Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Efficacy and safety of Piwei Peiyuan Prescription in the treatment of chronic atrophic gastritis: A multicenter, double-blind, double-simulated, randomized, controlled clinical trial.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.

Causal association between lipid-lowering drugs and cancers: A drug target Mendelian randomization study.

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.

Causal relationships between gut microbrome and digestive system diseases: A two-sample Mendelian randomization study.

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs.

Employing the sustained-release properties of poly(lactic-co-glycolic acid) nanoparticles to reveal a novel mechanism of sodium-hydrogen exchanger 1 in neuropathic pain.

Neuropathic pain is caused by injury or disease of the somatosensory system, and its course is usually chronic. Several studies have been dedicated to investigating neuropathic pain-related targets; however, little attention has been paid to the persistent alterations that these targets, some of which may be crucial to the pathophysiology of neuropathic pain. The present study aimed to identify potential targets that may play a crucial role in neuropathic pain and validate their long-term impact. Through bioinformatics analysis of RNA sequencing results, we identified Slc9a1 and validated the reduced expression of sodium-hydrogen exchanger 1 (NHE1), the protein that Slc9a1 encodes, in the spinal nerve ligation (SNL) model. Colocalization analysis revealed that NHE1 is primarily co-localized with vesicular glutamate transporter 2-positive neurons. In vitro experiments confirmed that poly(lactic-co-glycolic acid) nanoparticles loaded with siRNA successfully inhibited NHE1 in SH-SY5Y cells, lowered intracellular pH, and increased intracellular calcium concentrations. In vivo experiments showed that sustained suppression of spinal NHE1 expression by siRNA-loaded nanoparticles resulted in delayed hyperalgesia in naïve and SNL model rats, whereas amiloride-induced transient suppression of NHE1 expression yielded no significant changes in pain sensitivity. We identified Slc9a1, which encodes NHE1, as a key gene in neuropathic pain. Utilizing the sustained release properties of nanoparticles enabled us to elucidate the chronic role of decreased NHE1 expression, establishing its significance in the mechanisms of neuropathic pain.

Toll-Like Receptors 7/8: A Paradigm for the Manipulation of Immunologic Reactions for Immunotherapy.

The innate immune system recognizes conserved features of viral and microbial pathogens through pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are one type of PRR used by the innate immune system to mediate the secretion of proinflammatory cytokines and promote innate and adaptive immune responses. TLR family members TLR7 and TLR8 (referred to as TLR7/8 from herein) are endosomal transmembrane receptors that recognize purine-rich single-stranded RNA (ssRNA) and bacterial DNA, eliciting an immunologic reaction to pathogens. TLR7/8 were discovered to mediate the secretion of proinflammatory cytokines by activating immune cells. In addition, accumulating evidence has indicated that TLR7/8 may be closely related to numerous immune-mediated disorders, specifically several types of cancer, autoimmune disease, and viral disease. TLR7/8 agonists and antagonists, which are used as drugs or adjuvants, have been identified in preclinical studies and clinical trials as promising immune stimulators for the immunotherapy of these immune-mediated disorders. These results provided reasoning to further explore immunotherapy for the treatment of immune-mediated disorders. Nevertheless, numerous needs remain unmet, and the therapeutic effects of TLR7/8 agonists and antagonists are poor and exert strong immune-related toxicities. The present review aimed to provide an overview of the TLR family members, particularly TLR7/8, and address the underlying molecular mechanisms and clinical implications of TLR7/8 in immune-mediated disorders. The aim of the work is to discuss the underlying molecular mechanisms and clinical implications of TLR7/8 in immune-mediated disorders.

When biochar is involved in rhizosphere dissipation and plant absorption of pesticides: A meta-analysis.

Clarifying the influences of biochar input on the rhizosphere dissipation and plant absorption of pesticides is a crucial prerequisite for utilizing biochar in the restoration of pesticide-contaminated soils. Nevertheless, the application of biochar to pesticide-contaminated soils does not always achieve consistent results on the rhizosphere dissipation and plant absorption of pesticides. Under the new situation of vigorously promoting the application of biochar in soil management and carbon sequestration, a timely review is needed to further understand the key factors affecting biochar remediation of pesticide-contaminated soil. In this study, a meta-analysis was conducted utilizing variables from three dimensions of biochar, remediation treatment, and pesticide/plant type. The pesticide residues in soil and the pesticide uptake by plant were used as response variables. Biochar with high adsorption capacity can impede the dissipation of pesticides in soil and mitigate their absorption by plants. The specific surface area of biochar and the type of pesticide are critical factors that affect pesticide residues in soil and plant uptake, respectively. Applying biochar with high adsorption capacity, based on specific dosages and soil characteristics, is recommended for the remediation of continuously cultivated soil contaminated with pesticides. This article aims to provide a valuable reference and understanding for the application of biochar-based soil remediation technology and the treatment of pesticide pollution in soil.

Identification and verification of ferroptosis-related genes in gastric intestinal metaplasia.

Background: Gastric intestinal metaplasia (IM) is the key link of gastric precancerous lesions. Ferroptosis is a novel form of programmed cell death. However, its impact on IM is unclear. The focus of this study is to identify and verify ferroptosis-related genes (FRGs) that may be involved in IM by bioinformatics analysis. Materials and methods: Differentially expressed genes (DEGs) were obtained from microarray dataset GSE60427 and GSE78523 downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed ferroptosis-related genes (DEFRGs) were obtained from overlapping genes of DEGs and FRGs got from FerrDb. DAVID database was used for functional enrichment analysis. Protein-protein interaction (PPI) analysis and Cytoscape software were used to screen hub gene. In addition, we built a receiver operating characteristic (ROC) curve and verified the relative mRNA expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the CIBERSORT algorithm was used to analyze the immune infiltration in IM. Results: First, a total of 17 DEFRGs were identified. Second, a gene module identified by Cytoscape software was considered as hub gene: PTGS2, HMOX1, IFNG, and NOS2. Third, ROC analysis showed that HMOX1 and NOS2 had good diagnostic characteristics. qRT-PCR experiments confirmed the differential expression of HMOX1 in IM and normal gastric tissues. Finally, immunoassay showed that the proportion of T cells regulatory (Tregs) and macrophages M0 in IM was relatively higher, while the proportion of T cells CD4 memory activated and dendritic cells activated was lower. Conclusion: We found significant associations between FRGs and IM, and HMOX1 may be diagnostic biomarkers and therapeutic targets for IM. These results may enhance our understanding of IM and may contribute to its treatment.

Comprehensive pan-cancer analysis of STAT3 as a prognostic and immunological biomarker.

Numerous studies have indicated that STAT3 plays a key role in promoting oncogenesis and it is considered a potential therapeutic target for cancer treatment; however, there are no reports on STAT3 using pan-cancer analysis. Therefore, it is important to investigate the role of STAT3 in different types of tumors using pan-cancer analysis. In the present study, we used multiple databases to comprehensively analyze the relationship between STAT3 expression and prognosis, different stages of patients with cancer, investigate the clinical value of STAT3 in predicting prognosis, and the relationship between STAT3 genetic alteration and prognosis, drug sensitivity, and STAT3 expression, to determine whether STAT3 participates in tumor immunity, to provide a rationale for STAT3 as a treatment target for a broad-spectrum malignancies. Our results indicate that STAT3 can serve as a prognostic, sensitivity prediction biomarker and a target for immunotherapy, which has been of great value for pan-cancer treatment. Overall, we found that STAT3 significantly predicted cancer prognosis, drug resistance, and immunotherapy, providing a rationale for further experimental studies.

Cross-Linked and Doped Graphene Oxide Membranes with Excellent Antifouling Capacity for Rejection of Antibiotics and Salts.

Graphene oxide (GO) membranes have suffered from the instability of water permeability and low rejection of pollutant separation. In this paper, a reasonable modification protocol for GO nanosheets at the molecular level was proposed. A molecular cross-linking strategy was adopted to regulate the interlayer spacing of GO nanosheets, and nanofiltration membranes with high water stability and excellent antifouling capacity were prepared, which could effectively reject antibiotics and salts. The GO1-MPD0.5 (the mass ratio of GO nanosheets to MPD is 1:0.5) and GO/GO1-MPD0.5-0.25 (the doping ratio of GO1-MPD0.5 is 25%) membranes had stable water permeability of 4.22 ± 0.06 and 3.65 ± 0.11 L m-2 h-1 bar-1, and the rejection rates for ciprofloxacin (CIP) and ofloxacin (OFX) were 93.35 ± 3.62 and 95.48 ± 2.97 and 85.89 ± 6.52 and 88.21 ± 3.67%, respectively. Molecular dynamics simulations well explained the high water stability of membranes, and the cross-linked hydrophobic benzene ring played a role in the rejection of pollutant molecules. Moreover, the GO1-MPD0.5 membrane showed excellent antifouling capacity and the flux recovery ratio (FRR) was more than 98%. This paper provides a new idea for the design of nanofiltration membranes with high stability and good rejection permeability at the molecular level and provides a prospect for the application of nanofiltration membranes in practical water treatment and water purification.

PPAR-γ alleviates the inflammatory response in TNF-α-induced fibroblast-like synoviocytes by binding to p53 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by synovial inflammation, synoviocyte expansion and damage to cartilage and bone. We recently reported that peroxisome proliferator-activated receptor (PPAR)-γ inhibited the proliferation and activation of fibroblast-like synoviocytes (FLS), and was downregulated in RA synovial. In this study we investigated the role of PPAR-γ in RA and the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced in rats; from D15, AIA rats were orally administered pioglitazone (30 mg·kg-1·d-1) or rosiglitazone (4 mg·kg-1·d-1) for 14 days. Collagen-induced arthritis (CIA) was induced in wild-type and Ppar-γ+/- mice. We showed that the expression of PPAR-γ was significantly reduced, whereas that of TNF-α was markedly increased in human RA FLS. In CIA mice, knockdown of PPAR-γ expression (Ppar-γ+/-) aggravated the ankle inflammation. Similarly, T0070907 (a PPAR-γ antagonist) or si-PPAR-γ promoted the activation and inflammation of TNF-α-induced FLS in vitro. On the contrary, administration of PPAR-γ agonist pioglitazone or rosiglitazone, or injection of ad-Ppar-γ into the ankle of AIA rat in vivo induced overexpression of PPAR-γ, reduced the paw swelling and inflammation, and downregulated activation and inflammation of FLS in RA. Interesting, injection of ad-Ppar-γ into the ankle also reversed the ankle inflammation in Ppar-γ+/- CIA mice. We conducted RNA-sequencing and KEGG pathway analysis, and revealed that PPAR-γ overexpression was closely related to p53 signaling pathway in TNF-α-induced FLS. Co-IP study confirmed that p53 protein was bound to PPAR-γ in RA FLS. Taken together, PPAR-γ alleviates the inflammatory response of TNF-α-induced FLS by binding p53 in RA.

A CT-based nomogram for predicting the risk of adenocarcinomas in patients with subsolid nodule according to the 2021 WHO classification.

PURPOSE: To establish a nomogram for predicting the risk of adenocarcinomas in patients with subsolid nodules (SSNs) according to the 2021 WHO classification. METHODS: A total of 656 patients who underwent SSNs resection were retrospectively enrolled. Among them, 407 patients were assigned to the derivation cohort and 249 patients were assigned to the validation cohort. Univariate and multi-variate logistic regression algorithms were utilized to identity independent risk factors of adenocarcinomas. A nomogram based on the risk factors was generated to predict the risk of adenocarcinomas. The discrimination ability of the nomogram was evaluated using the concordance index (C-index), its performance was calibrated using a calibration curve, and its clinical significance was evaluated using decision curves and clinical impact curves. RESULTS: Lesion size, mean CT value, vascular change and lobulation were identified as independent risk factors for adenocarcinomas. The C-index of the nomogram was 0.867 (95% CI, 0.833-0.901) in derivation cohort and 0.877 (95% CI, 0.836-0.917) in validation cohort. The calibration curve showed good agreement between the predicted and actual risks. Analysis of the decision curves and clinical impact curves revealed that the nomogram had a high standardized net benefit. CONCLUSIONS: A nomogram for predicting the risk of adenocarcinomas in patients with SSNs was established in light of the 2021 WHO classification. The developed model can be adopted as a pre-operation tool to improve the surgical management of patients.

Construction and validation of a novel ten miRNA-pair based signature for the prognosis of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most predominate pathological subtype of renal cell carcinoma, causing a recurrence or metastasis rate as high as 20% to 40% after operation, for which effective prognostic signature is urgently needed. METHODS: The mRNA and miRNA profiles of ccRCC specimens were collected from the Cancer Genome Atlas. MiRNA-pair risk score (miPRS) for each miRNA pair was generated as a signature and validated by univariate and multivariate Cox proportional hazards regression analysis. Functional enrichment was performed, and immune cells infiltration, as well as tumor mutation burden (TMB), and immunophenoscore (IPS) were evaluated between high and low miPRS groups. Target gene-prediction and differentially expressed gene-analysis were performed based on databases of miRDB, miRTarBase, and TargetScan. Multivariate Cox proportional hazards regression analysis was adopted to establish the prognostic model and Kaplan-Meier survival analysis was performed. FINDINGS: A novel 10 miRNA-pair based signature was established. Area under the time-dependent receiver operating curve proved the performance of the signature in the training, validation, and testing cohorts. Higher TMB, as well as the higher CTLA4-negative PD1-negative IPS, were discovered in high miPRS patients. A prognostic model was built based on miPRS (1 year-, 5 year-, 10 year- ROC-AUC=0.92, 0.84, 0.82, respectively). INTERPRETATION: The model based on miPRS is a novel and valid tool for predicting the prognosis of ccRCC. FUNDING: This study was supported by research grants from the China National Natural Scientific Foundation (81903972, 82002018, and 82170752) and Shanghai Sailing Program (19YF1406700 and 20YF1406000).

PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis.

BACKGROUND: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). METHODS: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1ß and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1ß in FLS by WB. RESULT: When PLCL1 was silenced, the level of IL-6, IL-1ß and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1ß and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. CONCLUSION: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.

Nocardioides coralli sp. nov., an actinobacterium isolated from stony coral in the South China Sea.

A Gram-stain-positive, aerobic, non-pigmented and non-motile actinobacterium, designated strain SCSIO 67246T, was isolated from a stony coral sample collected from the Sanya sea area, Hainan province, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SCSIO 67246T shared the highest similarities with Nocardioides rotundus MCCC 1A10561T (96.5 %) and Nocardioides sonneratiae KCTC 39565T (96.1%). The novel strain grew at 15-37 °C, at pH 5.0-10.0 and in the presence of 0-10 % (w/v) NaCl. The genome length of strain SCSIO 67246T was 3.52 Mbp with a DNA G+C content of 72.0 mol% and 3397 protein-coding genes. The novel strain showed an average nucleotide identity value of 76.5 % and a digital DNA-DNA hybridization value of 20.1 % with N. rotundus MCCC 1A10561T. Strain SCSIO 67246T contained MK-8(H4) as the major menaquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and five phospholipids. The major cellular fatty acids were iso-C16 : 0, C17 : 1 ω8c and summed feature 9 (iso-C17 : 1 ω9c/10-methyl C16 : 0). ll-2,6-Diaminopimelic acid was the diagnostic diamino acid. The whole-cell sugars were galactose, glucose and ribose. Based on this polyphasic taxonomic study, strain SCSIO 67246T represents a novel species of the genus Nocardioides, for which the name Nocardioides coralli sp. nov. is proposed. The type strain is SCSIO 67246T (=MCCC 1K06251T=KCTC 49719T).

AIR-Net: A novel multi-task learning method with auxiliary image reconstruction for predicting EGFR mutation status on CT images of NSCLC patients.

Automated and accurate EGFR mutation status prediction using computed tomography (CT) imagery is of great value for tailoring optimal treatments to non-small cell lung cancer (NSCLC) patients. However, existing deep learning based methods usually adopt a single task learning strategy to design and train EGFR mutation status prediction models with limited training data, which may be insufficient to learn distinguishable representations for promoting prediction performance. In this paper, a novel multi-task learning method named AIR-Net is proposed to precisely predict EGFR mutation status on CT images. First, an auxiliary image reconstruction task is effectively integrated with EGFR mutation status prediction, aiming at providing extra supervision at the training phase. Particularly, we adequately employ multi-level information in a shared encoder to generate more comprehensive representations of tumors. Second, a powerful feature consistency loss is further introduced to constrain semantic consistency of original and reconstructed images, which contributes to enhanced image reconstruction and offers more effective regularization to AIR-Net during training. Performance analysis of AIR-Net indicates that auxiliary image reconstruction plays an essential role in identifying EGFR mutation status. Furthermore, extensive experimental results demonstrate that our method achieves favorable performance against other competitive prediction methods. All the results executed in this study suggest that the effectiveness and superiority of AIR-Net in precisely predicting EGFR mutation status of NSCLC.

PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis

Abstract Background: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result: When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.

Transcriptomic Analysis and Novel Gene Pair-Based Signatures for Hepatitis B-Related Hepatocellular Carcinoma.

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) misses the opportunity for surgery because it is not detected early. The molecular mechanism of hepatitis B-related liver cancer needs further understanding, and effective diagnostic and prognostic models are in urgent need. Expression profiles from the Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC) and GSE121248, GSE94660, GSE76724 and GSE14520 from Gene Expression Omnibus (GEO) database were obtained. Differentially expressed genes (DEGs) between normal and tumor HBV-related HCC samples. Gene pairs are generated by comparing the expression levels of every two DEGs. The diagnostic signature of pairs of DEGs was built using cross-validation Lasso and Best Subset Selection regression. Hub genes and significant modules were screened by Cytoscape, and potential drugs were predicted by DGIdb. The gene-pair based prognostic signature was established by Cox proportional hazards regression model. xCell and ssGSEA were utilized to reveal the cell composition and cancer hallmarks to get an elucidation for the risk. A total of 457 DEGs were screened. A powerful diagnostic signature of two pairs of DEGs was built and validated in TCGA-LIHC and GEO datasets repeatedly with assured performance. Ten Hub genes were screened out. The prognostic signature of four gene pairs had good efficacy both in training and validation cohorts, with stromal score and several hallmarks related to the increasing of risk. Taken together, the study provided sight into the molecular mechanism as well as a novel strategy for the early diagnosis and prognosis for HBV-related HCC.

Effects of virgin microplastics on the transport of Cd (II) in Xiangjiang River sediment.

River sediments are considered as sinks of microplastics (MPs). Although numerous studies have been conducted on MPs pollution in river sediments, the impact of MPs on the environmental behavior of Cd (II) in river sediments is still unknown. In this work, the effects of six MPs (polyethylene, polypropylene, polystyrene, polyvinyl chloride, polymethyl methacrylate and polylactic acid) on the adsorption of Cd (II) by Xiangjiang River sediment and the transport of Cd (II) in sediment were studied. The results showed that the adsorption ability of sediment to Cd (II) decreased with the increase of the content of MPs in sediment. When the content of MPs in sediment increased to 10%, polypropylene had the greatest effect on the adsorption affinity of sediments to Cd (II). Moreover, the addition of MPs accelerated transport of Cd (II) in sediment, and the transport of Cd (II) in sediment increased with the increase of the content of MPs. The reason may be that after adding MPs, the adsorption capacity of sediment to Cd (II) decreases, and the mass transfer resistance of Cd (II) to sediment reduces, which leads to faster transport of Cd (II) in sediment. Especially, when the content of MPs in sediment increased to 10% (w/w), the saturation point of the breakthrough curve decreased by about 70 pore volumes. This work hopes to provide helpful views on the environmental behavior and risk assessment of Cd (II) in the presence of MPs.

Smoked cigarette butts: Unignorable source for environmental microplastic fibers.

The pollution of microplastics and their potential environmental hazards have attracted considerable attention of the public. Cigarette butts, composed of cellulose acetate, are one of the most common plastic pollutants in the environment. Of all the litter that is discarded at will, cigarette butts are the most acceptable. Cigarette butts are dangerous pieces of plastic, but are usually not handled properly and consist of more than 15,000 detachable strands of plastic fiber. Discarded cigarette butts may be carried into rivers and lakes, and finally into the ocean. The plastic fibers will continuously release microplastic fibers into the environment. About 300,000 tons of potential microplastic fibers may enter the aquatic environment from this source per annum. Additionally, toxic substances, such as nicotine, carcinogenic tar, and polycyclic aromatic hydrocarbons, have strong toxic effect, which will cause serious damage to aquatic organisms. However, the mechanism and rate of microplastic fibers release from smoked cigarette butts and the joint toxicity of microplastic fibers and toxic pollutants to aquatic organisms are still in the initial stage. Therefore, it is necessary to understand the mechanism of cigarette butts releasing microplastic fibers, the potential impact on the environment and possible measures to reduce the impacts of cigarette butt litter. The aim of this paper is to evaluate the potential sources of smoked cigarette butts as environmental fiber microplastics and the potential ecological effects of the released microplastic fibers on the ecosystem. In addition, some ways which could help to tackle problem of smoked cigarette butts pollution have also been proposed.