Efficient heterologous expression of cellobiose 2-epimerase gene in Escherichia coli under the control of T7 lac promoter without addition of IPTG and lactose.

In this study, the cellobiose 2-epimerase gene csce from Caldicellulosiruptor saccharolyticus was expressed in Escherichia coli using TB medium containing yeast extract Oxoid and tryptone Oxoid. Interesting, it was found that when the concentration of isopropyl-beta-d-thiogalactopyranoside (IPTG) and lactose was 0 (no addition), the activity of cellobiose 2-epimerase reached 5.88 U/mL. It was 3.70-fold higher than the activity observed when 1.0 mM IPTG was added. When using M9 medium without yeast extract Oxoid and tryptone Oxoid, cellobiose 2-epimerase gene could not be expressed without IPTG and lactose. However, cellobiose 2-epimerase gene could be expressed when yeast extract Oxoid or tryptone Oxoid was added, indicating that these supplements contained inducers for gene expression. In the absence of IPTG and lactose, the addition of soy peptone Angel-1 or yeast extract Angel-1 to M9 medium significantly upregulated the expression of cellobiose 2-epimerase gene in E. coli BL21 pET28a-csce, and these inductions led to higher expression levels compared to tryptone Oxoid or yeast extract Oxoid. The relative transcription level of csce was consistent with its expression level in E. coli BL21 pET28a-csce. In the medium TB without IPTG and lactose and containing yeast extract Angel-1 and soy peptone Angel-1, the activity of cellobiose 2-epimerase reached 6.88 U/mL, representing a 2.2-fold increase compared to previously reported maximum activity in E. coli. The significance of this study lies in its implications for efficient heterologous expression of recombinant enzyme proteins in E. coli without the need for IPTG and lactose addition.

Tepidibacillus marianensis sp. nov., a novel heterotrophic iron-reducing bacterium isolated from Mariana Trench sediment.

A novel chemoheterotrophic iron-reducing micro-organism, designated as strain LSZ-M11000T, was isolated from sediment of the Marianas Trench. Phylogenetic analysis based on the 16S rRNA gene revealed that strain LSZ-M11000T belonged to genus Tepidibacillus, with 97 % identity to that of Tepidibacillus fermentans STGHT, a mesophilic bacterium isolated from the Severo-Stavropolskoye underground gas storage facility in Russia. The polar lipid profile of strain LSZ-M11000T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, as well as other unidentified phospholipids and lipids. The major fatty acids were C16 : 0 (28.4 %), C18 : 0 (15.8 %), iso-C15 : 0 (12.9 %), and anteiso-C15 : 0 (12.0 %). Strain LSZ-M11000T had no menaquinone. Genome sequencing revealed that the genome size of strain LSZ-M11000T was 2.97 Mb and the DNA G+C content was 37.9 mol%. The average nucleotide identity values between strain LSZ-M11000T and its close phylogenetic relatives, Tepidibacillus fermentans STGHT and Tepidibacillus decaturensis Z9T, were 76.4 and 72.6 %, respectively. The corresponding DNA-DNA hybridization estimates were 20.9 and 23.4 %, respectively. Cells of strain LSZ-M11000T were rod-shaped (1.0-1.5×0.3-0.5 µm). Using pyruvate as an electron donor, it was capable of reducing KMnO4, MnO2, As(V), NaNO3, NaNO2, Na2SO4, Na2S2O3, and K2Cr2O7. Based on phenotypic, genotypic, and phylogenetic evidence, strain LSZ-M11000T is proposed to be a novel strain of the genus Tepidibacillus, for which the name Tepdibacillus marianensis is proposed. The type strain is LSZ-M11000T (=CCAM 1008T=JCM 39431T).

An analysis of the potential association between obstructive sleep apnea and osteoporosis from the perspective of transcriptomics and NHANES.

BACKGROUND: Obstructive sleep apnea (OSA) and osteoporosis (OP) are prevalent diseases in the elderly. This study aims to reveal the clinical association between OSA and OP and explore potential crosstalk gene targets. METHODS: Participants diagnosed with OSA in the National Health and Nutrition Examination Survey (NHANES) database (2015-2020) were included, and OP was diagnosed based on bone mineral density (BMD). We explored the association between OSA and OP, and utilized multivariate logistic regression analysis and machine learning algorithms to explore the risk factors for OP in OSA patients. Overlapping genes of comorbidity were explored using differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Random Forest (RF) methods. RESULTS: In the OSA population, the weighted prevalence of OP was 7.0%. The OP group had more females, lower body mass index (BMI), and more low/middle-income individuals compared to the non-OP group. Female gender and lower BMI were identified as independent risk factors for OP in OSA patients. Gene expression profiling revealed 8 overlapping differentially expressed genes in OP and OSA patients. KCNJ1, NPR3 and WT1-AS were identified as shared diagnostic biomarkers or OSA and OP, all of which are associated with immune cell infiltration. CONCLUSION: This study pinpointed female gender and lower BMI as OP risk factors in OSA patients, and uncovered three pivotal genes linked to OSA and OP comorbidity, offering fresh perspectives and research targets.

The Mediating Role of Self-efficacy in Acute Myocardial Infarction Patients between Post-PCI Fatigue and Post-traumatic Stress Disorder.

Objective: This study aims to investigate the prevalence of post-traumatic stress disorder (PTSD) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Additionally, the study will analyze the correlation between self-efficacy and PTSD in patients with acute myocardial infarction who have undergone PCI. Methods: This study focused on 268 AMI patients admitted to our hospital between April 2019 and March 2022. We utilized the Posttraumatic Stress Disorder Scale-Civilian Version (PCL-C) to conduct a questionnaire survey and analyzed the correlation between self-efficacy, postoperative fatigue, and PTSD using Pearson. Additionally, we established a structural equation model (SEM) using Amos 21.0 software and conducted a mediation effect test. Results: (1) The PTSD score of 268 AMI patients in this study after PCI was (36.62 ± 4.62), the fatigue score was (8.62 ± 0.82), and the fatigue score was (8.62 ± 0.82). 0.82), and the self-efficacy score was (19.34 ± 2.24); (2) Gender, educational level, and complications were the influencing factors of PTSD in AMI patients (P < .05); (3) Pearson analysis showed that PTSD after PCI in AMI patients was correlated positively with fatigue and had a negative correlation with self-efficacy; fatigue It was negatively correlated with self-efficacy (both P < .01); (4) The mediating effect of self-efficacy between fatigue and PTSD in AMI patients after PCI was established, and the mediating effect value was 29.31%. Conclusion: PTSD, fatigue, and self-efficacy after PCI in AMI patients are all at moderate levels, which need clinical attention-29.31% mediating effect between fatigue and PTSD, confirming that fatigue can affect PTSD by regulating self-efficacy.

Comprehensive Analysis of angiogenesis associated genes and tumor microenvironment infiltration characterization in cervical cancer.

Background: Cervical cancer is among the most prevalent malignancies worldwide. This study explores the relationships between angiogenesis-related genes (ARGs) and immune infiltration, and assesses their implications for the prognosis and treatment of cervical cancer. Additionally, it develops a diagnostic model based on angiogenesis-related differentially expressed genes (ARDEGs). Methods: We systematically evaluated 15 ARDEGs using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA). Immune cell infiltration was assessed using a single-sample gene-set enrichment analysis (ssGSEA) algorithm. We then constructed a diagnostic model for ARDEGs using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and evaluated the diagnostic value of this model and the hub genes in predicting clinical outcomes and immunotherapy responses in cervical cancer. Results: A set of ARDEGs was identified from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and UCSC Xena database. We performed KEGG, GO, and GSEA analyses on these genes, revealing significant involvement in cell proliferation, differentiation, and apoptosis. The ARDEGs diagnostic model, constructed using LASSO regression analysis, showed high predictive accuracy in cervical cancer patients. We developed a reliable nomogram and decision curve analysis to evaluate the clinical utility of the ARDEG diagnostic model. The 15 ARDEGs in the model were associated with clinicopathological features, prognosis, and immune cell infiltration. Notably, ITGA5 expression and the abundance of immune cell infiltration (specifically mast cell activation) were highly correlated. Conclusion: This study identifies the prognostic characteristics of ARGs in cervical cancer patients, elucidating aspects of the tumor microenvironment. It enhances the predictive accuracy of immunotherapy outcomes and establishes new strategies for immunotherapeutic interventions.

Comprehensive analysis of autophagy associated genes and immune infiltrates in cervical cancer.

Objectives: Cervical cancer (CC) is the most common gynecological malignant tumor and the fourth leading cause of cancer-related death in women. The progression of CC is significantly affected by autophagy. Our objective was to use bioinformatics analysis to explore the expression, prognostic significance, and immune infiltration of autophagy-related genes in CC. Materials and Methods: We identified a set of autophagy-related differentially expressed genes (ARDEGs) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ARDEGs were further validated by The Human Protein Atlas (HPA), GSE52903, and GSE39001 dataset. Hub genes were found by the STRING network and Cytoscape. We performed Gene Set Enrichment Analysis (GSEA), Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis to further understand the functions of the hub genes. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) were used to check the hub genes. Results: A total of 10 up-regulated (CXCR4, BAX, SPHK1, EIF2AK2, TBK1, TNFSF10, ITGB4, CDKN2A, IL24, and BIRC5) and 19 down-regulated (PINK1, ATG16L2, ATG4D, IKBKE, MLST8, MAPK3, ERBB2, ULK3, TP53INP2, MTMR14, BNIP3, FOS, CCL2, FAS, CAPNS1, HSPB8, PTK6, FKBP1B , and DNAJB1) ARDEGs were identified. The ARDEGs were enriched in cell growth, apoptosis, human papillomavirus infection, and cytokine-mediated. Then, we found that low expression of MAPK3 was associated with poor prognosis in CC patients and was significantly enriched in immune pathways. In addition, the expression of MAPK3 was significantly positively correlated with the infiltration levels of macrophages, B cells, mast cell activation, and cancer-associated fibroblasts. Furthermore, MAPK3 was positively correlated with LGALS9, and negatively correlated with CTLA4 and CD40. Conclusion: Our results show that MAPK3 can be used as a new prognostic biomarker to predict the prognosis of patients with CC.

The femoral anterior tangent line could serve as a reliable alternative reference axis for distal femoral rotational alignment in total knee arthroplasty: an MRI-based study.

Background: This study aimed to evaluate the reference value of the femoral anterior tangent (FAT) line as a guidance of distal femoral rotation on magnetic resonance images (MRI). Methods: We retrospectively included 81 patients (106 knees) diagnosed as ailing from primary knee osteoarthritis. The indirect rotational axes including the FAT line, the perpendicular line to the anteroposterior axis (pAPA), and the posterior condylar axis (PCA) were identified on MRI, and their angles related to the clinical transepicondylar axis (cTEA) or surgical transepicondylar axis (sTEA) were measured. The patients were further divided into subgroups according to the Kellgren-Lawrence (K-L) grades, the joint-line convergence angle (JLCA), and the arithmetic hip-knee-ankle angle (aHKA) to assess the variance of different rotational reference axes. Results: The FAT line was -11.8° ± 3.6° internally rotated to the cTEA and -7.5° ± 3.6° internally rotated to the sTEA. The FAT/cTEA angle and the FAT/sTEA angle shared a similar frequency distribution pattern but a little greater variance to the pAPA/cTEA angle and the PCA/cTEA angle. The PCA/cTEA angle in the JLCA |x| ≥ 6° subgroup was significantly smaller than in the two other JLCA subgroups. The pAPA/cTEA angle and the PCA/cTEA angle also presented statistical significance within the aHKA subgroups. While the FAT/cTEA angle and the FAT/sTEA angle demonstrated superior stability among the different K-L grades, JLCA subgroups, and aHKA subgroups. Conclusion: The FAT line was less affected by the degree of knee osteoarthritis and lower limb alignment, which could serve as a reliable alternative reference axis for the distal femoral rotational alignment in total knee arthroplasty.

Psychometric properties of the Chinese version of the oncology nurses health behaviors determinants scale: a cross-sectional study.

Objective: To test the validity and reliability of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) in oncology nurses, the Chinese version was developed. Methods: The Brislin double translation-back translation approach was employed to forward translation, back translation, synthesis, cross-cultural adaptation, and pre-survey, resulting in the first Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON). A convenience sample technique was used to select 350 study participants in Liaoning, Shandong, and Jiangsu, China, who satisfied the inclusion and exclusion criteria, to assess the validity and reliability of the scale. Results: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) had six subscales (perceived threat, perceived benefits, perceived barriers, self-efficacy, cues to action, and personal protective equipment availability and accessibility), including 29 items. The average scale level was 0.931, and the content validity level of the items varied from 0.857 to 1.000. Each Cronbach's α coefficient had an acceptable internal consistency reliability range of 0.806 to 0.902. X2/df = 1.667, RMSEA = 0.044, RMR = 0.018, CFI = 0.959, NFI = 0.905, TLI = 0.954, and IFI = 0.960 were the model fit outcomes in the validation factor analysis. All of the model fit markers fell within reasonable bounds. Conclusion: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) has good reliability and validity and can be used as a tool to assess the influencing factors of chemotherapy exposure for oncology nurses in China.

Revisiting the hydrological legacy of revegetation on China's Loess Plateau using Eagleson's ecohydrological perspective.

Revegetation has resulted in a trend of increasing vegetation greenness on the Chinese Loess Plateau. However, it remains unclear whether the regional vegetation coverage exceeds hydroclimatic limitations in the context of revegetation, and the hydrological effects of greening are controversial. Eagleson's optimality hypothesis can explain some of the hydrological effects on the Loess Plateau. Here, building on previous research, the geospatial vegetation states were estimated for pre- and post-revegetation periods on the Loess Plateau from 1982 to 2015 using Eagleson's ecological optimality theory. Additionally, a drought composite analysis approach was utilized to investigate the hydrological effects related to drought (including sensitivity and partitioning) under various vegetation states. It was found that revegetation increased the proportion of catchments in the equilibrium state and decreased the proportion in the disturbed state, owing to a wetter climate compared with the pre-revegetation period. Root-zone soil drought, driven by precipitation (P) deficit, asymmetrically triggered hydrological effects for both the pre- and post-revegetation periods, with reduced runoff (Q) for both periods and a decrease in evapotranspiration (ET) during the pre-revegetation period but an increase in ET during the post-revegetation period. Moreover, catchments in an equilibrium state exhibited lower sensitivity between ET and P, and more stable partitioning of ET with regards to P, compared with those in a disturbed state. These results underscore the theoretical framework that an equilibrium state is crucial for maintaining ecosystem ET. Our results highlight the necessity of considering the hydrologic regulation of vegetation states when assessing the hydrological effects of vegetation change.

Smartphone-assisted ratiometric fluorescent sensor for visual detection of chlortetracycline.

The development of a highly selective and sensitive method for detecting chlortetracycline (CTC) is crucial for safeguarding public health and food safety. Herein, a novel ratiometric fluorescence sensor called SiC@ZIF-8@MIP was constructed to specifically recognize and sensitively detect CTC. The sensor has the advantages of fast response speed (7 min), wide linear range (0.1-18 µg mL-1), and low limit of detection (4.56 ng mL-1). With the addition of CTC, the fluorescence of SiC@ZIF-8@MIP is quenched at 410 nm due to the internal filtration effect (IFE) and a new fluorescence signal is generated at 515 nm by CTC due to the aggregation induced emission effect (AIE). Additionally, for rapid on-site detection of CTC, a smartphone is applied to digitize fluorescence images of SiC@ZIF-8@MIP, helping individuals read and analyze the images. This detection method is a promising strategy for on-site assessments of food safety and public health safety.

Innovative chitosan-onion polysaccharide composite films: A study on the preservation effects on cherry tomatoes.

Natural preservation materials have long been a focus of research in the quality control of fruits and vegetables. This study aimed to develop composite films with exceptional preservation properties by utilizing chitosan (CS) as the film-forming material and incorporating onion polysaccharide (ONP) as the active component. The CS-ONP composite films were prepared, and their performance and preservation effects were evaluated. The results demonstrated that increasing the ONP content significantly enhanced the shading, antimicrobial, and antioxidant capabilities of the CS-ONP composite films. Preservation experiments revealed that the CS-ONP composite films effectively delayed the quality decline of cherry tomatoes during storage. However, despite the improvements brought by ONP, certain drawbacks persisted, such as reduced mechanical properties and alterations in surface structure. In summary, the CS-ONP composite films exhibit promising potential as novel materials for fruit and vegetable preservation. PRACTICAL APPLICATION: The spoilage of fruits and vegetables can cause huge economic losses. This study addresses this challenge by using chitosan as the film-forming substrate and adding crude onion polysaccharide as the active ingredient to create composite films. The preservation effects of these films on cherry tomatoes were studied. Although only cherry tomatoes were tested in this study, the composite films demonstrated significant potential for broader applications in fruit and vegetable preservation.

Community stability of free-living and particle-attached bacteria in a subtropical reservoir with salinity fluctuations over 3 years.

Changes in salinity have a profound influence on ecological services and functions of inland freshwater ecosystems, as well as on the shaping of microbial communities. Bacterioplankton, generally classified into free-living (FL) and particle-attached (PA) forms, are main components of freshwater ecosystems and play key functional roles for biogeochemical cycling and ecological stability. However, there is limited knowledge about the responses of community stability of both FL and PA bacteria to salinity fluctuations. Here, we systematically explored changes in community stability of both forms of bacteria based on high-frequency sampling in a shallow urban reservoir (Xinglinwan Reservoir) in subtropical China for 3 years. Our results indicated that (1) salinity was the strongest environmental factor determining FL and PA bacterial community compositions - rising salinity increased the compositional stability of both bacterial communities but decreased their α-diversity. (2) The community stability of PA bacteria was significantly higher than that of FL at high salinity level with low salinity variance scenarios, while the opposite was found for FL bacteria, i.e., their stability was higher than PA bacteria at low salinity level with high variance scenarios. (3) Both bacterial traits (e.g., bacterial genome size and interaction strength of rare taxa) and precipitation-induced factors (e.g., changes in salinity and particle) likely contributed collectively to differences in community stability of FL and PA bacteria under different salinity scenarios. Our study provides additional scientific basis for ecological management, protection and restoration of urban reservoirs under changing climatic and environmental conditions.

Ecological and evolutionary processes involved in shaping microbial habitat generalists and specialists in urban park ecosystems.

Microbiomes are integral to ecological health and human well-being; however, their ecological and evolutionary drivers have not been systematically investigated, especially in urban park ecosystems. As microbes have different levels of tolerance to environmental changes and habitat preferences, they can be categorized into habitat generalists and specialists. Here, we explored the ecological and evolutionary characteristics of both prokaryotic and microeukaryotic habitat generalists and specialists from six urban parks across five habitat types, including moss, soil, tree hole, water, and sediment. Our results revealed that different ecological and evolutionary processes maintained and regulated microbial diversity in urban park ecosystems. Under ecological perspective, community assembly of microbial communities was mainly driven by stochastic processes; however, deterministic processes were higher for habitat specialists than generalists. Microbial interactions were highly dynamic among habitats, and habitat specialists played key roles as module hubs in intradomain networks. In aquatic interdomain networks, microeukaryotic habitat specialists and prokaryotic habitat specialists played crucial roles as module hubs and connectors, respectively. Furthermore, analyzing evolutionary characteristics, our results revealed that habitat specialists had a much higher diversification potential than generalists, while generalists showed shorter phylogenetic branch lengths as well as larger genomes than specialists. This study broadens our understanding of the ecological and evolutionary features of microbial habitat generalists and specialists in urban park ecosystems across multi-habitat. IMPORTANCE: Urban parks, as an important urban greenspace, play essential roles in ecosystem services and are important hotspots for microbes. Microbial diversity is driven by different ecological and evolutionary processes, while little is currently known about the distinct roles of ecological and evolutionary features in shaping microbial diversity in urban park ecosystems. We explored the ecological and evolutionary characteristics of prokaryotic and microeukaryotic habitat generalists and specialists in urban park ecosystems based on a representative set of different habitats. We found that different ecological and evolutionary drivers jointly maintained and regulated microbial diversity in urban park microbiomes through analyzing the community assembly process, ecological roles in hierarchical interaction, and species diversification potential. These findings significantly advance our understanding regarding the mechanisms governing microbial diversity in urban park ecosystems.

Dietary Replacement of Soybean Meal with Zanthoxylum bungeanum Seed Meal on Growth Performance, Blood Parameters, and Nutrient Utilization in Broiler Chickens.

Zanthoxylum bungeanum seed meal (ZBM), a novel plant protein raw material, has shown promising potential in enhancing the growth of broiler chickens as a substitute for soybean meal (SBM) in feed. In the artificial digestive experiment of vitro experiments, the digestibility of ZBM and SBM were assessed using the SDS-III Single Stomach Animal Biometric Digestion System. Subsequently, 180 1-day old AA chicks were divided into three groups for in vivo experiments: corn-soybean-meal-based diet (CON group); ZBM replacing 5% soybean meal in the basal diet (ZBM-1 group); ZBM replacing 10% soybean meal in the basal diet (ZBM-2 group). The experiment period lasted for 42 days. Compared to SBM, ZBM demonstrated higher crude protein content, dry matter digestibility, and extracorporeal digestible protein. Compared with the CON group, the broilers in the ZBM-2 group showed improved ADG and ADFI during the 1-21 d, 22-42 d, and 1-42 d periods (p < 0.05). Furthermore, the ZBM groups exhibited significant increases in slaughter performance compared with the CON group (p < 0.05). The substitution of ZBM for SBM also leads to a significant reduction in serum enzyme indicators (p < 0.05). Additionally, the lipoprotein and total cholesterol of the ZBM groups were significantly lower than those of the CON group (p < 0.05). Substituting SBM with ZBM significantly enhances the activity of superoxide dismutase and the content of immunoglobulin G in broiler serum, while reducing the content of malondildehyde (p < 0.05). The ZBM groups showed significantly higher utilization of dry matter, crude protein, and energy compared with the CON group (p < 0.05). In conclusion, the study confirmed that the substitution of SBM with 5-10% ZBM in broiler diets has a significant positive effect on growth, development, antioxidant capacity, immune function, and nutrient utilization. This study not only provides a theoretical foundation for the utilization of ZBM in broiler diets but also offers an effective approach for reducing reliance on soybean meal.

Correction: Positive Feedback-Loop of Telomerase Reverse Transcriptase and 15-Lipoxygenase-2 Promotes Pulmonary Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0083132.].

The Oncolytic virus VT1092M and an Anti-PD-L1 antibody synergize to induce systemic antitumor immunity in a murine bilateral tumor model.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

Examining the typical hemodynamic performance of nearly 3000 modern surgical aortic bioprostheses.

OBJECTIVES: The objective of this analysis was to assess the normal haemodynamic performance of contemporary surgical aortic valves at 1 year postimplant in patients undergoing surgical aortic valve replacement for significant valvular dysfunction. By pooling data from 4 multicentre studies, this study will contribute to a better understanding of the effectiveness of surgical aortic valve replacement procedures, aiding clinicians and researchers in making informed decisions regarding valve selection and patient management. METHODS: Echocardiograms were assessed by a single core laboratory. Effective orifice area, dimensionless velocity index, mean aortic gradient, peak aortic velocity and stroke volume were evaluated. RESULTS: The cohort included 2958 patients. Baseline age in the studies ranged from 70.1 ± 9.0 to 83.3 ± 6.4 years, and Society of Thoracic Surgeons risk of mortality was 1.9 ± 0.7 to 7.5 ± 3.4%. Twenty patients who had received a valve model implanted in fewer than 10 cases were excluded. Ten valve models (all tissue valves; n = 2938 patients) were analysed. At 1 year, population mean effective orifice area ranged from 1.46 ± 0.34 to 2.12 ± 0.59 cm2, and dimensionless velocity index, from 0.39 ± 0.07 to 0.56 ± 0.15. The mean gradient ranged from 8.6 ± 3.4 to 16.1 ± 6.2 mmHg with peak aortic velocity of 1.96 ± 0.39 to 2.65 ± 0.47 m/s. Stroke volume was 75.3 ± 19.6 to 89.8 ± 24.3 ml. CONCLUSIONS: This pooled cohort is the largest to date of contemporary surgical aortic valves with echocardiograms analysed by a single core lab. Overall haemodynamic performance at 1 year ranged from good to excellent. These data can serve as a benchmark for other studies and may be useful to evaluate the performance of bioprosthetic surgical valves over time. CLINICAL TRIAL REGISTRATION NUMBER: NCT02088554, NCT02701283, NCT01586910 and NCT01531374.

Five-Year Follow-Up from the CoreValve Expanded Use Transcatheter Aortic Valve-in-Surgical Aortic Valve Study.

Transcatheter aortic valve replacement (TAVR) provides an option for extreme-risk patients who underwent reoperation for a failed surgical aortic bioprosthesis. Long-term data on patients who underwent TAVR within a failed surgical aortic valve (TAV-in-SAV) are limited. The CoreValve Expanded Use Study evaluated patients at extreme surgical risk who underwent TAV-in-SAV. Outcomes at 5 years were analyzed by SAV failure mode (stenosis, regurgitation, or combined). Echocardiographic outcomes are site-reported. TAV-in-SAV was attempted in 226 patients with a mean age of 76.7 ± 10.8 years; 63.3% were male, the Society of Thoracic Surgeons predicted risk of mortality score was 9.0 ± 6.7%, and 87.5% had a New York Heart Association classification III or IV symptoms. Most of the failed surgical bioprostheses were stented (81.9%), with an average implant duration of 10.2 ± 4.3 years. The 5-year all-cause mortality or major stroke rate was 47.2% in all patients; 54.4% in the stenosis, 37.6% in the regurgitation, and 38.0% in the combined groups (p = 0.046). At 5 years, all-cause mortality was higher in patients with versus without 30-day severe prosthesis-patient mismatch (51.7% vs 38.3%, p = 0.026). The overall aortic valve reintervention rate was 5.9%; highest in the regurgitation group (12.6%). The mean aortic valve gradient was 14.1 ± 9.8 mm Hg and effective orifice area was 1.57 ± 0.70 at 5 years. Few patients had >mild paravalvular regurgitation at 5 years (5.5% moderate, 0.0% severe). TAV-in-SAV with supra-annular, self-expanding TAVR continues to represent a safe and lasting intermediate option for extreme-risk patients who have appropriate sizing of the preexisting failed surgical valve. Clinical and hemodynamic outcomes were stable through 5 years.

Destabilized microbial networks with distinct performances of abundant and rare biospheres in maintaining networks under increasing salinity stress.

Global changes such as seawater intrusion and freshwater resource salinization increase environmental stress imposed on the aquatic microbiome. A strong predictive understanding of the responses of the aquatic microbiome to environmental stress will help in coping with the "gray rhino" events in the environment, thereby contributing to an ecologically sustainable future. Considering that microbial ecological networks are tied to the stability of ecosystem functioning and that abundant and rare biospheres with different biogeographic patterns are important drivers of ecosystem functioning, the roles of abundant and rare biospheres in maintaining ecological networks need to be clarified. Here we showed that, with the increasing salinity stress induced by the freshwater-to-seawater transition, the microbial diversity reduced significantly and the taxonomic structure experienced a strong succession. The complexity and stability of microbial ecological networks were diminished by the increasing stress. The composition of the microorganisms supporting the networks underwent sharp turnovers during the freshwater-to-seawater transition, with the abundant biosphere behaving more robustly than the rare biosphere. Notably, the abundant biosphere played a much more important role than the rare biosphere in stabilizing ecological networks under low-stress environments, but the difference between their relative importance narrowed significantly with the increasing stress, suggesting that the environmental stress weakened the "Matthew effect" in the microbial world. With in-depth insights into the aquatic microbial ecology under stress, our findings highlight the importance of adjusting conservation strategies for the abundant and rare biospheres to maintain ecosystem functions and services in response to rising environmental stress.