased HCC risk regardless of liver cirrhosis, and in patients without family history of HCC. Multivariate Cox analyses indicated that male, increasing age, liver cirrhosis, and platelet count (≤100 × 109/L) increased, whereas HBV-ACLF episode decreased, HCC risk independently. In the propensity score-matched cohorts, HBV-ACLF episode reduced HCC incidence (10.20/1,000 vs. 4.66/1,000 person-years, p = 0.0326). The area under curve of nomogram was 0.812 for 3-year HCC probability. Conclusions: HBV-ACLF episode decreases HCC occurrence in chronic HBV patients. Older age and liver cirrhosis independently increased HCC occurrence. A nomogram-enrolled episode of ACLF reliably predicts the occurrence of HCC.

Chiral-at-Cage Carboranes for Circularly Polarized Luminescence and Aggregation-Induced Electrochemiluminescence.

Herein, we report the structures of chiral-at-cage carborane derivatives bearing carbazole chromophores that emit circularly polarized luminescence (CPL) and aggregation-induced electrochemiluminescence (AIECL). By adjusting the substituent positions on the carborane derivatives, two chiral luminescent molecules, Cb1 and Cb2, with different properties were obtained. The photoluminescence dissymmetry factors |gPL | of both (R/S)-Cb1 and (R/S)-Cb2 enantiomers in neat films were as high as 6.24×10-3 and 7.38×10-3 , respectively. Cb1 showed a deep blue emission peak at 434 nm in n-pentane. Interestingly, distinct fluorescence and CPL spectra were observed in solvents of different polarities due to the twisted intramolecular charge transfer effect, suggesting its potential use in solvent recognition. Meanwhile, Cb2 exhibited good AIECL property, excellent ECL stability and could be used for determining dopamine concentrations, suggesting its potential applications in biology and diagnosis.

G-CSF promotes the viability and angiogenesis of injured liver via direct effects on the liver cells.

BACKGROUND: Presently, liver transplantation is the only treatment strategy for liver failure (LF). Although granulocyte-colony stimulating factor (G-CSF) exhibits protective functions in LF, it is not clear whether it directly affects the liver cells. METHODS AND RESULTS: We established an injured liver cell model and observed that G-CSF treatment promoted cell viability and enhanced Ki67 and VEGF-A expression. Thereafter, human umbilical vein endothelial cells (HUVECs) were cultured in a conditioned medium collected from the G-CSF-treated injured liver cells. HUVECs' proliferation and tubule formation were promoted. Furthermore, in an injured liver mouse model, confirmed via haematoxylin-eosin staining, we evaluated serum alanine aminotransferase activity, Ki67 expression, and microvessel density (MVD). G-CSF treatment significantly relieved liver injury, upregulated Ki67 expression, and enhanced MVD in the injured mouse liver tissue. Additionally, AKT and ERK signal targets were explored, and it was demonstrated that the effects of G-CSF on injured liver cells were mediated through the AKT and ERK signalling pathways. CONCLUSIONS: G-CSF promotes injured liver viability and angiogenesis by directly affecting injured liver cells via the AKT and ERK signalling pathways. These findings improve our understanding of the role of G-CSF in recovery from LF.

Serinc2 deficiency causes susceptibility to sepsis-associated acute lung injury.

BACKGROUND: Severe sepsis and its subsequent complications cause high morbidity and mortality rates worldwide. The lung is one of the most vulnerable organs sensitive to the sepsis-associated inflammatory storm and usually develops into acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). The pathogenesis of sepsis-associated ALI is accompanied by coordinated transmembrane signal transduction and subsequent programmed cell death; however, the underlying mechanism remains largely unclear. RESULTS: Here we find that the expression of serine incorporator 2 (Serinc2), a protein involved in phosphatidylserine synthesis and membrane incorporation, is upregulated in cecal ligation and puncture (CLP)-induced ALI. Furthermore, the Serinc2-knockout (KO) mouse line is generated by the CRISPR-cas9 approach. Compared with wild-type mice, the Serinc2-KO mice exhibit exacerbated ALI-related pathologies after CLP. The expressions of pro-inflammatory factors, including IL1ß, IL6, TNFα, and MCP1, are significantly enhanced by Serinc2 deficiency, concurrent with over-activation of STAT3, p38 and ERK pathways. Conversely, Serinc2 overexpression in RAW264.7 cells significantly suppresses the inflammatory responses induced by lipopolysaccharide (LPS). Serinc2 KO aggravates CLP-induced apoptosis as evidenced by increases in TUNEL-positive staining, Bax expression, and cleaved caspase-3 and decreases in BCL-2 expression and Akt phosphorylation, whereas these changes are suppressed by Serinc2 overexpression in LPS-treated RAW264.7 cells. Moreover, the administration of AKTin, an inhibitor of Akt, abolishes the protective effects of Serinc2 overexpression against inflammation and apoptosis. CONCLUSIONS: Our findings demonstrate a protective role of Serinc2 in the lung through activating the Akt pathway, and provide novel insight into the pathogenesis of sepsis-induced ALI.

Reversibility of acute-on-chronic liver failure syndrome in hepatitis B virus-infected patients with and without prior decompensation.

Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome associated with high short-term mortality and reversibility. This study aimed to compare the characteristics of survival and reversibility in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) patients with and without previous decompensation. Overall, 1044 patients who fulfilled the acute hepatic insult criteria of the APASL-ACLF Research Consortium (AARC) definition were enrolled from a prospectively established cohort of HBV-related liver failure patients. These patients were divided into the AARC ACLF group and the non-AARC ACLF group according to prior decompensation. Mortality, reversibility of ACLF syndrome, and predicted factors associated with reversibility were evaluated. Liver transplantation-free mortality of the AARC ACLF group was significantly lower than that of the non-AARC ACLF group (28 days: 28.2% vs. 40.3%, p = .012; 90 days: 41.7% vs. 65.4%, p < .001). The 5-year cumulative reversal rates of ACLF syndrome were 88.0% (374/425) and 66.0% (31/47) in the AARC and non-AARC ACLF groups, respectively, (p = .039). Following reversibility of ACLF syndrome, 340/374 (90.9%) and 21/31 (67.7%) patients in the AARC and non-AARC ACLF groups, respectively, maintained a stable status within 5 years. Although prior decompensation indicated poor reversibility of ACLF syndrome, HBV-infected patients with prior decompensation who fulfilled the acute hepatic insult criteria of the AARC definition showed favourable reversibility and maintained a stable status after receiving nucleoside analogues. The AARC ACLF definition identified HBV-ACLF as a distinct syndrome with good reversibility. HBV-infected patients with prior decompensation could be included in the AARC ACLF management.

Relationship between the Level of Serum Golgi Protein 73 and the Risk of Short-term Death in Patients with ALD-ACLF.

Background and Aims: As a hepatocellular carcinoma biomarker, serum Golgi protein 73 (GP73) is reportedly related to inflammation. Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation. In this study, we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF (ALD-ACLF). Methods: This retrospective cohort study involved 126 Chinese adults with ALD-ACLF. Baseline serum GP73 level was measured using enzyme-linked immunosorbent assay. Patients were followed-up for 90 d and outcomes were assessed. Data were analyzed using multivariate Cox regression and piecewise linear regression analyses. The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves. Results: The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF. Compared with the lowest tertile, the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model [at 28 days: hazard ratio (HR): 4.29 (0.99-18.54), p=0.0511; at 90 days: HR: 3.52 (1.15-10.79), p=0.0276]. Further analysis revealed a positive linear association. GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score, model for end-stage liver disease score, and model for end-stage liver disease-sodium score in predicting short-time prognosis of patients with ALD-ACLF. Conclusions: The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF. GP73 improved the predictive value of classic prognostic scores.

Granulocyte Colony-Stimulating Factor Accelerates the Recovery of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure by Promoting M2-Like Transition of Monocytes.

Background and Aim: Acute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents. Methods: We performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 µg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments. Results: The survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments. Conclusion: G-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration Number: ClinicalTrials.gov, identifier (NCT02331745).

Synthesis of biochar@α-Fe2O3@Shewanella loihica complex for remediation of soil contaminated by hexavalent chromium: Optimization of conditions and mechanism.

The reduction of hexavalent chromium combined with the process of dissimilatory iron reduction is an important strategy for microbial remediation of chromium-contaminated soil. However, its applicability is limited by the slow speed of bacterial bioreduction and the toxic effect of heavy metals on bacteria. Here, biochar (BC) was used as a substrate and was loaded with iron oxide in the form of hematite and Shewanella loihica to synthesize a BC@α-Fe2O3@S. loihica complex and thus achieve combined microbial-chemical remediation. After optimization by a Box-Behnken design, the optimal dosages of the complex, humic acid (as an electron shuttle), and sodium lactate (as an electron donor) were found to be 1.38 mL/g, 33.94 mg/g, and 12.95%, respectively. The Cr(VI) reduction rate in soil contaminated with 1000 mg/kg Cr(VI) reached 98.26%, and remediation could be achieved within 7 days. Characterization of the BC@α-Fe2O3@S. loihica complex before and after it was used for remediation by energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy proved that the oxygen-containing functional groups and aromatic compounds on the surface of the BC participated in the adsorption and reduction of Cr(VI) and that the loaded hematite particles were fully utilized by microorganisms. Therefore, the BC@α-Fe2O3@S. loihica complex has great potential for the remediation of Cr(VI)-contaminated soil.

Low platelets: a new and simple prognostic marker for patients with hepatitis E virus-related acute liver failure.

BACKGROUND AND AIMS: Hepatitis E virus-related acute liver failure (HEV-ALF) rapidly worsens and has a high mortality. However, no simple and specific parameters for predicting short-term mortality are available. METHODS: A derivation cohort including 97 patients with HEV-ALF and another validation cohort were enrolled. Laboratory and clinical parameters were recorded. Platelet count, model for end-stage liver disease (MELD), and King's College criteria (KCC) were separately used for predicting mortality, and the levels of cytokines associated with systemic inflammation, platelet production, and platelet activation were measured. RESULTS: Platelet counts were significantly lower in patients with HEV-ALF, and nonsurvivors had lower platelet counts than survivors (p < 0.001). Platelet count was an independent risk factor for predicting 28- and 90-day mortality in patients with HEV-ALF. The AUROC of the baseline platelet count (cutoff, 131 × 109/L) for 28- and 90-day mortality was 0.786 and 0.764, respectively, which was superior to KCC score (p < 0.05) and comparable to MELD score. Furthermore, the platelet counts at 3 and 7 days after ALF diagnosis had similar predictive power for 28- and 90-day mortality. The value of platelet count was also confirmed in the validation cohort. Moreover, platelet-associated cytokines, including thrombopoietin, platelet factor 4, and P-selectin, were increased in patients with HEV-ALF. CONCLUSIONS: Decreased platelet count is a simple and reliable indicator for predicting 28- and 90-day mortality in patients with HEV-ALF. Overactivation of platelets is an important risk for platelet counts decrease, and treatment aiming at platelet count recovery may be considered.