Systemic immune-inflammation states in US adults with seropositivity to infectious pathogens: A nutrient-wide association study.

BACKGROUND: Limited understanding exists regarding the association between daily total dietary nutrient intakes and immune-inflammation states in US adults exposed to various pathogens. This study sought to examine the correlation between nutrient intakes and immune-inflammation indicators and to assess their performance in distinguishing immune-inflammation states. METHODS: This study was derived from the National Health and Nutrition Examination Survey (NHANES), which included 33,804 participants aged 20 years or older between 2005 and 2018. Multivariable linear regression and restricted cubic spline regression were conducted to evaluate the association between nutrient intakes and immune-inflammation indicators. Receiver operating characteristic curve analysis was performed to evaluate the discriminatory performance of identified nutrients for various immune-inflammation states measured by the systemic immune-inflammation index (SII). RESULTS: Ten key nutrients were significantly associated with immune-inflammation responses, including calcium, saturated fatty acid (SFA) 4:0, SFA 6:0, SFA 12:0, SFA 14:0, SFA 16:0, vitamin B2, total SFAs, retinol, and lutein + zeaxanthin, which show potential as dietary indicators. The area under the curve for discriminating various immune-inflammation states was improved by at least 0.03 compared with a model that included only covariates, with all P values <0.05 in the Delong tests, indicating a significant enhancement in model performance. CONCLUSIONS: Ten nutrients, including calcium, various SFAs, vitamin B2, retinol, and lutein + zeaxanthin, exhibit significant association with SII and potential as dietary indicators for distinguishing between different immune-inflammation states in US adults with seropositivity to various viruses.

Complexity of influences on atrazine phytoremediation of coexisting graphene oxide in water: Mitigating its phytotoxicity while decreasing plant removal contribution.

Phytoremediation is an efficient technology for the removal of herbicide atrazine (ATZ) contamination in water bodies, but its ability to reduce ATZ under combined pollution remains unclear, especially ATZ co-existing with the emerging pollutant graphene oxide (GO) that may have potential effects on ATZ fate, plants and microbes. Herein, we investigated the phytoremediation potential of an emergent plant (Iris pseudacorus) for ATZ and the response of bacteria in a hydroponic system with and without GO. The results showed that plants enhanced ATZ dissipation in water with the increased removal rate by a factor of 1.7-4.0. GO restricted ATZ uptake by plants, but favored ATZ bioconcentration in cell walls. The plant contributed most to changes in the bacterial communities, decreasing the alpha diversity, while enriching the functional categories involving in amino acid and carbohydrate metabolisms. These findings indicated that I. pseudacorus can be employed as an effective candidate of phytoremediation for ATZ co-existing with GO at environmentally relevant concentrations, tending to recruit bacteria with plant stress tolerance and growth-promotion activities more than with ATZ degradation activities; GO exerted a mitigating effect on ATZ stress improving the barrier function of cell walls, but decreased the contribution of plants to ATZ removal.

Predictive value of neutrophil to lymphocyte ratio for clinical outcome in patients with atrial fibrillation: a systematic review and meta-analysis.

Background: The association between the Neutrophil-to-Lymphocyte Ratio (NLR) and the prognosis of Atrial Fibrillation (AF) has been extensively studied, yet clinical outcomes have varied. Consequently, this analysis was undertaken to explore the link between NLR and the prognostic markers of AF. Methods: We conducted an exhaustive search across electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, to investigate the correlation between the NLR and indicators of adverse clinical outcomes associated with AF from the database establishment date through March 31, 2024. In this study, the recurrence rate of AF was the primary outcome measure, while the secondary outcome measures were mortality, stroke, and left atrial thrombus. Odds ratio (OR), relative risk (RR), hazard ratio (HR) and standard mean difference (SMD) with a 95% confidence interval (CI) were integrated for assessment, and the stability of prognostic outcomes and publication bias were verified by sensitivity analysis and Egger's test, respectively. Subgroup analyses were performed to pinpoint the sources of heterogeneity. Results: This analysis included 20 studies, encompassing a total of 59,256 patients. Our statistical analysis of both categorical and continuous variables revealed that an elevated NLR was significantly associated with increased risks in AF patients for recurrence (categorical variable: OR = 1.39, 95% CI = 1.21-1.60; continuous variable: SMD = 0.49, 95% CI = 0.24-0.74), mortality (categorical variable: OR = 1.87, 95% CI = 1.59-2.20), stroke (categorical variable: OR = 1.56, 95% CI = 1.13-2.17; continuous variable: SMD = 0.77, 95% CI = 0.63-0.91), and left atrial thrombus (categorical variable: OR = 1.87, 95% CI = 1.27-2.75; continuous variable: SMD = 0.59, 95% CI = 0.30-0.89). Subgroup analyses found that high NLR was significantly linked to AF recurrence when the NLR was >3. High NLR was significantly linked to the risk of stroke in AF when the NLR was ≤3. Conclusions: This study suggested that a high NLR is significantly linked to prognostic risk markers of AF, and NLR may be an effective biomarker for the prognosis of AF in clinical practice. Systematic Review Registration: PROSPERO (CRD42024530970).

A novel m7G-related miRNA prognostic signature for predicting clinical outcome and immune microenvironment in colon cancer.

Background: Colon cancer (CC) is a highly prevalent malignancy worldwide, characterized by elevated mortality rates and poor prognosis. N7-methylguanosine (m7G) methylation is an emerging RNA modification type and involved in the development of many tumors. Despite this, the correlation between m7G-related miRNAs and CC remains to be elucidated. This research aimed to investigate the clinical significance of m7G-related miRNAs in predicting both the prognosis and tumor microenvironment (TME) of CC. Method: We retrieved transcriptome data and associated clinical information from a publicly accessible database. Using univariate Cox and LASSO regression analyses, we established a signature of m7G-related miRNAs. Additionally, we used CIBERSORT and ssGSEA algorithms to explore the association between the prognostic risk score and the TME in CC patients. By considering the risk signature and immune infiltration, we identified differentially expressed genes that contribute to the prognosis of CC. Finally, the expression patterns of prognostic miRNAs were verified using quantitative reverse transcriptase PCR (qRT-PCR) in cell lines. Results: We constructed a prognostic risk signature based on seven m7G-related miRNAs (miR-136-5p, miR-6887-3p, miR-195-5p, miR-149-3p, miR-4433a-5p, miR-31-5p, and miR-129-2-3p). Subsequently, we observed remarkable differences in patient outcomes between the high- and low-risk groups. The area under the curve (AUC) for 1-, 3-, and 5-year survivals in the ROC curve were 0.735, 0.707, and 0.632, respectively. Furthermore, our results showed that the risk score can serve as an independent prognostic biomarker for overall survival prediction. In terms of immune analysis, the results revealed a significant association between the risk signature and immune infiltration, as well as immune checkpoint expression. Finally, our study showed that CCDC160 and RLN3 is the gene most relevant to immune cells and function in CC. Conclusion: Our study conducted a comprehensive and systematic analysis of m7G-associated miRNAs to construct prognostic profiles of CC. We developed a prognostic risk model based on m7G-miRNAs, with the resulting risk scores demonstrating considerable potential as prognostic biomarkers. These findings provide substantial evidence for the critical role of m7G-related miRNAs in colon cancer and may offer new immunotherapeutic targets for patients with this disease.

Chronic hypoxia drives the occurrence of ferroptosis in liver of fat greening (Hexagrammos otakii) by activating HIF-1α and promoting iron production.

BACKGROUND: Hypoxia caused by global climate change and human activities has become a growing concern eliciting serious effect and damages to aquatic animals. Hexagrammos otakii is usually a victim of hypoxia which caused by high density aquaculture and high nutrient input. The mechanism underlying ferroptosis regulation after hypoxia-stress in liver of H. otakii, however, remains elusive. METHODS: For a duration of 15 days, expose the H. otakii to low concentrations of dissolved oxygen (3.4 ± 0.2 mg/L). Detecting alterations in the H. otakii liver tissue by chemical staining, immunohistochemistry, and electron microscopy. The expression variations of relevant genes in the liver of the H. otakii were simultaneously detected using Western blot and qPCR. A correlation analysis was performed between HIF-1α and iron ion expression in the liver of H. otakii following hypoxic stress. RESULTS: In this study, we conducted the whole ferroptosis integrated analysis of H. otakii under chronic hypoxic condition. Reactive oxygen species (ROS) are highly accumulated under the hypoxia treatment (Superoxide Dismutase, SOD; Catalase, CAT), and which results in a significantly enhanced of lipid peroxidation (Lipid Peroxidation, LPO; Malondialdehyde, MDA; Aminotransferase, AST; Alanine aminotransferase, ALT) in liver tissue. The HIF-1α signaling is activated to cope with the hypoxia stress through strategies including changing iron ion concentration (Fe3+ and TFR1) to breaking the oxidation balance (GSH and GSH-Px), and enhancing ferroptosis gene expression (GPX4). The expression of genes related to ferroptosis pathway (DMT1, FTH1, STEAP3, ACSL4, γ-GCS, SLC7A11) is significantly upregulated and associated to the expression of iron and HIF-1α. CONCLUSIONS: It is demonstrated that the HIF-1α/Fe3+/ROS/GPX4 axis is involved in promoting ferroptosis in fat greening hepatocytes following hypoxia-stress. Ultimately, our findings unveil a process by which hypoxic stress strongly encourages ferroptosis by triggering HIF-1α and boosting iron synthesis.

Effects of total sleep deprivation on functional connectivity of the anterior cingulate cortex: Insights from resting-state fMRI in healthy adult males.

Inadequate sleep significantly impacts an individual's health by compromising inhibitory control and self-regulation abilities. This study employed resting-state functional magnetic resonance imaging (fMRI) to assess the functional connectivity between the anterior cingulate cortex (ACC) and the whole brain in 16 healthy adult males after 36 h of total sleep deprivation. Additionally, this study investigated alterations in individuals' inhibitory control functions and physiological mechanisms following sleep deprivation. The results showed a significant increase in functional connectivity between the ACC, the left angular gyrus, and the right hippocampus following 36 h of continuous sleep deprivation. Conversely, functional connectivity was notably decreased between the ACC and the right insular cortex, right paracingulate gyrus, and bilateral putamen. Furthermore, changes in ACC functional connectivity were significantly correlated with alterations in behavioral performance in the go/no-go task after sleep deprivation. This study contributes to understanding brain network mechanisms in the anterior cingulate gyrus after sleep deprivation. It clarifies the relationship between functional connectivity changes in the anterior cingulate gyrus and inhibitory control post-sleep deprivation.

Mutant ATRX: pathogenesis of ATRX syndrome and cancer.

The transcriptional regulator ATRX, a genetic factor, is associated with a range of disabilities, including intellectual, hematopoietic, skeletal, facial, and urogenital disabilities. ATRX mutations substantially contribute to the pathogenesis of ATRX syndrome and are frequently detected in gliomas and many other cancers. These mutations disrupt the organization, subcellular localization, and transcriptional activity of ATRX, leading to chromosomal instability and affecting interactions with key regulatory proteins such as DAXX, EZH2, and TERRA. ATRX also functions as a transcriptional regulator involved in the pathogenesis of neuronal disorders and various diseases. In conclusion, ATRX is a central protein whose abnormalities lead to multiple diseases.

Comparison of lecture-based learning with presentation-assimilation-discussion method in occupational bloodborne exposure education of nursing students, a randomised trial.

BACKGROUND: Occupational Bloodborne Exposures (OBEs) are incidents where healthcare workers come into contact with blood or other potentially infectious materials, leading to risks of transmitting bloodborne pathogens. Nursing students, often in direct contact with patients, face heightened risks due to their duties. METHODS: First, we conducted a cross-sectional survey using a OBEs questionnaire to explore the knowledge, attitudes, practices, and needs regarding OBEs among nursing students. Subsequently, we used a randomized controlled trial (RCT) to compare the impact of the Presentation-Assimilation-Discussion (PAD) method with the traditional lecture-based learning (LBL) method on OBEs education for nursing students. Pre-test, post-test, and retention test were used to observe the teaching effectiveness, and the students' feedback on the teaching method was also observed. RESULTS: In the cross-sectional survey, we found that nursing students lacked sufficient knowledge and management skills regarding OBEs but recognized the importance of standard precautions and expressed a desire for systematic OBEs training during their education and internships. In the RCT, the total, theoretical, and practical scores of the PAD and LBL groups were comparable in the pre-test (56.70 ± 3.47 vs. 56.40 ± 3.95, 33.09 ± 3.39 vs. 33.33 ± 2.44, 23.61 ± 4.66 vs. 23.07 ± 4.84, p > 0.05). After training, the PAD model demonstrated an advantage over the LBL model in immediate total (84.25 ± 4.06 vs. 78.95 ± 4.23, p < 0.001), theoretical (54.32 ± 2.43 vs. 51.44 ± 2.58, p < 0.001), and practical scores (29.93 ± 3.90 vs. 27.51 ± 4.33, p < 0.01). It also showed superior retention of total (69.05 ± 3.87 vs. 65.77 ± 2.94, p < 0.001) and theoretical scores (39.05 ± 3.05 vs. 36.23 ± 3.18, p < 0.001). However, there was no significant difference in the retention of practical scores between the two groups (30.00 ± 4.76 vs. 29.53 ± 3.73, p > 0.05). The PAD group benefited more across various learning dimensions but reported a higher study load. CONCLUSIONS: Our study reveals that the PAD model could be a valuable approach for teaching OBEs to nursing students.

Clonostachys rosea, a Pathogen of Brown Rot in Gastrodia elata in China.

Gastrodia elata, commonly known as Tian Ma, is a perennial mycoheterotrophic orchid. Qianyang Tian Ma (QTM), a geographical indication agricultural product from Hongjiang City, Hunan Province, China, is primarily characterized by the red variety, G. elata f. elata. A severe outbreak of tuber brown rot disease was documented in QTM during the harvesting season in Hunan. The fungal pathogen associated with the disease was isolated on potato saccharose agar (PSA) and identified through morphological and phylogenetic analyses. Pathogenicity tests were performed on healthy tubers of G. elata f. elata. The results showed that the representative isolate, named TMB, produced white hyphal colonies with a ring structure, broom-like phialides, partially curved ellipsoidal conidia, and orange-yellow spherical ascocarps on PSA. Phylogenetic analysis of the ITS, LSU, rpb2 and tub2 sequences using Bayesian and maximum-likelihood methods identified the isolate TMB as Clonostachys rosea, based on morphological and phylogenetic data. Pathogenicity tests revealed typical disease symptoms on healthy G. elata tubers 15 days post-inoculation with the isolate TMB. C. rosea is known to cause diseases in economically important crops, but there are no reports of its occurrence on G. elata f. elata in China. This study provides valuable insights into the occurrence, prevention, and control of brown rot disease in G. elata f. elata.

Histamine synthesis and transport are coupled in axon terminals via a dual quality control system.

Monoamine neurotransmitters generated by de novo synthesis are rapidly transported and stored into synaptic vesicles at axon terminals. This transport is essential both for sustaining synaptic transmission and for limiting the toxic effects of monoamines. Here, synthesis of the monoamine histamine by histidine decarboxylase (HDC) and subsequent loading of histamine into synaptic vesicles are shown to be physically and functionally coupled within Drosophila photoreceptor terminals. This process requires HDC anchoring to synaptic vesicles via interactions with N-ethylmaleimide-sensitive fusion protein 1 (NSF1). Disassociating HDC from synaptic vesicles disrupts visual synaptic transmission and causes somatic accumulation of histamine, which leads to retinal degeneration. We further identified a proteasome degradation system mediated by the E3 ubiquitin ligase, purity of essence (POE), which clears mislocalized HDC from the soma, thus eliminating the cytotoxic effects of histamine. Taken together, our results reveal a dual mechanism for translocation and degradation of HDC that ensures restriction of histamine synthesis to axonal terminals and at the same time rapid loading into synaptic vesicles. This is crucial for sustaining neurotransmission and protecting against cytotoxic monoamines.

Influence of surface water and groundwater gradient on spatial distribution of typical vegetation in the hinterland of Taklamakan desert.

Water resources are essential for desert oases and are key drivers of local ecological processes critical to the growth of desert vegetation. In this study, the oasis in the hinterland of the Taklamakan Desert, China, was selected as the research subject. Using high-precision classification of oasis vegetation through machine learning, surface water within the oasis was identified and extracted from multi-year Landsat remote sensing data. The spatial distribution patterns of the main community-building species, Populus euphratica and Tamarix ramosissima, were studied under different moisture gradients using environmental covariates and measured groundwater depth to invert its spatial distribution and K-mean clustering to construct surface water and groundwater moisture gradients. The results indicated that the classification accuracy for the two species reached 0.917. Gradients 1-5 were used to categorize the water resources, dividing surface water and groundwater into five gradients. Gradient 3 exhibited the optimal moisture conditions, with a high surface water distribution frequency (0.017) and shallow groundwater depth (3.158 m), while Gradient 4 showed the least optimal moisture conditions, characterized by a low surface water distribution frequency (0.008) and deep groundwater depth (4.820 m). The water gradient decreased in the following order: Gradient 3 > Gradient 5 > Gradient 1 > Gradient 2 > Gradient 4. The optimum gradients for growth of P. euphratica and T. ramosissima were gradients 5, 1, and 2. The normalized vegetation index spatial distribution patterns of the two species were consistent with that of the moisture gradient. Tamarix ramosissima was found to be more tolerant to salinity and drought than P. euphratica. Overall, this study provides valuable information on the effect of the spatial distribution of water resource gradients on oasis vegetation and can guide future water delivery policies in oases.

Birthweight influences liver structure, function and disease risk: Evidence of a causal association.

AIM: Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) about direct foetal-affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two-step MR analysis was used to further assess and quantify the mediating effects of the mediators. RESULTS: When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29-2.02, p < 0.001), higher magnetic resonance imaging [MRI] proton density fat fraction (PDFF) and higher serum gamma glutamyltransferase (GGT). Two-step MR identified two candidate mediators that partially mediate the direct foetal effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.29%) and triglycerides (6.50%). CONCLUSIONS: Our MR analysis reveals a direct causal association between lower birthweight and liver MRI PDFF, as well as the development of NAFLD, which persisted even after accounting for the potential influence of maternal factors. In addition, we identified fasting insulin and triglycerides as mediators linking birthweight and hepatic outcomes, providing insights for early clinical interventions.

Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission.

Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL)1-3, approximately 50% of patients relapse within the first year4-6, representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.4 years. Analysis of ligand-receptor interactions revealed that type 2 cells regulate a dysfunctional subset to maintain whole-population homeostasis, and the addition of IL-4 during antigen-specific activation alleviates CAR T cell dysfunction while enhancing fitness at both transcriptomic and epigenomic levels. Serial proteomic profiling of sera after treatment revealed a higher level of circulating type 2 cytokines in 5-year or 8-year relapse-free responders. In a leukaemic mouse model, type 2high CAR T cell products demonstrated superior expansion and antitumour activity, particularly after leukaemia rechallenge. Restoring antitumour efficacy in type 2low CAR T cells was attainable by enhancing their type 2 functionality, either through incorporating IL-4 into the manufacturing process or by priming manufactured CAR T products with IL-4 before infusion. Our findings provide insights into the mediators of durable CAR T therapy response and suggest potential therapeutic strategies to sustain long-term remission by boosting type 2 functionality in CAR T cells.

Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor.

BACKGROUND: Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases. AIM: To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models. METHODS: MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators. RESULTS: The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-ß and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05). CONCLUSION: MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

Efficacy study of neuronavigation-assisted stereotactic drilling of urokinase drainage versus craniotomy in the treatment of massive intracerebral haemorrhage in elderly patientsa.

To evaluate the efficacy of neuronavigation-assisted stereotactic drilling drainage compared with that of craniotomy in the treatment of massive intracerebral haemorrhage (ICH) in elderly patients. This was a randomized, controlled, blind endpoint clinical study. Elderly patients with massive ICH treated at our neurosurgery department, without the formation of brain herniation preoperatively, all underwent neurosurgical intervention. Patients were randomly assigned to two groups: the minimally invasive surgery (MIS) group, which received neuronavigation-assisted stereotactic drilling drainage, and the craniotomy haematoma removal surgery (CHRS) group. Patient characteristics, surgical anaesthesia methods, surgery duration, intraoperative bleeding volume, duration of ICU stay duration of hospital stay, complications, and modified Rankin scale (mRS) scores at 90 days posttreatment were compared between the two groups. Statistical analysis was performed on the collected data. A total of 67 patients were randomly assigned, with 33 (49.25%) in the MIS group and 34 (50.75%) in the CHRS group. Compared with the CHRS group, the MIS group had advantages, including the use of local anaesthesia, shorter surgery duration, less intraoperative bleeding, shorter ICU stay, and fewer complications (P < 0.05). The MIS group had a significantly improved patient prognosis at 90 days (mRS 0-3). However, there were no significant differences in hospital stay or 90-day survival rate between the two groups (P > 0.05). For elderly patients with massive ICH without brain herniation, stereotactic drilling drainage is a simple surgical procedure that can be performed under local anaesthesia. Patients treated with this approach seem to have better outcomes than those treated with craniotomy. In clinical practice, neuronavigation-assisted stereotactic drilling drainage is recommended for surgical treatment in elderly patients with massive ICH without brain herniation.Clinical trial registration number: NCT04686877.

Structural characteristics and nonvolatile metabolites of theabrownins and their impact on intestinal microbiota in high-fat-diet-fed mice.

This study prepared enzymatic theabrownins (TBs-e), alkaline theabrownins (TBs-a), and Pu-erh tea theabrownins (TBs-f), and investigated whether different preparation processes affected the structures, nonvolatile metabolites, and biofunctional activities of TBs. Structural characterization revealed that TBs were polymeric phenolic compounds rich in hydroxyl and carboxyl groups. Nontargeted metabolomics revealed that amino acids were the primary nonvolatile metabolites in TBs-e and TBs-a, accounting for over 70 % of the total nonvolatile content. TBs-f contained more polyphenols, caffeine, and flavonoids, accounting for 14.2 %, 3.9 %, and 0.8 % of total nonvolatile content, respectively. In vivo, at 560 mg/kg body weight, TBs-f were associated with regulation of blood glucose and lipid concentrations in mice. Moreover, 16S rRNA indicated that at 1120 mg/kg body weight, TBs-a were associated with increased numbers of microbiota linked with hypolipidemic activity. This study explores the impacts of different preparation processes on TBs and provides a theoretical foundation for the understanding of TBs.

CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors.

In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients. CAR-natural killer (CAR-NK) cell complements CAR-T cell therapy by offering several distinct advantages. CAR-NK cells do not require HLA compatibility and exhibit low safety concerns. Moreover, CAR-NK cells are conducive to "off-the-shelf" therapeutics, providing significant logistic advantages over CAR-T cells. Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration, as well as an immuno-suppressive tumor microenvironment. In this review, we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies, with a specific focus on the obstacles to their application in solid tumors. We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization. Finally, we explore future perspectives of these adoptive immunotherapies, highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.

The expression and clinical significance of ARHGAP25 in osteosarcoma based on bioinformatics analysis.

ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25's biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients.

Catalytic asymmetric functionalization and dearomatization of thiophenes.

The asymmetric synthesis of thiophene-derived compounds, including catalytic asymmetric dearomatization of thiophene and atroposelective synthesis of benzothiophene derivatives, has rarely been reported. In this work, the asymmetric transformation of the thiophene motif is investigated. Through the rational design of substrates with a thiophene structure, by using the vinylidene ortho-quinone methide (VQM) intermediate as a versatile tool, axially chiral naphthyl-benzothiophene derivatives and thiophene-dearomatized chiral spiranes were obtained in high yields with excellent enantioselectivities.