Oncogenic Roles of Laminin Subunit Gamma-2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma-2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non-tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over-expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2-mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C-terminus. Together LAMC2 and BiP generate a binding "pocket" of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2-high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2-high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR-targeted TKIs therapies.

Removal capacities and varying characteristics of substrates and microbial community structure in simultaneous sulfide and nitrate biological removal process'.

Under the background of carbon neutrality, resource and energy utilization technologies have become the focus of future research. The paper investigated the removal efficiencies and varying characteristics of substrates and microbial community structure in the simultaneous sulfide and nitrate biological removal (SSNBR) process. The results showed that the sulfide and nitrate removal loads reached 2.998 kg m-3∙d-1 and 1.011 kg m-3∙d-1 respectively when HRT was 2.4 h. The sulfide and nitrate molar ratios (S/N ratios) hardly influenced the removal efficiencies of sulfide and nitrate. However, the reaction products sulfate and nitrite concentrations in the effluent became higher as the S/N ratios decreased. Under the S/N ratio of 5:5, when the influent sulfide and nitrate concentrations were improved from 100 mg L-1 to 600 mg L-1 and from 87.5 mg L-1 to 306.25 mg L-1, respectively, the sulfide removal efficiencies were all above 99%, but the nitrate removal efficiencies reduced from 95.53% to 55.54%. Sulfide removal effect was better than nitrate. HRT had great effect on the nitrate removal efficiencies, but hardly affected the sulfide removal. When HRT was shortened from 12 h to 2.4 h, the sulfide removal efficiencies were all above 99%, while the nitrate removal efficiencies decreased from 93.14% to 77.04%. The main functional genera included Exiguobacterium, Clostridium, Bacillus, Thiobacillus and Sphingomonas, all of which had the nitrogen and sulfur removal functions.

Safety of inactivated SARS-CoV-2 vaccines in myasthenia gravis: A survey-based study.

Background: Vaccination remains the most effective measure to prevent SARS-CoV-2 infection and worse outcomes. However, many myasthenia gravis (MG) patients are hesitant to receive vaccine due to fear of worsening. Methods: MG patients were consecutively enrolled in two MG centers in North China. The "worsening" after vaccination was self-reported by MG patients, and severity was measured with a single simple question. The general characteristics and disease status immediately prior to the first dose were compared between the worsening and non-worsening groups. Independent factors associated with worsening were explored with multivariate regression analysis. Results: One hundred and seven patients were included. Eleven patients (10.3%) reported worsening after vaccination, including eight patients with mild or moderate worsening and three patients with severe worsening. Only one of them (0.9%) needed an escalation of immunosuppressive treatments. There were significant differences between the worsening and non-worsening groups in terms of Myasthenia Gravis Foundation of America classes immediately before the first dose and intervals since the last aggravation. Precipitating factors might contribute to the worsening in some patients. Logistic regression revealed that only interval since the last aggravation ≤6 months was associated with worsening after SARS-CoV-2 vaccination (P = 0.01, OR = 8.62, 95% CI: 1.93-38.46). Conclusion: SARS-CoV-2 vaccines (an overwhelming majority were inactivated vaccines) were found safe in milder Chinese MG patients who finished two doses. Worsening after vaccination was more frequently seen in patients who were presumed as potentially unstable (intervals since last aggravation ≤6 months). However, mild worsening did occur in patients who were presumed to be stable. Precipitating factors should still be sought and treated for better outcome.