Investigation of genomic and pathogenicity characteristics of Streptococcus suis ST1 human strains from Guangxi Zhuang Autonomous Region (GX) between 2005 and 2020 in China.

Streptococcus suis is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for S. suis human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of S. suis ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 S. suis ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of S. suis strains.

Cost-effectiveness of first-line immunotherapy for advanced non-small cell lung cancer with different PD-L1 expression levels: A comprehensive overview.

BACKGROUND: Immunotherapies can substantially improve treatment efficacy, despite their high cost. A comprehensive overview of the cost-effectiveness analysis (CEA) of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer based on different tumor proportion scores (TPSs) was conducted. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, and NHS Economic Evaluation databases were searched from their inception until August 24, 2022. Data relevant to the CEA results were recorded, and quality assessments conducted based on the Quality of Health Economic Studies (QHES) process. FINDINGS: Fifty-one original studies from seven countries were included. The mean QHES score was 77.0 (range: 53-95). Twenty-seven studies were classified as high-quality, and the rest as fair quality. Pembrolizumab, nivolumab, ipilimumab, atezolizumab, camrelizumab, cemiplimab, sintilimab, tislelizumab, and durvalumab were identified using three TPS categories. While nivolumab plus ipilimumab and pembrolizumab plus chemotherapy were unlikely to be cost-effective in China, the results for the US were uncertain. Atezolizumab combinations were not cost-effective in China or the US, and tislelizumab and sintilimab were cost-effective in China. For TPSs ≥ 50%, the pembrolizumab monotherapy could be cost-effective in some developed countries. Cemiplimab was more cost-effective than chemotherapy, pembrolizumab, and atezolizumab in the US. For TPSs ≥ 1%, the cost-effectiveness of pembrolizumab was controversial due to the different willingness-to-pay thresholds. CONCLUSIONS: None of the atezolizumab combination regimens were found to be cost-effective in any perspective of evaluations. Camrelizumab, tislelizumab, and sintilimab have lower ICERs compared to atezolizumab, pembrolizumab, and nivolumab in China. Cemiplimab may be a more affordable alternative to pembrolizumab or atezolizumab. However, it remains unclear which ICIs are the best choices for each country. Future CEAs are required to select comprehensive regimens alongside randomized trials and real-world studies to help verify the economics of ICIs in specific decision-making settings.

Probiotic Potential, Antibacterial, and Antioxidant Capacity of Aspergillus luchuensis YZ-1 Isolated From Liubao Tea.

Aspergillus fungi are widely used in the traditional fermentation of food products, so their safety risks and functions are worthy of investigation. In this study, one Aspergillus luchuensis YZ-1 isolated from Liubao tea was identified based on phylogenetic analyses of sequences of three genes coding for internal transcribed spacer 1 (ITS1), ß-tubulin (benA), and calmodulin (CaM). The results of hemolytic activity, DNase activity, cytotoxicity assay, and antibiotic resistance assay indicated that the strain is potentially safe. The excellent gastrointestinal fluid tolerance, acid tolerance, bile tolerance, auto-aggregation, co-aggregation, cell surface hydrophobicity, and adhesion to human colon adenocarcinoma (HT29) cell line were observed on analysis of the probiotic properties. Furthermore, the results of the antibacterial activity of A. luchuensis YZ-1 indicated that the strain had strong antagonistic effects against Gram-negative and Gram-positive bacteria as well as fungi. Simultaneously, the water extracts and 80% ethanolic extracts of A. luchuensis YZ-1 cells also showed strong ABTS, DPPH, and OH- scavenging ability. Taken together, our results suggest that A. luchuensis YZ-1 has desirable functional probiotic properties and can be proposed as a biocontrol agent in the food industry.

Cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non-small cell lung cancer: a modelling approach.

BACKGROUND: Many studies have explored the cost-effectiveness of immunotherapy versus chemotherapy alone. However, there is paucity of evidence on direct pharmacoeconomic studies related to immunotherapy combinations. Thus, we aimed at assessing the economic outcomes of first-line immunotherapy combinations in the treatment of advanced non-small cell lung cancer (NSCLC) from the Chinese health care perspective. METHODS: The mutual hazard ratios (HRs) of ten immunotherapy combinations and one chemotherapy regimen for the overall survival (OS) and progression-free survival (PFS) were obtained from a network meta-analysis. Based on proportional hazard (PH) assumption, adjusted OS and PFS curves were established to make the effects comparable. With the parameters of cost and utility, and of scale and shape from the fit of adjusted OS and PFS curves obtained from previous studies, a partitioned survival model was designed to estimate the cost-effectiveness of immunotherapy combinations versus chemotherapy alone. Parameter uncertainty in model inputs was assessed using one-way deterministic and probabilistic sensitivity analyses. RESULTS: The incremental cost of camrelizumab plus chemotherapy versus chemotherapy alone was $13,180.65, the lowest among all the other immunotherapy combinations. Furthermore, sintilimab plus chemotherapy (sint-chemo) provided the highest quality-adjusted life-year (QALY) benefit versus chemotherapy alone (incremental QALYs = 0.45). Sint-chemo yielded the best incremental cost-effectiveness ratio (ICER) versus chemotherapy alone (ICER = $34,912.09/QALY), at the current price. The cost-effectiveness probabilities were 32.01% and 93.91% for pembrolizumab plus chemotherapy, and atezolizumab plus bevacizumab plus chemotherapy, respectively (if the original price of the pembrolizumab, atezolizumab, and bevacizumab were decreased by 90%). CONCLUSIONS: Based on the fact that there is fierce competition in the PD-1/PD-L1 market, pharmaceutical enterprises should strive for greater efficacy, and optimal pricing strategy for therapies.

Mesoporous silica stabilized Cu-Fe bimetallic nanozymes for total antioxidant capacity assay of fruit foods.

Total antioxidant capacity (TAC) is currently considered as a vital indicator of food quality in antioxidant ability and attracts much attention for human healthcare. It is thus of great significance to realize the accurate and rapid detection of TAC in foods. Herein, we have constructed a preferable hybrid nanozyme based on the mesoporous silica-stabilized CuO composited Fe3O4 nanoparticles (Fe3O4@MSNs@CuO, FMC NPs), which possess the enhanced peroxidase (POD)-like activity via cascade response for specific and sensitive determination of TAC in fruit foods. The results showed the hybrid nanozyme displayed a remarkable POD-like activity, excellent selectivity and sensitivity, and the limit of detection (LOD) of the colorimetric sensor was 6.13 mM with the concentration range from 10 to 45 mM. Therefore, the fabricated hybrid nanozyme can be regarded as an effective biosensor for the evaluation of antioxidant quality in fruit foods in future. KEY POINTS: • The stabilized bimetallic nanozyme was constructed for TAC analysis in fruits. • The hybrid nanozyme possessed the enhanced POD-like activity by cascading effects. • The nanozyme was an effective biosensor for antioxidant quality evaluation in fruits.

Association between secondhand smoke and cancers in adults in the US population.

BACKGROUND: Tobacco use is the leading preventable cause of cancer and premature death, smoking has a clear causal relationship with a variety of cancers. However, the relationship between exposure to secondhand smoke (SHS) and other cancers besides lung cancer is not clear. In this study, we intend to investigate the cancers mortality risks especially other cancers besides lung cancer associated with exposure to SHS. METHODS: The National Health and Nutrition Examination Survey is a longitudinal population-based, nationally representative health survey and mortality rates linked to the National Death Index (NDI) database. In this study, the participants completed a questionnaire assessing sociodemographic data, anthropometry, and lifestyle information, including smoking and alcohol consumption, meanwhile, all the participants were screened for serum cotinine. First, Spearman correlation analysis was performed to confirm the correlation between serum cotinine level and exposure status. And then, exposure to SHS was divided into two groups: low exposure group (serum cotinine level between 0.015 and 10) and high exposure group (serum cotinine level ≥ 10), Cox proportional hazards regression modeling was used to evaluate the association between exposure to SHS and eight different types of smoke-related cancer. RESULTS: In this study, we evaluated a cohort of 25,794 US residents older than 19 years from 2005 to 2016 and were followed for mortality through the February 2019. We conducted Spearman correlation analysis to confirm the correlation between serum cotinine level and exposure status (including smoking and exposure to SHS), it demonstrated the correlation coefficient between serum cotinine level and exposure to smoke was 0.976, p < 0.00001. By Cox proportional hazards regression modeling, high exposure group were found to be positively associated with all neoplasms with a total Hazard Ratio (HR) of 1.748 (95% Confidence Interval (CI), 1.415-2.159), had higher all-cause mortality risks than non-exposure to tobacco smoke. Regarding the specific types, we found the following associations: cancer of the lung (HR, 1.484; 95% CI, 1.191-1.849), stomach (HR, 1.491; 95% CI, 1.199-1.854), bladder (HR, 1.487; 95% CI, 1.198,1.846), esophageal (HR, 1.487; 95% CI 1.194-1.852), kidney (HR, 1.497; 95% CI, 1.201-1.865), pancreatic (HR, 1.479; 95% CI 1.189-1.841), leukemia (HR, 1.479; 95% CI 1.190-1.839), cervical (HR, 1.490; 95% CI 1.198-1.853). However, low exposure group were non-existent statistically significant with a Hazard Ratio (HR) of 1.062 (95% Confidence Interval (CI), 0.953-1.183). CONCLUSIONS: The research demonstrated that serum cotinine has a significant correlation with smoke exposure status, which confirmed serum cotinine can be used as an indicator to reflect human smoke exposure. What's more, our results confirmed high exposure of SHS (serum cotinine level ≥ 10) has a significant effect on lung, stomach, bladder, esophagus, kidney, pancreatic, leukemia, cervical cancer.

Bacteroides fragilis ameliorates Cronobacter malonaticus lipopolysaccharide-induced pathological injury through modulation of the intestinal microbiota.

Cronobacter has attracted considerable attention due to its association with meningitis and necrotizing enterocolitis (NEC) in newborns. Generally, lipopolysaccharide (LPS) facilitates bacterial translocation along with inflammatory responses as an endotoxin; however, the pathogenicity of Cronobacter LPS and the strategies to alleviate the toxicity were largely unknown. In this study, inflammatory responses were stimulated by intraperitoneal injection of Cronobacter malonaticus LPS into Sprague-Dawley young rats. Simultaneously, Bacteroides fragilis NCTC9343 were continuously fed through gavage for 5 days before or after injection of C. malonaticus LPS to evaluate the intervention effect of B. fragilis. We first checked the morphological changes of the ileum and colon and the intestinal microbiota and then detected the generation of inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10) and the expression of Toll-like receptor 4 (TLR4), occludin, claudin-4, and iNOs. The results indicated that C. malonaticus LPS exacerbated intestinal infection by altering gut microbe profile, tight junction protein expression, and releasing inflammatory factors in a time- and dose-dependent manner. Intriguingly, treatment with B. fragilis obviously diminished the pathological injuries and expression of TLR4 caused by C. malonaticus LPS while increasing gut microbes like Prevotella-9. We note that Shigella, Peptoclostridium, and Sutterella might be positively related to C. malonaticus LPS infection, but Prevotella-9 was negatively correlated. The results suggested that the intestinal microbiota is an important target for the prevention and treatment of pathogenic injuries induced by C. malonaticus LPS.

LINC00511/miRNA-143-3p Modulates Apoptosis and Malignant Phenotype of Bladder Carcinoma Cells via PCMT1.

Bladder cancer has easy recurrence characteristics, but its occurrence and development mechanism are still unclear. Non-coding RNA is a kind of RNA that exists widely and cannot be translated into proteins, which has played a key role in the regulation of biological functions of tumor cells. However, the regulation mechanism of non-coding RNA on bladder tumors is not fully understood. By microarray analysis and database analysis, we found that LINC00511 was significantly highly expressed in bladder cancer. The expressions of LINC00511, miR-143-3p, and PCMT in bladder cancer tissues and cells were detected by quantitative reverse transcription-polymerase chain reaction. The relationship between the expressions of miR-143-3p and PCMT1 and the clinicopathological parameters of the tumor was analyzed. The proliferation and invasion of bladder cancer cells were detected by MTT assay and Transwell assay. The expression levels of E-cadherin and vimentin in bladder cancer cells were detected by Western blot. Cell apoptosis was detected by flow cytometry. In vivo, TCCSUP or SW780 cells were inoculated into BALB/c nude mice to detect tumor volume and weight. Bioinformatics and dual luciferase reporter gene were used to analyze the relationship between LINC00511 and miR-143-3p and its downstream target gene PCMT1. The results showed that LINC00511 could target miR-143-3p/PCMT1 to regulate the proliferation, migration, and apoptosis of bladder cancer TCCSUP or SW780 cells and promote the occurrence and development of bladder cancer.

The value of 4D fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography in the diagnosis of lung lesions.

OBJECTIVE: This study aimed to assess the clinical value of 4D fluorine-18-fluorodeoxyglucose PET/computed tomography (F-FDG PET/CT) in the differential diagnosis for lung lesions. PATIENTS AND METHODS: Fifty-eight patients with lung lesions including lung cancer, pneumonia nodules, and benign pulmonary nodules were enrolled. The PET/CT scan was performed immediately (15 min of dynamic scan), at 60 min (early scan), and at 120 min (delayed scan) after the injection of F-FDG. The time-activity curves (TACs) were generated from the dynamic PET. The maximum standardized uptake value (SUVmax) of each lesion at early and delayed scans was measured, and the retention index of SUVmax (RI-SUVmax) was calculated. The cutoff values for SUVmax were determined. RESULTS: Lung cancer lesions (27/31, 87.1%) exhibited a continuously rising slope of TAC, whereas pneumonia lesions (13/15, 86.66%) and benign pulmonary nodules (12/12, 100%) exhibited a continuously decreasing slope of TAC. The early-SUVmax and delayed-SUVmax in the pneumonia group were significantly lower than those in the lung cancer group, whereas notably higher than those in the benign pulmonary nodules group. The diagnostic accuracy was: delayed-SUVmax > early-SUVmax > RI-SUVmax. CONCLUSION: The 4D F-FDG PET/CT exhibited excellent performance with high accuracy in the dynamic PET/CT.

Pioglitazone prevents sevoflurane­induced neuroinflammation and cognitive decline in a rat model of chronic intermittent hypoxia by upregulating hippocampal PPAR­Î³.

Post­operative cognitive dysfunction is a common complication after anesthesia and surgery. Sevoflurane (SEV), a widely used inhalational anesthetic, can exaggerate neuroinflammation and cause cognitive dysfunction under chronic intermittent hypoxia (CIH) conditions by downregulating hippocampal peroxisome proliferator­activated receptor­Î³ (PPAR­Î³). In the present study, it was examined whether treatment with PPAR­Î³ agonist pioglitazone (PIO) is beneficial in counteracting SEV­induced neuroinflammation and cognitive decline in a rat model of CIH. Rats were exposed to CIH for 4 weeks. After 2 weeks of CIH, these animals underwent either 2.6% SEV or control (CON) exposure for 4 h. PIO (60 mg/kg) or vehicle (VEH) was administered orally twice daily for 2 weeks, starting one day prior to SEV or CON exposure. Compared with CIH­CON+VEH rats, CIH­SEV+VEH rats exhibited significant cognitive decline as indicated by increased latency to locate the hidden platform and shorter dwell­time in the goal quadrant in the Morris Water Maze task. Molecular studies revealed that CIH­SEV+VEH rats had increased proinflammatory cytokine expression and microglial activation in the hippocampus, which were associated with decreased PPAR­Î³ activity. Notably, SEV­induced cognitive decline and increases in proinflammatory cytokine expression and microglial activation were prevented by PIO, which increased hippocampal PPAR­Î³ activity. PIO also increased hippocampal PPAR­Î³ activity in CIH­CON rats but did not alter proinflammatory cytokine expression and microglial activation as well as cognitive function. Additionally, expression of hippocampal PPAR­α and PPAR­ß, two other PPAR isotypes, were comparable among the groups. These data suggest that PIO prevents SEV­induced exaggeration of neuroinflammation and cognitive decline under CIH conditions by upregulating hippocampal PPAR­Î³. PIO may have the potential to prevent anesthetic SEV­induced cognitive decline in surgical patients with obstructive sleep apnea.

MiR-515-5p acts as a tumor suppressor via targeting TRIP13 in prostate cancer.

MiR-515-5p has been suggested to function as tumor suppressor in various human cancers. However, the role of miR-515-5p in prostate cancer was still unclear. In this study, we observed miR-515-5p expression was reduced in prostate cancer tissues and prostate cancer cell lines compared with paired adjacent normal prostatic tissues and normal human prostate epithelial cell lines, respectively. Furthermore, we found miR-515-5p was negatively correlated with TRIP13 mRNA and protein expression in prostate cancer tissue samples, and miR-515-5p directly targeted TRIP13 3'-UTR and negatively regulated TRIP13 mRNA and protein expression. Moreover, miR-515-5p acted as a tumor suppressor to regulate cell proliferation, migration and invasion via targeting TRIP13 in prostate cancer. Besides, we observed that miR-515-5p expression in prostate cancer patients with advanced T stage subgroup or high Gleason score was significantly lower than its expression in prostate cancer patients with early T stage or low Gleason score. Survival analysis suggested that prostate cancer cases with high miR-515-5p expression had better prognosis than prostate cancer cases with low miR-515-5p expression. In conclusion, our study highlights the clinical and biological role of miR-515-5p as tumor suppressive microRNA in prostate cancer.

Anti-microRNA-132 causes sevoflurane­induced neuronal apoptosis via the PI3K/AKT/FOXO3a pathway.

In the present study, the mechanisms underlying the protective effects of microRNA­132 (miRNA­132) on sevoflurane­induced neuronal apoptosis were investigated. Reverse transcription­quantitative polymerase chain reaction and gene microarray hybridization were used to analyze alterations in microRNA levels. Cell viability, apoptosis and caspase­3/9 activity were measured using MTT, flow cytometry and caspase­3/9 activity kits. Immunofluorescence staining and western blot analysis were used to measure protein expression of phosphoinositide 3­kinase (PI3K) and phosphorylated (p­)AKT, forkhead box O3a (FOXO3a). In sevoflurane­induced rats, the expression of miRNA­132 was downregulated, compared with that in negative control rats. The downregulation of miRNA­132 increased neuronal apoptosis and the upregulation of miRNA­132 inhibited neuronal apoptosis in the sevoflurane­induced in vitro model. The downregulation of miRNA­132 suppressed the protein expression of PI3K and p­AKT, and suppressed the protein expression of FOXO3a in the sevoflurane­induced in vitro model. The PI3K inhibitor increased the effects of anti­miRNA­132 on neuronal apoptosis through the AKT/FOXO3a pathway in the sevoflurane­induced in vitro model. The promotion of FOXO3a inhibited the effects of anti­miRNA­132 on neuronal apoptosis through the AKT/FOXO3a pathway in the sevoflurane­induced in vitro model. These data suggested that miRNA­132 caused sevoflurane­induced neuronal apoptosis via suppression of the PI3K/AKT/FOXO3a pathway.

Comparative Study on Microstructural Stability of Pre-annealed Electrodeposited Nanocrystalline Nickel During Pack Rolling.

Microstructural stability is an important issue for nanocrystalline materials to be practically used in many fields. The present work shows how microstructure evolves with rolling strain in pre-annealed electrodeposited nanocrystalline nickel containing an initial strong fiber texture, on the basis of X-ray diffraction line profile analysis as well as transmission electron microscopy observation. The influence of shear strain on microstructural stability of the metal/roll contact interface is compared with that of the metal/metal contact interface; the latter would be closer to deformation in plane strain compression. From the statistical microstructural information, together with experimentally observed microstructure of deformed grains after the final rolling pass, it seems fair to conclude that the microstructure of the metal/metal contact interface is more stable during pack rolling than that of the metal/roll interface.

Sevoflurane exaggerates cognitive decline in a rat model of chronic intermittent hypoxia by aggravating microglia-mediated neuroinflammation via downregulation of PPAR-γ in the hippocampus.

Postoperative cognitive dysfunction is a common complication associated with anesthesia and surgery. Sevoflurane is a widely used volatile anesthetic in the clinical setting. Preclinical studies show that sevoflurane alone does not appear to cause cognitive dysfunction. Here, we examined whether sevoflurane induces cognitive decline under chronic intermittent hypoxia (CIH) conditions. Rats were exposed to CIH or control for 4 weeks. Two weeks after starting intermittent hypoxia, these animals underwent either 2.6% sevoflurane or vehicle exposure for 4 h. Four weeks after CIH, Morris Water Maze task showed that both groups of CIH rats exhibited significantly longer latency to locate the hidden platform and had shorter dwell-time in the goal quadrant compared with respective controls. Notably, CIH + sevoflurane rats had much higher latency and less dwell-time than CIH + vehicle rats. Molecular studies revealed that pro-inflammatory cytokine expression and activated microglia in the hippocampus were increased in both groups of CIH rats, with greater increases in CIH + sevoflurane rats. No differences in above measured parameters were observed between two control groups. Sevoflurane reduced PPAR-γ expression and activity in both control and CIH rats. Moreover, activated microglia was positively correlated with proinflammatory cytokine expression and negatively correlated with PPAR-γ expression and activity in CIH groups. The results suggest that microglia-mediated neuroinflammation in the hippocampus plays an important role in the pathogenesis of CIH-associated cognitive dysfunction, and that a moderate duration of sevoflurane exaggerates cognitive decline under CIH conditions by aggravating microglia-mediated neuroinflammation via downregulation of PPAR-γ in the hippocampus.

[Association of metabolic syndrome and colorectal cancer].

OBJECTIVE: To evaluate the association between metabolic syndrome and colorectal cancer. METHODS: A multicenter case-control study was conducted. A total of 1506 cases of colorectal cancer (936 males and 570 females), whose clinical data were complete and aged from 30 to 75, were collected in the Third, First and Second People's Hospital of Jingdezhen between 2000 and 2009. A total of 3354 controls (1766 males and 1588 females) were subjects admitted to the above 3 hospitals as cases with acute non-malignant non-digestive diseases. Multiple logistic regression models were used to analyze the association between metabolic syndrome and its components and colorectal cancer. RESULTS: Forty-eight cases of colorectal cancer (3.2%) and 59 controls (1.8%) were diagnosed as metabolic syndrome. Colorectal cancer risk was increased in cases with metabolic syndrome (OR=1.64, 95% CI:1.14-2.49, P<0.05) and in men with metabolic syndrome (OR=1.92, 95% CI:1.27-3.78, P<0.05), but not in women (P>0.05). As the number of component of metabolic syndrome increased, the risk of colorectal cancer increased in men (P<0.01), but not in women (P>0.05). CONCLUSION: Association between metabolic syndrome and colorectal cancer exists in men, but not in women.