Identification of genetic susceptibility for Chinese migraine with depression using machine learning.

Background: Migraine is a common primary headache that has a significant impact on patients' quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background. Objective: The aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort. Methods: In this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom's MALDI-TOF iPLEX platform. Results: In univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS). Conclusion: The study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients.

Vagus nerve stimulation (VNS) preventing postoperative cognitive dysfunction (POCD): two potential mechanisms in cognitive function.

Postoperative cognitive dysfunction (POCD) impacts a significant number of patients annually, frequently impairing their cognitive abilities and resulting in unfavorable clinical outcomes. Aimed at addressing cognitive impairment, vagus nerve stimulation (VNS) is a therapeutic approach, which was used in many mental disordered diseases, through the modulation of vagus nerve activity. In POCD model, the enhancement of cognition function provided by VNS was shown, demonstrating VNS effect on cognition in POCD. In the present study, we primarily concentrates on elucidating the role of the VNS improving the cognitive function in POCD, via two potential mechanisms: the inflammatory microenvironment and epigenetics. This study provided a theoretical support for the feasibility that VNS can be a potential method to enhance cognition function in POCD.

Impact of PD-L1 expression on the efficacy of first-line crizotinib in advanced ROS1-rearranged NSCLC.

BACKGROUND: The predictive value of programmed death-ligand 1 (PD-L1) expression for the efficacy of tyrosine kinase inhibitors (TKIs) in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC) remains underexplored. This study analyzed patients with advanced NSCLC harboring ROS1 rearrangements who received first-line crizotinib to evaluate the correlation between baseline PD-L1 expression and crizotinib efficacy. METHODS: In this study, the clinical data from 371 patients diagnosed with ROS1-rearranged NSCLC at Shanghai Chest Hospital between November 2017 and December 2022 were reviewed. The patients were categorized into three groups according to the baseline PD-L1 expression: tumor proportion score (TPS) <1%, TPS 1 %-49 %, and TPS≥50 %. The objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) following first-line crizotinib treatment were measured. RESULTS: A total of 64 patients were included in the analysis, with 16 patients in the TPS<1% group, 22 in the TPS 1 %-49 % group, and 26 in the TPS≥50 % group. The overall DCR was 100 %, and the overall ORR was 76.5 %. The ORRs were 81.2 % (13/16) in the TPS<1% group, 63.6 % (14/22) in the TPS 1 %-49 % group, and 84.6 % (22/26) in the TPS≥50 % group (p = 0.218). The median PFS across all patients was 20.21 months (95 % CI: 15.71-24.71), with a median PFS of 28.96 months (95 % CI: 19.87-38.04) in the TPS<1% group, 17.56 months (95 % CI: 12.25-22.86) in the TPS 1 %-49 % group, and 25.85 months (95 % CI: 18.52-33.17) in the TPS≥50 % group (p = 0.100). The median PFS for patients with CD74 fusion was 18.23 months (95 % CI: 15.24-21.22), while those with non-CD74 fusion exhibited a PFS of 16.49 months (95 % CI: 9.75-23.23) (p = 0.359). CONCLUSION: Patients with advanced ROS1-rearranged NSCLC were found to benefit from first-line crizotinib treatment, irrespective of baseline PD-L1 expression.

Towards Design Automation of Microfluidic Mixers: Leveraging Reinforcement Learning and Artificial Neural Networks.

Microfluidic mixers, a pivotal application of microfluidic technology, are primarily utilized for the rapid amalgamation of diverse samples within microscale devices. Given the intricacy of their design processes and the substantial expertise required from designers, the intelligent automation of microfluidic mixer design has garnered significant attention. This paper discusses an approach that integrates artificial neural networks (ANNs) with reinforcement learning techniques to automate the dimensional parameter design of microfluidic mixers. In this study, we selected two typical microfluidic mixer structures for testing and trained two neural network models, both highly precise and cost-efficient, as alternatives to traditional, time-consuming finite-element simulations using up to 10,000 sets of COMSOL simulation data. By defining effective state evaluation functions for the reinforcement learning agents, we utilized the trained agents to successfully validate the automated design of dimensional parameters for these mixer structures. The tests demonstrated that the first mixer model could be automatically optimized in just 0.129 s, and the second in 0.169 s, significantly reducing the time compared to manual design. The simulation results validated the potential of reinforcement learning techniques in the automated design of microfluidic mixers, offering a new solution in this field.

Association between atrial cardiopathy and stroke severity in acute ischemic stroke.

In this hospital-based cross-sectional analytic study, we retrospectively reviewed clinical data of patients with acute ischemic stroke (AIS) between January 2017 and April 2023. Atrial cardiopathy was defined as any presence of the following: left atrial diameter ≥ 52 mm (males) or ≥ 47 mm (females), elevated P-wave terminal force in V1 > 5000 µV ms, or serum N terminal pro B type natriuretic peptide > 250 pg/ml. Initial stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS; moderate-to-severe, ≥ 5; and severe, ≥ 15). Univariate and multivariate binary logistic regression analyses were performed to assess the association between atrial cardiopathy and stroke severity. Among 662 AIS patients (mean age 70 years [interquartile range 61-78], 31.3% women), 303 (45.8%) had atrial cardiopathy. Multivariable logistic regression analysis showed that the presence of atrial cardiopathy was significantly associated with a higher odd of moderate-to-severe stroke (adjusted odds ratio [OR] 2.16, 95% confidence interval [CI] 1.46-3.20, p < 0.001) and severe stroke (adjusted OR 4.89, 95%CI 2.45-9.76, p < 0.001). This association remained significant in a sensitivity analysis excluding those with atrial fibrillation or coronary artery disease. Findings of the current study revealed that the association of atrial cardiopathy was with initial stroke severity independent of atrial fibrillation and was even confirmed in patients without atrial fibrillation; future studies to explore improved stroke prevention strategies for patients with atrial cardiopathy are needed.

Credibility of the evidence on green space and human health: an overview of meta-analyses using evidence grading approaches.

BACKGROUND: Green space is an important part of the human living environment, with many epidemiological studies estimating its impact on human health. However, no study has quantitatively assessed the credibility of the existing evidence, impeding their translations into policy decisions and hindering researchers from identifying new research gaps. This overview aims to evaluate and rank such evidence credibility. METHODS: Following the PRISMA guideline, we systematically searched PubMed, Web of Science, and Embase databases for systematic reviews with meta-analyses concerning green spaces and health outcomes published up to January 15, 2024. We categorized the credibility of meta-analytical evidence from interventional studies into four levels (i.e., high, moderate, low, and very low) using the Grading of Recommendation, Assessment, Development and Evaluations framework, based on five domains including risk of bias, inconsistency, indirectness, imprecision, and publication bias. Further, we recalculated all the meta-analyses from observational studies and classified evidence into five levels (i.e., convincing, highly suggestive, suggestive, weak, and non-significant) by considering stringent thresholds for P-values, sample size, robustness, heterogeneity, and testing for biases. FINDINGS: In total, 154 meta-analysed associations (interventional = 44, observational = 110) between green spaces and health outcomes were graded. Among meta-analyses from interventional studies, zero, four (wellbeing, systolic blood pressure, negative affect, and positive affect), 20, and 20 associations between green spaces and health outcomes were graded as high, moderate, low, and very low credibility evidence, respectively. Among meta-analyses from observational studies, one (cardiovascular disease mortality), four (prevalence/incidence of diabetes mellitus, preterm birth, and small for gestational age infant, and all-cause mortality), 12, 22, and 71 associations were categorized as convincing, highly suggestive, suggestive, weak, and non-significant evidence, respectively. INTERPRETATION: The current evidence largely confirms beneficial associations between green spaces and human health. However, only a small subset of these associations can be deemed to have a high or convincing credibility. Hence, future better designed primary studies and meta-analyses are still needed to provide higher quality evidence for informing health promotion strategies. FUNDING: The National Natural Science Foundation of China of China; the Guangzhou Science and Technology Program; the Guangdong Medical Science and Technology Research Fund; the Research Grant Council of the Hong Kong SAR; and Sino-German mobility program.

Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alphaglucosaminidase to Parkinson's disease.

ABSTRACT: Parkinson's disease is the second most common progressive neurodegenerative disorder, and few reliable biomarkers are available to track disease progression. The proteins, DNA, mRNA, and lipids carried by exosomes reflect intracellular changes, and thus can serve as biomarkers for a variety of conditions. In this study, we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson's disease and the potential therapeutic roles of these proteins in Parkinson's disease. Using a tandem mass tag-based quantitative proteomics approach, we characterized the proteomes of plasma exosomes derived from individual patients, identified exosomal protein signatures specific to patients with Parkinson's disease, and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein. N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot. The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson's disease, but also decreased with increasing Hoehn-Yahr stage, suggesting that N-acetyl- alpha-glucosaminidase could be used to rapidly evaluate Parkinson's disease severity. Furthermore, western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with methyl-4-phenylpyridinium (MPP+) and cells overexpressing a-synuclein (α-syn) compared with control cells. Additionally, N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibited α-syn expression in MPP+-treated cells. Taken together, our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson's disease diagnosis, and that N-acetyl-alpha- glucosaminidase may reduce α-syn expression and MPP+-induced neurotoxicity, thus providing a new therapeutic target for Parkinson's disease.

Differences between Chronically Hepatitis B Virus-Infected Pregnant Women with and without Intrafamilial Infection: From Viral Gene Sequences to Clinical Manifestations.

INTRODUCTION: This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. METHODS: HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. RESULTS: The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (ß = -0.43, 95% confidence interval [CI]: -0.76 to -0.12, p = 0.009), HBeAg (ß = -195.15, 95% CI: -366.35 to -23.96, p = 0.027), and hemoglobin changes (ß = -8.09, 95% CI: -15.54 to -0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (ß = 73.9, 95% CI: 38.92-108.95, p < 0.001) and albumin (ß = 2.73, 95% CI: 0.23-5.23, p = 0.033). CONCLUSION: The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.

SIRT1 mediates the excitability of spinal CaMKIIα-positive neurons and participates in neuropathic pain by controlling Nav1.3.

AIMS: Neuropathic pain is a common chronic pain disorder, which is largely attributed to spinal central sensitization. Calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) activation in the spinal dorsal horn (SDH) is a major contributor to spinal sensitization. However, the exact way that CaMKIIα-positive (CaMKIIα+) neurons in the SDH induce neuropathic pain is still unclear. This study aimed to explore the role of spinal CaMKIIα+ neurons in neuropathic pain caused by chronic constriction injury (CCI) and investigate the potential epigenetic mechanisms involved in CaMKIIα+ neuron activation. METHODS: CCI-induced neuropathic pain mice model, Sirt1loxP/loxP mice, and chemogenetic virus were used to investigate whether the activation of spinal CaMKIIα+ neurons is involved in neuropathic pain and its involved mechanism. Transcriptome sequence, western blotting, qRT-PCR, and immunofluorescence analysis were performed to assay the expression of related molecules and activation of neurons. Co-immunoprecipitation was used to observe the binding relationship of protein. Chromatin immunoprecipitation (ChIP)-PCR was applied to analyze the acetylation of histone H3 in the Scn3a promoter region. RESULTS: The expression of sodium channel Nav1.3 was increased and the expression of SIRT1 was decreased in the spinal CaMKIIα+ neurons of CCI mice. CaMKIIα neurons became overactive after CCI, and inhibiting their activation relieved CCI-induced pain. Overexpression of SIRT1 reversed the increase of Nav1.3 and alleviated pain, while knockdown of SIRT1 or overexpression of Nav1.3 promoted CaMKIIα+ neuron activation and induced pain. By knocking down spinal SIRT1, the acetylation of histone H3 in the Scn3a (encoding Nav1.3) promoter region was increased, leading to an increased expression of Nav1.3. CONCLUSION: The findings suggest that an aberrant reduction of spinal SIRT1 after nerve injury epigenetically increases Nav1.3, subsequently activating CaMKIIα+ neurons and causing neuropathic pain.

Heterogeneity in PD-L1 expression between primary and metastatic lymph nodes: a predictor of EGFR-TKI therapy response in non-small cell lung cancer.

BACKGROUND: There is inconclusive evidence to suggest that the expression of programmed cell death ligand 1 (PD-L1) is a putative predictor of response to EGFR-TKI therapy in advanced EGFR-mutant non-small cell lung cancer (NSCLC). We evaluated the heterogeneity in PD-L1 expression in the primary lung site and metastatic lymph nodes to analyze the association between PD-L1 expression and response for patients treated with EGFR-TKI. METHODS: This study reviewed 184 advanced NSCLC patients with EGFR mutations who received first-generation EGFR-TKI as first-line treatment from 2020 to 2021 at Shanghai Chest Hospital. The patients were divided into the primary lung site group (n = 100) and the metastatic lymph nodes group (n = 84) according to the biopsy site. The patients in each group were divided into TPS < 1%, TPS 1-49%, and TPS ≥ 50% groups according to PD-L1 expression. RESULTS: The median PFS was 7 (95% CI: 5.7-8.3) months, and the median OS was 26 (95% CI: 23.5-28.5) months for all patients. No correlation existed between PFS or OS and PD-L1 expression. The median PFS in the primary lung site group was 11 months (95% CI: 9.6-12.4) in the TPS < 1% group, 8 months (95% CI: 6.6-9.4) in TPS 1-49% group, and 4 months (95% CI: 3.2-4.8) in TPS ≥ 50% group, with statistically significant differences (p = 0.000). The median OS of the TPS < 1% group and TPS ≥ 50% group showed a statistically significant difference (p = 0.008) in the primary lung site group. In contrast, PD-L1 expression in the lymph nodes of EGFR-mutant patients was unrelated to PFS or OS after EGFR-TKI therapy. CONCLUSION: PD-L1 expression from the primary lung site might predict clinical benefit from EGFR-TKI, whereas PD-L1 from metastatic lymph nodes did not. TRIAL REGISTRATION: This retrospective study was approved by the Ethics Committee of Shanghai Chest Hospital (ID: IS23060) and performed following the Helsinki Declaration of 1964 (revised 2008).

Erratum: Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al.

[This corrects the article DOI: 10.1016/j.omtn.2021.11.010.].

Endovascular repair for thoracic aortic pseudoaneurysm induced by pedicle screw implantation: a case report with 8 years follow-up.

BACKGROUND: Pedicle screw instrument surgeries can result in the development of aortic pseudoaneurysm, which is a rare yet potentially severe complication; therefore, the purpose of this work is to describe the case of pseudoaneurysm of the thoracic aorta caused by the severe migration of a pedicle screw after surgery. CASE PRESENTATION: We herein report a patient who underwent endovascular repair for the pseudoaneurysm of the descending thoracic aorta following thoracic vertebral fixation surgery. A 28-80 mm covered stent was initially inserted through the right femoral artery, and intraoperative aortography revealed a minor extravasation of contrast material. Subsequently, an additional 28-140 mm covered stent was implanted. The patient recovered well during the 8-year follow-up period. CONCLUSIONS: Vascular complications resulting from spinal surgery are severe and rare, necessitating early diagnosis and intervention.

Machine learning-enhanced predictive modeling for arbitrary deterministic lateral displacement design and test.

The separation of biological particles like cells and macromolecules from liquid samples is vital in clinical medicine, supporting liquid biopsies and diagnostics. Deterministic Lateral Displacement (DLD) is prominent for sorting particles in microfluidics by size. However, the design, fabrication, and testing of DLDs are complex and time-consuming. Researchers typically rely on finite element analysis to predict particle trajectories, which are crucial in evaluating the performance of DLD. Traditional particle trajectory predictions through finite element analysis often inaccurately reflect experimental results due to manufacturing and experimental variabilities. To address this issue, we introduced a machine learning-enhanced approach, combining past experimental data and advanced modeling techniques. Our method, using a dataset of 132 experiments from 40 DLD chips and integrating finite element simulation with a microfluidic-optimized particle simulation algorithm (MOPSA) and a Random Forest model, improves trajectory prediction and critical size determination without physical tests. This enhanced accuracy in simulation across various DLD chips speeds up development. Our model, validated against three DLD chip designs, showed a high correlation between predicted and experimental particle trajectories, streamlining chip development for clinical applications.

Study on the causes of changes in colour during Hibiscus syriacus flowering based on transcriptome and metabolome analyses.

BACKGROUND: The flower colour of H. syriacus 'Qiansiban' transitions from fuchsia to pink-purple and finally to pale purple, thereby enhancing the ornamental value of the cultivars. However, the molecular mechanism underlying this change in flower colour in H. syriacus has not been elucidated. In this study, the transcriptomic data of H. syriacus 'Qiansiban' at five developmental stages were analysed to investigate the impact of flavonoid components on flower colour variation. Additionally, five cDNA libraries were constructed from H. syriacus 'Qiansiban' during critical blooming stages, and the transcriptomes were sequenced to investigate the molecular mechanisms underlying changes in flower colouration. RESULTS: High-performance liquid chromatography‒mass spectrometry detected five anthocyanins in H. syriacus 'Qiansiban', with malvaccin-3-O-glucoside being the predominant compound in the flowers of H. syriacus at different stages, followed by petunigenin-3-O-glucoside. The levels of these five anthocyanins exhibited gradual declines throughout the flowering process. In terms of the composition and profile of flavonoids and flavonols, a total of seven flavonoids were identified: quercetin-3-glucoside, luteolin-7-O-glucoside, Santianol-7-O-glucoside, kaempferol-O-hexosyl-C-hexarbonoside, apigenin-C-diglucoside, luteolin-3,7-diglucoside, and apigenin-7-O-rutinoside. A total of 2,702 DEGs were identified based on the selected reference genome. Based on the enrichment analysis of differentially expressed genes, we identified 9 structural genes (PAL, CHS, FLS, DRF, ANS, CHI, F3H, F3'5'H, and UFGT) and 7 transcription factors (3 MYB, 4 bHLH) associated with flavonoid biosynthesis. The qRT‒PCR results were in good agreement with the high-throughput sequencing data. CONCLUSION: This study will establish a fundamental basis for elucidating the mechanisms underlying alterations in the flower pigmentation of H. syriacus.

Lactobacillus reuteri JCM 1112 ameliorates chronic acrylamide-induced glucose metabolism disorder via the bile acid-TGR5-GLP-1 axis and modulates intestinal oxidative stress in mice.

Acrylamide (AA) is a toxic food contaminant that has been reported to cause glucose metabolism disorders (GMD) at high doses. However, it is unclear whether chronic low-dose AA can induce GMD and whether probiotics can alleviate AA-induced GMD. Here, C57BL/6N mice were orally administered with 5 mg per kg bw AA for 10 weeks, followed by another 3 weeks of glucagon-like peptide-1 (GLP-1) analogue (dulaglutide) treatment. Chronic low-dose AA exposure increased the blood glucose level and decreased serum insulin and GLP-1 levels, whereas dulaglutide treatment decreased the blood glucose level and increased the serum insulin level in AA-exposed mice. Then, mice were administered with AA or AA + INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist) for 10 weeks. INT-777 treatment reversed AA-induced downregulation of ileal TGR5 and proglucagon (PG) gene expression and decreased the serum GLP-1 level. These findings indicated that chronic low-dose AA induced GMD via inhibiting the TGR5-GLP-1 axis. Finally, mice were administered with AA for 10 weeks, followed by another 3 weeks of Lactobacillus reuteri JCM 1112 supplementation. L. reuteri supplementation significantly increased serum glucose, insulin and GLP-1 levels, upregulated ileal TGR5 and PG gene expression, and effectively restored the imbalance of bile acid (BA) metabolism in AA-exposed mice, demonstrating that L. reuteri ameliorates chronic AA-induced GMD via the BA-TGR5-GLP-1 axis. In addition, L. reuteri significantly enhanced ileal superoxide dismutase and catalase activities and total antioxidant capacity, thereby preventing chronic AA-induced oxidative stress. Our research provides new insights into the GMD toxicity of chronic low-dose AA and confirms the role of probiotics in alleviating AA-induced GMD.

CD58 Alterations Govern Antitumor Immune Responses by Inducing PDL1 and IDO in Diffuse Large B-Cell Lymphoma.

Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and NK cells and is recurrently mutated and deleted in DLBCL, suggesting that it may play a role in regulating antitumor immunity. In this study, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA sequencing (RNA-seq), whole-exome sequencing, and single-cell RNA-seq in patients with newly diagnosed DLBCL. The CD58 mutation rate was 9.1%, and the copy number loss rate was 44.7% among all enrolled patients with DLBCL. Notably, CD58 genetic alterations, along with low CD58 expression, significantly correlated with reduced rates of response to R-CHOP therapy and inferior progression-free survival and overall survival. Single-cell RNA-seq revealed that CD58 expression in tumor cells was negatively correlated with CD8+ T-cell exhaustion/dysfunction status. Insufficient T-cell activation resulting from CD58 alterations could not be attributed solely to CD2 signaling. CD58 inhibited the activity of the JAK2/STAT1 pathway by activating the LYN/CD22/SH2 domain-containing phosphatase 1 (SHP1) axis, thereby limiting PDL1 and IDO expression. Elevated PDL1 and IDO expression in CD58-deficient DLBCL cells led to immune evasion and tumor-intrinsic resistance to chimeric antigen receptor T-cell therapy. Direct activation of CD58-CD2 costimulatory signaling in combination with anti-PDL1 blockade or IDO inhibitor sensitized CD58-deficient DLBCL to chimeric antigen receptor T-cell therapy. Collectively, this work identified the multiple roles of CD58 in regulating antitumor immune responses in DLBCL. Significance: Loss of CD58 mediates immune evasion and therapy resistance in diffuse large B-cell lymphoma by upregulating PDL1 and IDO through LYN/CD22/SHP1 signaling, providing potential targets and therapeutic strategies to improve patient treatment.

[Brief Analysis of Clinical Evaluation Concerns of Personalized Abutments and Abutment Crown Bridge Products].

Objective: The applications of personalized abutments and abutment crown bridge products have increased year by year, but there is no clear requirement for clinical evaluation of the same variety of such products. This study mainly introduces the clinical evaluation concerns of personalized abutments and abutment crown bridge products, in order to provide reference for the declaration and registration of such products. Methods: The clinical evaluation of personalized abutments and crown bridge products are summarized, and the research content of clinical evaluation is clarified. Results: The clinical evaluation requirements that need to be considered by enterprises are introduced. Conclusion: Personalized abutment and abutment crown bridge products can refer to this study when they are launched in China, mainly using in vitro performance comparison tests for equivalence verification.

Greenspace and human microbiota: A systematic review.

BACKGROUND: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program's office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively. RESULTS: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive. CONCLUSION: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota.

A universal inverse design methodology for microfluidic mixers.

The intelligent design of microfluidic mixers encompasses both the automation of predicting fluid performance and the structural design of mixers. This article delves into the technical trajectory of computer-aided design for micromixers, leveraging artificial intelligence algorithms. We propose an automated micromixer design methodology rooted in cost-effective artificial neural network (ANN) models paired with inverse design algorithms. Initially, we introduce two inverse design methods for micromixers: one that combines ANN with multi-objective genetic algorithms, and another that fuses ANN with particle swarm optimization algorithms. Subsequently, using two benchmark micromixers as case studies, we demonstrate the automatic derivation of micromixer structural parameters. Finally, we automatically design and optimize 50 sets of micromixer structures using the proposed algorithms. The design accuracy is further enhanced by analyzing the inverse design algorithm from a statistical standpoint.

A candidate competitive ELISA based on monoclonal antibody 3A8 for diagnosis of contagious bovine pleuropneumonia.

For the development of a competitive ELISA (cELISA) to detect serum antibodies against the Mycoplasma mycoides subsp. Mycoides (Mmm) (strain PG1), the causative agent of contagious bovine pleuropneumonia (CBPP), all the proteins of this pathogen were analyzed. Then, a specific extracellular region of a transmembrane protein with the potential for diagnosis was identified. After that, a monoclonal antibody (Mab) named 3A8 was obtained using this extracellular region as an immunogen. Finally, a cELISA was established with the extracellular domain of this transmembrane protein as the coating antigen, Mab 3A8 as the competitive antibody, and HRP-labeled goat anti-mouse IgG as the enzyme-labeled antibody. This established method was used to detect the antibody dynamic regularity of goats which are artificially immunized Mmm and was also compared with a commercial ELISA kit. Further, the sera of 1011 different cattle from border provinces of China were monitored using a candidate Mab 3A8 cELISA. The detection results of known background sera used in this study indicate that a candidate diagnostic marker was successfully identified by analyzing all the coding proteins of Mmm in this research, and the cELISA established based on the Mab 3A8 against this protein can detect CBPP-positive serum with specificity and has no cross-reaction with other related epidemic disease-positive sera. In addition, we tested the sera collected from the border areas of China using the established ELISA, and no positive sample was detected. The research protocol of the CBPP cELISA established in this study is different from the traditional method, which can greatly reduce the investment of manpower and capital and save development time. We believe that this study's protocol could serve as a reference for the development of detection methods for mycoplasma and other complex pathogens. KEY POINTS: • A Mmm-specific diagnostic marker was obtained based on protein characteristics. • A cELISA was established for CBPP serum antibody detection. • The serological investigation was conducted for CBPP in the border areas of China.