Tessaracoccus lacteus sp. nov., Isolated from the Sludge of a Wastewater Treatment Plant.

A bacterium, designated strain T21T, that is non-motile, rod-shaped, and formed pale white colonies, was isolated from the sludge of a wastewater treatment plant's secondary sedimentation tank in China. Strain T21T could grow at 20-40 °C (optimum growth at 30 °C), pH 3.0-10.0 (optimum growth at pH 5.0) and in the presence of 0-8.0% (w/v) NaCl (optimum growth at 2.0%). Based on phylogenetic analysis of 16S rRNA gene sequences and genome sequences, the isolate belongs to the genus Tessaracoccus in the phylum Actinomycetota. It exhibited a close relationship with Tessaracoccus palaemonis J1M15T, Tessaracoccus defluvii LNB-140T, Tessaracoccus flavescens SST-39T, and Tessaracoccus coleopterorum HDW20T. The 16S rRNA gene sequence similarities are 99.8%, 97.9%, 97.9%, and 97.8%, respectively. The major cellular fatty acids were anteiso-C15:0 and C16:0. The main respiratory quinone was MK-9(H4). The polar lipids included phosphatidylglycerol, diphosphatidylglycerol, glycolipid, and phospholipid. Genome annotation of strain T21T predicted the presence of 2829 genes, of which 2754 are coding proteins and 59 are RNA genes. The genomic DNA G+C content was 69.2%. Based on the results of phylogenetic, phenotypic, chemotaxonomic, and genotypic analyses, we propose the name Tessaracoccus lacteus sp. nov. for this novel species within the genus Tessaracoccus. The type strain is T21T (=CCTCC AB 2023031T = KCTC 49936T).

Description and Genomic Characteristics of Diaphorobacter limosus sp. nov., Isolated from a Sewage-Treatment Plant.

A Gram-stain-negative, rod-shaped, non-motile, catalase-positive, denitrifying bacterium, designated strain Y-1T, was isolated from an aeration tank of a sewage treatment plant in China and characterized using polyphasic taxonomic approaches. Strain Y-1T could grow at 10-37 °C (optimum 25 °C), at pH 5.0-10.0 (optimum 7.0) and in the presence of 0-3.0% (w/v) NaCl (optimum 0.5%). The phylogenetic tree based on the 16S rRNA gene sequences revealed that strain Y-1T was a member of genus Diaphorobacter, and showed the highest sequence similarities with Diaphorobacter oryzae RF3T (97.50%), Diaphorobacter nitroreducens NA10BT (97.38%) and Diaphorobacter aerolatus 8604S-37T (96.56%). In terms of carbon source utilization and enzyme activities, strain Y-1T was significantly different from its similar strains. The major respiratory quinone was Q-8, and the main polar lipid was phosphatidylethanolamine. Comparative genomic analysis of strain Y-1T and other Diaphorobacter species was conducted to explore the mechanisms underlying the differences among these strains. Strain Y-1T encoded 3957 genes, consisting of 3813 protein-coding genes and 144 RNA coding genes, and encoded 652 enzymes with 31 unique enzymes compared with other related species. The DNA G + C content was 69.95 mol%. Strain Y-1T exhibited 41.71% DNA-DNA relatedness and 95% ANIb with the most related type strains.On the basis of the evidence presented from polyphasic analysis, strain Y-1T was suggested as a novel species within the genus Diaphorobacter, for which the name Diaphorobacter limosus sp. nov. is proposed, with the type strain Y-1T (= KCTC 92852T = CCTCC AB 2023032T).

Regulatory T cells as crucial trigger and potential target for hyperprogressive disease subsequent to PD-1/PD-L1 blockade for cancer treatment.

PD-1/PD-L1 blockade therapy has brought great success to cancer treatment. Nevertheless, limited beneficiary populations and even hyperprogressive disease (HPD) greatly constrain the application of PD-1/PD-L1 inhibitors in clinical treatment. HPD is a special pattern of disease progression with rapid tumor growth and even serious consequences of patient death, which requires urgent attention. Among the many predisposing causes of HPD, regulatory T cells (Tregs) are suspected because they are amplified in cases of HPD. Tregs express PD-1 thus PD-1/PD-L1 blockade therapy may have an impact on Tregs which leads to HPD. Tregs are a subset of CD4+ T cells expressing FoxP3 and play critical roles in suppressing immunity. Tregs migrate toward tumors in the presence of chemokines to suppress antitumor immune responses, causing cancer cells to grow and proliferate. Studies have shown that deleting Tregs could enhance the efficacy of PD-1/PD-L1 blockade therapy and reduce the occurrence of HPD. This suggests that immunotherapy combined with Treg depletion may be an effective means of avoiding HPD. In this review, we summarized the immunosuppressive-related functions of Tregs in antitumor therapy and focused on advances in therapy combining Tregs depletion with PD-1/PD-L1 blockade in clinical studies. Moreover, we provided an outlook on Treg-targeted HPD early warning for PD-1/PD-L1 blockade therapy.

Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect.

Metformin, as the preferred antihyperglycemic drug for type 2 diabetes, has been found to have a significant effect in inhibiting tumor growth in recent years. However, metformin alone in cancer treatment has the disadvantages of high dose concentrations and few targeted cancer types. Increasing studies have confirmed that metformin can be used in combination with conventional anticancer therapy to obtain more promising clinical benefits, which is expected to be rapidly transformed and applied in clinic. Some combination therapy strategies including metformin combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy have been proven to have more significant antitumor effects and longer survival time than monotherapy. In this review, we summarize the synergistic antitumor effects and mechanisms of metformin in combination with other current conventional anticancer therapies. In addition, we update the research progress and the latest prospect of the metformin-combined application in the cancer treatment. This work could provide more evidence and future direction for the clinical application of metformin in antitumor.

Prediction of CAF-related genes in immunotherapy and drug sensitivity in hepatocellular carcinoma: a multi-database analysis.

This study aims to identify the cancer-associated fibroblasts (CAF)-related genes that can affect immunotherapy and drug sensitivity in hepatocellular carcinoma (HCC). Expression data and survival data associated with HCC were obtained in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted correlation network analysis (WGCNA) analysis was performed to obtain CAF-related genes. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for regression analysis and risk models. Subsequently, Gene Set Enrichment Analysis (GSEA) analysis, Gene Set Enrichment Analysis (ssGSEA) analysis, Tumor Immune Dysfunction and Exclusion (TIDE) analysis and drug sensitivity analysis were performed on the risk models. Survival analysis of CAF scores showed that the survival rate was lower in samples with high CAF scores than those with low scores. However, this difference was not significant, suggesting CAF may not directly influence the prognosis of HCC patients. Further screening of CAF-related genes yielded 33 CAF-related genes. Seven risk models constructed based on CDR2L, SPRED1, PFKP, ENG, KLF2, FSCN1 and VCAN, showed significant differences in immunotherapy and partial drug sensitivity in HCC. Seven CAF-related genes may have important roles in immunotherapy, drug sensitivity and prognostic survival in HCC patients.

Sonodynamic therapy combined with phototherapy: Novel synergistic strategy with superior efficacy for antitumor and antiinfection therapy.

Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection therapy. Sonodynamic therapy (SDT), as a novel noninvasive therapy with a deeper penetration depth (>8 cm), fewer side effects and non-phototoxicity than PT, has drawn much attention in recent years. However, both PT and SDT have intrinsic limitations. By combining PT with SDT, the dualmodel therapy with advanced sensitizers overcome the intrinsic limitations and show higher efficacy than traditional monotherapy. Moreover, the photo-diagnosis modality could be easily integrated into synergistic therapy so that the sensitizer acts as a tracer for fluorescence/photoacoustic imaging, and the treatment process is visualized in a way that SDT combined with other therapies cannot achieve. This review summarizes the advanced sensitizers and the application of combination therapy, and explores the improvement strategies for promoting clinical transformation.

General self-efficacy and frailty in hospitalized older patients: The mediating effect of loneliness.

This study aimed to explore the relationship between general self-efficacy and frailty in hospitalized older adults with chronic diseases, and to examine the mediating role of loneliness. A total of 327 hospitalized older patients aged 60 years or above with chronic diseases were recruited. Cross-sectional data on the patients' general self-efficacy, frailty and loneliness were collected using questionnaires. The PROCESS macro of the bias correction bootstrapping method was used to test the mediation model. The results showed that the significant mediating role of loneliness between general self-efficacy and frailty (B = -0.735, 95% CI [-0.923, -0.564]) explained 42.4% of the total effect of general self-efficacy on frailty. These findings highlighted the importance of loneliness in older patients with chronic diseases in hospital, especially those with low general self-efficacy.

PGM1 and ENO1 Promote the Malignant Progression of Bladder Cancer via Comprehensive Analysis of the m6A Signature and Tumor Immune Infiltration.

BACKGROUND: While N6-methyladenosine (m6A) modification of RNA and the tumor immune microenvironment both influence the progression of cancer, little attention has been paid to interactions between these two factors. Thus, we systematically explored potential biomarkers in the malignant progression of bladder urothelial carcinoma (BLCA) via combining expression of m6A methylation regulators with tumor immune infiltration. METHODS: We extracted m6A regulators from published literature, downloaded BLCA RNA-seq and clinical information from the Cancer Genome Atlas database, and integrated three main bioinformatic methods and qPCR to explore the biological variations in the malignant progression of BLCA. RESULTS: FTO, IGF2BP3, and YTHDC1 have a significant difference in bladder cancer and prognosis. Two subgroups (clusters 1 and 2) were identified according to three key m6A regulators; cluster 1 was preferentially associated with poor prognosis and immune infiltration relative to cluster 2 significantly. We further identified PGM1 and ENO1 as potential prognostic biomarkers, as they were correlated with FTO and IGF2BP3 positively but with YTHDC1, negatively. M2 macrophage and TFH cells were highly infiltrated in BLCA and were associated with BLCA prognosis. Finally, PGM1 and ENO1 were correlated with M2 macrophage and TFH cells and their surface markers CD163and CXCR5. CONCLUSIONS: PGM1 and ENO1 are highly correlated with the malignant progression of BLCA, and the expression of these genes may be new indicators for the diagnosis and prognosis of BLCA.

Outer membrane protein A (OmpA) may be used as a novel target to enrich and detect Escherichia coli in milk samples.

In recent years, food safety incidents caused by Escherichia coli have occurred and have endangered human health. Due to the complex matrix of milk samples and the long pretreatment time, the existing methods cannot quickly detect E. coli in milk samples. It is necessary to enrich the E. coli in the complex matrix to improve the detection sensitivity. The E. coli outer membrane protein A (OmpA) is widely present on the cell membrane of E. coli and may be used as a new target to enrich E. coli. In this study, the purified recombinant OmpA protein was used to immunize BALB/c mice to produce polyclonal antibody. Immunomagnetic beads were combined with the polyclonal antibody to enrich the E. coli in the artificially contaminated milk samples. The products of immunoprecipitation were further used for PCR assay. The bacteria in the PCR sample can be pre-enriched, and the limit of detection is 10 × 100 cfu/mL, which is about 100 times more sensitive than samples not processed by this method. Then, the artificially contaminated milk, coffee, juice, and soybean milk samples were tested separately, and it was found that the E. coli gene could be amplified. The whole analysis time was about 120 min, including the enrichment of bacteria and the detection of eluate. We found that OmpA combined with immunomagnetic beads was more efficient, fast, and convenient than the conventional method. Bacteria can be enriched more efficiently without extracting genomic DNA and culturing bacteria. Therefore, this method has potential value for improving the detection sensitivity and shortening the detection time of E. coli in food samples.

Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin-induced apoptosis in human hepatocellular carcinoma cells.

Capsaicin, which is the pungent ingredient of red hot chili peppers, has been reported to possess anticancer activity, including that against hepatocellular carcinoma. However, the precise molecular mechanisms by which capsaicin exerts its anticancer effects remain poorly understood. Herein, we have tested the involvement of autophagy in the capsaicin mechanism of action in human hepatocellular carcinoma. HepG2 cancer cells were treated with different doses of capsaicin (50, 100 and 200µmol/L) for 6, 12, and 24 h. Flow cytometry and Caspase-3 activity assay were performed to determine cell apoptosis. Immunofluorescence was performed to visualize LC3-positive puncta. Western blotting was used to detect the expression of the hallmarks of apoptosis and autophagy. Capsaicin can induce apoptosis in HepG2 cells. The expression levels of CL-PARP and Bcl-2 were significantly increased. In line with the apoptosis, capsaicin can trigger autophagy in HepG2 cells. Capsaicin increased LC3-II and beclin-1 expression and GFP-LC3-positive autophagosomes. Pharmacological or genetic inhibition of autophagy further sensitized HepG2 cells to capsaicin-induced apoptosis. Mechanistically, capsaicin upregulated the Stat3 activity which contributed to autophagy. Importantly, we found that capsaicin triggered reactive oxygen species (ROS) generation in hepatoma cells and that the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Moreover, NAC abrogated the effects of capsaicin on Stat3-dependent autophagy. In this study, we demonstrated that capsaicin increased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3)-dependent autophagy through the generation of ROS signaling pathways in human hepatoma. Inhibiting autophagy could enhance capsaicin-induced apoptosis in human hepatocellular carcinoma.

Utility of multidetector CT in the diagnosis of gastric bare area invasion by proximal gastric carcinoma.

PURPOSE: To investigate the utility of multidetector CT (MDCT) in the diagnosis of gastric bare area (GBA) invasion by proximal gastric carcinoma (PGC). METHODS: Sixty-eight consecutive patients with biopsy-proven PGC underwent MDCT scan prior to gastrectomy. We evaluated the CT images separately for the site, size, depth, lymph node, and enhancement characteristic of each case. Each postsurgical stomach specimen was axially sectioned and comparison was made to determine the correlation between the CT findings and the pathological examination of each tumor bearing slice. RESULTS: The sensitivity for detecting GBA involvement in patients with PGC was 84%. MDCT correctly identified 32 of 38 patients with GBA invasion and 10/13 (77%) tumors with metastatic lymph node greater than 5 mm in GBA or subphrenic retroperitoneal space. 33/36 (92%) patients with tumor extension within the edge of the gastric wall and 28/32 (88%) patients with tumor infiltration into subphrenic fat were correctly identified. MDCT correctly predicted the infiltration of tumor into the diaphragm in all 14 patients and identified 6/11 (55%) patients with gastrophrenic ligament invasion. CONCLUSION: MDCT may be of value in assessing the important radiological characteristics of GBA invasion in patients with PGC.