Biosensor Based on ZIF-67-HRP and MWCNTs Nanocomposite Modified Glass Carbon Electrode for the Detection of Luteolin in Vegetables.

Luteolin has various pharmacological properties, including anti-inflammatory, antioxidant, and antitumor characteristics. Due to its potential value in drugs and functional foods, it is important to develop an efficient method for detecting luteolin. In this work, the poor selectivity of existing luteolin nonenzymatic sensors was solved by translating the enzyme-catalyzed reaction from bulk solution to the surface of a horseradish peroxidase (HRP) modified electrode through an electrocatalytic oxidation process. Here, we modified the surface of a glassy carbon electrode (GCE) with metal-organic frameworks (MOFs; ZIF-67 here, abbreviated as ZIF), functional nanomaterials, and HRP and finally covered it with Nafion (NF). In this case, luteolin acts as a hydrogen donor, and the electrode acts as a hydrogen acceptor; the oxidation reaction occurs on the electrode surface. The use of ZIF-67 ensured the conformational stability of HRP to ensure the selectivity and anti-interference property, and SDS-dispersed multiwalled carbon nanotubes (MWCNTs) enhanced the electrode conductivity. The use of NF avoids shedding of the electrode material during the testing process. A UV-vis spectrophotometer was used to study the selectivity of luteolin by HRP and the compatibility between HRP and ZIF. The materials were characterized and analyzed by scanning electron microscopy and transmission electron microscopy. Due to the synergistic effect of these nanomaterials, the linear range of NF/ZIF-HRP/MWCNTs-SDS/GCE was 1.0 × 10-2 to 6.0 µM, with detection limits of 25.3 nM (S/N = 3). The biosensor showed long-term stability and reproducibility, with a relative standard deviation of 4.2% for the peak current (n = 5). Finally, the biosensor was successfully used to detect luteolin in carrots, celery, and cauliflower.

Sigma-1 receptor recruits LC3 mRNA to ER-associated omegasomes to promote localized LC3 translation enabling functional autophagy.

Autophagosome formation initiated on the endoplasmic reticulum (ER)-associated omegasome requires LC3. Translational regulation of LC3 biosynthesis is unexplored. Here we demonstrate that LC3 mRNA is recruited to omegasomes by directly binding to the ER transmembrane Sigma-1 receptor (S1R). Cell-based and in vitro reconstitution experiments show that S1R interacts with the 3' UTR of LC3 mRNA and ribosomes to promote LC3 translation. Strikingly, the 3' UTR of LC3 is also required for LC3 protein lipidation, thereby linking the mRNA-3' UTR to LC3 function. An autophagy-defective S1R mutant responsible for amyotrophic lateral sclerosis cannot bind LC3 mRNA or induce LC3 translation. We propose a model wherein S1R de-represses LC3 mRNA via its 3' UTR at the ER, enabling LC3 biosynthesis and lipidation. Because several other LC3-related proteins use the same mechanism, our data reveal a conserved pathway for localized translation essential for autophagosome biogenesis with insights illuminating the molecular basis of a neurodegenerative disease.

Whole-genome sequence of Sclerotium delphinii, a pathogenic fungus of Dendrobium officinale southern blight.

Dendrobium officinale is a rare and precious medicinal plant. Southern blight is a destructive disease in the artificial cultivation of D. officinale, and one of its pathogens is Sclerotium delphinii. S. delphinii is a phytopathogenic fungus with a wide host range with extremely strong pathogenicity. In this study, S. delphinii was isolated from D. officinale with southern blight. Subsequently, this specific strain underwent thorough whole-genome sequencing using the PacBio Sequel II platform, which employed single-molecule real-time (SMRT) technology. Comprehensive annotations were obtained through functional annotation of protein sequences using various publicly available databases. The genome of S. delphinii measures 73.66 Mb, with an N90 contig size of 2,707,110 bp, and it contains 18,506 putative predictive genes. This study represents the first report on the genome size assembly and annotation of S. delphinii, making it the initial species within the Sclerotium genus to undergo whole-genome sequencing, which can provide solid data and a theoretical basis for further research on the pathogenesis, omics of S. delphinii.

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

Initial study and phylogenetic analysis of hard ticks (Acari: Ixodidae) in Nantong, China along the route of avian migration.

The growing concern about migratory birds potentially spreading ticks due to global warming has become a significant issue. The city of Nantong in this study is situated along the East Asia-Australasian Flyway (EAAF), with numerous wetlands serving as roosting sites for migratory birds. We conducted an investigation of hard ticks and determined the phylogenetic characteristics of tick species in this city. We utilized three different genes for our study: the mitochondrial cytochrome oxidase subunit 1 (COX1) gene, the second internal transcribed spacer (ITS2), and the mitochondrial small subunit rRNA (12 S rRNA) gene. The predominant tick species were Haemaphysalis flava (H. flava) and Haemaphysalis longicornis (H. longicornis). Additionally, specimens of Haemaphysalis campanulata (H. campanulata) and Rhipicephalus sanguineus (R. sanguineus) were collected. The H. flava specimens in this study showed a close genetic relationship with those from inland provinces of China, as well as South Korea and Japan. Furthermore, samples of H. longicornis exhibited a close genetic relationship with those from South Korea, Japan, Australia, and the USA, as well as specific provinces in China. Furthermore, R. sanguineus specimens captured in Nantong showed genetic similarities with specimens from Egypt, Nigeria, and Argentina.

Conditional Survival of Patients with Limited-Stage Small Cell Lung Cancer After Surgery: A National Real-World Cohort Study.

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.

EtOS2K as a C1 Source: Solvent- and Temperature-Controlled Selective Synthesis of Quinoline-2-thione and Quinoline-2-one Derivatives.

Herein, we disclosed a highly chemoselective synthesis of quinoline-2-one and quinoline-2-thione derivatives using EtOS2K as the C1 source. Quinoline-2-one derivatives were synthesized selectively with NaCl as a catalyst in the solvent DMSO/H2O, while quinoline-2-thione derivatives were produced without the need for any catalyst in an environmentally friendly solvent EtOH/H2O. The reaction conditions were mild and had good functional group tolerance.

CCDC88C variants are associated with focal epilepsy and genotype-phenotype correlation.

CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.

Prolonged myelin deficits contribute to neuron loss and functional impairments after ischaemic stroke.

Ischaemic stroke causes neuron loss and long-term functional deficits. Unfortunately, effective approaches to preserving neurons and promoting functional recovery remain unavailable. Oligodendrocytes, the myelinating cells in the CNS, are susceptible to oxygen and nutrition deprivation and undergo degeneration after ischaemic stroke. Technically, new oligodendrocytes and myelin can be generated by the differentiation of oligodendrocyte precursor cells (OPCs). However, myelin dynamics and their functional significance after ischaemic stroke remain poorly understood. Here, we report numerous denuded axons accompanied by decreased neuron density in sections from ischaemic stroke lesions in human brain, suggesting that neuron loss correlates with myelin deficits in these lesions. To investigate the longitudinal changes in myelin dynamics after stroke, we labelled and traced pre-existing and newly-formed myelin, respectively, using cell-specific genetic approaches. Our results indicated massive oligodendrocyte death and myelin loss 2 weeks after stroke in the transient middle cerebral artery occlusion (tMCAO) mouse model. In contrast, myelin regeneration remained insufficient 4 and 8 weeks post-stroke. Notably, neuronal loss and functional impairments worsened in aged brains, and new myelin generation was diminished. To analyse the causal relationship between remyelination and neuron survival, we manipulated myelinogenesis by conditional deletion of Olig2 (a positive regulator) or muscarinic receptor 1 (M1R, a negative regulator) in OPCs. Deleting Olig2 inhibited remyelination, reducing neuron survival and functional recovery after tMCAO. Conversely, enhancing remyelination by M1R conditional knockout or treatment with the pro-myelination drug clemastine after tMCAO preserved white matter integrity and neuronal survival, accelerating functional recovery. Together, our findings demonstrate that enhancing myelinogenesis is a promising strategy to preserve neurons and promote functional recovery after ischaemic stroke.

Construction and validation of a risk-scoring model to predict lymph node metastasis in T1b-T2 esophageal cancer.

BACKGROUND: Lymph node status is an important factor in determining preoperative treatment strategies for stage T1b-T2 esophageal cancer (EC). Thus, the aim of this study was to investigate the risk factors for lymph node metastasis (LNM) in T1b-T2 EC and to establish and validate a risk-scoring model to guide the selection of optimal treatment options. METHODS: Patients who underwent upfront surgery for pT1b-T2 EC between January 2016 and December 2022 were analyzed. On the basis of the independent risk factors determined by multivariate logistic regression analysis, a risk-scoring model for the prediction of LNM was constructed and then validated. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminant ability of the model. RESULTS: The incidence of LNM was 33.5% (214/638) in our cohort, 33.4% (169/506) in the primary cohort and 34.1% (45/132) in the validation cohort. Multivariate analysis confirmed that primary site, tumor grade, tumor size, depth, and lymphovascular invasion were independent risk factors for LNM (all P < 0.05), and patients were grouped based on these factors. A 7-point risk-scoring model based on these variables had good predictive accuracy in both the primary cohort (AUC, 0.749; 95% confidence interval 0.709-0.786) and the validation cohort (AUC, 0.738; 95% confidence interval 0.655-0.811). CONCLUSION: A novel risk-scoring model for lymph node metastasis was established to guide the optimal treatment of patients with T1b-T2 EC.

[Plastic and reconstruction surgery for non-healing wound after posterior spinal surgery].

OBJECTIVE: To investigate the clinical significance of different plastic surgeries in the treatment of poor healing wound after posterior spinal internal fixation. METHODS: In this study, 16 patients with poor incision healing after posterior spinal internal fixation were retrospectively included, and dif-ferent plastic surgery treatment plans were determined according to the wound characteristics and defect condition. The measures included debridement, vacuum sealing drainage (VSD), and different tissue flaps according to the location and extent of the defect. RESULTS: A total of 16 patients meeting the criteria were included, of whom 3 were treated with debridement combined with VSD and wound suture directly, 6 were treated with debridement combined with Z-flap for wound repair, 1 was treated with bilateral sacrospinous muscle flap for dural defect repair combined with Z-flap for skin wound repair, 1 was treated with lectus dorsi flap for wound repair, 3 were treated with the fourth lumbar artery perforator flap for wound repair. The wound was repaired with local rotating flap in 1 case and gluteus maximus musculocutaneous flap in 1 case. Among the 16 patients, 7 cases were positive for wound culture, including 3 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa, 1 case of Staphylococcus epidermidis, 1 case of Escherichia coli, 1 case of Klebsiella pneumoniae, and the other 9 cases were negative. After surgery, there were 7 patients with different degrees of poor wound healing, including 3 patients undergoing dressing change, 2 patients undergoing secondary debridement and suture, 1 patient undergoing free scalp skin graft, and 1 patient undergoing local effusion suction treatment. All the above 7 patients were discharged from hospital after improvement, and the remaining 9 patients had good first-stage wound hea-ling after surgery. None of the 16 patients underwent internal fixation. CONCLUSION: Multiple factors could lead to poor wound healing after posterior spinal internal fixation. Early intervention, thorough debridement, removal of necrotic/infected tissue, and selection of suitable skin flap for effective wound fil-ling and covering were important means to ensure wound healing after spinal surgery and reduce removal of internal fixation.

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

BACKGROUND: Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. METHODS: A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. RESULTS: The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. CONCLUSION: This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

The atlastin ER morphogenic proteins promote formation of a membrane penetration site during non-enveloped virus entry.

During entry, non-enveloped viruses penetrate a host membrane to cause infection, although how this is accomplished remains enigmatic. Polyomaviruses (PyVs) are non-enveloped DNA viruses that penetrate the endoplasmic reticulum (ER) membrane to reach the cytosol en route to the nucleus for infection. To penetrate the ER membrane, the prototype PyV simian virus 40 (SV40) induces formation of ER-escape sites, called foci, composed of repeating units of multi-tubular ER junctions where the virus is thought to exit. How SV40 triggers formation of the ER-foci harboring these multi-tubular ER junctions is unclear. Here, we show that the ER morphogenic atlastin 2 (ATL2) and ATL3 membrane proteins play critical roles in SV40 infection. Mechanistically, ATL3 mobilizes to the ER-foci where it deploys its GTPase-dependent membrane fusion activity to promote formation of multi-tubular ER junctions within the ER-foci. ATL3 also engages an SV40-containing membrane penetration complex. By contrast, ATL2 does not reorganize to the ER-foci. Instead, it supports the reticular ER morphology critical for the integrity of the ATL3-dependent membrane complex. Our findings illuminate how two host factors play distinct roles in the formation of an essential membrane penetration site for a non-enveloped virus. IMPORTANCE Membrane penetration by non-enveloped viruses, a critical infection step, remains enigmatic. The non-enveloped PyV simian virus 40 (SV40) penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol en route for infection. During ER-to-cytosol membrane penetration, SV40 triggers formation of ER-associated structures (called ER-foci) that function as the membrane penetration sites. Here, we discover a role of the ATL ER membrane proteins-known to shape the ER morphology-during SV40-induced ER-foci formation. These findings illuminate how a non-enveloped virus hijacks host components to construct a membrane penetration structure.

Ozone exposure associates with sperm quality indicators: Sperm telomere length as a potential mediating factor.

Evidence linking O3 exposure and human semen quality is limited and conflicting and the mechanism underlying the association remains unclear. Therefore, we investigated the associations between ambient O3 exposure and sperm quality parameters and explored the mediating role of sperm mitochondrial DNA copy number (mtDNAcn) and sperm telomere length (STL) among 1068 potential sperm donors who provided 5002 repeated semen samples over approximately 90 days. We found that every 10 µg/m3 increase in O3 exposure was associated with a decrease in STL, sperm concentration, total count, total motile sperm number, and semen volume. However, O3 exposure was associated with increased total motility and progressive motility. The association for sperm quality parameters was stronger when exposure was measured at spermatogenesis stages I and II. For STL, the strongest association was observed when exposure was measured at spermatogenesis stage II. Additionally, we found that approximately 9% and 8% of the association between O3 exposure and sperm concentration and count was mediated by STL, respectively. In summary, our findings suggest that O3 pollution may affect sperm telomere length, eventually leading to reduced semen quality.

Advances in genetic etiology, diagnosis and treatment of developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathy (DEE) is a clinically and genetically heterogeneous group of age-dependent neurological disorders characterized by onset of refractory seizures in infancy or early childhood and affected individuals with delayed or regressive psychomotor development. With the development of next-generation sequencing technology, especially the application of whole-exome sequencing technology, more and more genes have been found to be associated with DEE.These discoveries provide a basis for the detection of pathogenic genes for DEE in clinical work, and also help to deepen our understanding of the pathogenesis of DEE. In this review, we provide a comprehensive review of the genetic etiology, diagnosis and treatment of DEE, in order to assist clinicians in early identification of relevant gene mutations, thereby expediting disease diagnosis and timely implementation of optimal treatment.

Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.

A comprehensive study on flocculation of anionic dyes using the bioflocculant produced by Bacillus thuringiensis: Kinetics, affecting factors, and perspectives.

Bioflocculants have received more and more attention as alternatives to chemical flocculants because of their innocuousness, environmental friendliness, and high effectiveness. This study aims to investigate various factors that influence the performance of the novel bioflocculant produced by Bacillus thuringiensis (BF-TWB10) and analyze its adsorption kinetics to optimize its flocculation performance for real applications. The best-fit kinetic model was pseudo-second order with R2 = 0.999. The effects of pretreatment temperature, pH, and the presence of cations on flocculation were assessed. Further investigations of flocculation, including zeta potential analysis and particle size analysis, were also conducted. Thermal pretreatment of BF-TWB10 or the presence of divalent cations could stimulate the decolorization efficiency of the bioflocculant. BF-TWB10 manifested outstanding dye removal performances with over 90% for all tested anionic dyes at pH 2 and 3. Its decolorization efficiency on anionic dyes decreased with the increase of pH values. Zeta potential analysis revealed that the electrostatic repulsion between anionic dyes decreased after the addition of BT-TWB10 and further diminished by adjusting the reaction mixture to pH 2 before flocculation, suggesting the occurrence of adsorption bridging and charge neutralization. These findings proposed that BF-TWB10 might be a promising bioflocculant for the removal of dyes in textile wastewater. PRACTITIONER POINTS: Bioflocculant BF-TWB10 shows outstanding performance in flocculation. Adsorption process follows pseudo-second-order kinetic model. Flocculation process is pH-responsive. High-temperature pretreatment or divalent cations enhance its flocculation performance. The analyses suggest the occurrence of charge neutralization and adsorption bridging.

Glucose Biosensor Based on Glucose Oxidase Immobilized on BSA Cross-Linked Nanocomposite Modified Glassy Carbon Electrode.

Glucose sensors based blood glucose detection are of great significance for the diagnosis and treatment of diabetes because diabetes has aroused wide concern in the world. In this study, bovine serum albumin (BSA) was used to cross-link glucose oxidase (GOD) on a glassy carbon electrode (GCE) modified by a composite of hydroxy fullerene (HFs) and multi-walled carbon nanotubes (MWCNTs) and protected with a glutaraldehyde (GLA)/Nafion (NF) composite membrane to prepare a novel glucose biosensor. The modified materials were analyzed by UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and cyclic voltammetry (CV). The prepared MWCNTs-HFs composite has excellent conductivity, the addition of BSA regulates MWCNTs-HFs hydrophobicity and biocompatibility, and better immobilizes GOD on MWCNTs-HFs. MWCNTs-BSA-HFs plays a synergistic role in the electrochemical response to glucose. The biosensor shows high sensitivity (167 µA·mM-1·cm-2), wide calibration range (0.01-3.5 mM), and low detection limit (17 µM). The apparent Michaelis-Menten constant Kmapp is 119 µM. Additionally, the proposed biosensor has good selectivity and excellent storage stability (120 days). The practicability of the biosensor was evaluated in real plasma samples, and the recovery rate was satisfactory.

CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice.

BACKGROUND: Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear. METHODS: Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids. RESULTS: Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway. CONCLUSIONS: CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH.

Knockout of transient receptor potential ankyrin 1 (TRPA1) modulates the glial phenotype and alleviates perihematomal neuroinflammation after intracerebral hemorrhage in mice via MAPK/NF-κB signaling.

The objective is to explore the role of astrocytic transient receptor potential ankyrin 1 (TRPA1) in glial phenotype transformation in neuroinflammation after intracerebral hemorrhage (ICH). Wild-type astrocytes and TRPA1-/- astrocytes were subjected to 6-h hemin treatment, and the calcium ions and transcriptome sequencing were assessed. A mouse autologous blood injection ICH model was established to evaluate the proliferation and phenotypes of astrocytes and microglia around the hematoma. The neuroinflammation and behavioral performance of wild-type ICH mice and TRPA1-/- ICH mice were assessed. Knockout of astrocytic TRPA1 decreased calcium ions of astrocytes after hemin treatment in-vitro, and microglial and astrocytes around the hematoma proliferated after the ICH model. Furthermore, RNA-sequencing (RNA-seq), immunofluorescence, and Western blotting results showed that the activated astrocytes transformed into the A2 phenotype in TRPA1-/- ICH mice. The 'ameboid' microglia were observed around the hematoma in TRPA1-/- ICH mice. The proliferation of A2 astrocytes and 'ameboid' microglia ameliorated the neuroinflammation after ICH. The inflammatory response was reduced by inhibiting the mitogen-activated protein kinase/nuclear factor kappa-B signaling pathway, and neurologic deficits were improved in TRPA1-/- ICH mice compared with wild-type ICH mice. This research suggests that astrocytic TRPA1 is a new therapeutic target to rescue neuroinflammation by modulating the glial phenotype after ICH.