Correlation between gut microbiota characteristics and non-small cell lung cancer based on macrogenomics sequencing.

OBJECTIVE: Non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and immunotherapy experience disturbances in the gut microbiota. This study intends to find out the correlation between gut microbiota and clinical indices before and after radiotherapy for NSCLC. METHODS: Ten patients with primary NSCLC were screened, and plasma and fecal samples were collected before and after radiotherapy, respectively. Inflammatory indices in plasma were detected. Genomic DNA was extracted from fecal specimens and sequenced on on Illumina HiSeq2000 sequencing platform. Thee sequenced data were subjected to Metagenome assembly, gene prediction, species annotation, and gene function analysis to study and analyze gut microbiota and metabolic functions. The correlation between the diversity of gut microbiota and the clinical indicators of NSCLC patients was evaluated, and the changes of gut microbiota before and after radiotherapy were observed. RESULTS: The diversity of gut microbiota in NSCLC patients did not correlate with smoking, pathology, and inflammatory markers. The abundance of phylum (p)_Bacteroidetes increased; p_Firmicutes and p_Bacteroidetes accounted for the highest proportion in NSCLC patients, and the abundance of both was dominantly exchanged after radiotherapy. There was a decrease in genus (g)_Bifidobacterium after radiotherapy in NSCLC patients. There was no significant correlation between the diversity of gut microbiota after radiotherapy and radiotherapy sensitivity, and the structural composition and abundance of gut microbiota remained stable. CONCLUSION: The diversity of gut microbiota is altered after radiotherapy in NSCLC patients, showing an increase in harmful bacteria and a decrease in beneficial bacteria.

Carbonized Ganoderma Lucidum/V2O3 Composites as a Superior Cathode for High-Performance Aqueous Zinc-Ion Batteries.

In response to the suboptimal electrochemical performance of low-valence vanadium oxides, Ganoderma lucidum biomass-derived carbon@V2O3 (V2O3@CGL) composites were prepared by evaporative self-assembly technology and high-temperature calcination. In the prepared composites, V2O3 effectively encapsulates CGL, serving as a support for V2O3 and enhancing electrical conductivity and structural stability. This results in improved overall performance for the composites. They revealed satisfactory electrochemical properties when assembled in aqueous zinc-ion batteries (AZIBs). The preliminary discharge specific capacity of the V2O3@CGL-2 (VOCG-2) composite electrode reached 407.87 mAh g-1 at 0.05 A g-1. After 1000 cycles, the capacity retention is 93.69% at 3 A g-1. This research underscores the feasibility of employing V2O3 and abundantly available biomass for high-performance AZIB cathodes.

Exploring the relationship between intestinal microbiota and immune checkpoint inhibitors in the treatment of non-small cell lung cancer: insights from the "lung and large intestine stand in exterior-interior relationship" theory.

Objective: This study is aim to discern the Traditional Chinese Medicine (TCM) syndrome classifications relevant to immunotherapy sensitive in non-small cell lung cancer (NSCLC) patients, and to delineate intestinal microbiota biomarkers and impact that wield influence over the efficacy of NSCLC immunotherapy, grounded in the TCM theory of "lung and large intestine stand in exterior-interior relationship." Methods: The study cohort consisted of patients with advanced NSCLC who received treatment at the Oncology Department of Chengdu Fifth People's Hospital. These patients were categorized into distinct TCM syndrome types and subsequently administered immune checkpoint inhibitors (ICIs), specifically PD-1 inhibitors. Stool specimens were collected from patients both prior to and following treatment. To scrutinize the differences in microbial gene sequences and species of the intestinal microbiota, 16S rRNA amplicon sequencing technology was employed. Additionally, peripheral blood samples were collected, and the analysis encompassed the assessment of T lymphocyte subsets and myeloid suppressor cell subsets via flow cytometry. Subsequently, alterations in the immune microenvironment pre- and post-treatment were thoroughly analyzed. Results: The predominant clinical manifestations of advanced NSCLC patients encompassed spleen-lung Qi deficiency syndrome and Qi-Yin deficiency syndrome. Notably, the latter exhibited enhanced responsiveness to ICIs with a discernible amelioration of the immune microenvironment. Following ICIs treatment, significant variations in microbial abundance were identified among the three strains: Clostridia, Lachnospiraceae, and Lachnospirales, with a mutual dependency relationship. In the subset of patients manifesting positive PD-L1 expression and enduring therapeutic benefits, the study recorded marked increases in the ratios of CD3+%, CD4+%, and CD4+/CD8+ within the T lymphocyte subsets. Conversely, reductions were observed in the ratios of CD8%, Treg/CD4+, M-MDSC/MDSC, and G-MDSC/MDSC. Conclusion: The strains Clostridia, Lachnospiraceae, and Lachnospirales emerge as potential biomarkers denoting the composition of the intestinal microbiota in the NSCLC therapy. The immunotherapy efficacy of ICIs markedly accentuates in patients displaying durable treatment benefits and those expressing positive PD-L1.

Entero-toxigenic Bacteroides fragilis contributes to intestinal barrier injury and colorectal cancer progression by mediating the BFT/STAT3/ZEB2 pathway.

Our previous findings confirmed the high enrichment of Bacteroides fragilis (BF) in fecal samples from patients with colorectal cancer (CRC). The intestinal mucosal barrier is the first defense of the organism against commensal flora and intestinal pathogens and is closely associated with the occurrence and development of CRC. Therefore, this study aimed to investigate the molecular mechanisms through which BF mediates intestinal barrier injury and CRC progression. SW480 cells and a Caco2 intestinal barrier model were treated with entero-toxigenic BF (ETBF), its enterotoxin (B. fragilis toxin, BFT), and non-toxigenic BF (NTBF). Cell counting kit-8, flow cytometry, wound healing and transwell assays were performed to analyze the proliferation, apoptosis, migration, and invasion of SW480 cells. Transmission electron microscopy, FITC-dextran, and transepithelial electrical resistance (TEER) were used to analyze damage in the Caco2 intestinal barrier model. The Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) animal model was established to evaluate the effect of ETBF on intestinal barrier injury and CRC progression in vivo. ETBF and BFT enhanced the viability, wound healing ratio, invasion, and EMT of SW480 cells. In addition, ETBF and BFT disrupted the tight junctions and villus structure in the intestinal barrier model, resulting in increased permeability and reduced TEER. Similarly, the expression of intestinal barrier-related proteins (MUC2, Occludin and Zo-1) was restricted by ETBF and BFT. Interestingly, the STAT3/ZEB2 axis was activated by ETBF and BFT, and treatment with Brevilin A (a STAT3 inhibitor) or knockdown of ZEB2 limited the promotional effect of ETBF and BFT on the SW480 malignant phenotype. In vivo experiments also confirmed that ETBF colonization accelerated tumor load, carcinogenesis, and intestinal mucosal barrier damage in the colorectum of the AOM/DSS animal model, and that treatment with Brevilin A alleviated these processes. ETBF-secreted BFT accelerated intestinal barrier damage and CRC by activating the STAT3/ZEB2 axis. Our findings provide new insights and perspectives for the application of ETBF in CRC treatment.

Bio-Template Synthesis of V2O3@Carbonized Dictyophora Composites for Advanced Aqueous Zinc-Ion Batteries.

In terms of new-generation energy-storing devices, aqueous zinc-ion batteries (AZIBs) are becoming the prime candidates because of their inexpensive nature, inherent safety, environmental benignity and abundant resources. Nevertheless, due to a restrained selection of cathodes, AZIBs often perform unsatisfactorily under long-life cycling and high-rate conditions. Consequently, we propose a facile evaporation-induced self-assembly technique for preparing V2O3@carbonized dictyophora (V2O3@CD) composites, utilizing economical and easily available biomass dictyophora as carbon sources and NH4VO3 as metal sources. When assembled in AZIBs, the V2O3@CD exhibits a high initial discharge capacity of 281.9 mAh g-1 at 50 mA g-1. The discharge capacity is still up to 151.9 mAh g-1 after 1000 cycles at 1 A g-1, showing excellent long-cycle durability. The extraordinary high electrochemical effectiveness of V2O3@CD could be mainly attributed to the formation of porous carbonized dictyophora frame. The formed porous carbon skeleton can ensure efficient electron transport and prevent V2O3 from losing electrical contact due to volume changes caused by Zn2+ intercalation/deintercalation. The strategy of metal-oxide-filled carbonized biomass material may provide insights into developing high-performance AZIBs and other potential energy storage devices, with a wide application range.

Bioinformatics Analysis for Identifying Differentially Expressed MicroRNAs Derived from Plasma Exosomes Associated with Radiotherapy Resistance in Non-Small-Cell Lung Cancer.

Objective: To explore the differentially expressed microRNAs (DEmiRs) derived from plasma exosomes related to radiotherapy resistance and their corresponding pathways in non-small-cell lung cancer (NSCLC). Methods: Plasma samples from NSCLC patients were retrieved and analyzed. The patients were divided into 3 groups based on the tumor regression grade criteria, assessed by radiological imaging after radiotherapy. TRG1 referred to tumor shrinkage of ≤30% after radiotherapy, TRG2 as 30% < TRG < 50%, and TRG3 as TRG ≥ 50%. High-throughput sequencing and bioinformatics analysis were used to compare the DEmiRs between the three groups. The miRanda, PITA, and RNAhybrid software were used to identify potential target genes of the DEmiRs. GO function enrichment and KEGG pathway enrichment analyses were performed on the target gene set. Results: There were 24 DEmiRs (12 were upregulated and 12 downregulated) between the TRG1 and TRG2 groups, 11 between the TRG1 and TRG3 groups (6 upregulated and 5 downregulated), and 35 between the TRG2 and TRG3 groups. The common DEmiRs between the three groups were miR-92a-3p. GO analysis showed that the target genes of the DEmiRs were mainly enriched in unicellular organism processes, cell transformation, cell localization, and their establishment. KEGG enrichment analysis showed that target genes were significantly enriched in the Ras signaling pathway and associated with endocytosis. Among the 135 identified target genes of miR-92a-3p, 4 were involved in the PI3K-Akt signaling pathway (the downstream pathway of the Ras gene) and 3 in the cAMP signaling pathway (the upstream pathway of the Ras gene). Further, 2 other target genes were involved in the Rap1 signaling pathway (the upstream pathway of PI3K-Akt). Conclusion: By assessing the expression and functional profile of DEmiRs in the plasma exosomes of NSCLC patients after radiotherapy, miR-92a-3p was identified as a promising target affecting radiotherapy outcomes through the Ras signaling pathway.

Overexpression of the lncRNA AC012213.3 Promotes Proliferation, Migration and Invasion of Breast Cancer via RAD54B/PI3K/AKT Axis and is Associated with Worse Patient Prognosis.

BACKGROUND: Long noncoding RNA (LncRNA) has been shown to mediate the development of human malignancies. However, data on its role in breast cancer remains scant. We aimed to evaluate the prognostic potential of lncRNAs in breast cancer. METHODS: We downloaded data on breast cancer patients from The Cancer Genome Atlas (TCGA) database. Tissues were obtained from The Fifth People's Hospital of Chengdu. We then used the DESeq2 package to profile the expression of the lncRNAs between the patients and normal samples. Besides, we performed prognosis and survival analysis using survival tools in R package. We then assayed the role of the differentially expressed lncRNAs, AC012213.3 (ENSG00000266289), in cancer cell lines. Quantitative real-time PCR and Western blot analysis were performed to evaluate the expression of the gene in the cell lines and then assessed its role in the progression of breast cancer using cell proliferation (CCK8 and colony formation assays), migration, invasion (transwell and wound-healing assays) and apoptotic (flow cytometry) assays. RESULTS: Our data showed high expression of lncRNA AC012213.3 in breast cancer tissues and cell lines. The high expression of the AC012213.3 was associated with the worse prognosis and clinical features. Besides, in vitro assays demonstrated that downregulation of AC012213.3 suppresses the proliferation and invasion of breast cancer cells. Further analysis showed that RAD54B is a downstream AC012213.3 target gene and was upregulated in breast cancer. Interestingly, RAD54B expression was associated with shorter survival in breast cancer. In addition, AC012213.3 was shown to facilitate breast cancer progression through the RAD54B/PI3K/AKT axis. CONCLUSION: Taken together, our data demonstrated that lncRNA AC012213.3 is upregulated in breast cancer and could enhance breast cancer progression through RAD54B/PI3K/AKT axis.

Comparison of Induction Chemotherapy Plus Concurrent Chemoradiotherapy and Concurrent Chemoradiotherapy Alone in Locally Advanced Nasopharyngeal Carcinoma.

PURPOSE: Induction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma. METHODS: We thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1. RESULTS: Seven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively). CONCLUSIONS: Induction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

Comparison of induction chemotherapy plus concurrent chemoradiotherapy and induction chemotherapy plus radiotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) is a standard treatment regimen for locally advanced nasopharyngeal carcinoma (LA-NPC). However, the increased acute toxicity of this intensified chemotherapy may counteract its efficacy. The results of studies focusing on the omission of concurrent chemotherapy (CC) regimens are controversial. Therefore, we carried out a meta-analysis to elucidate the efficacy and toxicity of IC + CCRT versus IC plus radiotherapy alone (IC + RT) for LA-NPC. METHODS: Studies available on PubMed, Embase, Cochrane Library and ClinicalTrails.gov were independently searched by two investigators from inception to March 1, 2020. Review Manager software 5.3 (RevMan 5.3) was employed to calculate pooled hazard ratios (HRs), risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Eight studies with a total of 2605 patients were analysed. The results showed that no significant difference between IC + RT and IC + CCRT for disease-free survival (HR = 1.09, 95% CI: 0,85-1.39, P = 0.50), overall survival (HR = 0.92, 95% CI: 0.78-1.09, P = 0.34), local recurrence-free survival (HR = 1.26, 95% CI: 0.95-1.67; P = 0.10), or distant metastasis-free survival (HR = 1.03, 95% CI: 0.84-1.26, P = 0.79). Notably, the incidence of treatment-related grade 3/4 acute haematological toxicity during radiation was higher in the IC + CCRT group. Subgroup analysis showed similar survival outcomes for IC + CCRT and IC + RT with and without the two-dimensional RT technique. CONCLUSIONS: IC + RT was as effective as IC + CCRT for the management of LA-NPC. The IC + RT regimen has the possibility of replacing the IC + CCRT regimen for LA-NPC in the future due to the lower toxicity, although more high-level evidence is urgently needed for verification.

Synthesis of Hollow Carbon Microspheres with Tunable Shell Numbers for High-Performance Anode Material in Lithium-Ion Batteries.

In this paper, hollow carbon microspheres (HCMs) with tunable shell numbers were controllably synthesized by the combination of facile hydrothermal method and etching treatment. The microstructure, morphology and electrochemical performance of HCMs were investigated by X-ray photoelectron, spectra SEM and TEM measurements, and galvanostatic charge-discharge tests. The size of HCMs was uniform and increased with increasing the number of inner carbon shells. Compared to the single-layer carbon microspheres and double-layer carbon microspheres, threelayer HCMs (TLCs) with diameters of 310-360 nm exhibited the highest reversible capacity presenting original discharge and charge capacity of 626.04 and 575.68 mAh·g-1 at 0.1 C. Moreover, the capacitance retention reached to 360 mAh ·g-1 and charge-discharge efficiency was still over 97% after 100 cycles. The superior properties of TLCs can be mainly attributed to their unique three-layer hollow structure which can significantly enhance the pore volume and specific surface area, and thus provides more Li-ions reaction sites and larger contact area between electrodes. Furthermore, the design strategy of HCMs is expected to provide a novel guidance for the design of multi-layer carbon structure with improved electrochemical properties.

The Emerging Roles of miR-125b in Cancers.

MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNA molecules of 22 nucleotides in length. MiRNAs have both tumor-suppressive properties and oncogenic properties that can control critical processes in tumors. Mature miR-125b originates from miR-125b-1 and miR-125b-2 and leads to the degradation of target mRNAs or the inhibition of translation through binding to the 3' untranslated regions (3'-UTR) of target mRNAs. Importantly, miR-125b is involved in regulating NF-κB, p53, PI3K/Akt/mTOR, ErbB2, Wnt, and another signaling pathways, thereby controlling cell proliferation, differentiation, metabolism, apoptosis, drug resistance and tumor immunity. This review aims to summarize the recent literature on the role of miR-125b in the regulation of tumorigenesis and to explore its potential clinical application in the diagnosis, prognosis and clinical treatment of tumors.

Facile Synthesis of Tremella-Like Li3V2(PO4)3/C Composite Cathode Materials Based on Oroxylum for Use in Lithium-Ion Batteries.

Oroxylum as a traditional Chinese medicine, was used as a green and novel bio-template to synthesize tremella-like Li3V2(PO4)3/C composite (LVPC) cathode materials by adopting a facile immersion method. The microstructures were analyzed by X-ray diffraction analysis, scanning electron microscopy, and transmission electron microscopy. The electrochemical properties were investigated by galvanostatic charge-discharge experiments. The LVPC revealed specific capacity of 95 mAh·g-1 at 1 C rate within potential range of 3.0-4.3 V. After 100 cycles at 0.2 C, the retention of discharge capacity was 96%. The modified electrochemical performance is mainly resulted from the distinct tremella-like structure.