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Background While some lung adenocarcinoma (LUAD) patients benefit long-term from treatment with immune checkpoint inhibitors, the sad reality is that a considerable proportion of patients do not. The classification of the LUAD tumor microenvironment (TME) can be used to conceptually comprehend primary resistance mechanisms. In addition, the most recent research demonstrates that the release of damage-associated molecular pattern (DAMP) in TME by immunogenic cell death (ICD) may contribute to the adaptive immune response. Currently, however, there is no such comprehensive research on this topic in LUAD patients. Therefore, we set out to investigate how to reverse the poor infiltration characteristics of immune cells and boost antitumor immunity by identifying DAMP model. Methods In this study, ICD-related DAMP genes were selected to investigate their effects on the prognosis of LUAD. To create a risk signature using the TCGA-LUAD cohort, the univariate COX regression and the least absolute shrinkage and selection operator regression were carried out, and the results were verified in a GEO dataset. Subsequently, the multivariate COX regression was applied to establish a prognostic nomogram. And the ESTIMATE and ssGSEA algorithms were utilized to analyze immune activity and the TIDE algorithm was for responsiveness to immunotherapy. Moreover, clinical tissue samples were used to verify the differential expression of 9 DAMP genes in the signature. Results We identified two distinct DAMP molecular subtypes, and there are remarkable differences in survival probability between the two subtypes, and patients with higher levels of DAMP-related genes are “hot tumors” with increased immune activity. In addition, 9 DAMP genes were selected as prognostic signature genes, and clinical outcomes and immunotherapy response were better for participants in the low-risk group. Importantly, according to the area under the curve (AUC) value in evaluating the efficacy of immunotherapy, this signature is superior to existing predictors, such as PD-L1 and TIDE. Conclusions Our study suggests ICD plays an important part in modeling the TME of LUAD patients. And this signature could be utilized as a reliable predictor to estimate clinical outcomes and predict immunotherapy efficacy among LUAD patients.

Assessment of contaminated food through the dietary intake is essential for human health. To investigate the health risk of rare earth element (REE) exposure to fruits and vegetables in mining areas in China, we collected 288 fruit samples and 942 vegetable samples from four representative mining points (Bayan Obo in Inner Mongolia, Weishan in Shandong, Maoming in Guangdong, Longnan in Jiangxi) and their control areas. The content of REEs was determined by inductively coupled plasma-mass spectrometry (ICP-MS). The total REEs in fruits from mining and control areas were 12.90 μg kg

Precision medicine is the ultimate goal for current disease therapies, including tumor and infection. The lack of specific targeted drugs for liver cancer and the lack of specific anti-infective drugs in the treatment of diabetic foot ulcer with infection (DFI) are the representative obstacles in those 2 major diseases currently plaguing human beings. Inventing natural biocompatible polymers derived from natural materials is one of the main development directions of current bio-medical materials. Though previous studies have demonstrated the potential application values of human black hair-derived nanoparticles (HNP) in cancer, methicillin-resistant Staphylococcus aureus (MRSA) infection, and thrombosis scenarios treatments, it still has not solved the problem of low local therapeutic concentration and general targeting ability. Here, we firstly modified the HNP with membrane encapsulations, which endowed these dual-pure natural bio-fabricated materials with better targeting ability at the disease sites with no reduction in photothermal therapy (PTT) effect. HNP coated by red blood cell membrane loaded with DSPE-PEG-cRGD peptide for the therapeutic application of liver cancer greatly prolonged in vivo circulation time and enhanced local targeting efficacy as well as low toxicity; HNP coated by the murine macrophage cell membrane (RAWM) for the DFIs treatment greatly promoted the adhesive ability of HNP on the bacteria and thereby improved the killing effect. Briefly, the appropriate cell membranes camouflaged HNP nanomedicine has the characteristics of excellent photothermal effect, an all-natural source with excellent biocompatibility and easy access, which is expected to have huge potential in both benign and malignant diseases.

Pyroptosis, as a proinflammatory form of regulated cell death, plays an important role in multiple cancers. However, the diagnostic and prognostic values of pyroptosis and its interaction with tumor immunity in pan-cancer are still unclear. Here, we show an elevated general expression of 17 pyroptosis-associated genes of tumor patients with high-immune-activity and a reduced pyroptosis in low-immune-activity tumors. Moreover, pyroptosis is positively correlated with immune infiltration and immune-related signatures across 30 types of cancer. Furthermore, our experimental data suggest that pyroptosis directly modulate the expression of immune checkpoint molecules and cytokines. We generate a pyroptosis score model as a potential independent prognostic indicator in melanoma patients. Interestingly, 3 of pyroptosis-associated genes including CASP1, CASP4 and PYCARD, can predict the effectiveness of anti-PD-1 immunotherapy for patients with melanoma. Our study demonstrates that pyroptosis correlates with tumor immunity and prognosis, might be used as a potential target for immune therapy.

Introduction Acute gastrointestinal bleeding (GIB) is a major cause of death in liver cirrhosis. This multicenter study aims to develop and validate a novel and easy-to-access model for predicting the prognosis of patients with cirrhosis and acute GIB. Methods Patients with cirrhosis and acute GIB were enrolled and randomly divided into the training (n = 865) and validation (n = 817) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses, and then a new prognostic model (i.e., CAGIB score) was established. Area under curve (AUC) of CAGIB score was calculated by receiver operating characteristic curve analysis and compared with Child–Pugh, model for end-stage liver disease (MELD), MELD-Na, and neutrophil–lymphocyte ratio (NLR) scores. Results In the training cohort, hepatocellular carcinoma (HCC), diabetes, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and serum creatinine (Scr) were independent predictors of in-hospital death. CAGIB score = diabetes (yes = 1, no = 0) × 1.040 + HCC (yes = 1, no = 0) × 0.974 + TBIL (μmol/L) × 0.005 − ALB (g/L) × 0.091 + ALT (U/L) × 0.001 + Scr (μmol/L) × 0.012 − 3.964. In the training cohort, the AUC of CAGIB score for predicting in-hospital death was 0.829 (95% CI 0.801–0.854, P

Tripterygium Wilfordii Hook F has been exploited as a treatment for several diseases due to its neuroprotective, anti-tumor, and anti-inflammatory effects. Triptolide is one of its key bioactive compounds. Currently, the role of triptolide in cognitive dysfunction remains unclear. Here, the role of triptolide on cognitive dysfunction was investigated using chronic cerebral hypoperfusion-induced vascular dementia (VD) rat model. SD rats were administrated with Triptolide (5 μg/kg) for 6 weeks after undergoing permanent bilateral common carotid artery occlusion. The results show that triptolide treatment conferred neuroprotective effects in VD rats. Intraperitoneal injection of triptolide attenuated oxidative stress, learning and memory deficits, and neuronal apoptosis in the hippocampi. Moreover, triptolide enhanced the expression of SIRT1, PGC-1α, ZO-1, Claudin-5, and decreased the serum levels of NSE and S100B significantly. It also improved CCH-induced learning and memory deficits, and this is attributed to its capacity to promote SIRT1/PGC-1α signaling, confer antioxidant effects, and inhibit neuronal apoptosis. These findings indicate that triptolide may be an effective therapeutic agent for vascular cognitive dysfunction.

p62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear. Herein, we confirmed that p62 was up-regulated in hepatocellular carcinoma and its higher expression was associated with shorter overall survival in patients. The knockdown of p62 in hepatocellular carcinoma cells decreased cell growth in vitro and in vivo. Intriguingly, p62 protein stability could be reduced by its acetylation at lysine 295, which was regulated by deacetylase Sirt1 and acetyltransferase GCN5. Acetylated p62 increased its association with the E3 ligase Keap1, which facilitated its poly-ubiquitination-dependent proteasomal degradation. Moreover, Sirt1 was up-regulated to deacetylate and stabilize p62 in hepatocellular carcinoma. Additionally, Hepatocyte Sirt1 conditional knockout mice developed much fewer liver tumors after Diethynitrosamine treatment, which could be reversed by the re-introduction of exogenous p62. Taken together, Sirt1 deacetylates p62 at lysine 295 to disturb Keap1-mediated p62 poly-ubiquitination, thus up-regulating p62 expression to promote hepato-carcinogenesis. Therefore, targeting Sirt1 or p62 is a reasonable strategy for the treatment of hepatocellular carcinoma.