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1.
Int J Biol Macromol ; 269(Pt 2): 132139, 2024 May 06.
Article En | MEDLINE | ID: mdl-38719008

Accumulating salinity in soil critically affected growth, development, and yield in plant. However, the mechanisms of plant against salt stress largely remain unknown. Herein, we identified a gene named SmCYP78A7a, which encoded a cytochrome P450 monooxygenase and belonged to the CYP78A sub-family, and its transcript level was significantly up-regulated by salt stress and down-regulated by dehydration stress. SmCYP78A7a located in the endoplasmic reticulum. Silencing of SmCYP78A7a enhanced susceptibility of eggplant to salt stress, and significantly down-regulated the transcript levels of salt stress defense related genes SmGSTU10 and SmWRKY11 as well as increased hydrogen peroxide (H2O2) content and decreased catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) enzyme activities. In addition, SmCYP78A7a transient expression enhanced eggplant tolerance to salt stress. By chromatin immunoprecipitation PCR (ChIP-PCR), luciferase reporter assay, and electrophoretic mobility shift assay (EMSA), SmWRKY11 activated SmCYP78A7a expression by directly binding to the W-box 6-8 (W-box 6, W-box 7, and W-box 8) within SmCYP78A7a promoter to confer eggplant tolerance to salt stress. In summary, our finds reveal that SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11, and provide a new insight into regulatory mechanisms of eggplant to salt stress.

2.
BMC Health Serv Res ; 24(1): 615, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730381

BACKGROUND: Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors. METHODS: We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay. RESULTS: In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024-2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548-32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236-0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216-0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207-0.679), moderate stroke (OR: 0.644, 95% CI: 0.462-0.901), and severe stroke (OR: 0.506, 95% CI: 0.285-0.908). CONCLUSIONS: Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.


COVID-19 , Ischemic Stroke , Time-to-Treatment , Humans , COVID-19/epidemiology , Female , Male , China/epidemiology , Prospective Studies , Ischemic Stroke/epidemiology , Ischemic Stroke/therapy , Aged , Middle Aged , Time-to-Treatment/statistics & numerical data , Risk Factors , SARS-CoV-2 , Aged, 80 and over , East Asian People
3.
Quant Imaging Med Surg ; 14(5): 3501-3518, 2024 May 01.
Article En | MEDLINE | ID: mdl-38720828

Background: In the field of medical imaging, the rapid rise of convolutional neural networks (CNNs) has presented significant opportunities for conserving healthcare resources. However, with the wide spread application of CNNs, several challenges have emerged, such as enormous data annotation costs, difficulties in ensuring user privacy and security, weak model interpretability, and the consumption of substantial computational resources. The fundamental challenge lies in optimizing and seamlessly integrating CNN technology to enhance the precision and efficiency of medical diagnosis. Methods: This study sought to provide a comprehensive bibliometric overview of current research on the application of CNNs in medical imaging. Initially, bibliometric methods were used to calculate the frequency statistics, and perform the cluster analysis and the co-citation analysis of countries, institutions, authors, keywords, and references. Subsequently, the latent Dirichlet allocation (LDA) method was employed for the topic modeling of the literature. Next, an in-depth analysis of the topics was conducted, and the topics in the medical field, technical aspects, and trends in topic evolution were summarized. Finally, by integrating the bibliometrics and LDA results, the developmental trajectory, milestones, and future directions in this field were outlined. Results: A data set containing 6,310 articles in this field published from January 2013 to December 2023 was complied. With a total of 55,538 articles, the United States led in terms of the citation count, while in terms of the publication volume, China led with 2,385 articles. Harvard University emerged as the most influential institution, boasting an average of 69.92 citations per article. Within the realm of CNNs, residual neural network (ResNet) and U-Net stood out, receiving 1,602 and 1,419 citations, respectively, which highlights the significant attention these models have received. The impact of coronavirus disease 2019 (COVID-19) was unmistakable, as reflected by the publication of 597 articles, making it a focal point of research. Additionally, among various disease topics, with 290 articles, brain-related research was the most prevalent. Computed tomography (CT) imaging dominated the research landscape, representing 73% of the 30 different topics. Conclusions: Over the past 11 years, CNN-related research in medical imaging has grown exponentially. The findings of the present study provide insights into the field's status and research hotspots. In addition, this article meticulously chronicled the development of CNNs and highlighted key milestones, starting with LeNet in 1989, followed by a challenging 20-year exploration period, and culminating in the breakthrough moment with AlexNet in 2012. Finally, this article explored recent advancements in CNN technology, including semi-supervised learning, efficient learning, trustworthy artificial intelligence (AI), and federated learning methods, and also addressed challenges related to data annotation costs, diagnostic efficiency, model performance, and data privacy.

4.
Mol Carcinog ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38726928

Reactive oxygen species (ROS) are metabolic by-products of cells, and abnormal changes in their levels are often associated with tumor development. Our aim was to determine the role of collagen and calcium binding EGF domain 1 (CCBE1) in oxidative stress and tumorigenesis in non-small cell lung cancer cells (NSCLC). We investigated the tumorigenic potential of CCBE1 in NSCLC using in vitro and in vivo models of CCBE1 overexpression and knockdown. Immunohistochemical staining results showed that the expression of CCBE1 in cancer tissues was significantly higher than that in adjacent tissues. Cell counting Kit 8, clonal formation, wound healing, and transwell experiments showed that CCBE1 gene knockdown significantly inhibited the migration, invasion, and proliferation of NSCLC cell lines. In terms of mechanism, the silencing of CCBE1 can significantly promote the morphological abnormalities of mitochondria, significantly increase the intracellular ROS level, and promote cell apoptosis. This change of oxidative stress can affect cell proliferation, migration, and invasion by regulating the phosphorylation level of ERK/JNK/P38 MAPK. Specifically, the downregulation of CCBE1 inhibits the phosphorylation of ERK/P38 and promotes the phosphorylation of JNK in NSCLC, and this regulation can be reversed by the antioxidant NAC. In vivo experiments confirmed that downregulating CCBE1 gene could inhibit the growth of NSCLC in BALB/c nude mice. Taken together, our results confirm the tumorigenic role of CCBE1 in promoting tumor invasion and migration in NSCLC, and reveal the molecular mechanism by which CCBE1 regulates oxidative stress and the ERK/JNK/P38 MAPK pathway.

5.
Cell Mol Life Sci ; 81(1): 212, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724675

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.


Infertility, Male , Leydig Cells , Pre-B-Cell Leukemia Transcription Factor 1 , Testis , Testosterone , Animals , Male , Leydig Cells/metabolism , Leydig Cells/pathology , Pre-B-Cell Leukemia Transcription Factor 1/metabolism , Pre-B-Cell Leukemia Transcription Factor 1/genetics , Mice , Testosterone/metabolism , Testis/metabolism , Testis/pathology , Infertility, Male/genetics , Infertility, Male/pathology , Infertility, Male/metabolism , Cell Differentiation/genetics , Spermatogenesis/genetics , Mice, Inbred C57BL , Mice, Knockout
6.
Medicine (Baltimore) ; 103(15): e37778, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38608115

The impact of pulmonary rehabilitation (PR) on patients with different chronic respiratory diseases (CRDs) during hospitalization has not been thoroughly evaluated before. The objectives of the current research were to assess the effect of comprehensive PR management on inpatients' self-management skills, exercise capacity, nutrition assessment and mental health issues and explore whether impacts of PR vary in different CRDs. This retrospective study analyzed the clinical data from 272 inpatients with CRDs receiving PR management during hospitalization between October 2020 and March 2022 in Beijing Chao-Yang Hospital. Significant improvements were found in the patients' ability of daily living (ADL), dyspnea (assessed by modified medical research council dyspnea scale (MMRC)), handgrip strength, maximal inspiratory and expiratory pressure, anxiety (using the 7-item generalized anxiety disorder scale (GAD-7)) and depression (the 9-item patient health questionnaire score (PHQ-9)). There was no significant change in nutrition assessment pre-post PR management during hospitalization. The subgroup analyses were conducted on hospitalized patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, interstitial lung diseases (ILDs) and other CRDs (e.g., lung cancer, diaphragm hemiparesis, obesity, etc.). The results showed that ADL, MMRC score, MIP, MEP, PHQ-9 score improved in all subgroups with CRDs. Handgrip strength of left hand was increased in COPD inpatients and anxiety was improved in all subgroups except for ILDs. Comprehensive PR management was necessary and beneficial for patients with different CRDs during hospitalization.


Pulmonary Disease, Chronic Obstructive , Respiration Disorders , Humans , Hand Strength , Retrospective Studies , Hospitalization , Dyspnea
7.
Front Immunol ; 15: 1368099, 2024.
Article En | MEDLINE | ID: mdl-38665923

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of Escherichia coli. For in vitro experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)-stem cell factor receptor (c-kit)+stem cell antigen-1 (Sca-1)-, lin-c-kit+, and lin- cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of experiments, marrow lin-c-kit+ cells from green fluorescence protein (GFP)+ mice, i.v. challenged with heat-inactivated E. coli or saline for 24 h, were subcutaneously implanted in Matrigel plugs for 5 weeks. Marrow lin-c-kit+ cells from Sca-1 knockout (KO) mice challenged with heat-inactivated E. coli for 24 h were cultured in the Matrigel medium for 8 weeks. The marrow pool of EPCs bearing the lin-c-kit+Sca-1+VEGF receptor 2 (VEGFR2)+ (LKS VEGFR2+) and LKS CD133+VEGFR2+ surface markers expanded rapidly following septic infection, which was supported by both proliferative activation and phenotypic conversion of marrow stem/progenitor cells. Increase in marrow EPCs and their reprogramming for enhancing angiogenic activity correlated with cell-marked upregulation of Sca-1 expression. Sca-1 was coupled with Ras-related C3 botulinum toxin substrate 2 (Rac2) in signaling the marrow EPC response. Septic infection caused a substantial increase in plasma levels of IFN-γ, VEGF, G-CSF, and SDF-1. The early increase in circulating EPCs was accompanied by their active homing and incorporation into pulmonary microvasculature. These results demonstrate that the marrow EPC response is a critical component of the host defense system. Sca-1 signaling plays a pivotal role in the regulation of EPC response in mice with septic infection.


Endothelial Progenitor Cells , Membrane Proteins , Sepsis , Animals , Endothelial Progenitor Cells/metabolism , Endothelial Progenitor Cells/immunology , Sepsis/immunology , Sepsis/metabolism , Mice , Mice, Knockout , Escherichia coli/immunology , Escherichia coli Infections/immunology , Mice, Inbred C57BL , Vascular Endothelial Growth Factor A/metabolism , Antigens, Ly/metabolism , Bone Marrow Cells/metabolism , Bone Marrow Cells/immunology , Cells, Cultured , Male
8.
Front Oncol ; 14: 1344829, 2024.
Article En | MEDLINE | ID: mdl-38665955

Leptomeningeal disease (LMD) is a serious cancer complication associated with poor prognosis. Approximately 5%-25% of patients with melanoma develop LMD. Currently, no standard treatment protocol exists and very few cases have been reported. Despite ongoing advances in new therapies, treatment options for LMD remain limited. Herein, we report a case of intrathecal pembrolizumab administration in a patient with melanoma and LMD. Intrathecal pembrolizumab administration was feasible and safe at the doses tested. Drawing from this case, along with our expertise and the existing evidence on systemic immunotherapy, we propose that an immunotherapy approach involving intrathecal administration for patients with LMD from melanoma warrants additional exploration in clinical trials.

9.
Int J Biol Macromol ; 268(Pt 2): 131547, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38641281

Eicosapentaenoic acid regulates glucose uptake in skeletal muscle and significantly affects whole-body energy metabolism. However, the underlying molecular mechanism remains unclear. Here we report that eicosapentaenoic acid activates phosphoglycerate mutase 2, which mediates the conversion of 2-phosphoglycerate into 3-phosphoglycerate. This enzyme plays a pivotal role in glycerol degradation, thereby facilitating the proliferation and differentiation of satellite cells in skeletal muscle. Interestingly, phosphoglycerate mutase 2 inhibits mitochondrial metabolism, promoting the formation of fast-type muscle fibers. Treatment with eicosapentaenoic acid and phosphoglycerate mutase 2 knockdown induced opposite transcriptomic changes, most of which were enriched in the PI3K-AKT signaling pathway. Phosphoglycerate mutase 2 activated the PI3K-AKT signaling pathway, which inhibited the phosphorylation of FOXO1, and, in turn, inhibited mitochondrial function and promoted the formation of fast-type muscle fibers. Our results suggest that eicosapentaenoic acid promotes skeletal muscle growth and regulates glucose metabolism by targeting phosphoglycerate mutase 2 and activating the PI3K/AKT signaling pathway.

10.
RSC Adv ; 14(19): 13367-13373, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38660529

This study introduces a miniaturized fiber-optic Fabry-Perot (FP) interferometric biosensor, distinctively engineered for cost-effective, rapid, and quantitative DNA sequence detection. By leveraging the interference patterns generated within a Fabry-Perot microcavity, our sensor precisely monitors DNA hybridization events in real-time. We have verified the sensor's biofunctionalization via fluorescent labeling and have extensively validated its performance through numerous hybridization and regeneration cycles with 1 µM single-stranded DNA (ssDNA) solutions. Demonstrating remarkable repeatability and reusability, the sensor effectively discerns ssDNA sequences exhibiting varying degrees of mismatches. Its ability to accurately distinguish between sequences with 2 and 7 mismatches underscores its potential as a valuable asset for swift DNA analysis. Characterized by its rapid response time-typically yielding results within 6 minutes-and its adeptness at mismatch identification, our biosensor stands as a potent tool for facilitating accelerated DNA diagnostics and research.

11.
Phytopathology ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38669603

Sclerotinia sclerotiorum is an economically damaging fungal pathogen that causes Sclerotinia stem rot in legumes, producing enormous yield losses. This pathogen is difficult to control due to its wide host spectrum and ability to produce sclerotia, which are resistant bodies that can remain active for long periods under harsh environmental conditions. Here, the biocontrol methods for the management of S. sclerotiorum in legumes are reviewed. Bacillus strains, which synthesized lipopeptides and VOCs, showed high efficacies in soybean plants, whereas the highest efficacies for the control of the pathogen in alfalfa and common bean were observed when using Coniothyrium minitans and Streptomyces spp., respectively. The biocontrol efficacies in fields were under 65%, highlighting the lack of strategies to achieve a complete control. Overall, while most studies involved extensive screenings using different biocontrol agent concentrations and application conditions, there is a lack of knowledge regarding the specific antifungal mechanisms, which limits the optimization of the reported methods.

12.
J Dairy Sci ; 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38642661

Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

13.
Sci Total Environ ; 927: 172064, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38569968

Soil parent material is the second most influential factor in pedogenesis, influencing soil properties and microbial communities. Different assembly processes shape diverse functional microbial communities. The question remains unresolved regarding how these ecological assembly processes affect microbial communities and soil functionality within soils on different parent materials. We collected soil samples developed from typical parent materials, including basalt, granite, metamorphic rock, and marine sediments across soil profiles at depths of 0-20, 20-40, 40-80, and 80-100 cm, within rubber plantations on Hainan Island, China. We determined bacterial community characteristics, community assembly processes, and soil enzyme-related functions using 16S rRNA high-throughput sequencing and enzyme activity analyses. We found homogeneous selection, dispersal limitation, and drift processes were the dominant drivers of bacterial community assembly across soils on different parent materials. In soils on basalt, lower pH and higher moisture triggered a homogeneous selection-dominated assembly process, leading to a less diverse community but otherwise higher carbon and nitrogen cycling enzyme activities. As deterministic process decreased, bacterial community diversity increased with stochastic process. In soils on marine sediments, lower water, carbon, and nutrient content limited the dispersal of bacterial communities, resulting in higher community diversity and an increased capacity to utilize relative recalcitrant substrates by releasing more oxidases. The r-strategy Bacteroidetes and genera Sphingomonas, Bacillus, Vibrionimonas, Ochrobactrum positively correlated with enzyme-related function, whereas k-strategy Acidobacteria, Verrucomicrobia and genera Acidothermus, Burkholderia-Caballeronia-Paraburkholderia, HSB OF53-F07 showed negative correlations. Our study suggests that parent material could influence bacterial community assembly processes, diversity, and soil enzyme-related functions via soil properties.


Bacteria , Microbiota , Soil Microbiology , Soil , Soil/chemistry , China , RNA, Ribosomal, 16S , Biodiversity
14.
Food Chem X ; 22: 101300, 2024 Jun 30.
Article En | MEDLINE | ID: mdl-38571574

The composition of volatile compounds in beer is crucial to the quality of beer. Herein, we identified 23 volatile compounds, namely, 12 esters, 4 alcohols, 5 acids, and 2 phenols, in nine different beer types using GC-MS. By performing PCA of the data of the flavor compounds, the different beer types were well discriminated. Ethyl caproate, ethyl caprylate, and phenylethyl alcohol were identified as the crucial volatile compounds to discriminate different beers. PLS regression analysis was performed to model and predict the contents of six crucial volatile compounds in the beer samples based on the characteristic wavelength of the FTIR spectrum. The R2 value of each sample in the prediction model was 0.9398-0.9994, and RMSEP was 0.0122-0.7011. The method proposed in this paper has been applied to determine flavor compounds in beer samples with good consistency compared with GC-MS.

15.
Phys Rev Lett ; 132(15): 150603, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38682974

Ground state preparation is classically intractable for general Hamiltonians. On quantum devices, shallow parametrized circuits can be effectively trained to obtain short-range entangled states under the paradigm of variational quantum eigensolver, while deep circuits are generally untrainable due to the barren plateau phenomenon. In this Letter, we give a general lower bound on the variance of circuit gradients for arbitrary quantum circuits composed of local 2-designs. Based on our unified framework, we prove the absence of barren plateaus in training finite local-depth circuits (FLDC) for the ground states of local Hamiltonians. FLDCs are allowed to be deep in the conventional circuit depth to generate long-range entangled ground states, such as topologically ordered states, but their local depths are finite, i.e., there is only a finite number of gates acting on individual qubits. This characteristic sets FLDC apart from shallow circuits: FLDC in general cannot be classically simulated to estimate local observables efficiently by existing tensor network methods in two and higher dimensions. We validate our analytical results with extensive numerical simulations and demonstrate the effectiveness of variational training using the generalized toric code model.

16.
J Neuroinflammation ; 21(1): 105, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38649885

BACKGROUND: NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat. METHODS: Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2 -/- mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O2-) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study. RESULTS: We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst. CONCLUSIONS: Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.


Blood-Retinal Barrier , Intraocular Pressure , Mice, Inbred C57BL , NADPH Oxidase 2 , Neuroinflammatory Diseases , Animals , NADPH Oxidase 2/metabolism , NADPH Oxidase 2/genetics , Mice , Blood-Retinal Barrier/pathology , Blood-Retinal Barrier/metabolism , Intraocular Pressure/physiology , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/pathology , Mice, Knockout , Cell Proliferation/physiology , MAP Kinase Signaling System/physiology , Neuroglia/metabolism , Neuroglia/pathology , Ocular Hypertension/pathology , Ocular Hypertension/metabolism , Glaucoma/pathology , Glaucoma/metabolism , Oxidative Stress/physiology
17.
BMC Genomics ; 25(1): 400, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658807

BACKGROUND: Skeletal muscle is composed of muscle fibers with different physiological characteristics, which plays an important role in regulating skeletal muscle metabolism, movement and body homeostasis. The type of skeletal muscle fiber directly affects meat quality. However, the transcriptome and gene interactions between different types of muscle fibers are not well understood. RESULTS: In this paper, we selected 180-days-old Large White pigs and found that longissimus dorsi (LD) muscle was dominated by fast-fermenting myofibrils and soleus (SOL) muscle was dominated by slow-oxidizing myofibrils by frozen sections and related mRNA and protein assays. Here, we selected LD muscle and SOL muscle for transcriptomic sequencing, and identified 312 differentially expressed mRNA (DEmRs), 30 differentially expressed miRNA (DEmiRs), 183 differentially expressed lncRNA (DElRs), and 3417 differentially expressed circRNA (DEcRs). The ceRNA network included ssc-miR-378, ssc-miR-378b-3p, ssc-miR-24-3p, XR_308817, XR_308823, SMIM8, MAVS and FOS as multiple core nodes that play important roles in muscle development. Moreover, we found that different members of the miR-10 family expressed differently in oxidized and glycolytic muscle fibers, among which miR-10a-5p was highly expressed in glycolytic muscle fibers (LD) and could target MYBPH gene mRNA. Therefore, we speculate that miR-10a-5p may be involved in the transformation of muscle fiber types by targeting the MYHBP gene. In addition, PPI analysis of differentially expressed mRNA genes showed that ACTC1, ACTG2 and ACTN2 gene had the highest node degree, suggesting that this gene may play a key role in the regulatory network of muscle fiber type determination. CONCLUSIONS: We can conclude that these genes play a key role in regulating muscle fiber type transformation. Our study provides transcriptomic profiles and ceRNA interaction networks for different muscle fiber types in pigs, providing reference for the transformation of pig muscle fiber types and the improvement of meat quality.


Gene Regulatory Networks , Animals , Swine , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Expression Profiling , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Transcriptome , RNA, Messenger/genetics , RNA, Messenger/metabolism
18.
Cell Insight ; 3(3): 100170, 2024 Jun.
Article En | MEDLINE | ID: mdl-38590928

The RNA-binding protein LUC7L3 is the human homolog of yeast U1 small nuclear RNA (snRNA)-related splicing factor Luc7p. While the primary function of LUC7L3 as an RNA-binding protein is believed to be involved in RNA metabolism, particularly in the splicing process, its exact role and other functions are still not fully understood. In this study, we aimed to elucidate the role of LUC7L3 and its impact on cell proliferation. Our study revealed that LUC7L3 depletion impairs cell proliferation compared to the other Luc7p paralogs, resulting in cell apoptosis and senescence. We explored the underlying mechanisms and found that LUC7L3 depletion leads to R-loop accumulation, DNA replication stress, and genome instability. Furthermore, we discovered that LUC7L3 depletion caused abnormalities in spindle assembly, leading to the formation of multinuclear cells. This was attributed to the dysregulation of protein translation of spindle-associated proteins. Additionally, we investigated the interplay between LUC7L3 and SRSF1 and identified SRSF1 as an upper stream regulator of LUC7L3, promoting the translation of LUC7L3 protein. These findings highlight the importance of LUC7L3 in maintaining genome stability and its relationship with SRSF1 in this regulatory pathway.

19.
Acta Crystallogr E Crystallogr Commun ; 80(Pt 4): 347-350, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38584727

The title compound, C14H12N2O4, was obtained from 2-acetyl-6-amino-naphthalene through two-step reactions of acetyl-ation and nitration. The mol-ecule comprises the naphthalene ring system consisting of functional systems bearing a acetyl group (C-2), a nitro group (C-5), and an acetyl-amino group (C-6). In the crystal, the mol-ecules are assembled into two-dimensional sheet-like structures by inter-molecular N-H⋯O and C-H⋯O hydrogen-bonding inter-actions. Hirshfeld surface analysis illustrates that the most important contributions to the crystal packing are from O⋯H/H⋯O (43.7%), H⋯H (31.0%), and C⋯H/H⋯C (8.5%) contacts.

20.
Int J Surg ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38608040

BACKGROUND: Traumatic brain injury (TBI) is a serious public health burden worldwide, with a mortality rate of 20%-30%; however, reducing the incidence and mortality rates of TBI remains a major challenge. This study provides a multidimensional analysis to explore the potential breakthroughs in TBI over the past two decades. MATERIALS AND METHODS: We used bibliometric and Latent Dirichlet Allocation (LDA) analyses to analyze publications focusing on TBI published between 2003 and 2022 from the Web of Science Core Collection (WOSCC) database to identify core journals and collaborations among countries/regions, institutions, authors, and research trends. RESULTS: Over the past 20 years, 41,545 articles on TBI from 3,043 journals were included, with 12,916 authors from 20,449 institutions across 145 countries/regions. The annual number of publications has increased ten-fold compared to previous publications. This study revealed that high-income countries, especially the United States, have a significant influence. Collaboration was limited to several countries/regions. The LDA results indicated that the hotspots included four main areas: "Clinical finding", "Molecular mechanism", "Epidemiology", and "Prognosis". Epidemiological research has consistently increased in recent years. Through epidemiological topic analysis, the main etiology of TBI has shifted from traffic accidents to falls in a demographically aging society. CONCLUSION: Over the past two decades, TBI research has developed rapidly, and its epidemiology has received increasing attention. Reducing the incidence of TBI from a preventive perspective is emerging as a trend to alleviate the future social burden; therefore, epidemiological research might bring breakthroughs in TBI.

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