TR4 worsen urosepsis by regulating GSDMD.

BACKGROUND: Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. METHODS: The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. RESULTS: TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. CONCLUSIONS: TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.

Anaerobic syntrophic system composed of phosphate solubilizing bacteria and dissimilatory iron reducing bacteria induces cadmium immobilization via secondary mineralization.

Secondary mineralization is a promising method for remediating cadmium (Cd) pollution in sediments, but the poor stability of Cd-containing secondary minerals is a bottleneck that limits the development of this approach. The existence of phosphate can enhance the formation of stable secondary minerals and points a new direction for Cd immobilization. In this research, a novel syntrophic system composed of phosphate solubilizing bacteria (PSB) and dissimilatory iron reducing bacteria (DIRB) was established and the effect and mechanism of Cd immobilization in the system were also explored. The results showed that under the conditions of DIRB:PSB (V:V)= 3:1, syntrophic bacteria dosage of 5% and glucose dosage of 5 g/L, Cd incorporated in the secondary minerals could account for about 60% of the total Cd. In the pH range of 5-9, alkaline environment was conducive to the immobilization of Cd and the percentage of combined Cd was up to 58%, while the combined Cd in secondary minerals decreased from 62% to 56% with the increase of initial Cd concentration from 0.1 to 0.3 mmol/L. In addition, XRD, XPS, Mössbauer and other characterization results showed that secondary minerals, such as Cd exchange hydroxyapatite (Cd-HAP) and kryzhanovskite (Fe3(PO4)2(OH)3) were formed in this new system. The established syntrophic system of PSB and DIRB is thus a prospective bioremediation technology for Cd immobilization in sediments and can avoid the potential risk might be caused by the addition of phosphorus-containing materials.

Humic acid and fulvic acid facilitate the formation of vivianite and the transformation of cadmium via microbially-mediated iron reduction.

The effects of humic acids (HA) and fulvic acids (FA) on the fate of Cd in anaerobic environment upon microbial reduction of Cd-bearing ferrihydrite (Fh) with Geobacter metallireducens were investigated. The results showed that HA and FA could promote the reductive dissolution of Fh and the formation of vivianite. After incubation of 38 d, vivianite accounted for 47.19%, 59.22%, and 48.53% of total Fe in biological control batch (BCK), HA and FA batches (C/Fe molar ratio of 1.0), respectively, by Mössbauer spectroscopy analysis. In terms of Cd, HA and FA could promote the release of adsorbed Cd during the initial bioreduction process, but reassuringly, after 38 d the dissolved Cd with HA and FA addition batches were 0.58-0.91 and 0.99-1.08 times of the BCK, respectively. The proportions of residual Cd in HA batches were higher than FA and BCK batches, indicating that HA was better than FA in immobilizing Cd. This might be because the quinone groups in HA could act as electron shuttle. This study showed that HA facilitated the transformation of vivianite better than FA, and Cd can be stabilized by resorption or co-precipitation with vivianite, providing a theoretical support for the translocation of Cd in sediment-water interface.

Predictive value of modified systemic inflammation score for postoperative unplanned ICU admission in patients with NSCLC.

Background: The purpose of this study was to investigate the predictive value of the modified systemic inflammation score (mSIS) in postoperative unplanned admission to the intensive care unit (ICU) in patients with non-small-cell lung cancer (NSCLC). Methods: The clinical data of 1,321 patients with NSCLC treated with thoracic surgery in our hospital from August 2019 to June 2021 were analyzed retrospectively. The preoperative mSIS, which takes into account the serum albumin (ALB) level and lymphocyte-to-monocyte ratio (LMR), was recorded as 0, 1 or 2 and then was used to identify high-risk patients with unplanned admission to the ICU. The independent risk factors for unplanned admission to the ICU in patients with NSCLC after surgery were identified by multivariate logistic regression analysis. Results: A total of 1,321 patients, including 549 (41.6%) males and 772 (58.4%) females, were included. The median age was 57 years (range 16-95 years). The incidence of unplanned admission to the ICU in patients with mSIS = 2 was significantly higher than that in those with mSIS = 0 and mSIS = 1. The multivariate analysis showed that an mSIS of 2 (OR = 3.728; P = 0.004; 95% CI, 1.520-9.143), an alcohol consumption history (OR = 2.791, P = 0.011; 95% CI, 1.262-6.171), intraoperative infusion volume (OR = 1.001, P = 0.021; 95% CI, 1.000-1.001) and preoperative underlying diseases (OR = 3. 57, P = 0.004; 95% CI, 1.497-8.552) were independent risk factors for unplanned admission to the ICU after lung cancer surgery. In addition, the multivariate logistic regression model showed that the C-statistic value was 0.799 (95% CI: 0.726∼0.872, P < 0.001). Conclusions: The mSIS scoring system can be used as a simplified and effective predictive tool for unplanned ICU admission in patients with NSCLC.

The Cell-Isolation Capsules with Rod-Like Channels Ensure the Survival and Response of Cancer Cells to Their Microenvironment.

Current macrocapsules with semipermeable but immunoprotective polymeric membranes are attractive devices to achieve the purpose of immunoisolation, however, their ability to allow diffusion of essential nutrients and oxygen is limited, which leads to a low survival rate of encapsulated cells. Here, a novel method is reported by taking advantage of thermotropic liquid crystals, sodium laurylsulfonate (SDS) liquid crystals (LCs), and rod-like crystal fragments (LCFs) to develop engineered alginate hydrogels with rod-like channels. This cell-isolation capsule with an engineered alginate hydrogel-wall allows small molecules, large molecules, and bacteria to diffuse out from the capsules freely but immobilizes the encapsulated cells inside and prevents cells in the microenvironment from moving in. The encapsulated cells show a high survival rate with isolation of host immune cells and long-term growth with adequate nutrients and oxygen supply. In addition, by sharing and responding to the normal molecular and vesicular microenvironment (NMV microenvironment), encapsulated cancer cells display a transition from tumorous phenotypes to ductal features of normal epithelial cells. Thus, this device will be potentially useful for clinical application in cell therapy by secreting molecules and for establishment of patient-derived xenograft (PDX) models that are often difficult to achieve for certain types of tumors, such as prostate cancer.

Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer: A meta-analysis.

BACKGROUND: The use of standard cytotoxic chemotherapy seems to have reached a "treatment plateau". The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC. METHODS: According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted. RESULTS: The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001). CONCLUSION: Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.