The value of thromboelastography in evaluating the efficacy of Xueshuantong combined with edaravone in the treatment of acute cerebral infarction.

To explore the value of thromboelastography (TEG) in evaluating the efficacy of Xueshuantong combined with edaravone for the treatment of acute cerebral infarction (ACI). We retrospectively analyzed the clinical data of 96 patients with ACI treated with Xueshuantong combined with edaravone and monitored by TEG. The correlation between the results of TEG examination and treatment outcomes in patients after treatment was analyzed. After treatment, 65 of 96 patients showed good efficacy and 31 had poor efficacy. kinetic time (KT), reaction time (RT), and the percentage of clot lysis at 30 minutes after Ma value (LY30) of patients with good therapeutic effects were significantly higher than those with poor therapeutic effects; However, maximum amplitude (MA) and coagulation index (CI) were significantly lower than those with poor efficacy (P < .05). There was a significant positive correlation between KT, RT, and LY30 and the therapeutic effect of ACI, and a significant negative correlation between the therapeutic effects of MA, CI, and ACI (P < .05). Logistic analysis confirmed that KT, RT, and LY30 were protective factors for the therapeutic effect of ACI; MA and CI were risk factors for the therapeutic effect of ACI (P < .05). TEG has a high value in evaluating the efficacy of Xueshuantong combined with edaravone in the treatment of ACI. It can clarify changes in the coagulation function of patients, thereby guiding clinical follow-up treatment.

Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress.

INTRODUCTION: Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. METHODS: Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety- and depression-like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography-tandem mass spectrometry-based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. RESULTS: Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. CONCLUSION: The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.

Respiratory failure as first presentation of myasthenia gravis: a case report.

Myasthenia gravis (MG) is often complicated by respiratory failure, an exacerbation known as myasthenic crisis. However, most patients with MG develop respiratory symptoms during the late course of the disease. Respiratory failure as an exclusive initial and primary complaint in patients with MG is rare and seldom reported. We herein describe a woman in her late 50s who presented with respiratory failure and was diagnosed with obesity hypoventilation syndrome at a local hospital. Her condition gradually worsened during the next 4 months and became accompanied by dysphagia. After 1 year of medical investigation, she was diagnosed in our hospital. A high level of anti-muscle-specific receptor tyrosine kinase antibody was found in her serum, and stimulation and electromyography results suggested MG. The patient's symptoms were improved by intravenous immunoglobulin and hormone therapy. This case reminds physicians to consider MG when encountering a patient who initially presents with respiratory failure.

Association between high-resolution magnetic resonance vessel wall imaging characteristics and recurrent stroke in patients with intracranial atherosclerotic steno-occlusive disease: A prospective multicenter study.

BACKGROUND: High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) is a promising technique for identifying intracranial vulnerable plaques beyond lumen narrowing. However, the association between HRMR-VWI characteristics and recurrent stroke remains uncertain. AIMS: This study aimed to investigate the association between HRMR-VWI characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS). METHODS: This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (>50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multiparametric magnetic resonance imaging (MRI) including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HRMR-VWI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HRMR-VWI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis. RESULTS: Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12 month ipsilateral recurrence incidence was 4.1% (95% confidence interval (CI): 1.6-6.6%). Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs 6.5%) and eccentric plaque (90.0% vs 48.2%), and lower occurrence of occlusive thrombus (10.0% vs 23.7%). Plaque length (5.69 ± 2.21 mm vs 6.67 ± 4.16 mm), plaque burden (78.40 ± 7.37% vs 78.22 ± 8.32%), degree of stenosis (60.25 ± 18.95% vs 67.50% ± 22.09%) and remodeling index (1.07 ± 0.27 vs 1.03 ± 0.35) on HRMR-VWI did not differ between patients with and without recurrent ipsilateral stroke. In the multivariable Cox regression analysis, IPH (hazard ratio: 6.64, 95% CI: 1.23-35.8, p = 0.028) was significantly associated with recurrent ipsilateral stroke after adjustment.Conclusions:Our results suggest intraplaque hemorrhage (IPH) is significantly associated with recurrent ipsilateral stroke and has potential value in the selection of patients for aggressive treatment strategies. DATA ACCESS STATEMENT: Data from this study are available and can be accessed upon request.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Serum uric acid predicts the development of atherosclerosis in women but not in men: A ten-year cohort study in China.

BACKGROUND AND AIM: Atherosclerosis is becoming a significant health burden. Serum uric acid (SUA) is the final enzymatic product of purine metabolism and can contribute to the development of atherosclerosis. The aim of this study was to explore the possible predictive value of SUA in the development of atherosclerosis in a healthy Chinese population. METHODS AND RESULTS: In this study, a total of 11,222 healthy subjects with no carotid plaque at baseline were enrolled and divided into sex-specific groups, and then the occurrence of carotid plaque during the follow-up time was documented. The association between carotid plaque and SUA levels was examined using Cox proportional-hazards regression models. The mean SUA level was 5.35 ± 1.41 mg/dL. A total of 2,911 individuals (25.94%) developed carotid plaque during the follow-up time, including 1,071 females and 1,840 males. After adjusting for potential confounding factors, the hazard ratio (HR) and 95% confidence interval (95% CI) in women for the occurrence of carotid plaque associated with SUA levels were 1.163 (1.017-1.330), but no significant correlation was found in men, as the HR was 1.050 (0.965-1.143). CONCLUSION: Our results indicate that SUA levels predict the development of carotid plaque independent of traditional risk factors only in women.

Signaling pathways in brain ischemia: Mechanisms and therapeutic implications.

Ischemic stroke occurs when the arteries supplying blood to the brain are narrowed or blocked, inducing damage to brain tissue due to a lack of blood supply. One effective way to reduce brain damage and alleviate symptoms is to reopen blocked blood vessels in a timely manner and reduce neuronal damage. To achieve this, researchers have focused on identifying key cellular signaling pathways that can be targeted with drugs. These pathways include oxidative/nitrosative stress, excitatory amino acids and their receptors, inflammatory signaling molecules, metabolic pathways, ion channels, and other molecular events involved in stroke pathology. However, evidence suggests that solely focusing on protecting neurons may not yield satisfactory clinical results. Instead, researchers should consider the multifactorial and complex mechanisms underlying stroke pathology, including the interactions between different components of the neurovascular unit. Such an approach is more representative of the actual pathological process observed in clinical settings. This review summarizes recent research on the multiple molecular mechanisms and drug targets in ischemic stroke, as well as recent advances in novel therapeutic strategies. Finally, we discuss the challenges and future prospects of new strategies based on the biological characteristics of stroke.

Association of triglyceride-glucose index with major depressive disorder: A cross-sectional study.

The triglyceride-glucose (TyG) index has been proposed as a new marker for insulin resistance, which is associated with a risk of major depressive disorder (MDD). This study aims to explore whether the TyG index is correlated with MDD. In total, 321 patients with MDD and 325 non-MDD patients were included in the study. The presence of MDD was identified by trained clinical psychiatrists using the International Classification of Diseases 10th Revision. The TyG index was calculated as follows: Ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The results revealed that the MDD group presented higher TyG index values than the non-MDD group (8.77 [8.34-9.17] vs 8.62 [8.18-9.01], P < .001). We also found significantly higher morbidity of MDD in the highest TyG index group than in the lower TyG index group (59.9% vs 41.4%, P < .001). Binary logistic regression revealed that TyG was an independent risk factor for MDD (odds ratio [OR] 1.750, 95% confidence interval: 1.284-2.384, P < .001). We further assessed the effect of TyG on depression in sex subgroups. The OR was 3.872 (OR 2.014, 95% confidence interval: 1.282-3.164, P = .002) for the subgroup of men. It is suggested that the TyG index could be closely associated with morbidity in MDD patients; thus, it may be a valuable marker for identifying MDD.

Longitudinal Associations Between Serum Bilirubin Level and Carotid Atherosclerosis Plaque in a Health Screening Population.

This study aimed to determine the relationship between bilirubin levels and carotid atherosclerosis (CAS) in the health screening population. After propensity score matching, this retrospective cohort study included 4360 subjects who underwent health examinations regularly in Hebei General Hospital between January 2010 and December 2019 and had no carotid plaque at baseline. After an average follow-up of 26.76 months, the main endpoint Cox regression analysis of carotid plaques was performed. After adjusting the confounding factors, Cox regression analysis showed that when serum total bilirubin (TBIL) and unconjugated bilirubin (UCB) increased by 1 standard deviation (SD), the risk of carotid plaque decreased by 7.30% (95% confidence interval (CI): 2.80-11.60%) and 15.70% (95% CI: 11.40-19.80%), respectively. When conjugated bilirubin (CB) increased by 1 SD, the risk of carotid plaques increased by 24.3% (95% CI: 19.7-29.0%). TBIL and UCB levels were negatively associated with CAS, and CB levels were positively associated with CAS.

High-throughput Sequencing and Bioinformatics Analysis Reveals the Neurogenesis Key Targets of Curcumin Action in Mouse Brain with MCAO.

BACKGROUND: Experimental studies have shown that curcumin exerts neuroprotective effects in animal models with middle cerebral artery occlusion (MCAO). However, the mechanisms of protective effects of curcumin in MCAO are not fully understood. OBJECTIVE: This study aims to investigate the key neurogenesis targets of curcumin action in mouse brain with MCAO. METHODS: The MCAO models were established in mice. High-throughput sequencing was used to identify differentially expressed mRNA, lncRNA, and circRNA. The reverse expressed mRNAs, lncRNA, and circRNA in sham vs. MCAO and MCAO vs. curcumin were identified. Biological functions were determined by gene ontology (GO) analyses. The protein-protein interaction (PPI) network of neurogenesis-related genes was constructed. Next, neurogenesis-related lncRNA/ circRNA-miRNA-mRNA ceRNA networks were constructed. RESULTS: The total of reverse expressed 1215 mRNAs, 32 lncRNAs, and 43 circRNAs were filtered based on the 2 series (sham vs. MCAO and MCAO vs. Curcumin). The functional enrichment analysis of 1215 reverse expressed mRNAs found that they were involved in neurogenesis, neuron generation, neurogenesis regulation, and others. The PPI network of neurogenesis-related genes consisted of 115 nodes, including 27 down-regulated genes and 36 up-regulated genes. Furthermore, the neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNAs networks were constructed, and 5 lncRNA ceRNA networks and 3 circRNA ceRNA networks were explored. CONCLUSION: Our study revealed that curcumin exerts neuroprotective effects by regulating neurogenesis. The neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNA networks are potential therapeutic targets of curcumin in MCAO. This study provided a theoretical basis for curcumin exerting neuroprotective effects in MCAO.

Development and validation of a nomogram predictive model for cerebral small vessel disease: a comprehensive retrospective analysis.

Background: Cerebral small vessel disease (CSVD) is a significant contributor to stroke, intracerebral hemorrhages, and vascular dementia, particularly in the elderly. Early diagnosis remains challenging. This study aimed to develop and validate a novel nomogram for the early diagnosis of cerebral small vessel disease (CSVD). We focused on integrating cerebrovascular risk factors and blood biochemical markers to identify individuals at high risk of CSVD, thus enabling early intervention. Methods: In a retrospective study conducted at the neurology department of the Affiliated Hospital of Hebei University from January 2020 to June 2022, 587 patients were enrolled. The patients were randomly divided into a training set (70%, n = 412) and a validation set (30%, n = 175). The nomogram was developed using multivariable logistic regression analysis, with variables selected through the Least Absolute Shrinkage and Selection Operator (LASSO) technique. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: Out of 88 analyzed biomarkers, 32 showed significant differences between the CSVD and non-CSVD groups. The LASSO regression identified 12 significant indicators, with nine being independent clinical predictors of CSVD. The AUC-ROC values of the nomogram were 0.849 (95% CI: 0.821-0.894) in the training set and 0.863 (95% CI: 0.810-0.917) in the validation set, indicating excellent discriminative ability. Calibration plots demonstrated good agreement between predicted and observed probabilities in both sets. DCA showed that the nomogram had significant clinical utility. Conclusions: The study successfully developed a nomogram predictive model for CSVD, incorporating nine clinical predictive factors. This model offers a valuable tool for early identification and risk assessment of CSVD, potentially enhancing clinical decision-making and patient outcomes.

An intelligent peptide recognizes and traps Mycobacterium tuberculosis to inhibit macrophage phagocytosis.

Tuberculosis is a major public health concern worldwide, and it is a serious threat to human health for a long period. Macrophage phagocytosis of Mycobacterium tuberculosis (M. tuberculosis) is a crucial process for granuloma formation, which shelters the bacteria and gives them an opportunity for re-activation and spread. Herein, we report an intelligent anti-microbial peptide that can recognize and trap the M. tuberculosis, inhibiting the macrophage phagocytosis process. The peptide (Bis-Pyrene-KLVFF-WHSGTPH, in abbreviation as BFH) first self-assembles into nanoparticles, and then forms nanofibers upon recognizing and binding M. tuberculosis. Subsequently, BFH traps M. tuberculosis by the in situ formed nanofibrous networks and the trapped M. tuberculosis are unable to invade host cells (macrophages). The intelligent anti-microbial peptide can significantly inhibit the phagocytosis of M. tuberculosis by macrophages, thereby providing a favorable theoretical basis for inhibiting the formation of tuberculosis granulomas.

Temperature-dependent development and reproduction of Tarsonemus confusus (Acari: Tarsonemidae): an important pest mite of horticulture.

The tarsonemid mite Tarsonemus confusus Ewing has become an economically important pest in orchards in China. This study investigated the temperature-dependent development and reproduction of T. confusus at 15, 20, 25, 30, 33 and 35 °C. Eggs failed to hatch at 35 °C. When temperature increased from 15 to 30 °C, the developmental rate of eggs, larvae and quiescent larvae and that from egg to adulthood of both sexes significantly increased, and the time period required by females to commence oviposition significantly decreased. The lower temperature threshold (T0) for the development of eggs, larvae and quiescent larvae was between 9.3 and 12.0 °C and both sexes required about 60 degree days (DD) to complete a life cycle. Females were expected to start oviposition at 12.9 °C. The number of eggs laid, the number of female offspring produced and the egg hatch rate were significantly higher at 20, 25 and 30 °C than at 15 and 33 °C. Increasing temperature shortened the longevity of both sexes but increased the intrinsic rate of increase (rm) and finite capacity for increase (λ) with significantly shorter generation time (T) and doubling time (DT) within a temperature range of 15-30 °C. The net reproductive rate (R0) was highest at 25 °C. Results of this study may improve our knowledge of fundamental biology and ecology in genus Tarsonemus in general and in T. confusus in particular. Based on the local climate conditions, the applications of these results in predicting the seasonal population dynamics of T. confusus and timing the pest management are discussed.

Ligustrazine exerts neuroprotective effects via circ_0008146/miR-709/Cx3cr1 axis to inhibit cell apoptosis and inflammation after cerebral ischemia/reperfusion injury.

BACKGROUND: Ligustrazine is a traditional Chinese herbal medicine that has long been used to treat cerebral ischemic disorders. However, the molecular mechanisms of ligustrazine in cerebral ischemia/reperfusion (I/R) damage have not been clear elucidated. The aim of this study was to examine the neuroprotective mechanisms of ligustrazine in cerebral I/R. METHODS: 9 C57BL/6 mice were randomly divided to three groups: Sham group (n = 3), Middle cerebral artery occlusion (MCAO) group (n = 3), and MCAO + Ligustrazine group (n = 3). The neurological deficit score was evaluated, the cerebral infarct volume was measured by triphenylterazolium chloride (TTC) staining. Differentially expressed (DE) messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were analyzed using the R package DEseq2 based on P-value < 0.05 and Log2 |fold change (FC)| ≥ 2 in sham group vs MCAO group and MCAO group vs ligustrazine group by high-throughput sequencing. Function enrichment analysis, the protein-protein interaction (PPI) of neurogenesis related genes were performed. The neurogenesis related competitive endogenous RNA (ceRNA) network was constructed. RESULTS: The expression of circ_0008146 was considerably higher in the MCAO group than the Sham group, and ligustrazine treatment markedly decreased the expression of circ_0008146 in MCAO. Next, the circ_0008146 ceRNA network was established, including circ_0008146-miR-709-Cx3cr1 ceRNA network. Besides, real time quantitative polymerase chain reaction (RT-qPCR) assay identified that miR-709 expression was considerably lower and Cx3cr1 expression was higher in the MCAO group than Sham group, and ligustrazine treatment markedly increased the miR-709 expression and reduced Cx3cr1 expression in MCAO. Further, silencing of circ_0008146 inhibited the concentration of Interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-α) and reduced neuron cell death and up-regulated miR-709 expression and down-regulated Cx3cr1 expression in Lipopolysaccharide (LPS) induced BV-2 cells. Dual-Luciferase reporter gene assay verified that circ_0008146 targeted miR-709. CONCLUSION: Ligustrazine targets circ_0008146/miR-709/Cx3cr1 axis to inhibit cell apoptosis and inflammation after cerebral ischemia/reperfusion injury.

Preparation and performance of composite activated slag-based binder for cemented paste backfill.

The utilization of blast furnace slag (BFS) and fly ash (FA) to replace ordinary portland cement (OPC) has become a hot topic in the preparation of low-cost cemented paste backfill (CPB). This study has prepared a composite activated slag-based binder (CASB) using BFS and FA as the basic raw materials and desulfurization gypsum (DG) and cement clinker (CC) as the activator. The optimum ratio of CASB was determined based on the orthogonal test and the efficacy coefficient method. The hydration products and hydration mechanism of CASB materials were further investigated using XRD, TG, and SEM tests; on this basis, the compressive strength of hardened CASB-CPB under different working conditions and the rheological properties of fresh slurry were investigated, and the cost analysis and environmental effects of CASB were carried out. The results show that the optimum ratio of CASB was 15:12:13:60 for FA: CC: DG: BFS; the hydration mechanism of CASB was the coupled alkali-sulfate activation of CC and DG, and the main hydration products were hydrated calcium silicate gels (C-S-H gels) and ettringite (AFt); increasing the mass concentration (Cw) at a constant cement-aggregate ratio (C/A), which caused a significant improvement in the compressive strength at 7 and 28 d while reduced the flowability of the slurry; CASB considerably reduced the filling cost compared to OPC, and effectively immobilization the heavy metals in the tailings. This paper has developed a cement alternative binder of CASB, which has considerable significance for the comprehensive utilization of solid waste, reduction of filling costs, and improvement of economic and ecological benefits of the mine.

Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats.

Introduction Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain, kidney, and other tissues. This study evaluates the efficacy of a third generation lipophilic Mn porphyrin, MnTnBuOE-2-PyP5+, Mn(III) ortho meso-tetrakis (N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE, BMX-001), in both mouse and rat models of CA. Methods Forty-eight animals were subjected to 8 min of CA and resuscitated subsequently by chest compression and epinephrine infusion. Vehicle or MnBuOE was given immediately after resuscitation followed by daily subcutaneous injections. Body weight, spontaneous activity, neurologic deficits, rotarod performance, and neuronal death were assessed. Kidney tubular injury was assessed in CA mice. Data were collected by the investigators who were blinded to the treatment groups. Results Vehicle mice had a mortality of 20%, which was reduced by 50% by MnBuOE. All CA mice had body weight loss, spontaneous activity decline, neurologic deficits, and decreased rotarod performance that were significantly improved at three days post MnBuOE daily treatment. MnBuOE treatment reduced cortical neuronal death and kidney tubular injury in mice (p < 0.05) but not hippocampus neuronal death (23% MnBuOE vs. 34% vehicle group, p = 0.49). In rats, they had a better body-weight recovery and increased rotarod latency after MnBuOE treatment when compared to vehicle group (p < 0.01 vs. vehicle). MnBuOE-treated rats had a low percentage of hippocampus neuronal death (39% MnBuOE vs. 49% vehicle group, p = 0.21) and less tubular injury (p < 0.05) relative to vehicle group. Conclusions We demonstrated the ability of MnBuOE to improve post-CA survival, as well as functional outcomes in both mice and rats, which jointly account for the improvement not only of brain function but also of the overall wellbeing of the animals. While MnBuOE bears therapeutic potential for treating CA patients, the females and the animals with comorbidities must be further evaluated before advancing toward clinical trials.

The construction of neurogenesis-related ceRNA network of ischemic stroke treated by oxymatrine.

BACKGROUND: Known as a disease associated with high mortality, disability and a significant financial burden, ischemic stroke ranks as one of the three diseases threatening human health. Recent advances in omics technology created opportunities to uncover the mechanism in ischemic stroke occurrence and treatment. In this study, we aimed to construct the competitive endogenous RNA (ceRNA) networks of ischemic stroke treated by oxymatrine intervention. METHOD: The middle cerebral artery occlusion (MCAO) mouse model of ischemic stroke was constructed, and oxymatrine was administered. Then RNA-Sequencing was performed and integrated analysis of mRNAs, lncRNAs and circRNAs was conducted to reveal the pharmacology of oxymatrine. Functional enrichment analysis was performed to explore the underlying mechanism of differentially expressed (DE) mRNAs. The protein-protein interaction (PPI) network of neurogenesis-related genes and long noncoding RNAs (lncRNAs)/circular RNAs (circRNAs) based ceRNA networks were constructed. RESULTS: First, this study revealed the DE-mRNAs, DE-lncRNAs and DE-circRNAs between Oxymatrine treated group and the MCAO group. Then, the common 1231 DE-mRNAs, 32 DE-lncRNAs and 31 DE-circRNAs with opposite trends were identified. The Kyoto Encyclopedia of Genes and Genomes to identify the functional enrichment of 1231 DE-mRNAs were enriched in neurogenesis-related biological processes. Based on neurogenesis-related DE-mRNAs, the PPI network was constructed, and hub genes were identified based on centrality. Finally, both the lncRNA-based and circRNAs-based ceRNA networks were constructed. CONCLUSION: In summary, this study identified novel coding and noncoding ischemic stroke targets of oxymatrine-treated MCAO. Most importantly, we identified lncRNAs and circRNAs candidates as potential oxymatrine targets and constructed the neurogenesis-related ceRNA networks.

A Long-Read Genome Assembly of a Native Mite in China Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae) Reveals Gene Expansion in Toxin-Related Gene Families.

Pyemotes zhonghuajia Yu, Zhang & He (Prostigmata: Pyemotidae), discovered in China, has been demonstrated as a high-efficient natural enemy in controlling many agricultural and forestry pests. This mite injects toxins into the host (eggs, larvae, pupae, and adults), resulting in its paralyzation and then gets nourishment for reproductive development. These toxins have been approved to be mammal-safe, which have the potential to be used as biocontrol pesticides. Toxin proteins have been identified from many insects, especially those from the orders Scorpions and Araneae, some of which are now widely used as efficient biocontrol pesticides. However, toxin proteins in mites are not yet understood. In this study, we assembled the genome of P. zhonghuajia using PacBio technology and then identified toxin-related genes that are likely to be responsible for the paralytic process of P. zhonghuajia. The genome assembly has a size of 71.943 Mb, including 20 contigs with a N50 length of 21.248 Mb and a BUSCO completeness ratio of 90.6% (n = 1367). These contigs were subsequently assigned to three chromosomes. There were 11,183 protein coding genes annotated, which were assessed with 91.2% BUSCO completeness (n = 1066). Neurotoxin and dermonecrotic toxin gene families were significantly expanded within the genus of Pyemotes and they also formed several gene clusters on the chromosomes. Most of the genes from these two families and all of the three agatoxin genes were shown with higher expression in the one-day-old mites compared to the seven-day-pregnant mites, supporting that the one-day-old mites cause paralyzation and even death of the host. The identification of these toxin proteins may provide insights into how to improve the parasitism efficiency of this mite, and the purification of these proteins may be used to develop new biological pesticides.

Negative pressure promotes macrophage M1 polarization after Mycobacterium tuberculosis infection via the lncRNA XIST/microRNA-125b-5p/A20/NF-κB axis.

Experiments have demonstrated the regulation of long noncoding RNA (lncRNA) in tuberculosis (TB), and negative pressure treatment has been associated with the alleviation of TB. Here, we investigated the interaction of negative pressure and the lncRNA X-inactive specific transcript (XIST) in modulating Mycobacterium tuberculosis (MTB) infection. Initially, we established an in vitro cell model of MTB infection and an in vivo mouse model of MTB infection, followed by treatment with negative pressure. Then, we examined the expression of XIST, followed by analysis of the downstream miRNA of XIST. XIST was overexpressed or underexpressed through cell transfection to examine its effects on macrophage polarization via the miR-125b-5p/A2 axis. The MTB models were characterized by upregulated XIST and downregulated miR-125b-5p. XIST bound to miR-125b-5p, leading to its downregulation, and thus causing higher MTB survival in an ESAT-6-dependent manner. Additionally, negative pressure treatment decreased MTB-driven XIST expression through downregulation of A20 (an NF-κB repressor) via miR-125b-5 expression, promoting the M1 polarization program in macrophages through activation of the NF-κB pathway. In summary, negative pressure treatment after MTB infection can promote the polarization of macrophages to the proinflammatory M1 phenotype by regulating the XIST/miR-125b-5p/A20/NF-κB axis.

Dl-3-n-Butylphthalide Improves Neuroinflammation in Mice with Repeated Cerebral Ischemia-Reperfusion Injury through the Nrf2-Mediated Antioxidant Response and TLR4/MyD88/NF-κB Signaling Pathway.

Increasing evidence shows that oxidative stress and neuroinflammation play a crucial role in the pathology of vascular dementia (VD). Previously, we have found that Dl-3-n-butylphthalide (NBP) has antioxidant and anti-inflammatory activities in VD, whereas little is known about its mechanism. Therefore, the objective of our study was to explore the contribution of nuclear factor erythroid-2 related factor 2 (Nrf2) to NBP and its effects on anti-inflammatory activity in a mouse model of VD. Our studies revealed that NBP could effectively mitigate cognitive deficits, neuron cell loss, and apoptosis in mice subjected to repeated cerebral ischemia-reperfusion (RCIR). Additionally, NBP promoted both the expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in hippocampus tissue. NBP exhibited antioxidant activity by enhancing Nrf2 nuclear accumulation, increasing HO-1 and NQO1 expression, enhancing SOD activity, and inhibiting RCIR-induced MDA and 8-iso PGF2α generation in the hippocampus. NBP also significantly inhibited TLR4/MyD88/NF-κB signaling and suppressed microglial proliferation and the production of proinflammatory mediators in RCIR mice. Importantly, the antioxidant, antineuroinflammatory, and neuroprotective effects of NBP above were abolished by Nrf2 knockout. Collectively, these results indicated the effects of NBP on neuroinflammation were strongly associated with the Nrf2 pathway. Modulation of TLR4/MyD88/NF-κB pathway by Nrf2 is involved in the neuroprotective effect of NBP against VD induced by RCIR injury. With antioxidant and anti-neuroinflammatory properties, NBP could be a promising drug candidate for the prevention and/or treatment of VD and other neuroinflammatory disorders.