Emerging biologic frontiers for Sjogren's syndrome: Unveiling novel approaches with emphasis on extra glandular pathology.

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

Design and conduct of a randomized controlled feeding trial in a residential setting with mitigation for COVID-19.

BACKGROUND: Evaluating effects of different macronutrient diets in randomized trials requires well defined infrastructure and rigorous methods to ensure intervention fidelity and adherence. METHODS: This controlled feeding study comprised two phases. During a Run-in phase (14-15 weeks), study participants (18-50 years, BMI, ≥27 kg/m2) consumed a very-low-carbohydrate (VLC) diet, with home delivery of prepared meals, at an energy level to promote 15 ± 3% weight loss. During a Residential phase (13 weeks), participants resided at a conference center. They received a eucaloric VLC diet for three weeks and then were randomized to isocaloric test diets for 10 weeks: VLC (5% energy from carbohydrate, 77% from fat), high-carbohydrate (HC)-Starch (57%, 25%; including 20% energy from refined grains), or HC-Sugar (57%, 25%; including 20% sugar). Outcomes included measures of body composition and energy expenditure, chronic disease risk factors, and variables pertaining to physiological mechanisms. Six cores provided infrastructure for implementing standardized protocols: Recruitment, Diet and Meal Production, Participant Support, Assessments, Regulatory Affairs and Data Management, and Statistics. The first participants were enrolled in May 2018. Participants residing at the conference center at the start of the COVID-19 pandemic completed the study, with each core implementing mitigation plans. RESULTS: Before early shutdown, 77 participants were randomized, and 70 completed the trial (65% of planned completion). Process measures indicated integrity to protocols for weighing menu items, within narrow tolerance limits, and participant adherence, assessed by direct observation and continuous glucose monitoring. CONCLUSION: Available data will inform future research, albeit with less statistical power than originally planned.

Widespread distribution of human-infective Enterocytozoon bieneusi genotypes in small rodents in northeast China and phylogeny and zoonotic implications revisited.

Enterocytozoon bieneusi features high genetic diversity among host species and environmental sources and over 500 genotypes in 11 phylogenetic groups have been defined. Here we investigated 291 small rodents in Heilongjiang province, northeast China, for the presence of E. bieneusi by PCR of the ribosomal internal transcribed spacer (ITS). Nine of 60 (15.0 %) gray squirrels from a park in Harbin, 120 of 201 (59.7 %) guinea pigs from a pet shop in Harbin, and two of 30 (6.7 %) peridomestic rats from a pasture in Qiqihar were positive for the parasite. Six known genotypes (EbpB, SCC-1, SCC-2, D, S7 and HLJ-CP1) and two novel genotypes (NESQ1 and NEGP1) were identified by sequence analysis of the ITS, with EbpB, SCC-1, SCC-2 and NESQ1 found in squirrels, D, S7 and NEGP1 in guinea pigs, and EbpB and HLJ-CP1 in rats. Widespread distribution of human-infective Group 10 genotype S7 and Group 1 genotype D in guinea pigs raised our concerns about the importance of pet animals as zoonotic reservoirs of microsporidiosis. Co-occurrence of Group 1 genotypes D and HLJ-CP1 in cancer patients and rodents in Heilongjiang indicated a possibility of zoonotic transmission. The host range of Group 1 genotype EbpB previously considered pig-adapted was extended. A potential variant of genotype S7, namely NESQ1, went into the existing Group 10 in phylogenetic analysis. The other new genotype, NEGP1, was clustered in an undefined clade we proposed as Group 15. With the emerging epidemiologic evidence, the host specificity of existing E. bieneusi genotypes is now being challenged.

C-reactive protein to albumin ratio predict responses to programmed cell death-1 inhibitors in hepatocellular carcinoma patients.

BACKGROUND: Over the years, programmed cell death-1 (PD-1) inhibitors have been routinely used for hepatocellular carcinoma (HCC) treatment and yielded improved survival outcomes. Nonetheless, significant heterogeneity surrounds the outcomes of most studies. Therefore, it is critical to search for biomarkers that predict the efficacy of PD-1 inhibitors in patients with HCC. AIM: To investigate the role of the C-reactive protein to albumin ratio (CAR) in evaluating the efficacy of PD-1 inhibitors for HCC. METHODS: The clinical data of 160 patients with HCC treated with PD-1 inhibitors from January 2018 to November 2022 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. RESULTS: The optimal cut-off value for CAR based on progression-free survival (PFS) was determined to be 1.20 using x-tile software. Cox proportional risk model was used to determine the factors affecting prognosis. Eastern Cooperative Oncology Group performance status [hazard ratio (HR) = 1.754, 95% confidence interval (95%CI) = 1.045-2.944, P = 0.033], CAR (HR = 2.118, 95%CI = 1.057-4.243, P = 0.034) and tumor number (HR = 2.932, 95%CI = 1.246-6.897, P = 0.014) were independent prognostic factors for overall survival. CAR (HR = 2.730, 95%CI = 1.502-4.961, P = 0.001), tumor number (HR = 1.584, 95%CI = 1.003-2.500, P = 0.048) and neutrophil to lymphocyte ratio (HR = 1.120, 95%CI = 1.022-1.228, P = 0.015) were independent prognostic factors for PFS. Two nomograms were constructed based on independent prognostic factors. The C-index index and calibration plots confirmed that the nomogram is a reliable risk prediction tool. The ROC curve and decision curve analysis confirmed that the nomogram has a good predictive effect as well as a net clinical benefit. CONCLUSION: Overall, we reveal that the CAR is a potential predictor of short- and long-term prognosis in patients with HCC treated with PD-1 inhibitors. If further verified, CAR-based nomogram may increase the number of markers that predict individualized prognosis.

The growth of Ge and direct bandgap Ge1-xSnx on GaAs (001) by molecular beam epitaxy.

Germanium tin (GeSn) is a tuneable narrow bandgap material, which has shown remarkable promise for the industry of near- and mid-infrared technologies for high efficiency photodetectors and laser devices. Its synthesis is challenged by the lattice mismatch between the GeSn alloy and the substrate on which it is grown, sensitively affecting its crystalline and optical qualities. In this article, we investigate the growth of Ge and GeSn on GaAs (001) substrates using two different buffer layers consisting of Ge/GaAs and Ge/AlAs via molecular beam epitaxy. The quality of the Ge layers was compared using X-ray diffraction, atomic force microscopy, reflection high-energy electron diffraction, and photoluminescence. The characterization techniques demonstrate high-quality Ge layers, including atomic steps, when grown on either GaAs or AlAs at a growth temperature between 500-600 °C. The photoluminescence from the Ge layers was similar in relative intensity and linewidth to that of bulk Ge. The Ge growth was followed by the growth of GeSn using a Sn composition gradient and substrate gradient approach to achieve GeSn films with 9 to 10% Sn composition. Characterization of the GeSn films also indicates high-quality gradients based on X-ray diffraction, photoluminescence, and energy-dispersive X-ray spectroscopy measurements. Finally, we were able to demonstrate temperature-dependent PL results showing that for the growth on Ge/GaAs buffer, the direct transition has shifted past the indirect transition to a longer wavelength/lower energy suggesting a direct bandgap GeSn material.

The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer.

BACKGROUND: Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from the epithelial cells of the pancreatic duct and acinar cells. This particular neoplasm has a highly unfavorable prognosis due to its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, and limited survival duration. Cellular immunotherapy is the ex vivo culture and expansion of immune effector cells, granting them the capacity to selectively target malignant cells using specialized techniques. Subsequently, these modified cells are reintroduced into the patient's organism with the purpose of eradicating tumor cells and providing therapeutic intervention for cancer. PRESENT SITUATION: Presently, the primary cellular therapeutic modalities employed in the treatment of pancreatic cancer encompass CAR T-cell therapy, TCR T-cell therapy, NK-cell therapy, and CAR NK-cell therapy. AIM OF REVIEW: This review provides a concise overview of the mechanisms and primary targets associated with various cell therapies. Additionally, we will explore the prospective outlook of cell therapy in the context of treating pancreatic cancer.

KLK10/LIPH/PARD6B/SLC52A3 are promising molecular biomarkers for the prognosis of pancreatic cancer through a ceRNA network.

Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%-90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.

Proteomics Sequencing Reveals the Role of TGF-ß Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride.

The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.

T-2 toxin induces mitochondrial dysfunction in chondrocytes via the p53-cyclophilin D pathway.

Kashin-Beck disease is an endemic joint disease characterized by deep chondrocyte necrosis, and T-2 toxin exposure has been confirmed its etiology. This study investigated mechanism of T-2 toxin inducing mitochondrial dysfunction of chondrocytes through p53-cyclophilin D (CypD) pathway. The p53 signaling pathway was significantly enriched in T-2 toxin response genes from GeneCards. We demonstrated the upregulation of the p53 protein and p53-CypD complex in rat articular cartilage and ATDC5 cells induced by T-2 toxin. Transmission electron microscopy showed the damaged mitochondrial structure of ATDC5 cells induced by T-2 toxin. Furthermore, it can lead to overopening of the mitochondrial permeability transition pore (mPTP), decreased mitochondrial membrane potential, and increased reactive oxygen species generation in ATDC5 cells. Pifithrin-α, the p53 inhibitor, alleviated the increased p53-CypD complex and mitochondrial dysfunction of chondrocytes induced by T-2 toxin, suggesting that p53 played an important role in T-2 toxin-induced mitochondrial dysfunction. Mechanistically, T-2 toxin can activate the p53 protein, which can be transferred to the mitochondrial membrane and form a complex with CypD. The increased binding of p53 and CypD mediated the excessive opening of mPTP, changed mitochondrial membrane permeability, and ultimately induced mitochondrial dysfunction and apoptosis of chondrocytes.

Sex-biased gut dopamine signaling in multiple sclerosis.

Multiple sclerosis shows a strong sex bias, with unclear mechanisms. In this issue of Immunity, Peng et al. elucidate a female-biased increase in intestinal dopamine signaling that diminishes protective Lactobacillus and exacerbates inflammation in a mouse model of multiple sclerosis.

The expression of immune related genes and potential regulatory mechanisms in schizophrenia.

OBJECTIVE: This study aimed to investigate the role of immune dysfunction in the pathogenesis of schizophrenia through single-cell transcriptome and bulk RNA data analyses. METHODS: The single-cell RNA sequencing (scRNA-seq) was selected to assess the cellular composition and gene expression profiles of the brain tissue. Further, bulk RNA sequencing data was utilized to corroborate findings from the single-cell analyses and provide additional insights into the molecular changes associated with the disease. Gene-drug interaction data was also included to identify potential therapeutic drugs targeting these dysregulated immune-related genes in schizophrenia. RESULTS: We discovered significant differences in cellular composition within schizophrenia tissue, including increased infiltration of fibroblasts, horizontal basal cells, monocytes, mesenchymal cells, and smooth muscle cells. The investigation of immune-related genes revealed significantly different expression of genes such as S100A2, CCL14, IGHA1, BPIFA1, GDF15, IL32, BPIFB2, HLA-DRA, S100A8, PTX3, TPM2, TNFRSF12A, GREM1 and others. These genes possibly contribute to the progression of schizophrenia through various pathways such as humoral immune response, IL-17 signaling pathway, adaptive immune response, antigen processing and presentation, and gut IgA production. Our findings also suggest possible transcriptional regulation in schizophrenia's immune dysfunction by transcription factors in monocytes, neutrophils, endothelial cells, and epithelial cells. Lastly, potential therapeutic drugs were identified through gene-drug interaction data, such as those targeting HLA-A and HLAB. CONCLUSION: The cellular heterogeneity and immune-related gene dysregulation play important roles in schizophrenia, which provides a foundation for understanding the pathogenesis and developing new treatment methods.

Intestinal epithelial dopamine receptor signaling drives sex-specific disease exacerbation in a mouse model of multiple sclerosis.

Although the gut microbiota can influence central nervous system (CNS) autoimmune diseases, the contribution of the intestinal epithelium to CNS autoimmunity is less clear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2) promoted sex-specific disease progression in an animal model of multiple sclerosis. Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory response in the CNS and reduced disease progression. In contrast, overexpression or activation of IEC DRD2 by phenylethylamine administration exacerbated disease severity. This was accompanied by altered lysozyme expression and gut microbiota composition, including reduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived from Lactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our study indicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increases susceptibility to CNS autoimmune diseases in a female-biased manner, opening up future avenues for sex-specific interventions of CNS autoimmune diseases.

Study of all-group-IV SiGeSn mid-IR lasers with dual wavelength emission.

Direct band gap GeSn alloys have recently emerged as promising lasing source materials for monolithic integration on Si substrate. In this work, optically pumped mid-infrared GeSn lasers were studied with the observation of dual-wavelength lasing at 2187 nm and 2460 nm. Two simultaneous lasing regions include a GeSn buffer layer (bulk) and a SiGeSn/GeSn multiple quantum well structure that were grown seamlessly using a chemical vapor deposition reactor. The onset of dual lasing occurs at 420 kW/cm2. The wider bandgap SiGeSn partitioning barrier enables the independent operation of two gain regions. While the better performance device in terms of lower threshold may be obtained by using two MQW regions design, the preliminary results and discussions in this work paves a way towards all-group-IV dual wavelength lasers monolithically integrated on Si substrate.

"GeSn Rule-23"-The Performance Limit of GeSn Infrared Photodiodes.

Group-IV GeSn photodetectors (PDs) compatible with standard complementary metal-oxide-semiconductor (CMOS) processing have emerged as a new and non-toxic infrared detection technology to enable a wide range of infrared applications. The performance of GeSn PDs is highly dependent on the Sn composition and operation temperature. Here, we develop theoretical models to establish a simple rule of thumb, namely "GeSn-rule 23", to describe GeSn PDs' dark current density in terms of operation temperature, cutoff wavelength, and Sn composition. In addition, analysis of GeSn PDs' performance shows that the responsivity, detectivity, and bandwidth are highly dependent on operation temperature. This rule provides a simple and convenient indicator for device developers to estimate the device performance at various conditions for practical applications.

The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation.

Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation and extracellular trap formation. Notably, Mlkl deficiency leads to increased mortality, increased bacterial colonization, severe destruction of organ architecture, and elevated inflammatory cell infiltration in murine models of S. pluranimalium pulmonary and systemic infection. In vivo and in vitro data provided evidence that potassium efflux-dependent NLRP3 inflammasome signalling downstream of active MLKL confers host protection against S. pluranimalium infection and initiates bacterial killing and clearance. Moreover, Mlkl deficiency results in defects in extracellular trap-mediated bactericidal activity. In summary, this study revealed that MLKL mediates the host defence response to S. pluranimalium, and suggests that MLKL is a potential drug target for preventing and controlling pathogen infection.

Identification of apoptosis-related key genes and the associated regulation mechanism in thoracic aortic aneurysm.

BACKGROUND: This study investigated the role of apoptosis-related genes in thoracic aortic aneurysms (TAA) and provided more insights into TAA's pathogenesis and molecular mechanisms. MATERIAL/METHODS: Two gene expression datasets (GSE9106 and GSE26155) were retrieved from the Gene Expression Omnibus (GEO) database. Apoptosis-related genes were obtained from the KEGG apoptosis pathway (hsa04210). Differentially expressed apoptosis-related genes were identified by performing differential expression analysis using limma for TAA blood and tissue samples. GO and KEGG enrichment analysis of the differentially expressed apoptosis genes was performed using the Metascape web tool. The miRNA-mRNA regulatory network was reconstructed using the ENCORI and miRDB databases, and functional enrichment analysis was performed on the related miRNAs using the miEAA tool. The correlation between the expression levels of differentially expressed apoptosis-related genes and genes involved in immune infiltration in TAA was calculated using the CIBERSORT algorithm. The apoptosis modification patterns mediated by differentially expressed apoptosis-related genes were systematically assessed in TAA samples. RESULTS: A total of 9 differentially-expressed apoptosis-related genes were identified in TAA samples compared with normal samples. 150 miRNAs and 6 mRNAs regulatory networks were reconstructed using the ENCORI and miRDB databases. Immune infiltration analysis revealed that the GZMB had the strongest positive correlation with activated NK cells and the DFFA presented the strongest positive correlation with T cells follicular helper. 3 distinct apoptosis modification patterns mediated by 9 differentially-expressed apoptosis-related genes were identified. They differ in immune characteristics and drug sensitivity, and their biological functions in these subtypes were further studied. CONCLUSIONS: This study identified key apoptosis-related genes related to TAA and evaluated the modification patterns of key apoptosis genes in TAA, providing insights into potential targets and mechanisms of TAA pathogenesis and progression.

Transitional meningioma malignant transformation and rib metastases following surgery: A case report.

The majority of benign meningiomas exhibit a slow growth rate and are associated with a good prognosis. The recurrence and extracranial metastases of meningioma are rare. The present report describes the case of a patient with recurrence of transitional meningioma for which total resection had been performed 8 years prior. Furthermore, the transitional meningioma transformed into atypical meningioma, and metastasized to the ribs. The present report aimed to describe the clinical features and pathological findings of a case of malignant transformation and distant metastasis of benign meningioma. A review of the literature was also performed.

The association between Urban and Rural Resident Basic Medical Insurance and instrumental activity of daily living disability among middle-aged and older adults in China.

BACKGROUND: Previous studies have not investigated the association between medical insurance and instrumental activity of daily living (IADL) disability. To fulfill this research gap, this study aims to explore the association between Urban and Rural Resident Basic Medical Insurance (URRBMI) and IADL disability among middle-aged and older adults in China. METHODS: The data of this study were sourced from the 2018 wave of China Health and Retirement Longitudinal Study (CHARLS). Logit regression models were used to analyze the association between URRBMI and odds of suffering from IADL disability. Furthermore, we used IV-Probit regression model to address the potential endogeneity problem. Moreover, propensity score matching and generalized random forest model were employed to conduct robustness checks. RESULTS: The logit regression results reveal that URRBMI participation was significantly related to reduced odds of suffering from IADL disability by 39.86% after adjusting for the control variables (p < 0.01). The results of IV-Probit estimation show that URRBMI was an exogenous variable. Further robustness checks reported similar estimation results. The results of heterogeneity analysis reveal that URRBMI produced a statistically stronger effect on IADL disability for the older adults (OR = 0.5815, p < 0.01) when compared with the middle-aged adults (OR = 0.5690, p < 0.05). The results of impact channel analysis indicate that physical exercise was a channel involving the effect of URRBMI on IADL disability. CONCLUSION: This study finds that the middle-aged and older adults who were covered by URRBMI had a reduced possibility of suffering from IADL disability when compared with those without URRBMI. Furthermore, it is found that URRBMI produced a statistically stronger effect on IADL disability for the older adults when compared with the middle-aged adults. Moreover, we obtain evidence indicating that physical exercise was a channel involving the effect of URRBMI on IADL disability.

Effect of implantable cardiac monitors on preventing stroke: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIM: Implantable cardiac monitors (ICM) can facilitate the detection of asymptomatic atrial fibrillation episodes. We performed a systematic review and meta-analysis to investigate whether ICM can prevent stroke in patients with prior stroke and risk factors for stroke. METHODS: This study included randomized controlled trials comparing ICM with conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. We searched Medline, Embase, and CENTRAL from inception until January 5, 2022, without language restriction. Quantitative pooling of the data was undertaken using a random-effects model. The primary outcome was ischemic stroke at the longest follow-up. RESULTS: Four trials comprising 7237 patients were included. ICM was significantly associated with decreased risk of ischemic stroke (RR 0.76; 95% CI, 0.59-0.97; moderate-quality evidence) in patients with prior stroke and risk factors for stroke. ICM was associated with higher detection of atrial fibrillation (RR 4.21, 95% CI 2.26-7.85) and use of oral anticoagulants (RR 2.29, 95% CI 2.07-2.55). CONCLUSIONS: ICM results in a significantly lower risk of ischemic stroke than conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. Due to the clinical heterogeneity of study population and limited related studies, more trials were needed to furtherly explore the topic in patients with prior stroke or high risk of stroke.

Single-atom Zn with nitrogen defects on biomimetic 3D carbon nanotubes for bifunctional oxygen electrocatalysis.

Single atoms catalysts (SACs) have promising development in electrocatalytic energy conversion. Nevertheless, rational design SACs with reversible oxygen electrocatalysis still remain challenge. Herein, we synthesized atomically dispersed Zn with N defect on three-dimensional (3D) biomimetic carbon nanotubes by secondary pyrolysis (Zn-N-C-2), which possesses excellent oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalytic activities. The biomimetic 3D structure and unique "leaf-branch" system are beneficial to fully expose the active sites. Density functional theory (DFT) calculations show that Zn-N3-D can optimize the charge distribution and facilitate electron transfer step of OH*→O*. Zn-N-C-2 exhibits higher ORR activity than commercial Pt/C with a half-wave potential (E1/2) of 0.85 V and OER overpotential of 450 mV at 10 mA cm-2. After being assembled into the air cathode of aqueous Zn-air battery (ZAB), it demonstrates superior performances with long-term charge and discharge for more than 200 h. This work not only clarifies the controlled synthesis of N-defects Zn SACs with excellent bifunctional electrocatalyst, but also provide in-depth understanding of structural-performance relationships by regulating local microenvironments.