Unveiling the role of HIST2H2AC in stroke through single-cell and transcriptome analysis.

Stroke is a leading cause of death and disability, and genetic risk factors play a significant role in its development. Unfortunately, effective therapies for stroke are currently limited. Early detection and diagnosis are critical for improving outcomes and developing new treatment strategies. In this study, we aimed to identify potential biomarkers and effective prevention and treatment strategies for stroke by conducting transcriptome and single-cell analyses. Our analysis included screening for biomarkers, functional enrichment analysis, immune infiltration, cell-cell communication, and single-cell metabolism. Through differential expression analysis, enrichment analysis, and protein-protein interaction (PPI) network construction, we identified HIST2H2AC as a potential biomarker for stroke. Our study also highlighted the diagnostic role of HIST2H2AC in stroke, its relationship with immune cells in the stroke environment, and our improved understanding of metabolic pathways after stroke. Overall, our research provided important insights into the pathogenesis of stroke, including potential biomarkers and treatment strategies that can be explored further to improve outcomes for stroke patients.

Dynamic changes in and correlations between microbial communities and physicochemical properties during the composting of cattle manure with Penicillium oxalicum.

BACKGROUND: Penicillium oxalicum is an important fungal agent in the composting of cattle manure, but the changes that occur in the microbial community, physicochemical factors, and potential functions of microorganisms at different time points are still unclear. To this end, the dynamic changes occurring in the microbial community and physicochemical factors and their correlations during the composting of cattle manure with Penicillium oxalicum were analysed. RESULTS: The results showed that the main phyla observed throughout the study period were Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, Halanaerobiaeota, Apicomplexa and Ascomycota. Linear discriminant analysis effect size (LEfSe) illustrated that Chitinophagales and Eurotiomycetes were biomarker species of bacteria and eukaryote in samples from Days 40 and 35, respectively. Bacterial community composition was significantly correlated with temperature and pH, and eukaryotic microorganism community composition was significantly correlated with moisture content and NH4+-N according to redundancy analysis (RDA). The diversity of the microbial communities changed significantly, especially that of the main pathogenic microorganisms, which showed a decreasing trend or even disappeared after composting. CONCLUSIONS: In conclusion, a combination of high-throughput sequencing and physicochemical analysis was used to identify the drivers of microbial community succession and the composition of functional microbiota during cattle manure composting with Penicillium oxalicum. The results offer a theoretical framework for explaining microecological assembly during cattle manure composting with Penicillium oxalicum.

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways.

Hexafluoropropylene oxide dimer acid (HFPO-DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 µg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 µM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1ß, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.

Exploring Mycoplasma ovipneumoniae NXNK2203 infection in sheep: insights from histopathology and whole genome sequencing.

BACKGROUND: Mycoplasma ovipneumoniae (M. ovipneumoniae) is a significant pathogen causing respiratory infections in goats and sheep. This study focuses on investigating vulnerability of Hu sheep to M. ovipneumoniae infection in the context of late spring's cold weather conditions through detailed autopsy of a severely affected Hu sheep and whole genome sequencing of M. ovipneumoniae. RESULTS: The autopsy findings of the deceased sheep revealed severe pulmonary damage with concentrated tracheal and lung lesions. Histopathological analysis showed tissue degeneration, mucus accumulation, alveolar septum thickening, and cellular necrosis. Immunohistochemistry analysis indicated that M. ovipneumoniae was more in the bronchi compared to the trachea. Genome analysis of M. ovipneumoniae identified a 1,014,835 bp with 686 coding sequences, 3 rRNAs, 30 tRNAs, 6 CRISPRs, 11 genomic islands, 4 prophages, 73 virulence factors, and 20 secreted proteins. CONCLUSION: This study investigates the vulnerability of Hu sheep to M. ovipneumoniae infection during late spring's cold weather conditions. Autopsy findings showed severe pulmonary injury in affected sheep, and whole genome sequencing identified genetic elements associated with pathogenicity and virulence factors of M. ovipneumoniae.

Radiological characteristics and injury mechanism of Logsplitter injury: a descriptive and retrospective study.

BACKGROUND: Logsplitter Injury is a type of high-energy ankle fracture dislocation. The mechanism of injury has not been described in detail. A detailed understanding of the radiological features and pathological changes can further guide treatment. METHODS: Between April 2009 and December 2018, a retrospective analysis was conducted on 62 patients with Logsplitter injury. The study analysed the characteristics of fibular injury, tibial injury, syndesmosis injury, medial injury and lateral ligament injury on preoperative X-ray and CT scans. The incidence of the different injury types was summarised. The correlation between Logsplitter injuries and the mechanisms causing them were analysed using the Lauge-Hansen classification of ankle fractures. RESULTS: The study provides data on the types of fractures observed. Of the total fractures, 98.4% were open fractures. The fibula injuries were classified as no fracture (1.6%), transverse or short oblique fractures (61.3%), butterfly fragments (25.8%), and comminuted fractures (11.3%). The tibial injuries included compression of lateral articular surfaces (38.7%) and posterior compressions (6.5%). Medial injuries, including medial malleolar fractures, accounted for 87.1%, and deltoid ligament rupture accounted for 12.9%. The study found that injuries to the syndesmosis consisted of simple ligament ruptures (11.3%), Tillaux fractures (8.1%), Volkmann fractures (43.5%), and Tillaux and Volkmann fractures (37.1%). In 12.9% of cases, there was a complete rupture of the lateral collateral ligament. Based on the Lauge-Hansen classification, 87.1% of injuries were pronation-abduction injuries, while 8.1% were pronation and external rotation injuries, and 1.6% were supination external rotation injuries. Furthermore, 3.2% of cases could not be classified. CONCLUSION: The pathoanatomic characteristics of Logsplitter injury are diverse, with some cases accompanied by collateral ligament injury. It is important to note that these evaluations are objective and based on current results. The most common injury mechanism is vertical violence combined with abduction, although in some cases, it may be a vertical combined external-rotation injury. LEVEL OF EVIDENCE: (4) case series. TRIAL REGISTRATION: This study has been approved by the ethical research committee of the Honghui Hospital of Xi'an Jiaotong University, under the code: 202,003,002.

Metabolomics-based study of the effect of dietary N-carbamoylglutamic acid addition to heifers in late pregnancy on newborn calves.

It has been demonstrated that supplementing late-gestation cow diets with NCG (N-carbamoylglutamic acid) increases the serum protein level, boosts immunological function, and increases the birth weight of the calves. However, the underlying mechanism remains unclear. In this experiment, 30 late-gestation Angus heifers almost at same conditions were chosen for this experiment. They were randomly divided into two groups of 15 cows each. A basal diet was provided to the control group, and 30 g/(d-head) of NCG was added to the basal diet of the test group (NCG group). Blood samples were collected from the jugular vein after birth and before the end (when the calves were 90 days old) of the experiment for plasma metabolomics analysis. The metabolomics analysis identified 53 metabolites between the NCG group and control group, with 40 significantly up-regulated and 13 significantly down-regulated. Among them, 33 lipids and lipid-like molecules made up 57.89% of all the metabolites that were found. Thirty-three metabolic pathways enriched by metabolites showed p.adjust <0.05, among which glycerophospholipid and sphingolipid metabolism pathways were the most abundant. In conclusion, the addition of NCG in late-gestation cows appears to primarily affect calf growth and development through the regulation of phospholipid metabolism, which plays a role in nerve conduction, brain activity, and cell metabolism and function. This study provides valuable insights into how nutritional supplementation by late-gestation cows might improve the growth and development of newborn calves.

Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update.

Covalent inhibitors and other types of covalent modalities have seen a revival in the past two decades, with a variety of new targeted covalent drugs having been approved in recent years. A key feature of such molecules is an intrinsically reactive group, typically a weak electrophile, which enables the irreversible or reversible formation of a covalent bond with a specific amino acid of the target protein. This reactive group, often called the "warhead", is a critical determinant of the ligand's activity, selectivity, and general biological properties. In 2019, we summarized emerging and re-emerging warhead chemistries to target cysteine and other amino acids (Gehringer, M.; Laufer, S. A. J. Med. Chem. 2019, 62, 5673-5724; DOI: 10.1021/acs.jmedchem.8b01153). Since then, the field has rapidly evolved. Here we discuss the progress on covalent warheads made since our last Perspective and their application in medicinal chemistry and chemical biology.

Oxidative stress in the alveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia.

OBJECTIVE: To investigate the correlation between oxidative stress in the bronchoalveolar lavage fluid (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and the clinical characteristics of severe MPP (SMPP) and refractory MPP (RMPP). METHODS: Clinical and BALF-related data were collected from 83 patients with MPP, of which 29 had SMPP and 54 had general MPP (GMPP); 37 patients were in the RMPP group and 46 in the non-RMPP group. The levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPP) as well as the activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in BALF were detected. Logistic regression analyses were performed on MDA, AOPP, SOD, GSH-PX, gender, heat peak, neutrophil percentage, C-reactive protein, lactate dehydrogenase, d-dimer, lung consolidation, sputum embolus, and pleural effusion. RESULTS: The levels of MDA and AOPP in the BALF of the MPP group were significantly higher than those in the control group (p < .05), whereas SOD and GSH-PX levels were lower than those in the control group (p < .05). The BALF AOPP levels in the RMPP group were higher than those in the non-RMPP group, and the SOD and GSH-PX levels in the BALF were lower than those in the non-RMPP group; the difference was statistically significant (p < .05). The levels of MDA and AOPP in the BALF of children in the SMPP group were higher than those in the GMPP group, and the levels of SOD and GSH-PX were lower than those in the GMPP group, with statistically significant differences (p < .05). The C-index of the logistic regression model was 0.960 (95% confidence interval 0.958-0.963), which indicates that the model has good predictive ability. CONCLUSION: Advanced oxidation protein products may be a marker for predicting the conditions of SMPP and RMPP, and the prediction model can assess the risk of progression in children to RMPP, which is conducive to clinical diagnosis and treatment.

[Clinical comparative study on resection and non-resection of the fifth metatarsal to rheumatoid forefoot deformity].

OBJECTIVE: To explore clinical effect of the fifth metatarsal head excision and non-excision in rheumatoid arthritis (RA) forefoot deformity reconstruction. METHODS: Retrospective analysis was performed on 50 patients (76 feet) with moderate to severe forefoot deformity caused by RA treated from May 2015 to January 2019. According to degeneration of the fifth metatarsophalangeal joint,the fifth metatarsal head was retained or excised by wind-like forefoot reconstruction,and divided into the fifth metatarsal head preservation group (preservation group) and the fifth metatarsal head resection group (resection group). Twenty-four female patients in preservation group,aged from 47 to 81 years old with an average of (60.37±8.60) years old;the course of disease ranged from 13 to 22 years with an average of (19.00±3.06) years;body mass index (BMI) ranged from 21 to 28 kg·m-2 with an average of (23.53±2.47) kg·m-2;six patients (6 feet) with moderate hallux valgus deformity and 18 patients (30 feet) with severe hallux valgus deformity;treated with the first metatarsophalangeal joint fusion combined with the second th the fourth metatarsophalangeal joint arthroplasty and the fifth metatarsophalangeal joint cleanup. Twenty-six female patients in resection group were female,aged from 30 to 80 years old with an average of (58.53±13.70) years old;the course of disease ranged from 8 to 25 years with an average of (17.94±3.92) years;BMI raged from 20 to 28 kg·m-2 with an average of (24.60±2.03) kg·m-2;4 patients (4 feet) with moderate bunion valgus deformity and 22 patients (36 feet) with severe bunion valgus deformity;treated by the first metatarsophalangeal joint fusion combined with the second th the fifth metatarsophalangeal joint resection of the metatarsophalangeal head. Operation time and postoperative complications between two groups were observed,hallux valgus angle (HVA),intermetatarsal angles between the first and the second metatarsals (IMAFS),intermetatarsal angles between the first and fifth metatarsals (IMAFF),Japanese Society for Surgery of Foot (JSSF) score before surgery and at the latest follow-up were compared. RESULTS: Fifty patients were followed-up from 14 to 46(25.30±8.83) months in resection group and 12 to 48 with an average of (24.30±11.12) months in preservation group,while no significant difference between two groups (P>0.05). There were no significant difference in operation time and postoperative complications between two groups (P>0.05). JSSF scores,HVA,IMAFS and IMAFF in fesection group were improved from (45.09±3.35) points,(38.90±13.67) °,(12.88±1.72) °,(32.50±2.99) ° before operation to (81.60±3.27) points,(15.40±0.90),(9.06±2.27) °,(22.20±1.98) ° at the latest follow-up (P<0.05);preservation group were improved from (47.09±3.96) points,(43.30±12.65) °,(13.99±3.13) °,(33.20±6.14) ° to (83.10±3.66) points,(15.20±1.54) °,(8.99±1.02) °,(24.70±1.88) °,respectively. There were no significant difference in JSSF score,HVA,IMAFS and IMAFF between two groups before operation and the latest follow-up (P>0.05). At the latest follow-up,there were statistically significant differences in pain and deformity in JSSF scores between two groups (P<0.05). CONCLUSION: Both rheumatoid anterior foot reconstruction and anterior foot reconstruction fifth metatarsophalangeal joint debridement showed significant improvement in clinical efficacy and imaging results. Compared with rheumatoid prefoot reconstruction,the fifth metatarsophalangeal joint reconstruction for the treatment of moderate and severe deformity of rheumatoid prefoot showed better improvement in pain,but worse improvement in deformity. For the moderate to severe deformity of the forefoot caused by rheumatoid disease,patients with mild to moderate degenerative deformity of the articular surface of the fifth metatarsal phalanges may be considered for use.

Lnc-Clic5 as a sponge for miR-212-5p to inhibit cow barn PM2.5-induced apoptosis in rat alveolar macrophages.

Particulate matter 2.5 (PM2.5) is a highly hazardous airborne particulate matter that poses a significant risk to humans and animals. Urban airborne particulate matter contributes to the increased incidence and mortality of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), in humans. However, the specific mechanism by which PM2.5 affects animals in barn environments is yet to be elucidated. In this study, we investigated the effect of exposure to cow barn PM2.5 on rat alveolar macrophages (NR8383) and found that it induced apoptosis via the miR-212-5p/RASSF1 pathway. We found that lnc-Clic5 expression was downregulated in NR8383 cells exposed to cow barn PM2.5. Lnc-Clic5 plays a competitive endogenous RNA (ceRNA) regulatory role by sponging miR-212-5p to attenuate the regulation of RASSF1. Moreover, lnc-Clic5 overexpression inhibited NR8383 apoptosis by targeting the miR-212-5p/RASSF1 pathway. Co-treatment with miR-212-5p and lnc-Clic5 in the presence of cow barn PM2.5 revealed that lnc-Clic5 reversed NR8383 cell apoptosis induced by PM2.5 when miR-212-5p was overexpressed. These findings contribute to the study of ncRNAs and ceRNAs regulating PM2.5-induced apoptosis in animal farms, provide therapeutic targets for lung macrophage apoptosis, and may be useful for further evaluating the toxicological effects of PM2.5 in farmhouses on the respiratory systems of humans and animals.

Process Manufacturing Intelligence Empowered by Industrial Metaverse: A Survey.

The intelligent goal of process manufacturing is to achieve high efficiency and greening of the entire production. Whereas the information system it used is functionally independent, resulting to knowledge gaps between each level. Decision-making still requires lots of knowledge workers making manually. The industrial metaverse is a necessary means to bridge the knowledge gaps by sharing and collaborative decision-making. Considering the safety and stability requirements of the process manufacturing, this article conducts a thorough survey on the process manufacturing intelligence empowered by industrial metaverse. First, it analyzes the current status and challenges of process manufacturing intelligence, and then summarizes the latest developments about key enabling technologies of industrial metaverse, such as interconnection technologies, artificial intelligence, cloud-edge computing, digital twin (DT), immersive interaction, and blockchain technology. On this basis, taking into account the characteristics of process manufacturing, a construction approach and architecture for the process industrial metaverse is proposed: a virtual-real fused industrial metaverse construction method that combines DTs with physical avatar, which can effectively ensure the safety of metaverse's application in industrial scenarios. Finally, we conducted preliminary exploration and research, to prove the feasibility of proposed method.

A promise for neuronal repair: reprogramming astrocytes into neurons in vivo.

Massive loss of neurons following brain injury or disease is the primary cause of central nervous system dysfunction. Recently, much research has been conducted on how to compensate for neuronal loss in damaged parts of the nervous system and thus restore functional connectivity among neurons. Direct somatic cell differentiation into neurons using pro-neural transcription factors, small molecules, or microRNAs, individually or in association, is the most promising form of neural cell replacement therapy available. This method provides a potential remedy for cell loss in a variety of neurodegenerative illnesses, and the development of reprogramming technology has made this method feasible. This article provides a comprehensive review of reprogramming, including the selection and methods of reprogramming starting cell populations as well as the signaling methods involved in this process. Additionally, we thoroughly examine how reprogramming astrocytes into neurons can be applied to treat stroke and other neurodegenerative diseases. Finally, we discuss the challenges of neuronal reprogramming and offer insights about the field.

Decoding single-cell molecular mechanisms in astrocyte-to-iN reprogramming via Ngn2- and Pax6-mediated direct lineage switching.

BACKGROUND: The limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach. METHODS: We utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis. RESULTS: The scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition. CONCLUSIONS: This study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process.

Physical exercise in the promotion of gene therapy auxiliary effect / O exercício físico na promoção de efeitos auxiliares da terapia genética / El ejercicio físico en la promoción de efectos auxiliares de la terapia genética

ABSTRACT Introduction: In recent years, genetic engineering has made outstanding contributions to sports, and it has played a huge role in promoting the development of sports-related fields. Objective: We analyze the tissue source of bone growth and healing by studying the role of bone morphogenetic protein and transforming growth factors in fracture injuries caused by sports. Methods: We established a human fracture model to express the shape and content of bone morphogenetic protein and transforming growth factor during fracture healing. Results: In the fracture healing stage caused by different sports, the expression levels of the two genes are different. Bone morphogenetic protein has a high content in the osteogenesis stage of the membrane, while transforming growth factor is high in the cartilage ossification stage. Conclusion: Gene therapy for fractures caused by physical exercise has certain advantages. Osteoblasts and chondrocytes are involved in the synthesis of transforming growth factors. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Nos últimos anos, a engenharia genética tem contribuído de forma notável para os esportes, além de ter uma função importante na promoção do desenvolvimento de áreas relacionadas ao esporte. Objetivo: Analisamos a origem de tecidos do crescimento ósseo e sua regeneração através do estudo da proteína morfogenética óssea e fatores de transformação do crescimento em fraturas causadas pela prática do esporte. Métodos: Criamos um modelo de fratura humana para expressar a forma e o conteúdo da proteína morfogenética óssea e de fatores de transformação do crescimento durante a recuperação de fraturas. Resultados: Na fase de recuperação da fratura causada por diversos esportes, os níveis de expressão dos dois genes são diferentes. A proteína morfogenética óssea se apresenta em alta quantidade na fase osteogenetica da membrana, e o fator de transformação de crescimento apresenta alta quantidade na fase de ossificação da cartilagem. Conclusão: A terapia genética para fraturas causadas por exercícios físicos apresenta diversas vantagens. Osteoblastos e condrócitos tem um papel na síntese dos fatores de transformação do crescimento. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: En los últimos años, la ingeniería genética ha contribuido de forma notable para los deportes, además de tener una función importante en la promoción del desarrollo de áreas relacionadas al deporte. Objetivo: Analizamos el origen de tejidos del crecimiento óseo y su regeneración a través del estudio de la proteína morfogenética ósea y factores de crecimiento transformante en fracturas causadas por la práctica del deporte. Métodos: Creamos un modelo de fractura humana para expresar la forma y el contenido de la proteína morfogenética ósea y de factores de crecimiento transformante durante la recuperación de fracturas. Resultados: En la fase de recuperación de la fractura causada por diversos deportes, los niveles de expresión de los dos genes son diferentes. La proteína morfogenética ósea se presenta en alta cantidad en la fase osteogénica de la membrana, y el factor de crecimiento transformante presenta alta cantidad en la fase de osificación del cartílago. Conclusión: La terapia genética para fracturas causadas por ejercicios físicos presenta diversas ventajas. Osteoblastos y condrocitos tienen un papel en la síntesis de los factores de crecimiento transformante. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.