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Coxsackieviruses possess two proteases that are engaged in cleaving viral polyprotein and hijacking host cell processes such as RNA biosynthesis. Integrator subunit 10 (INTS10), a subunit of the integrator complex, facilitates the processing of small nuclear RNAs (U1 and U2 snRNAs) to regulate cellular transcription. We found that INST10 can be cleaved by Coxsackievirus B (CVB). Hence, we hypothesized that INST10 may play a role in CVB infection. In this study, INTS10 is identified as the substrate of CVB3 protease 3C (3Cpro). The cleavage occurs at the residue Q221 and yields a fragment. Depletion of INTS10 enhanced CVB3 replication and blocked snRNA processing. Overexpression of U1 snRNA inhibited CVB3 infection, whereas its knockdown conversely enhanced it. Similarly, knockdown of U2 snRNA was found to promote CVB3 replication. Taken together, the 3Cpro-mediated cleavage of INTS10 disrupts U snRNA processing, which in turn counteracts the inhibitory effect of snRNA U1 and U2 on virus replication and subverts host defenses.

Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment.

The creation and development of classical multifunctional nanomaterials are crucial for the advancement of nanotherapeutic treatments for tumors. Currently, metal–organic frameworks (MOFs) modified with polydopamine (PDA) are at the forefront of nanomedicine research, particularly in tumor diagnostics and therapy, owing to their exceptional biocompatibility, expansive specific surface area, multifaceted functionalities, and superior photothermal properties, which led to significant advancements in anti-tumor research. Consequently, a range of anti-cancer strategies has been devised by leveraging the exceptional capabilities of MOFs, including intelligent drug delivery systems, photodynamic therapy, and photothermal therapy, which are particularly tailored for the tumor microenvironment. In order to gain deeper insight into the role of MOFs@PDA in cancer diagnosis and treatment, it is essential to conduct a comprehensive review of existing research outcomes and promptly analyze the challenges associated with their biological applications. This will provide valuable perspectives on the potential of MOFs@PDA in clinical settings.

Abnormal pulmonary arterial smooth muscle cells (PASMCs) proliferation is an important pathological process in hypoxic pulmonary arterial hypertension. Mitochondrial dynamics and quality control have a central role in the maintenance of the cell proliferation–apoptosis balance. However, the molecular mechanism is still unknown. We used hypoxic animal models, cell biology, and molecular biology to determine the effect of mitofusin 1 (Mfn1) on hypoxia-mediated PASMCs mitochondrial homeostasis. We found that Mfn1 expression was increased in hypoxia, which was crucial for hypoxia-induced mitochondrial dysfunction and smooth muscle cell proliferation as well as hypoxia-stimulated cell-cycle transition from the G 0 /G 1 phase to S phase. Subsequently, we studied the role of microRNAs in mitochondrial function associated with PASMC proliferation under hypoxic conditions. The promotive effect of Mfn1 on pulmonary vascular remodeling was alleviated in the presence of miR-125a agomir, and miR-125a antagomir mimicked the hypoxic damage effects to mitochondrial homeostasis. Moreover, in vivo and in vitro treatment with miR-125a agomir protected the pulmonary vessels from mitochondrial dysfunction and abnormal remodeling. In the present study, we determined that mitochondrial homeostasis, particularly Mfn1, played an important role in PASMCs proliferation. MiR-125a, an important underlying factor, which inhibited Mfn1 expression and decreased PASMCs disordered growth during hypoxia. These results provide a theoretical basis for the prevention and treatment of pulmonary vascular remodeling. Key messages Hypoxia leads to upregulation of mitofusin 1 (Mfn1) both in vivo and in vitro. Mfn1 is involved in hypoxia-induced PASMCs proliferation. Mfn1-mediated mitochondrial homeostasis is regulated by miR-125a. MiR-125a plays a role in PASMCs oxidative phosphorylation and glycolysis.

The incidence of central nervous system (CNS) disease has persistently increased over the last several years. There is an urgent need for effective methods to improve the cure rates of CNS disease. However, the precise molecular basis underlying the development and progression of major CNS diseases remains elusive. A complete molecular map will contribute to research on CNS disease treatment strategies. Emerging technologies such as single-cell RNA sequencing (scRNA-seq) and Spatial Transcriptomics (ST) are potent tools for exploring the molecular complexity, cell heterogeneity, and functional specificity of CNS disease. scRNA-seq and ST can provide insights into the disease at cellular and spatial transcription levels. This review presents a survey of scRNA-seq and ST studies on CNS diseases, such as chronic neurodegenerative diseases, acute CNS injuries, and others. These studies offer novel perspectives in treating and diagnosing CNS diseases by discovering new cell types or subtypes associated with the disease, proposing new pathophysiological mechanisms, uncovering novel therapeutic targets, and identifying putative biomarkers. Graphical Abstract Implications of scRNA-seq and ST for CNS diseases. A comprehensive understanding of cellular information and spatial context using scRNA-seq and ST, helping to elucidate the biological functions, the intricate connection between crucial regulatory pathways, and cell communication after CNS diseases.

The pillar burst disaster in deep engineering significantly constrains project construction. To reveal the fracture mechanism of rock pillars under instantaneous unloading, a self-designed rigid true triaxial experimental apparatus, equipped with two high-speed cameras and an acoustic emission (AE) monitoring system, was utilized to conduct instantaneous horizontal bidirectional unloading tests on granite with different stress states. The results indicate that granite undergoes severe and irreversible deformation during instantaneous unloading, with vertical strain rapidly increasing at higher axial stress. Analysis of AE time- and frequency-domain indicates that different stress states can alter crack type and crack mechanism. The wavelet transform was performed on all AE signal waveforms, and it revealed that the energy of AE signals caused by unloading was concentrated in low-frequency bands (15.625–62.5 kHz). Additionally, nonlinear characteristics of the b -value and the Hurst index explained the fracture evolution process, and the mutation point of the b -value and the Hurst index can be considered warning precursors of rock pillar burst. Finally, the damage evolution process based on the accumulated AE counts was segmented into two stages and fitted by a linear function and the Weibull distribution. The parameter m of the Weibull distribution was used to reflect the brittleness, and the effect of parameter m on the growth speed of damage was discussed. Highlights A novel horizontal bidirectional unloading method was proposed to simulate pillar bursts. The fracture evolution process was revealed by AE time- and frequency-domain. The damage evolution equation was discussed based on AE signals and the relationship between coefficient m and lag time Δ T was revealed.

Coxsackievirus B (CVB) is the major causative pathogen for severe diseases such as viral myocarditis, meningitis, and pancreatitis. There is no effective antiviral therapy currently available for CVB infection primarily due to that the pathogenesis of CVB has not been completely understood. Viruses are obligate intracellular pathogens which subvert cellular processes to ensure viral replication. Dysregulation of ubiquitination has been implicated in CVB infection. However, how ubiquitination is involved in CVB infection remains unclear. Here we found that the 3D protein of CVB3, the RNA-dependent RNA polymerase, was modified at K220 by K48-linked polyubiquitination which promoted its degradation through proteasome. Proteomic analysis showed that the E3 ligase TRIM56 was upregulated in CVB3-infected cells, while the majority of TRIMs remained unchanged. Pull-down and immunoprecipitation analyses showed that TRIM56 interacted with CVB3 3D. Immunofluorescence observation showed that viral 3D protein was colocalized with TRIM56. TRIM56 overexpression resulted in enhanced ubiquitination of CVB3 3D and decreased virus yield. Moreover, TRIM56 was cleaved by viral 3C protease in CVB3-infected cells. Taken together, this study demonstrated that TRIM56 mediates the ubiquitination and proteasomal degradation of the CVB3 3D protein. These findings demonstrate that TRIM56 is an intrinsic cellular restriction factor against CVB infection, and enhancing viral protein degradation could be a potential strategy to control CVB infection.

Based on observation data of temperature from automatic meteorological stations in all towns and the national weather station in Guilin City,annual and monthly variations of average temperature,distribution of high-temperature days in Guilin in 2013,and weather situations causing high temperature in Guilin were analyzed.The results showed that in 2013,annual average temperature in Guilin was 1.4℃higher than the multiyear average.The hottest weather occurred in Wenqiao Township,Quanzhou County in the northeast,followed by the urban district and suburbs of Guilin,Lianhua Town of Gongcheng County in the south,Tongan,Zhangjia and Dafa towns of Pingle County,Dongchang and Datang towns of Lipu County.Terrain had distinct effects on regional high temperature,that is,there was no hot weather with daily maximum temperature of≥35.0℃in mountainous areas with an altitude of≥1 200 m;temperature was abnormally high in low-lying areas surrounded by mountains.In addition,the Western Pacific subtropical high pressure was the main weather system leading to hot weather in Guilin.

Compared with active filter, PFC circuit has simple structure and convenient operation. Introducing it into SS4G electric locomotive can greatly reduce system harmonics. Therefore, firstly, the corresponding PFC circuit is built, and the suppression measures of peak section and discontinuous section are proposed. By improving the discontinuous section, the waveform conduction angle is expanded from 129.564° to 162.882°. Accordingly, the current harmonic at the input side is reduced from 27.38% to 16.19%. After the voltage multiplier is further introduced, the harmonic is reduced to 15.77%. Then, the circuit is designed to absorb the high-order harmonic power in the peak section, and the harmonic is further reduced by about 0.33% to 15.44%. Two small order smoothing capacitors are connected in parallel in the load section to further absorb higher harmonics, which can reduce harmonics to 9.95%. Because the discontinuous section will also produce some spikes in the improvement process, improving the spikes can reduce the harmonics by 4.42% to 5.53%. Then the final improved circuit is introduced into SS4G circuit, and the current harmonic content of the circuit is reduced from 30.02% to 15.59%. The improved PFC circuit has achieved good results in SS4G.

Background Moral injury among physicians and other health professionals has attracted attention in the mainstream literature, this study aim to assess the psychometric properties of the 10-item Moral Injury Symptoms Scale-Health Professional (MISS-HP) among healthcare professionals in China. Methods A total of 583 nurses and 2423 physicians were recruited from across mainland China. An online survey was conducted from March 27 to April 26, 2020 (during the middle of the COVID-19 pandemic) using the Chinese version of the MISS-HP. Reliability was assessed by internal consistency reliability and test-retest reliability. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to determine scale structure. Results Cronbach’s α of the scale for both samples was acceptable (0.71 for nurses and 0.70 for physicians), as was test-retest reliability (ICCs for the individual items ranged from 0.41 to 0.74, with 0.77 for the overall scale in physicians). EFA suggested three factors, and the CFA indicated good fit to the data. Convergent validity was demonstrated with the 4-item Expressions of Moral Injury Scale ( r  = 0.45 for physicians, r  = 0.43 for nurses). Discriminant validity was demonstrated by correlations with burnout and well-being ( r  = 0.34–0.47), and concurrent validity was suggested by correlations with depression and anxiety symptoms ( r  = 0.37–0.45). Known groups validity was indicated by a higher score in those exposed to workplace violence (B = 4.16, 95%CI: 3.21–5.10, p  < 0.001). Conclusions The MISS-HP demonstrated acceptable reliability and validity in a large sample of physicians and nurses in mainland China, supporting its use as a screening measure for moral injury symptoms among increasingly stressed health professionals in this country during the COVID-19 pandemic.