Novel target and PCR assay for identification of hypervirulent ST1 (BI/NAP1/027) Clostridioides difficile and detection of toxigenic C. Difficile.

BACKGROUND AND AIMS: The incidence of Clostridioides difficile infection and the prevalence of hypervirulent ST1 (BI/NAP1/027)strain are increasing, especially in developing countries. We aimed to develop a new PCR assay for the identification of hypervirulent ST1 strains and toxigenic C. difficile in stool samples. MATERIALS AND METHODS: We established a quadruplex TaqMan real-time PCR (pilW_4-plex PCR) assay targeting the pilW, a ST1-specific type Ⅳ minor pilin gene, and three C. difficile genes including cdtB, tcdB, and hsp. The sensitivity and specificity of the assay was tested using 403C. difficile isolates and 180 unformed stool sample. The results were compared with anaerobic culture-based conventional PCR method and MLST. RESULTS: The pilW_4-plex PCR identified toxigenic C. difficile in 333 (82.6%, 333/403) isolates with 100% sensitivity and specificity, and in 78 (43.3%, 78/180) stool samples with the sensitivity and specificity of 94.7% and 93.3%, respectively. Hypervirulent ST1 were detected in 21 strains and nine stool samples by the pilW_4-plex PCR. The pilW_4-plex PCR assay has no cross-reaction with non-toxigenic C. difficile or other bacteria. CONCLUSION: The pilW_4-plex PCR assay is an accurate and rapid method with high sensitivity and specificity for identification of ST1 and detection of toxigenic C. difficile in stool.

Diversity in Pyracantha fortuneana fruits maturity stages enables discrepancy in the phenolic compounds, antioxidant activity, and tyrosinase inhibitory activity.

Pyracantha fortuneana (P. fortuneana) fruit is a wild fruit that is popular because of its delicious taste and numerous nutrients, and phenolic compounds are considered to be the main bioactive components in P. fortuneana fruits. However, the relationship between phenolic compounds and their antioxidant and tyrosinase (TYR) inhibitory activities during the ripening process is still unclear. The study compared the influence of the five developmental stages on the accumulation of phenolic compounds, antioxidant activity, and TYR inhibitory activity in the fruits of P. fortuneana. The compounds were identified by offline two-dimensional liquid chromatography-electrochemical detection (2D-LC-ECD) combined with liquid chromatography-tandem mass spectrometry, and the main active ingredients were quantified. The results showed that stage II had higher total phenolic and flavonoid content, as well as higher antioxidant and TYR inhibitory activity, but the total anthocyanin content was lowest at this stage. A total of 30 compounds were identified by 2D-LC-ECD. Orthogonal partial least squares discriminant analysis screened out six major potential markers, including phenolic acids, procyanidins, and flavonoids. In addition, it was found that caffeoylquinic acids, procyanidins, and flavonoids were higher in stage II than in stages I, III, IV, and V, whereas anthocyanins accumulated gradually from stages III to V. Therefore, this study suggests that the changes in antioxidant and TYR inhibitory activities of P. fortuneana during the five developmental stages may be due to the transformation of procyanidins, caffeoylquinic acids, and phenolic glycosides into other forms during the fruit maturation process. Practical Application: Differences in chemical constituents, antioxidant, and tyrosinase inhibitory activities in fruit maturity stages of P. fortuneana were elucidated to provide reference for rational harvesting and utilization of the fruits and their bioactive components. These findings are expected to provide a comprehensive assessment of the bioactive profile and guide the food industrial production.

CdS QDs grown on ellipsoidal BiVO4 for efficient photocatalytic degradation of tetracycline.

Designing efficient, inexpensive, and stable photocatalysts to degrade organic pollutants and antibiotics has become an effective way for environmental remediation. In this work, we successfully performed in situ growth of CdS QDs on the surface of elliptical BiVO4 to try to show the advantage of the binary heterojuncted photocatalyst (BVO@CdS) for the photocatalytic degradation of tetracycline (TC). The In situ growth of CdS QDs can provide a large number of reactive sites and also generate a larger contact area with BiVO4. In addition, compared with mechanical composite materials, in situ growth can significantly reduce the energy barrier at the interface between BiVO4 and CdS, providing more channels for the separation and migration of photogenerated charge carriers, and further improving reaction activity. As a result, BVO@CdS-0.05 shows the best degradation efficiency, with a degradation rate of 88% after 30 min under visible light. The TC photodegradation follows a pseudo-second-order reaction with a dynamic constant of 0.472 min-1, which is 6.47 times that of pure BiVO4, 7.24 times that of pure CdS QDs and 2 times that of the mechanical composite. The degradation rate of BVO@CdS-0.05 decreases to 77.8% with a retention rate of 88.5% after four cycles, demonstrating excellent stability. Through liquid chromatography-mass spectrometry (LC-MS) analysis, two possible pathways for TC degradation are proposed. Through free radical capture experiments, electron spin resonance measurements, and photoelectrochemical comprehensive analysis, it is confirmed that BVO@CdS composites have constructed an efficient Z-scheme heterojunction via in situ growth, thereby highly enhancing the separation and transport efficiency of charge carriers.

An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy.

Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in the tumor microenvironment (TME), leading to inefficacious immunotherapies in most patients with cancer. By contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in the TME. To leverage TBYS cells in the TME to eliminate tumor cells, we engineered oncolytic virus (OV) encoding TBYS epitopes (OV-BYTE) to redirect the antigen specificity of tumor cells to pre-existing TBYS cells, leading to effective tumor inhibition in multiple preclinical models. Mechanistically, OV-BYTE induced epitope spreading of tumor antigens to elicit more diverse tumor-specific T cell responses. Remarkably, the OV-BYTE strategy targeting human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory efficiently inhibited tumor progression in a human tumor cell-derived xenograft model, providing important insights into the improvement of cancer immunotherapies in a large population with a history of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination.

Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration.

BACKGROUND: Evidence from observational studies suggests an association between chronic obstructive pulmonary disease (COPD) and lung cancer. The potential interactions between the immune system and the lungs may play a causative role in COPD and lung cancer and offer therapeutic prospects. However, the causal association and the immune-mediated mechanisms between COPD and lung cancer remain to be determined. METHODS: We employed a two-sample Mendelian randomization (MR) approach to investigate the causal association between COPD and lung cancer. Additionally, we examined whether immune cell signals were causally related to lung cancer, as well as whether COPD was causally associated with immune cell signals. Furthermore, through two-step Mendelian randomization, we investigated the mediating effects of immune cell signals in the causal association between COPD and lung cancer. Leveraging publicly available genetic data, our analysis included 468,475 individuals of European ancestry with COPD, 492,803 individuals of European ancestry with lung cancer, and 731 immune cell signatures of European ancestry. Additionally, we conducted single-cell transcriptome sequencing analysis on COPD, lung cancer, and control samples to validate our findings. FINDINGS: We found a causal association between COPD and lung cancer (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.31-2.02, P-value < 0.001). We also observed a causal association between COPD and regulatory T cells (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01-1.40, P-value < 0.05), as well as a causal association between regulatory T cells and lung cancer (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.002-1.045, P-value < 0.05). Furthermore, our two-step Mendelian randomization analysis demonstrated that COPD is associated with lung cancer through the mediation of regulatory T cells. These findings were further validated through single-cell sequencing analysis, confirming the mediating role of regulatory T cells in the association between COPD and lung cancer. INTERPRETATION: As far as we are aware, we are the first to combine single-celled immune cell data with two-sample Mendelian randomization. Our analysis indicates a causal association between COPD and lung cancer, with regulatory T cells playing an intermediary role.

Comprehensive single-cell transcriptomic profiling reveals molecular subtypes and prognostic biomarkers with implications for targeted therapy in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a genetically heterogeneous disease with poor clinical outcomes. Identification of biomarkers linked to DNA replication stress may enable improved prognostic risk stratification and guide therapeutic decision making. We performed integrated single-cell RNA sequencing and computational analyses to define the molecular determinants and subtypes underlying ESCC heterogeneity. METHODS: Single-cell RNA sequencing was performed on ESCC samples and analyzed using Seurat. Differential gene expression analysis was used to identify esophageal cell phenotypes. DNA replication stress-related genes were intersected with single-cell differential expression data to identify potential prognostic genes, which were used to generate a DNA replication stress (DRS) score. This score and associated genes were evaluated in survival analysis. Putative prognostic biomarkers were evaluated by Cox regression and consensus clustering. Mendelian randomization analyses assessed the causal role of PRKCB. RESULTS: High DRS score associated with poor survival. Four genes (CDKN2A, NUP155, PPP2R2A, PRKCB) displayed prognostic utility. Three molecular subtypes were identified with discrete survival and immune properties. A 12-gene signature displayed robust prognostic performance. PRKCB was overexpressed in ESCC, while PRKCB knockdown reduced ESCC cell migration. CONCLUSIONS: This integrated single-cell sequencing analysis provides new insights into the molecular heterogeneity and prognostic determinants underlying ESCC. The findings identify potential prognostic biomarkers and a gene expression signature that may enable improved patient risk stratification in ESCC. Experimental validation of the role of PRKCB substantiates the potential clinical utility of our results.

Illuminating Shared Genetic Associations Between Oesophageal Carcinoma and Pulmonary Carcinoma Risk.

Background: Lung cancer and oesophageal cancer are prevalent malignancies with rising incidence and mortality worldwide. While some environmental and behavioural risk factors for these cancers are established, the contribution of genetic factors to their pathogenesis remains incompletely defined. This study aimed to interrogate the intricate genetic relationship between lung cancer and oesophageal cancer and their potential comorbidity. Methods: We utilised linkage disequilibrium score regression (LDSC) to analyse the genetic correlation between oesophageal carcinoma and lung carcinoma. We then employed several approaches, including pleiotropic analysis under the composite null hypothesis (PLACO), multi-marker analysis of genomic annotation (MAGMA), cis-expression quantitative trait loci (eQTL) analysis, and a pan-cancer assessment to identify pleiotropic loci and genes. Finally, we performed bidirectional Mendelian randomisation (MR) to evaluate the causal relationship between these malignancies. Results: LDSC revealed a significant genetic correlation between oesophageal carcinoma and lung carcinoma. Further analysis identified shared gene loci including PGBD1, ZNF323, and WNK1 using PLACO. MAGMA identified enriched pathways and 9 pleiotropic genes including HIST1H1B, HIST1H4L, and HIST1H2BL. eQTL analysis integrating oesophageal, lung, and blood tissues revealed 26 shared genes including TERT, NKAPL, RAD52, BTN3A2, GABBR1, CLPTM1L, and TRIM27. A pan-cancer exploration of the identified genes was undertaken. MR analysis showed no evidence for a bidirectional causal relationship between oesophageal carcinoma and lung carcinoma. Conclusions: This study provides salient insights into the intricate genetic links between lung carcinoma and oesophageal carcinoma. Utilising multiple approaches for genetic correlation, locus and gene analysis, and causal assessment, we identify shared genetic susceptibilities and regulatory mechanisms. These findings reveal new leads and targets to further elucidate the genetic basis of lung and oesophageal carcinoma, aiding development of preventive and therapeutic strategies.

Occurrence and Prognosis of Mixed Subtype Adenocarcinoma and Adeno-Squamous Carcinoma in Esophageal Cancer.

Purpose: To gain a deeper understanding of the incidence and survival rates of rare esophageal mixed adenoacanthoma (EAM) and esophageal mixed adeno-squamous carcinoma (EASC) to promote a more comprehensive understanding of these two subtypes. Background: EAM and EASC are rare subtypes of esophageal cancer with limited literature available. Extensive research has been conducted on the clinical and pathological characteristics of gastric and colorectal mixed adenoacanthomas, but there is relatively little literature on esophageal mixed adenoacanthomas. Therefore, this study aims to investigate the incidence and survival rates of these two subtypes in depth. Methods: Patients diagnosed with EAM and EASC between 2000 and 2019 were selected from the SEER database for the study. Joinpoint software was used to calculate the incidence rates of esophageal AM and ASC patients, and differences in cancer overall survival (OS) and cancer-specific survival (CSS) based on Kaplan-Meier curves were compared. Multivariate Cox regression analysis was employed to identify independent prognostic factors for OS and CSS, and a prognostic model was established and validated for accuracy. Results: The study found that the incidence of EAM increased until 2014, followed by a decline, while the incidence of EASC decreased until 2017, followed by an increase. Both of these subtypes were more common in male patients and those over the age of 65. For EAM patients, preoperative chemoradiotherapy was associated with better survival rates, while for EASC patients, preoperative radiotherapy combined with adjuvant chemotherapy improved survival. Finally, we constructed nomograms for predicting the overall survival of EAM and EASC patients by incorporating identified risk factors, which demonstrated good sensitivity and specificity. Conclusion: EAM and EASC are rare subtypes of esophageal cancer, and an in-depth exploration of their incidence and survival rates provides valuable data and insights for understanding these rare esophageal cancer subtypes. This information can assist clinical decision-making for healthcare professionals.

FABP6 serves as a new therapeutic target in esophageal tumor.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors with high incidence and mortality rates. Despite the continuous development of treatment options, the prognosis for esophageal cancer patients remains poor. Therefore, there is an urgent need for new diagnostic and therapeutic targets in clinical practice to improve the survival of patients with esophageal cancer. METHODS: In this study, we conducted a comprehensive scRNA-seq analysis of the tumor microenvironment in primary esophageal tumors to elucidate cell composition and heterogeneity. Using Seurat, we identified eight clusters, encompassing non-immune cells (fibroblasts, myofibroblasts, endothelial cells, and epithelial cells) and immunocytes (myeloid-derived cells, T cells, B cells, and plasma cells). Compared to normal tissues, tumors exhibited an increased proportion of epithelial cells and alterations in immune cell infiltration. Analysis of epithelial cells revealed a cluster (cluster 0) with a high differentiation score and early distribution, suggesting its importance as a precursor cell. RESULTS: Cluster 0 was characterized by high expression of FABP6, indicating a potential role in fatty acid metabolism and tumor growth. T cell analysis revealed shifts in the balance between Treg and CD8+ effector T cells in tumor tissues. Cellular communication analysis identified increased interactions between FABP6+ tumor cells and T cells, with the involvement of the MIF-related pathway and the CD74-CD44 interaction. This study provides insights into the cellular landscape and immune interactions within esophageal tumors, contributing to a better understanding of tumor heterogeneity and potential therapeutic targets.

Clinical and Genomic Characteristics of a Clinical Listeria Monocytogenes ST120 Isolate Recovered from a Pregnant Woman.

Background: Maternal-fetal listeriosis, caused by Listeria monocytogenes, is a rare but serious infection. Herein, we report the clinical and genomic characteristics of a clinical L. monocytogenes ST120 isolate recovered from a pregnant woman. Methods: The clinical symptoms and treatment in pregnant woman were described in detail. Whole genome sequencing (WGS) was performed on the L. monocytogenes isolate SJZ_LM001, and the genomic characterization of the isolate was deeply analyzed. Results: The clinical symptoms in pregnant women were mainly fever, and the placenta experienced severe inflammation. The pregnant woman was treated with ampicillin for effective anti-infective therapy. Genomic analysis showed that isolate SJZ_LM001 is sequence type (ST) 120, belong to clonal complex (CC)8 and lineage II of L. monocytogenes. Additionally, the isolates SJZ_LM001 harbored a novel plasmid pSJZ_LM001, which carried arsenical resistance genes (arsACD and acr3), and cadmium resistance genes (cadAC). Drug susceptibility testing showed that the isolate SJZ-LM001 was susceptible to ampicillin, meropenem, penicillin, and cotrimoxazole. Conclusion: This is the first to identify a clinical case of infection in a pregnant woman caused by ST120 L. monocytogenes in China. These findings could benefit our understanding of the genomic characteristics of L. monocytogenes, and the pregnancy-related listeriosis and providing early diagnosis and effective targeted treatment.

Internet use, physical activity and depressive symptoms in older adults: A cross-lagged panel analysis.

BACKGROUND: Existing cross-sectional studies suggest a strong positive association between Internet use, physical activity, and mental health in older adults; however, longitudinal studies reporting the relationship between Internet use, physical activity, and levels of depressive symptoms in older adults are lacking. This study aimed to examine the bidirectional relationship between Internet use and depressive symptoms in older adults and its underlying mechanisms. METHODS: We used two waves of follow-up data (2016 and 2018) from the China Family Panel Studies, including 5837 participants aged 60 years or above. The bidirectional relationship between Internet usage time and depressive symptoms was examined using a cross-lagged model. The mediating role of physical exercise was examined using a half-longitudinal mediation model. RESULTS: The results revealed a bidirectional relationship between Internet use time, frequency of physical activity, and depressive symptoms. Longer Internet use predicted lower levels of depressive symptoms, and the frequency of physical activity mediated the longitudinal relationship between Internet use and depressive symptoms in older adults. LIMITATIONS: First, our study used self-report-based variables. Second, our study did not obtain the specific timing of the application of various functions of the Internet and the intensity of physical activity among older adults. Finally, based on the availability of data, our study involved only two waves of data. This may not be sufficient for a full longitudinal mediation effect test. CONCLUSIONS: Internet use and depressive symptoms were interrelated over time among older adults. The frequency of physical activity was a mediator of Internet use and depressive symptoms. This underscores the importance of Internet-based technologies to enable healthy living and prevent depression and loneliness in older adults.

Quantification of Phosphatidylserine Molecules on the Surface of Individual Cells Using Single-Molecule Force Spectroscopy.

Identification of the phosphatidylserine (PS) discrepancies occurring on the cellular membrane during apoptotic processes is of the utmost importance. However, monitoring the quantity of PS molecules in real-time at a single-cell level currently remains a challenging task. Here, we demonstrate this objective by leveraging the specific binding and reversible interaction exhibited by the zinc(II) dipyridinamine complex (ZnDPA) with PS. Lipoic acid-functionalized ZnDPA (LP-ZnDPA) was subsequently immobilized onto the surface of an atomic force microscopy cantilever to form a force probe, ALP-ZnDPA, enabling a PS-specific dynamic imaging and detection mode. By utilizing this technique, we can not only create a heat map of the expression level of PS with submicron resolution but also quantify the number of molecules present on a single cell's surface with a detection limit of 1.86 × 104 molecules. The feasibility of the proposed method is demonstrated through the analysis of PS expression levels in different cancer cell lines and at various stages of paclitaxel-induced apoptosis. This study represents the first application of a force probe to quantify PS molecules on the surface of individual cells, providing insight into dynamic changes in PS content during apoptosis at the molecular level and introducing a novel dimension to current detection methodologies.

Characteristics and outcomes of COVID-19 in Chinese immune thrombocytopenia patients: A prospective cohort study.

The coronavirus disease 2019 (COVID-19) pandemic has a significant impact on the immune system. This is the first and largest study on pre-existing immune thrombocytopenia (ITP) patients infected with COVID-19 in China. We prospectively collected ITP patients infected with COVID-19 enrolled in the National Longitudinal Cohort of Hematological Diseases (NICHE, NCT04645199) and followed up for at least 1 month after infection. One thousand and one hundred forty-eight pre-existing ITP patients were included. Two hundred and twelve (18.5%) patients showed a decrease in the platelet (PLT) count after infection. Forty-seven (4.1%) patients were diagnosed with pneumonia. Risk factors for a decrease in the PLT count included baseline PLT count <50 × 109/L (OR, 1.76; 95% CI, 1.25-2.46; p = 0.001), maintenance therapy including thrombopoietin receptor agonists (TPO-RAs) (OR, 2.27; 95% CI, 1.60-3.21; p < 0.001) and previous splenectomy (OR, 1.98; 95% CI, 1.09-3.61; p = 0.03). Risk factors for pneumonia included age ≥40 years (OR, 2.45; 95% CI, 1.12-5.33; p = 0.02), ≥2 comorbidities (OR, 3.47; 95% CI, 1.63-7.64; p = 0.001), maintenance therapy including TPO-RAs (OR, 2.14; 95% CI, 1.17-3.91; p = 0.01) and immunosuppressants (OR, 3.05; 95% CI, 1.17-7.91; p = 0.02). In this cohort study, we described the characteristics of pre-existing ITP patients infected with COVID-19 and identified several factors associated with poor outcomes.

Potential impact of cuproptosis-related genes on tumor immunity in esophageal carcinoma.

Cuproptosis involves a direct interaction with the tricarboxylic acid (TCA) lipid acylation components. This process intricately intersects with post-transcriptional lipid acylation (LA) and is linked to mitochondrial respiration and LA metabolism. Copper ions form direct bonds with acylated DLAT, promoting DLAT oligomerization, reducing Fe-S cluster proteins, and inducing a protein-triggered toxic stress response that culminates in cell demise. Simultaneously, the importance of immune contexture in cancer progression and treatment has significantly increased. We assessed the expression of cuproptosis-related genes (CRGs) across TCGA and validated our findings using the GEO data. Consensus clustering divided esophageal cancer (ESCA) patients into two clusters based on the expression of 7 CRGs. We evaluated the expression of immune checkpoint inhibitor (ICI) targets and calculated the elevated tumor mutational burden (TMB). Weighted gene co-expression network analysis (WGCNA) identified genes associated with the expression of CRGs and immunity. Cluster 1 exhibited increased immune infiltration, higher expression of ICI targets, higher TMB, and a higher incidence of deficiency in mismatch repair-microsatellite instability-high status. WGCNA analysis identified 14 genes associated with the expression of CRGs and immune scores. ROC analysis revealed specific hub genes with strong predictive capabilities. The expression levels of SLC6A3, MITD1, and PDHA1 varied across different pathological stages; CCS, LIPT2, PDHB, and PDHA1 showed variation in response to radiation therapy; MITD1 and PDHA1 exhibited differences related to the pathological M stages of ESCA. CRGs influence the immune contexture and can potentially transform cold tumors into hot tumors in ESCA patients.

Identification of the immunogenic membrane proteins, catalase, PgbA, and PgbB, as potential antigens against Helicobacter pylori.

AIMS: This study aims to investigate the specific membrane antigens that are targeted by antibodies raised against Helicobacter pylori. METHODS AND RESULTS: Bovine milk antibodies were prepared using whole H. pylori, purified membrane proteins, or both. Enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments revealed that these immunogens triggered anti-H. pylori antibody production in milk. The highest antibody titer was induced by the mixture of whole bacteria and purified membrane proteins. The antibodies induced by mixed immunogens significantly inhibited H. pylori growth in vitro and were used to identify catalase, plasminogen-binding protein A (PgbA), and PgbB via western blotting, immunoprecipitation, and two-dimensional western blotting followed by liquid chromatography with tandem mass spectrophotometry. The immunogenicity of PgbA and PgbB was verified in mice vaccinated with their B-cell epitope vaccines. Following prophylactic vaccination of C57BL/6 mice, each of the three antigens alone and their combination reduced the weight loss in mice, increased antibody titers, and relieved the inflammatory status of the gastric mucosa following H. pylori infection. CONCLUSIONS: Catalase, PgbA, and PgbB could serve as valuable membrane antigens for the development of anti-H. pylori immunotherapies.

Seawater as supplemental moisture: The effect of Co-hydrothermal carbonization products obtained from chicken manure and cornstalk.

The use of seawater as a substitute for pure water as supplemental moisture raises questions about its effect on the physicochemical properties of hydrochar. Therefore, this study aimed to investigate the feasibility of using seawater as supplemental moisture by comparing the physicochemical properties of products obtained through Co-hydrothermal carbonization of chicken manure and cornstalk under seawater and deionized water conditions. By varying the HTC temperature and blending ratios of CM and CS to investigate comprehensively the effect of seawater. Results indicated that the hydrochar yield experienced a variation from 54.54% to 57.40%, while the IC value changed from 7.69% to 8.46% as the ratio of CM:CS shifted from 3:1 to 1:3 under seawater conditions. The higher heating value of the hydrochars obtained under seawater conditions was lower than those obtained under deionized water conditions. This suggests that seawater conditions promote the hydrolysis reaction of organic solid waste. Furthermore, it was observed that when no lignin hydrolysis reaction occurred, seawater conditions had no discernible effect on the fuel quality of the hydrochar. However, at an HTC temperature of 250 °C, the fuel quality of the hydrochar obtained under seawater conditions was notably inferior to that of the hydrochar obtained under deionized water. Thus, an HTC temperature lower than 250 °C is necessary for the hydrothermal carbonization of organic solid waste under seawater conditions. Moreover, the relative content of surface -C-(C, H)/CC of the hydrochar obtained under seawater conditions was lower than that obtained under deionized water conditions, indicating that the hydrochar had a low degree of aromatization. Additionally, there was a significant increase in the immobilized Mg atoms in the hydrochar under seawater conditions, which affected the hydrochar yield and higher heating value of the hydrochar. This research presents a theoretical foundation for preparing solid fuels and materials using hydrothermal carbonization of saltwater as supplemental moisture.

PD-1/PD-L1 blockade restores tumor-induced COVID-19 vaccine bluntness.

The COVID-19 vaccinations are crucial in protecting against the global pandemic. However, accumulating studies revealed the severely blunted COVID-19 vaccine effectiveness in cancer patients. The PD-1/PD-L1 immune checkpoint blockade (ICB) therapy leads to durable therapeutic responses in a subset of cancer patients and has been approved to treat a wide spectrum of cancers in the clinic. In this regard, it is pivotal to explore the potential impact of PD-1/PD-L1 ICB therapy on COVID-19 vaccine effectiveness during ongoing malignancy. In this study, using preclinical models, we found that the tumor-suppressed COVID-19 vaccine responses are largely reverted in the setting of PD-1/PD-L1 ICB therapy. We also identified that the PD-1/PD-L1 blockade-directed restoration of COVID-19 vaccine effectiveness is irrelevant to anti-tumor therapeutic outcomes. Mechanistically, the restored COVID-19 vaccine effectiveness is entwined with the PD-1/PD-L1 blockade-driven preponderance of follicular helper T cell and germinal center responses during ongoing malignancy. Thus, our findings indicate that PD-1/PD-L1 blockade will greatly normalize the responses of cancer patients to COVID-19 vaccination, while regardless of its anti-tumor efficacies on these patients.

Prevalence and antimicrobial resistance profiles of Vibrio spp. and Enterococcus spp. in retail shrimp in Northern California.

Shrimp is one of the most consumed seafood products globally. Antimicrobial drugs play an integral role in disease mitigation in aquaculture settings, but their prevalent use raises public health concerns on the emergence and spread of antimicrobial resistant microorganisms. Vibrio spp., as the most common causative agents of seafood-borne infections in humans, and Enterococcus spp., as an indicator organism, are focal bacteria of interest for the monitoring of antimicrobial resistance (AMR) in seafood. In this study, 400 samples of retail shrimp were collected from randomly selected grocery stores in the Greater Sacramento, California, area between September 2019 and June 2020. The prevalence of Vibrio spp. and Enterococcus spp. was 60.25% (241/400) and 89.75% (359/400), respectively. Subsamples of Vibrio (n = 110) and Enterococcus (n = 110) isolates were subjected to antimicrobial susceptibility testing (AST). Vibrio isolates had high phenotypic resistance to ampicillin (52/110, 47.27%) and cefoxitin (39/110, 35.45%). Enterococcus were most frequently resistant to lincomycin (106/110, 96.36%), quinupristin-dalfopristin (96/110, 87.27%), ciprofloxacin (93/110, 84.55%), linezolid (86/110, 78.18%), and erythromycin (58/110, 52.73%). For both Vibrio and Enterococcus, no significant associations were observed between multidrug resistance (MDR, resistance to ≥3 drug classes) in isolates from farm raised and wild caught shrimp (p > 0.05) and in isolates of domestic and imported origin (p > 0.05). Whole genome sequencing (WGS) of a subset of Vibrio isolates (n = 42) speciated isolates as primarily V. metschnikovii (24/42; 57.14%) and V. parahaemolyticus (12/42; 28.57%), and detected 27 unique antimicrobial resistance genes (ARGs) across these isolates, most commonly qnrVC6 (19.05%, 8/42), dfrA31 (11.90%, 5/42), dfrA6 (9.5%, 4/42), qnrVC1 (9.5%, 4/42). Additionally, WGS predicted phenotypic resistance in Vibrio isolates with an overall sensitivity of 11.54% and specificity of 96.05%. This study provides insights on the prevalence and distribution of AMR in Vibrio spp. and Enterococcus spp. from retail shrimp in California which are important for food safety and public health and exemplifies the value of surveillance in monitoring the spread of AMR and its genetic determinants.

Clostridioides difficile infection in infants: a case report and literature review.

BACKGROUND: Clostridioides difficile (C. difficile) is the major pathogen causing antibiotic-associated diarrhea. There are a variety of symptoms associated with C. difficile infection (CDI) in adults, including self-limiting diarrhea, pseudomembranous colitis, toxic megacolon, septic shock, and even death from the infection. However, the infant's intestine appears to be completely resistant to the effects of C. difficile toxins A and B with rare development of clinical symptoms. CASE PRESENTATION: In this study, we reported a 1-month-old girl with CDI who was born with neonatal hypoglycemia and necrotizing enterocolitis. Her symptom of diarrhea occurred after extensive use of broad-spectrum antibiotics during hospitalization and was accompanied by elevated white blood cell, platelet, and C-reactive protein levels, and repeated routine stool examinations were abnormal. She was recovered by norvancomycin (an analogue of vancomycin) and probiotic treatment. The results of 16 S rRNA gene sequencing also demonstrated the recovery of intestinal microbiota with the enrichment of Firmicutes and Lactobacillus. CONCLUSIONS: Based on the literature review and this case report, clinicians should also pay attention to diarrhea caused by C. difficile in infants and young children. More strong evidence is needed to explain the true prevalence of CDI in this population and to better understand the C. difficile-associated diarrhea in infants.