The Associations between Healthy Eating Patterns and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Case-Control Study.

BACKGROUND: Although several epidemiological studies have identified an inverse association between healthy dietary patterns and metabolic dysfunction-associated steatotic liver disease (MASLD)/non-alcoholic fatty liver disease (NAFLD), little is known about the contribution of the food component to MASLD risk and the association between dietary patterns and severity of MASLD. This study aimed to investigate the association between healthy eating patterns and MASLD risk and severity of MASLD. METHODS: A case-control study including 228 patients diagnosed with MASLD and 228 controls was conducted. The modified Alternate Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH) score, and Alternative Mediterranean Diet (AMED) score were evaluated based on information collected via a validated food-frequency questionnaire. MASLD was confirmed if participants presented with ultrasound-diagnosed fatty liver diseases along with at least one of five cardiometabolic risk factors and no other discernible cause. The logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of MASLD for dietary scores. RESULTS: Compared with participants in the lowest tertile, those in the highest tertile of AHEI had a 60% reduced risk of MASLD (OR: 0.40; 95% CI: 0.25-0.66). Similar associations were also observed for DASH and AMED, with ORs comparing extreme tertiles of 0.38 (95% CI: 0.22-0.66) and 0.46 (95% CI: 0.28-0.73), respectively. Further Stratified analysis revealed that the inverse associations between AHEI and DASH with MASLD risks were stronger among women than men, and the inverse associations between AMED and MASLD risks were more pronounced among participants with normal weight (OR: 0.22; 95% CI: 0.09-0.49). For components within the dietary score, every one-point increase in vegetable score and whole grain score within the AHEI was associated with an 11% (95% CI: 5-16%) and a 6% (95% CI: 0-12%) lower MASLD risk, respectively. Similar inverse associations with those scores were observed for the DASH and AMED. CONCLUSION: Greater adherence to healthy eating patterns was associated with reduced risk of MASLD, with vegetables and whole grains predominately contributing to these associations. These findings suggested that healthy eating patterns should be recommended for the prevention of MASLD.

Cation Occupation Engineering Realizes Valence Modulation of Manganese-Activated ZnGa2O4.

Herein, a series of Mn-activated ZnGa2O4 (ZGO) phosphors have been developed for multifunctional applications. The characteristic green and red emission at 503 and 668 nm of Mn-activated ZGO phosphors can be observed under excitation of 247 and 375 nm, respectively, attributed to the partial oxidation of Mn2+ ions resulting in the coexistence of Mn2+ and Mn4+ ions in the host lattice. The valence modulation of Mn content not only realizes the adjustment of red and green luminescence intensity but also achieves the management of persistent luminescence time and thermo-luminescence time. Further, the codoping of Mg2+ could transform the position occupancy preference of Mn and effectively facilitate the conversion of Mn2+ to Mn4+, leading to the regulation of the valence state of manganese ions. Surprisingly, the existence of Mg2+ ions broadens the emission band of Mn4+ and enhances the photoluminescence intensity to 3.8 times, which can be ascribed to the weakened crystal field leading to the downward shift of the 4T2 energy level and the increase of Mn4+ concentration. For this valence modulation behavior, two different hypotheses about the occupancy of Mg2+ have been proposed to explain the corresponding phenomenon. Finally, the potential applications of the synthesized phosphors have been explored in advanced anticounterfeiting strategies, information storage, and plant lighting field.

Multiparameter MRI-based radiomics nomogram for preoperative prediction of brain invasion in atypical meningioma:a multicentre study.

OBJECTIVE: To develop a nomogram based on tumor and peritumoral edema (PE) radiomics features extracted from preoperative multiparameter MRI for predicting brain invasion (BI) in atypical meningioma (AM). METHODS: In this retrospective study, according to the 2021 WHO classification criteria, a total of 469 patients with pathologically confirmed AM from three medical centres were enrolled and divided into training (n = 273), internal validation (n = 117) and external validation (n = 79) cohorts. BI was diagnosed based on the histopathological examination. Preoperative contrast-enhanced T1-weighted MR images (T1C) and T2-weighted MR images (T2) for extracting meningioma features and T2-fluid attenuated inversion recovery (FLAIR) sequences for extracting meningioma and PE features were obtained. The multiple logistic regression was applied to develop separate multiparameter radiomics models for comparison. A nomogram was developed by combining radiomics features and clinical risk factors, and the clinical usefulness of the nomogram was verified using decision curve analysis. RESULTS: Among the clinical factors, PE volume and PE/tumor volume ratio are the risk of BI in AM. The combined nomogram based on multiparameter MRI radiomics features of meningioma and PE and clinical indicators achieved the best performance in predicting BI in AM, with area under the curve values of 0.862 (95% CI, 0.819-0.905) in the training cohort, 0.834 (95% CI, 0.780-0.908) in the internal validation cohort and 0.867 (95% CI, 0.785-0.950) in the external validation cohort, respectively. CONCLUSIONS: The nomogram based on tumor and PE radiomics features extracted from preoperative multiparameter MRI and clinical factors can predict the risk of BI in patients with AM.

The role of immune cells in different stages of atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of immune cells in the intima of arteries. Experimental and clinical evidence shows that both innate and adaptive immunity orchestrate the progression of atherosclerosis. The heterogeneous nature of immune cells within atherosclerosis lesions is important. Studies utilizing high-dimensional mass spectrometry and single-cell RNA sequencing of leukocytes from atherosclerotic lesions show the diversity and adaptability of these immune cell subtypes. Their migration, compositional changes, phenotypic alterations, and adaptive responses are key features throughout atherosclerosis progression. Understanding how these immune cells and their subtypes affect atherogenesis would help to develop novel therapeutic approaches that control atherosclerosis progression. Precise targeting of specific immune system components involved in atherosclerosis, rather than broad suppression of the immune system with anti-inflammatory agents, can more accurately regulate the progress of atherosclerosis with fewer side effects. In this review, we cover the most recent advances in the field of atherosclerosis to understand the role of various immune cells on its development. We focus on the complex network of immune cells and the interaction between the innate immune system and adaptive immune system.

Efficacy and safety of Qushi Huayu, a traditional Chinese medicine, in patients with nonalcoholic fatty liver disease in a randomized controlled trial.

BACKGROUND: The effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation. HYPOTHESIS/PURPOSE: This study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial. STUDY DESIGN: A total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24. RESULTS: Both QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p < 0.05). Compared to DFLG, QSHY treatment improved ALT (ß, -0.128 [95 % CI, -0.25, -0.005], p = 0.041), aspartate transaminase (ß, -0.134 [95 % CI, -0.256 to -0.012], p = 0.032), and fibrosis-4 score (ß, -0.129 [95 % CI, -0.254 to -0.003], p = 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid. CONCLUSION: Our results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.

Copper-Bearing Metal-Organic Framework with Mucus-Penetrating Function for the Multi-Effective Clearance of Mucosal Colonized Helicobacter pylori.

Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of "bacterioplankton ↔ biofilm", thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models.

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Metal-Organic Framework Based Mucoadhesive Nanodrugs for Multifunction Helicobacter Pylori Targeted Eradication, Inflammation Regulation and Gut Flora Protection.

The prevalence of drug-resistant bacteria presents a significant challenge to the antibiotic treatment of Helicobacter pylori (H. pylori), while traditional antimicrobial agents often suffer from shortcomings such as poor gastric retention, inadequate alleviation of inflammation, and significant adverse effects on the gut microbiota. Here, a selenized chitosan (CS-Se) modified bismuth-based metal-organic framework (Bi-MOF@CS-Se) nanodrug is reported that can target mucin through the charge interaction of the outer CS-Se layer to achieve mucosal adhesion and gastric retention. Additionally, the Bi-MOF@CS-Se can respond to gastric acid and pepsin degradation, and the exposed Bi-MOF exhibits excellent antibacterial properties against standard H. pylori as well as clinical antibiotic-resistant strains. Remarkably, the Bi-MOF@CS-Se effectively alleviates inflammation and excessive oxidative stress by regulating the expression of inflammatory factors and the production of reactive oxygen species (ROS), thereby exerting therapeutic effects against H. pylori infection. Importantly, this Bi-MOF@CS-Se nanodrug does not affect the homeostasis of gut microbiota, providing a promising strategy for efficient and safe treatment of H. pylori infection.

Modulating Cholesterol Metabolism via ACAT1 Knockdown Enhances Anti-B-Cell Lymphoma Activities of CD19-Specific Chimeric Antigen Receptor T Cells by Improving the Cell Activation and Proliferation.

CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo.

Tonghua Liyan granules in the treatment of Laryngopharyngeal reflux disease with stagnation of phlegm and qi syndrome: a randomized, double-blind, placebo-controlled study.

Background: Laryngopharyngeal reflux disease (LPRD) is an extraesophageal syndromic manifestation of gastroesophageal reflux disease (GERD). Despite the increasing incidence of and concern about LPRD, treatment with proton pump inhibitors (PPIs) is unsatisfactory. Here, LPRD was treated with Tonghua Liyan (THLY) granules in combination with PPIs to evaluate treatment efficacy and possible adverse reactions. Methods: Seventy-six LPRD patients with stagnation of phlegm and qi syndrome (SPQS) were randomly divided into an experimental group and a control group. The experimental group received THLY granules combined with rabeprazole capsules. The control group received THLY granule placebo combined with rabeprazole capsules. A parallel, randomized, double-blind, placebo-controlled clinical trial was conducted with these two groups. The treatment cycle was 8 weeks. The reflux symptom index (RSI), clinical symptom score, salivary pepsin content, reflux finding score (RFS) and gastroesophageal reflux disease questionnaire (GerdQ) were used to evaluate clinical efficacy. The final efficacy rate was evaluated according to the RSI and clinical symptom score. Results: Compared with those at baseline, all the indicators in the experimental group and control group significantly improved (p < 0.01). In terms of the RSI, clinical symptom score, and RFS, the experimental group had a higher degree of improvement (p < 0.05), and the overall efficacy rate was higher (p < 0.05). In terms of the salivary pepsin concentration and GerdQ, there was no significant difference between the test group and the control group (p > 0.05). Both groups of safety indicators showed no abnormalities and did not cause any allergic reactions in the body. Conclusion: Compared with PPIs alone, THLY granules combined with PPIs are more effective in the treatment of LPRD patients with SPQS in terms of symptoms and signs. This combination treatment, because of its higher clinical efficacy and lack of obvious adverse reactions, is worthy of clinical promotion and further in-depth study. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046614.

A distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy sensitive than papillary thyroid cancer.

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Diagnosis of pulmonary tuberculosis with 3D neural network based on multi-scale attention mechanism.

This paper presents a novel multi-scale attention residual network (MAResNet) for diagnosing patients with pulmonary tuberculosis (PTB) by computed tomography (CT) images. First, a three-dimensional (3D) network structure is applied in MAResNet based on the continuity and correlation of nodal features on different slices of CT images. Secondly, MAResNet incorporates the residual module and Convolutional Block Attention Module (CBAM) to reuse the shallow features of CT images and focus on key features to enhance the feature distinguishability of images. In addition, multi-scale inputs can increase the global receptive field of the network, extract the location information of PTB, and capture the local details of nodules. The expression ability of both high-level and low-level semantic information in the network can also be enhanced. The proposed MAResNet shows excellent results, with overall 94% accuracy in PTB classification. MAResNet based on 3D CT images can assist doctors make more accurate diagnosis of PTB and alleviate the burden of manual screening. In the experiment, a called Grad-CAM was employed to enhance the class activation mapping (CAM) technique for analyzing the model's output, which can identify lesions in important parts of the lungs and make transparent decisions.

Bibliometric analysis of pancreatic diseases and gut microbiota research from 2002 to 2022.

Background: An increasing number of studies have indicated that pancreatic diseases are associated with the structure of the gut microbiota. We aimed to assess the research hotspots and trends in this field through a quantitative method. Materials and methods: Articles related to pancreatic diseases and the gut microbiota published from 2002 to 2022 were retrieved from the Web of Science database. We visualized the countries/regions, institutions, authors, journals, and keywords using VOSviewer and CiteSpace software. The interplay between pancreatic diseases and the gut microbiota was also analysed. Results: A total of 129 publications were finally identified. The number of papers increased gradually, and China held the dominant position with respect to publication output. Shanghai Jiao Tong University was the most influential institution. Zeng Yue ranked highest in the number of papers, and Scientific Reports was the most productive journal. The keywords "gut", "bacterial translocation", and "acute pancreatitis" appeared early for the first time, and "gut microbiota", "community", and "diversity" have been increasingly focused on. The predominant pancreatic disease correlated with the gut microbiota was pancreatic inflammatory disease (50.39%). Pancreatic diseases are associated with alterations in the gut microbiota, characterized by a decrease in beneficial bacteria and an increase in harmful bacteria. Conclusion: This is the first comprehensive bibliometric analysis of all pancreatic diseases and the gut microbiota. The research on the relationship between them is still in the preliminary stage, and the trend is toward a gradual deepening of the research and precise treatment development. The interaction between the gut microbiota and pancreatic diseases will be of increasing concern in the future.

The Prognostic and Immune Significance of CILP2 in Pan-Cancer and Its Relationship with the Progression of Pancreatic Cancer.

Cartilage intermediate layer protein 2 (CILP2) facilitates interactions between matrix components in cartilage and has emerged as a potential prognostic biomarker for cancer. This study aimed to investigate the function and mechanisms of CILP2 in pan-cancer. We evaluated the pan-cancer expression, methylation, and mutation data of CILP2 for its clinical prognostic value. Additionally, we explored the immunological characteristics of CILP2 in pan-cancer and then focused specifically on pancreatic ductal adenocarcinoma (PAAD). The subtype analysis of PAAD identified subtype-specific expression and immunological characteristics. Finally, in vitro and in vivo experiments assessed the impact of CILP2 on pancreatic cancer progression. CILP2 exhibited high expression in most malignancies, with significant heterogeneity in epigenetic modifications across multiple cancer types. The abnormal methylation and copy number variations in CILP2 were correlated with poor prognoses. Upregulated CILP2 was associated with TGFB/TGFBR1 and more malignant subtypes. CILP2 exhibited a negative correlation with immune checkpoints in PAAD, suggesting potential for immunotherapy. CILP2 activated the AKT pathway, and it increased proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) in pancreatic cancer. We demonstrated that CILP2 significantly contributes to pancreatic cancer progression. It serves as a prognostic biomarker and a potential target for immunotherapy.

Integrated single-cell and spatial transcriptomics reveals heterogeneity of fibroblast and pivotal genes in psoriasis.

Psoriasis, which is one of the most common skin diseases, involves an array of complex immune constituents including T cells, dendritic cells and monocytes. Particularly, the cytokine IL17A, primarily generated by TH17 cells, assumes a crucial function in the etiology of psoriasis. In this study, a comprehensive investigation utilizing bulk RNA analysis, single-cell RNA sequencing, and spatial transcriptomics was employed to elucidate the underlying mechanisms of psoriasis. Our study revealed that there is an overlap between the genes that are differentially expressed in psoriasis patients receiving three anti-IL17A monoclonal antibody drugs and the genes that are differentially expressed in lesion versus non-lesion samples in these patients. Further analysis using single-cell and spatial data from psoriasis samples confirmed the expression of hub genes that had low expressions in psoriasis tissue but were up-regulated after anti-IL17A treatments. These genes were found to be associated with the treatment effects of brodalumab and methotrexate, but not adalimumab, etanercept, and ustekinumab. Additionally, these genes were predominantly expressed in fibroblasts. In our study, fibroblasts were categorized into five clusters. Notably, hub genes exhibited predominant expression in cluster 3 fibroblasts, which were primarily engaged in the regulation of the extracellular matrix and were predominantly located in the reticular dermis. Subsequent analysis unveiled that cluster 3 fibroblasts also established communication with epithelial cells and monocytes via the ANGPTL-SDC4 ligand-receptor configuration, and their regulation was governed by the transcription factor TWIST1. Conversely, cluster 4 fibroblasts, responsible for vascular endothelial regulation, were predominantly distributed in the papillary dermis. Cluster 4 predominantly engaged in interactions with endothelial cells via MDK signals and was governed by the distinctive transcription factor, ERG. By means of an integrated analysis encompassing bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics, we have discerned genes and clusters of fibroblasts that potentially contribute to the pathogenesis of psoriasis.

Co-expression of IL-4/IL-15-based inverted cytokine receptor in CAR-T cells overcomes IL-4 signaling in immunosuppressive pancreatic tumor microenvironment.

The efficacy of CAR-T cell therapy has been hindered by several factors that are intrinsic to the tumor microenvironment. Many strategies are being employed to overcome these barriers and improve immunotherapies efficacy. Interleukin (IL)- 4 is a cytokine released by tumor cells inside the tumor microenvironment and it can oppose T cell effector functions via engagement with the IL-4 receptor on the surface of T cells. To overcome IL-4-mediated immunosuppressive signals, we designed a novel inverted cytokine receptor (ICR). Our novel CAR construct (4/15NKG2D-CAR), consisted of an NKG2D-based chimeric antigen receptor, co-expressing IL-4R as an extracellular domain and IL-15R as a transmembrane and intracellular domain. In this way, IL-4R inhibitory signals were converted into IL-15R activation signals downstream. This strategy increased the efficacy of NKG2D-CAR-T cells in the pancreatic tumor microenvironment in vitro and in vivo. 4/15NKG2D-CAR-T cells exhibited increased activation, degranulation, cytokine release, and cytotoxic ability of NKG2D-CAR-T cells against IL-4+ pancreatic cell lines. Furthermore, 4/15NKG2D-CAR-T cells exhibited more expansion, less exhaustion, and an increased percentage of less differentiated T cell phenotypes in vitro when compared with NKG2D-CAR-T cells. That is why IL-4R/IL-15R-modified CAR-T cells eradicated more tumors in vivo and outperformed NKG2D-CAR-T cells. Thus, we report here a novel NKG2D-CAR-T cells that could overcome IL-4-mediated immunosuppression in solid tumors.

Research trends on the relationship between Helicobacter pylori and microbiota: A bibliometric analysis.

BACKGROUND: Increasing evidence has indicated that Helicobacter pylori infection is associated with the complex microbiota in the digestive tract of the human body. We aimed to assess the research trends and hotspots in the field of H. pylori and microbiota using a quantitative method. MATERIALS AND METHODS: The clinical studies on H. pylori and microbiota published from 2001 to 2022 were extracted from the Web of Science database. We visualized and analyzed countries/regions, institutions, authors, journals, and keywords through VOSviewer and CiteSpace software. The test techniques, specimen type, as well as microbiota variation after H. pylori infection and eradication were also evaluated. RESULTS: A total of 98 publications were finally identified, and the number of annual papers increased gradually. China showed its dominant position in the publication outputs, and Nanchang University was the most productive institution. Cong He, Xu Shu, and Yin Zhu published the highest number of papers, whereas Helicobacter was the most productive journal. "Helicobacter pylori" ranked highest in the keyword occurrences. 16S rRNA gene sequencing was the most frequently used method for microbiota analysis. Fecal samples had the highest frequency of use, followed by gastric mucosa and saliva. H. pylori infection was associated with the alterations of microbiota through the digestive tract, characterized by the enrichment of Helicobacter in the stomach. Triple and quadruple therapy were the most utilized eradication regimens, and probiotics supplementation therapy has been proven to reduce side effects and restore microbial diversity. CONCLUSIONS: This bibliometric analysis provides an overview of advancements in the field of H. pylori and microbiota. While numerous studies have been conducted on the correlation between H. pylori and the alterations of microbiota, future research is warranted to investigate the mechanisms underlying the interplay between H. pylori and other microbes in the development of related diseases.

Unleashing the Potential of EIL Transcription Factors in Enhancing Sweet Orange Resistance to Bacterial Pathologies: Genome-Wide Identification and Expression Profiling.

The ETHYLENE INSENSITIVE3-LIKE (EIL) family is one of the most important transcription factor (TF) families in plants and is involved in diverse plant physiological and biochemical processes. In this study, ten EIL transcription factors (CsEILs) in sweet orange were systematically characterized via whole-genome analysis. The CsEIL genes were unevenly distributed across the four sweet orange chromosomes. Putative cis-acting regulatory elements (CREs) associated with CsEIL were found to be involved in plant development, as well as responses to biotic and abiotic stress. Notably, quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that CsEIL genes were widely expressed in different organs of sweet orange and responded to both high and low temperature, NaCl treatment, and to ethylene-dependent induction of transcription, while eight additionally responded to Xanthomonas citri pv. Citri (Xcc) infection, which causes citrus canker. Among these, CsEIL2, CsEIL5 and CsEIL10 showed pronounced upregulation. Moreover, nine genes exhibited differential expression in response to Candidatus Liberibacter asiaticus (CLas) infection, which causes Citrus Huanglongbing (HLB). The genome-wide characterization and expression profile analysis of CsEIL genes provide insights into the potential functions of the CsEIL family in disease resistance.

Interpretable machine-learning model for Predicting the Convalescent COVID-19 patients with pulmonary diffusing capacity impairment.

INTRODUCTION: The COVID-19 patients in the convalescent stage noticeably have pulmonary diffusing capacity impairment (PDCI). The pulmonary diffusing capacity is a frequently-used indicator of the COVID-19 survivors' prognosis of pulmonary function, but the current studies focusing on prediction of the pulmonary diffusing capacity of these people are limited. The aim of this study was to develop and validate a machine learning (ML) model for predicting PDCI in the COVID-19 patients using routinely available clinical data, thus assisting the clinical diagnosis. METHODS: Collected from a follow-up study from August to September 2021 of 221 hospitalized survivors of COVID-19 18 months after discharge from Wuhan, including the demographic characteristics and clinical examination, the data in this study were randomly separated into a training (80%) data set and a validation (20%) data set. Six popular machine learning models were developed to predict the pulmonary diffusing capacity of patients infected with COVID-19 in the recovery stage. The performance indicators of the model included area under the curve (AUC), Accuracy, Recall, Precision, Positive Predictive Value(PPV), Negative Predictive Value (NPV) and F1. The model with the optimum performance was defined as the optimal model, which was further employed in the interpretability analysis. The MAHAKIL method was utilized to balance the data and optimize the balance of sample distribution, while the RFECV method for feature selection was utilized to select combined features more favorable to machine learning. RESULTS: A total of 221 COVID-19 survivors were recruited in this study after discharge from hospitals in Wuhan. Of these participants, 117 (52.94%) were female, with a median age of 58.2 years (standard deviation (SD) = 12). After feature selection, 31 of the 37 clinical factors were finally selected for use in constructing the model. Among the six tested ML models, the best performance was accomplished in the XGBoost model, with an AUC of 0.755 and an accuracy of 78.01% after experimental verification. The SHAPELY Additive explanations (SHAP) summary analysis exhibited that hemoglobin (Hb), maximal voluntary ventilation (MVV), severity of illness, platelet (PLT), Uric Acid (UA) and blood urea nitrogen (BUN) were the top six most important factors affecting the XGBoost model decision-making. CONCLUSION: The XGBoost model reported here showed a good prognostic prediction ability for PDCI of COVID-19 survivors during the recovery period. Among the interpretation methods based on the importance of SHAP values, Hb and MVV contributed the most to the prediction of PDCI outcomes of COVID-19 survivors in the recovery period.