Interstitial lung diseases associated with ANCA positivity: A different disease spectrum from interstitial pneumonia with autoimmune features.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA) is a type of autoantibodies associated with vasculitis. ANCA positivity is commonly observed in interstitial lung disease (ILD) patients. 7%-10% of ANCA-positive ILD patients don't present any symptoms of systemic vasculitis and are termed ANCA-positive idiopathic interstitial pneumonia (ANCA-IIP). Some researchers propose that ANCA-IIP should be categorized as interstitial pneumonia with autoimmune features (IPAF), although the official ATS/ERS statements exclude ANCA-IIP from this classification. Whether ANCA-IIP should be categorized into the entity of IPAF is still debatable. METHODS: Patients diagnosed with ANCA-IIP and those with IPAF were analyzed in a retrospective study of ILD. The clinical outcomes were determined through pulmonary function tests (PFTs) after a one-year follow-up, as well as assessing all-cause mortality. RESULTS: 27 patients with ANCA-IIP and 143 patients with IPAF were analyzed from a cohort of 995 patients with ILD. Patients in the ANCA-IIP group had an older age and a high proportion of males compared to those in the IPAF group. PFT results at baseline were similar between the two groups, except for a better FEV1% in the ANCA-IIP group. Glucocorticoid and immunosuppressive therapy improved pulmonary function in patients with IPAF, but it continued to deteriorate after one year of treatment in the ANCA-IIP group. Furthermore, the all-cause mortality rate was significantly higher in the ANCA-IIP group than in the IPAF group (22.2% vs. 6.3%, P = 0.017). CONCLUSION: The responses to glucocorticoid and immunosuppressive therapy differ between the ANCA-IIP and IPAF groups, leading to divergent prognoses. Therefore, it is inappropriate to classify ANCA-IIP as part of IPAF.

Association of soluble TREM2 with Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.

Objective: Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a potential neuroinflammatory biomarker linked to the pathogenesis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Previous studies have produced inconsistent results regarding sTREM2 levels in various clinical stages of AD. This study aims to establish the correlation between sTREM2 levels and AD progression through a meta-analysis of sTREM2 levels in cerebrospinal fluid (CSF) and blood. Methods: Comprehensive searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library to identify observational studies reporting CSF and blood sTREM2 levels in AD patients, MCI patients, and healthy controls. A random effects meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs). Results: Thirty-six observational studies involving 3,016 AD patients, 3,533 MCI patients, and 4,510 healthy controls were included. CSF sTREM2 levels were significantly higher in both the AD [SMD = 0.28, 95% CI (0.15, 0.41)] and MCI groups [SMD = 0.30, 95% CI (0.13, 0.47)] compared to the healthy control group. However, no significant differences in expression were detected between the AD and MCI groups [SMD = 0.09, 95% CI (-0.09, 0.26)]. Furthermore, increased plasma sTREM2 levels were associated with a higher risk of AD [SMD = 0.42, 95% CI (0.01, 0.83)]. Conclusion: CSF sTREM2 levels are positively associated with an increased risk of AD and MCI. Plasma sTREM2 levels were notably higher in the AD group than in the control group and may serve as a promising biomarker for diagnosing AD. However, sTREM2 levels are not effective for distinguishing between different disease stages of AD. Further investigations are needed to explore the longitudinal changes in sTREM2 levels, particularly plasma sTREM2 levels, during AD progression. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024514593.

A robust primary liver cancer subtype related to prognosis and drug response based on a multiple combined classifying strategy.

The recurrence or resistance to treatment of primary liver cancer (PLL) is significantly related to the heterogeneity present within the tumor. In this study, we integrated prognosis risk score, mRNAsi index, and immune characteristics clustering to classify patients. The four subtypes obtained from the combined classification are associated with PLC's prognosis and drug response. In these subtypes, we observed mRNAsiH_ICCA subtype, the intersection between high mRNAsi and immune characteristics clustering A, had the worst prognosis. Specifically, immune characteristics clustering B (ICC_B) had high drug sensitivity in most drugs regardless of the value of mRNAsi. On the other hand, patients with low mRNAsi responded better to ten drugs including KU-55933 and NU7441, while patients with high mRNAsi might benefit from drugs like Leflunomide. By matching the specific characteristics of each combined subtype with the drug-induced cell line expression profile, we identified a group of potential therapeutic drugs that might regulate the expression of disease signature genes. We developed a feasible multiple combined typing strategy, hoping to guide therapeutic selection and promote the development of precision medicine.

[Retracted] MicroRNA­425 is downregulated in nasopharyngeal carcinoma and regulates tumor cell viability and invasion by targeting hepatoma­derived growth factor.

[This retracts the article DOI: 10.3892/ol.2018.8128.].

The lncRNA GAS5 upregulates ANXA2 to mediate the macrophage inflammatory response during atherosclerosis development.

Inflammatory macrophages play a crucial role in atherosclerosis development. The long non-coding RNA growth arrest-specific 5 (GAS5) regulates THP-1 macrophage inflammation by sponging microRNAs. The purpose of this study was to investigate the regulatory mechanism of GAS5 in atherosclerosis development. GSE40231, GSE21545, and GSE28829 datasets from the Gene Expression Omnibus database were integrated after adjusting for batch effect. Differential analysis was performed on the integrated dataset and validated using the Genotype-Tissue Expression and GSE57691 datasets. Potential biological functions of GAS5 and annexin A2 (ANXA2) were identified using gene set enrichment analysis (GSEA). ssGSEA, CIBERSORTx, and ImmuCellAI algorithms were used to identify immune infiltration in plaque samples. GAS5 and ANXA2 expression levels in RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL) were measured by qRT-PCR and Western blot. Small interfering and short hairpin RNA were used to silence GAS5 expression. Plasmids of ANXA2 were used to establish ANXA2 overexpression. Apoptosis and inflammatory markers in macrophages were detected by Western blot. Aortic samples from APOE-/- mice were collected to validate the expression of GAS5 and ANXA2. GAS5 expression was significantly increased during atherosclerosis. GAS5 expression was positively correlated with macrophage activation and ANXA2 expression in plaques. Furthermore, ANXA2 upregulation was also related to the activation of macrophage. GSEA indicated similar biological functions for GAS5 and ANXA2 in plaques. Moreover, in vitro experiments showed that both GAS5 and ANXA2 contributed to macrophage apoptosis and inflammation. Rescue assays revealed that the inflammatory effects of GAS5 on macrophages were ANXA2-dependent. In vivo experiments confirmed the highly expression of Gas5 and Anxa2 in the plaque group. We identified the atherogenic roles of GAS5 and ANXA2 in the inflammatory response of macrophages. The inflammatory response in ox-LDL-treated macrophages was found to be mediated by GAS5-ANXA2 regulation, opening new avenues for atherosclerosis therapy.

LncRNA GAS5 downregulates NLRP3 inflammasome activation-mediated pyroptosis in sepsis-induced myocardial injury by targeting SIRT3/AMPKα.

An increasing body of studies has demonstrated the significance of long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) in inflammation and myocardial injury in septic shock. This research aims to determine whether GAS5 contributes to the pathological development of sepsis-induced cardiac damage and NLRP3 inflammasome-mediated myocardial cell pyroptosis. Cecal ligation and puncture (CLP) surgery was used to cause septic shock in C57BL/6 wild-type mice. After CLP, inflammatory, pyroptosis parameters of myocardial tissue, survival rate, and Murine Sepsis Score (MSS) were assessed to evaluate the involvement of GAS5 in the mouse myocardial depression. To investigate GAS5's function in lipopolysaccharide (LPS) induced myocardial cell pyroptosis, gain- and loss-of-function experiments were conducted in vitro on HL-1 cells. Our findings indicated that CLP dramatically reduced survival rates, MSS, SIRT3 and p-AMPK expression, and activated the Nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome-mediated pyroptosis. The NF-κB and pyroptosis pathways were greatly elevated while SIRT3/p-AMPKα was dramatically decreased as a result of GAS5 being downregulated. Meanwhile, the regulatory effect could be suppressed by SIRT3 and AMPKα activator. Our observations supported the idea that GAS5 has a crucial protective impact against myocardial inflammation and pyroptosis in sepsis.

Migratory Pulmonary Infiltrates in a B-Cell-Depleted COVID-19 Patient.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rampant around the world. Immunocompromised patients are prone to have long-term infection with coronavirus disease 2019 (COVID-19). However, it is difficult to decide on an appropriate treatment for persistent SARS-CoV-2 infection. Case Presentation: We present a case of prolonged SARS-CoV-2 infection in a patient who had undergone B-cell depletion therapy. Chest computed tomography (CT) revealed notable migratory pulmonary infiltrates, and bronchoalveolar lavage fluid was positive for SARS-CoV-2 (day-120). The patient responded well to the combination treatment of antiviral medication, convalescent plasma, and corticosteroid. Conclusion: When chest CT shows migratory pulmonary infiltrates in patients with recent COVID-19, it is necessary to be alert to the possibility of persistent SARS-CoV-2 infection, especially in B-cell-depleted immunocompromised patients. Once the diagnosis is confirmed, repeated antiviral therapy and intravenous convalescent plasma should be considered.

Biological roles of RNA m7G modification and its implications in cancer.

M7G modification, known as one of the common post-transcriptional modifications of RNA, is present in many different types of RNAs. With the accurate identification of m7G modifications within RNAs, their functional roles in the regulation of gene expression and different physiological functions have been revealed. In addition, there is growing evidence that m7G modifications are crucial in the emergence of cancer. Here, we review the most recent findings regarding the detection techniques, distribution, biological functions and Regulators of m7G. We also summarize the connections between m7G modifications and cancer development, drug resistance, and tumor microenvironment as well as we discuss the research's future directions and trends.

Involvement of 5-HT1A receptors of the thalamic descending pathway in the analgesic effect of intramuscular heating-needle stimulation in a rat model of lumbar disc herniation.

Background: Intramuscular (IM) heating-needle therapy, a non-painful thermal therapy, has been found to exert an analgesic effect via the thalamic ventromedial (VM) nucleus, solely by reducing the triggering threshold for descending inhibition; this could be modulated by intracephalic 5-hydroxytryptamine-1A (5-HT1A) receptors, rather than via the regular analgesia pathway. In this study, the effect and the potential serotonergic mechanism of IM heating-needle stimulation at 43°C were explored in the case of the pathological state of lumbar disc herniation (LDH). Methods: A modified classic rat model of LDH, induced via autologous nucleus pulposus implantation, was utilized. IM inner heating-needles were applied at the attachment point of skeletal muscle on both sides of the L4 and L5 spinous processes. WAY-100635 and 8-OH-DAPT, 5-HT1A receptor antagonist and agonist, were separately injected into the bilateral thalamic mediodorsal (MD) and VM nucleus via an intrathalamic catheter. Nociception was assessed by bilateral paw withdrawal reflexes elicited by noxious mechanical and heat stimulation. Results: IM heating-needle stimulation at a temperature of 43°C for 30 or 45 min significantly relieved both mechanical and heat hyperalgesia in the rat model of LDH (P < 0.05). Heat hyperalgesia was found to be significantly enhanced by administration of WAY-100635 into the thalamic VM nucleus, blocking the effect of heating-needle stimulation in a dose-dependent manner (P < 0.05), while no effects were detected after injection into the thalamic MD nucleus (P > 0.05). Injection of 8-OH-DAPT into the thalamic MD nucleus exerted no modulating effects on either mechanical or heat hyperalgesia (P > 0.05). Conclusion: IM heating-needle stimulation at 43°C for 30 min may activate 5-HT1A mechanisms, via the thalamic VM nucleus, to attenuate hyperalgesia in a rat model of LDH. This innocuous form of thermal stimulation is speculated to selectively activate the descending inhibition mediated by the thalamic VM nucleus, exerting an analgesic effect, without the involvement of descending facilitation of the thalamic MD nucleus.

Effect of Penthorum Chinense Pursh Compound on AFB1-Induced Immune Imbalance via JAK/STAT Signaling Pathway in Spleen of Broiler Chicken.

Aflatoxin B1(AFB1) is the main secondary metabolite produced by Aspergillus flavus, which is highly toxic, carcinogenic, mutagenic and teratogenic. It can induce immune imbalance in animals or humans. Penthorum chinense Pursh (PCP) is a traditional herbal plant that has been used as a hepatoprotective drug with a long history in China. Based on the theory of traditional Chinese Medicine, we prepared Penthorum chinense Pursh Compound (PCPC) by combining four herbal medicines: 5 g Penthorum chinense Pursh, 5 g Radix bupleuri, 1 g Artemisia capillaris Thunb and 1 g Radix glycyrrhizae. The role of the Penthorum chinense Pursh Compound (PCPC) in preventing AFB1-induced immune imbalance in broiler chickens was studied. A total of 180 broiler chickens were equally distributed in six groups: controls, AFB1, YCHD and high-, medium- and low-dose PCPC treatment groups. After 28 days, broilers were anesthetized, and serum spleen and thymus samples were collected for analysis. Results show that AFB1 significantly increased and decreased the relative organ weight of the spleen and thymus, respectively. Pathological section of hematoxylin/eosin (H&E) stained spleen sections showed that AFB1 resulted in splenic tissue damage. Both the serum levels of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) were suppressed in the AFB1 group. IL-6 was elevated in the AFB1 group. The balance between pro-inflammatory cytokines (IFN-γ and IL-2) and anti-inflammatory cytokine (IL-4) was disturbed by AFB1. The apoptosis-related protein and JAK/STAT pathway-related gene expression indicated that AFB1-induced apoptosis via JAK/STAT pathway. PCPC has proven its immunoprotective effects by preventing AFB1-induced immune imbalance. PCPC can be applied as a novel immune-modulating medicine in broiler chickens. It can be applied as a novel immune modulator in veterinary clinical practice.

Durability of Hepatitis B surface antigen seroclearance in patients experienced nucleoside analogs or interferon monotherapy: A real-world data from Electronic Health Record.

Little is known about the difference in durability of HBsAg seroclearance induced by nucleoside analogs (NAs) or by interferon (IFN). A real-world, retrospective cohort study was conducted. Patients were assigned into two groups: NAs monotherapy-induced HBsAg seroclearance subjects and IFN monotherapy induced-HBsAg seroclearance subjects. A total of 198 subjects, comprised by 168 NAs monotherapy-induced and 30 IFN monotherapy-induced, who achieved HBsAg seroclearance were included in this study. The one-year probabilities of confirmed HBsAg seroclearance were significantly different in patients with NAs monotherapy and IFN monotherapy (0.960 (with 95% CI 0.922-0.999) vs. 0.691 (with 95% CI 0.523-0.913), log-rank-P = 4.04e-4). 73.3% (11 of 15) HBsAg recurrence occurred within one year after HBsAg seroclearance. The one-year probabilities of confirmed HBsAg seroclearance were higher in IFN monotherapy patients with anti-HBs than in IFN monotherapy patients without anti-HBs (0.839 (with 95% CI 0.657-1.000) vs. 0.489 (with 95% CI 0.251-0.953), log-rank test, P = 0.024). Our study thus provided novel insights into the durability of HBsAg seroclearance induced by NAs or IFN monotherapy. In particular, the HBsAg seroreversion rate was relatively high in IFN monotherapy subjects. The presence of anti-HBs was significantly correlated with a longer durability of functional cure induced by IFN treatment. And one-year follow-up in HBsAg seroclearance achieved individuals is proper for averting HBsAg seroreversion and other liver disease.

Facile preparation of organosilanes from benzylboronates and gem-diborylalkanes mediated by KOtBu.

Methods to efficiently synthesize organosilanes are valuable in the fields of synthetic chemistry and materials science. During the past decades, boron conversion has become a generic and powerful approach for constructing carbon-carbon and other carbon-heteroatom bonds, but its potential application in forming carbon-silicon remains unexplored. Herein, we describe an alkoxide base-promoted deborylative silylation of benzylic organoboronates, geminal bis(boronates) or alkyltriboronates, allowing for straightforward access to synthetically valuable organosilanes. This selective deborylative methodology exhibits operational simplicity, broad substrate scope, excellent functional group compatibility and convenient scalability, providing an effective and complementary platform for the generation of diversified benzyl silanes and silylboronates. Detailed experimental results and calculated studies revealed an unusual mechanistic feature of this C-Si bond formation.

Liquid Biopsy in Coronary Heart Disease.

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality globally. Accumulating evidence indicates that coronary heart disease (CHD) contributes to the majority of cardiovascular deaths. With the development of precision medicine, the diagnosis and treatment of coronary heart disease are becoming more refined and individualized. Molecular diagnosis technology and individualized treatment are gradually applied to the clinical diagnosis and treatment of CHD. It is great significance to seek sensitive biological indicators to help early diagnosis and improve prognosis of CHD. Liquid biopsy is a minimally invasive technique, which is widely used to detect molecular biomarkers of tumors without invasive biopsy. Compared with the field of oncology, it is not easy to get the diseased tissue in CVD, especially CHD. Therefore, the idea of "fluid biopsy" is very attractive, and its progress may provide new and useful noninvasive indicators for CHD. By analyzing circulating cells or their products in blood, saliva, and urine samples, we can investigate the molecular changes that occur in each patient at a specific point in time, thus continuously monitoring the evolution of CHD. For example, the assessment of cell-free DNA (cfDNA) levels may help predict the severity of acute myocardial infarction and diagnose heart transplant rejection. Moreover, the unmethylated FAM101A gene may specifically track the cfDNA derived from cardiomyocyte death, which provides a powerful diagnostic biomarker for apoptosis during ischemia. In addition, the changes of plasma circulating miR-92 levels may predict the occurrence of acute coronary syndrome (ACS) onset in patients with diabetes. Liquid biopsy can reflect the disease state through patients' body fluids and may noninvasively provide dynamic and rich molecular information related to CHD. It has great application potential in early warning and auxiliary diagnosis, real-time monitoring of curative effect, medication guidance and exploration of drug resistance mechanism, prognosis judgment, and risk classification of CHD. This chapter will review the latest progress of liquid biopsy in accurate diagnosis and treatment of CHD, meanwhile explore the application status and clinical prospect of liquid biopsy in CHD, in order to improve the importance of precision medicine and personalized treatment in this field.

Evaluation of liver function using Gd-EOB-DTPA-enhanced MRI with T1 mapping.

PURPOSE: To evaluate the value of MRI T1 mapping with Gd-EOB-DTPA for assessing liver function. METHODS: Seventy-two patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions at Beijing Friendship Hospital from August 2020 to March 2022 were prospectively enrolled, and variable-flip-angle T1 mapping was performed before and 20 min after enhancement. The Child-Pugh (C-P) score and albumin-bilirubin (ALBI) grade of liver function were assessed using the clinical data of the patients. Correlation analysis was used to evaluate the correlation between T1 mapping parameters and liver function grading and laboratory tests. Nonparametric tests were used to compare the differences among different liver function groups. The liver function classification efficiency of each image index was evaluated with receiver operating characteristic (ROC) curves. RESULTS: T1post was positively correlated with the C-P grade and the ALBI grade (r = 0.717 and r = 0.652). ΔT1 was negatively correlated with the C-P grade and the ALBI grade (r = -0.790 and r = -0.658). T1post and ΔT1 significantly differed among different liver function grades (p < 0.05). For the C-P grade, T1post and ΔT1 were significantly different between each pair of groups (p < 0.05), and ΔT1 had a better diagnostic efficiency than T1post. For the ALBI grade, ΔT1 and T1post were significantly different between the NLF and ALBI1 groups (p < 0.05), and ΔT1 had a better diagnostic efficacy than T1post. T1post significantly differed between the ALBI1 and ALBI2 + 3 groups (p < 0.05), while ΔT1 had a weak ability to differentiate between these two groups. CONCLUSION: T1post and ΔT1 were strongly correlated with the two liver function grades and can be noninvasive imaging indexes for evaluating liver function.

Penthorum chinense Pursh compound flavonoids supplementation alleviates Aflatoxin B1-induced liver injury via modulation of intestinal barrier and gut microbiota in broiler.

Aflatoxin B1 (AFB1) is a commonly occurring toxicant in animal and human diets, leading to hazardous effects on health. AFB1 is known to be a hepato-toxicant, and the intestinal barrier may play a crucial role in reversing AFB1-induced liver injury. This study aimed to optimize the extraction conditions of Penthorum chinense Pursh Compound Flavonoids (PCPCF) by the response surface method with a Box-Behnken design and investigate the effects of PCPCF on AFB1-induced liver injury in broilers. A total of 164 one-day-old broilers were divided into seven groups, including Control, PCPCF (400 mg PCPCF/kg feed), AFB1 (3 mg AFB1/kg feed), and YCHT (Yin-Chen-Hao-Tang extract, 3 mg AFB1 +10 mL YCHT/kg feed) and low, medium, and high dose groups (PCPCF at 3 mg AFB1 +200, 400, 600 mg respectively). Samples of serum, liver, duodenum, and cecum contents were collected at 14th and 28th days for further analysis. The results showed that the maximum extraction rate of PCPCF was 8.15 %. PCPCF was rich in rutin, quercetin, liquiritin and kaempferol, and significantly inhibited the growth of Aspergillus flavus. The addition of PCPCF improved the growth performance of AFB1-injury broilers, modulated liver function, and increased serum immunoglobulin levels. PCPCF also alleviated liver pathological and oxidative stress damages caused by AFB1 and decreased AFB1-DNA and AFB1-lysine content in the liver. Furthermore, PCPCF supplementation ameliorated intestinal pathological damage, improved intestinal permeability of duodenum in the AFB1-induced broilers, and repaired the intestinal mucosal and mechanical barrier associated with the Notch signaling pathway. Meanwhile, PCPCF improved the intestinal flora structure of AFB1-damaged broilers and increased the abundance of beneficial bacteria. In conclusion, PCPCF ameliorated the adverse effects of AFB1 on growth performance and alleviated liver damage by repairing the intestinal barrier and improving intestinal health of broiler chicken.

COVID-19 imaging, where do we go from here? Bibliometric analysis of medical imaging in COVID-19.

OBJECTIVES: We conducted a systematic and comprehensive bibliometric analysis of COVID-19-related medical imaging to determine the current status and indicate possible future directions. METHODS: This research provides an analysis of Web of Science Core Collection (WoSCC) indexed articles on COVID-19 and medical imaging published between 1 January 2020 and 30 June 2022, using the search terms "COVID-19" and medical imaging terms (such as "X-ray" or "CT"). Publications based solely on COVID-19 themes or medical image themes were excluded. CiteSpace was used to identify the predominant topics and generate a visual map of countries, institutions, authors, and keyword networks. RESULTS: The search included 4444 publications. The journal with the most publications was European Radiology, and the most co-cited journal was Radiology. China was the most frequently cited country in terms of co-authorship, with the Huazhong University of Science and Technology being the institution contributing with the highest number of relevant co-authorships. Research trends and leading topics included: assessment of initial COVID-19-related clinical imaging features, differential diagnosis using artificial intelligence (AI) technology and model interpretability, diagnosis systems construction, COVID-19 vaccination, complications, and predicting prognosis. CONCLUSIONS: This bibliometric analysis of COVID-19-related medical imaging helps clarify the current research situation and developmental trends. Subsequent trends in COVID-19 imaging are likely to shift from lung structure to function, from lung tissue to other related organs, and from COVID-19 to the impact of COVID-19 on the diagnosis and treatment of other diseases. Key Points • We conducted a systematic and comprehensive bibliometric analysis of COVID-19-related medical imaging from 1 January 2020 to 30 June 2022. • Research trends and leading topics included assessment of initial COVID-19-related clinical imaging features, differential diagnosis using AI technology and model interpretability, diagnosis systems construction, COVID-19 vaccination, complications, and predicting prognosis. • Future trends in COVID-19-related imaging are likely to involve a shift from lung structure to function, from lung tissue to other related organs, and from COVID-19 to the impact of COVID-19 on the diagnosis and treatment of other diseases.

AuNP/Cu-TCPP(Fe) metal-organic framework nanofilm: a paper-based electrochemical sensor for non-invasive detection of lactate in sweat.

Effective and real-time detection of lactate (LA) content in human sweat has attracted considerable attention from researchers. In this work, a novel electrochemical paper-based analysis device (ePAD) was developed for the non-invasive detection of LA in sweat. The electrocatalytic properties of AuNP/Cu-TCPP(Fe) hybrid nanosheets, which were prepared by an optimised synthetic method, were studied by CV and EIS electrochemical methods for the first time and the working electrode can be fabricated using a drip coating method. The lactate sensor was optimised and validated for usability, adoptability and interpretability. To the best of our knowledge, this was the fastest, lowest detection line and widest linear range method reported to date for the detection of lactate. It achieved the detection limit of 0.91 pM and a linear range from 0.013 nM to 100 mM. The dual catalytic effects of the hybrid NSs shortened the detection time by nearly two times and enhanced the sensitivity approximately two times, an accuracy unmatched until now. Furthermore, this sensor was employed for LA analysis and validated by high performance liquid chromatography (HPLC). The ePAD shows superior biocompatibility, accuracy, and high sensitivity and can be easily manufactured. Hence, it is applicable for the long-term monitoring of sweat LA concentrations in point-of-care testing, athletic testing of athletes and military personnel and other subjects in different extreme environments.

A fluorescence aptasensor based on hybridization chain reaction for simultaneous detection of T-2 toxins and zearalenone1.

It is extremely necessary to establish a rapid and high-throughput method to detect mycotoxins in food, because grains and cereals are greatly vulnerable to mycotoxins before and after harvest. In this study, we developed a portable aptasensor based on streptavidin magnetic microspheres (MMPs) and hybridization chain reaction (HCR) to simultaneously detect T-2 toxin and zearalenone (ZEN) in corn and oat flour. The MMPs compete with the aptamer for binding, which releases more H0 and triggers HCR with the H1 intermediate modified using 6-FAM and BHQ-1 and the unmodified H2. Subsequently, placing the HCR system corresponding to T-2 and ZEN in a constant-temperature fluorescence detector resulted in well-recovered fluorescence of the HCR products. T-2 and ZEN exhibited good fluorescence response in the dynamic range of 0.001-10 ng mL-1 and 0.01-100 ng mL-1 with detection limits of 0.1 pg mL-1 and 1.2 pg mL-1, respectively. In addition, this strategy achieved the selective detection of T-2 and ZEN in the spiked corn and oat flour samples. The results are also in good agreement with those obtained using commercial ELISA kits. This developed aptasensor with the characteristics of simple operation and portability has the application potential of establishing sensitive and portable field detection of various mycotoxins.

Cerebello-cerebral resting-state functional connectivity in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder characterized by progressive motor and nonmotor deficits concomitant with degenerative pathophysiological changes within the cerebellum. The cerebellum is topographically organized into cerebello-cerebral circuits that create distinct functional networks regulating movement, cognition, and affect. SCA3-associated motor and nonmotor symptoms are possibly related not only to intracerebellar changes but also to disruption of the connectivity within these cerebello-cerebral circuits. However, to date, no comprehensive investigation of cerebello-cerebral connectivity in SCA3 has been conducted. The present study aimed to identify cerebello-cerebral functional connectivity alterations and associations with downstream clinical phenotypes and upstream topographic markers of cerebellar neurodegeneration in patients with SCA3. This study included 45 patients with SCA3 and 49 healthy controls. Voxel-based morphometry and resting-state functional magnetic resonance imaging (MRI) were performed to characterize the cerebellar atrophy and to examine the cerebello-cerebral functional connectivity patterns. Structural MRI confirmed widespread gray matter atrophy in the motor and cognitive cerebellum of patients with SCA3. We found reduced functional connectivity between the cerebellum and the cerebral cortical networks, including the somatomotor, frontoparietal, and default networks; however, increased connectivity was observed between the cerebellum and the dorsal attention network. These abnormal patterns correlated with the CAG repeat expansion and deficits in global cognition. Our results indicate the contribution of cerebello-cerebral networks to the motor and cognitive impairments in patients with SCA3 and reveal that such alterations occur in association with cerebellar atrophy. These findings add important insights into our understanding of the role of the cerebellum in SCA3.

Macrophages regulate vascular smooth muscle cell function during atherosclerosis progression through IL-1ß/STAT3 signaling.

Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis progression, but the functional changes in VSMCs and the associated cellular crosstalk during atherosclerosis progression remain unknown. Here we show that scRNA-seq analysis of proximal adjacent (PA) and atherosclerotic core (AC) regions of human carotid artery plaques identifies functional alterations in macrophage-like VSMCs, elucidating the main state differences between PA and AC VSMCs. And, IL-1ß mediates macrophage-macrophage-like VSMC crosstalk through regulating key transcription factors involved in macrophage-like VSMCs functional alterations during atherosclerosis progression. In vitro assays reveal VSMCs trans-differentiated into a macrophage-like phenotype and then functional alterations in response to macrophage-derived stimuli. IL-1ß promots the adhesion, inflammation, and apoptosis of macrophage-like VSMCs in a STAT3 dependent manner. The current findings provide interesting insight into the macrophages-macrophage-like VSMC crosstalk, which would drive functional alterations in the latter cell type through IL-1ß/STAT3 axis during atherosclerosis progression.