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Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs-mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.
Subject(s)
Biomarkers, Tumor , Endometrial Neoplasms , Polycystic Ovary Syndrome , Sedentary Behavior , Humans , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/immunology , Polycystic Ovary Syndrome/metabolism , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/immunology , Biomarkers, Tumor/genetics , Gene Regulatory Networks , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Expression Profiling , Machine LearningABSTRACT
Acute pancreatitis (AP) is an inflammatory disease of the pancreas and the main cause of hospital admissions for gastrointestinal diseases. Here, the work studied the circular RNA DTNB/microRNA-485-5p/MCL1 axis in AP and hoped to unravel the related mechanism. Caerulein exposure replicated an AP model in AR42J cells, and caerulein-mediated expression of circDTNB, miR-485-5p, and MCL1 was recorded. After exposure, cells were intervened with transfection plasmids and tested for LDH release, apoptosis, and inflammation. To determine the interwork of circDTNB, miR-485-5p, and MCL1, prediction results and verification experiments were conducted. Caerulein exposure reduced circDTNB and MCL1, while elevated miR-485-5p levels in AR42J cells. Upregulating circDTNB protected AR42J cells from caerulein-induced LDH cytotoxicity, apoptosis, and inflammation, but circDTNB upregulation-induced protections could be muffled by inhibiting MCL1. On the contrary, downregulating circDTNB further damaged AR42J cells under caerulein exposure, however, this phenomenon could be partially rescued after silencing miR-485-5p. miR-485-5p was mechanistically verified to be a target of circDTNB to mediate MCL1. Overall, the circDTNB/miR-485-5p/MCL1 axis protects inflammatory response and apoptosis in caerulein-exposed AR42J cells, promisingly identifying circDTNB as a novel molecule for AP treatment.
Subject(s)
Apoptosis , Ceruletide , Inflammation , MicroRNAs , Myeloid Cell Leukemia Sequence 1 Protein , RNA, Circular , MicroRNAs/genetics , MicroRNAs/metabolism , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Animals , Rats , Inflammation/genetics , Pancreatitis/genetics , Pancreatitis/metabolism , Pancreatitis/chemically induced , Pancreatitis/pathology , Cell LineABSTRACT
Behavioral plasticity allows animals to modulate their behavior based on experience and environmental conditions. Caenorhabditis elegans exhibits experience-dependent changes in its behavioral responses to various modalities of sensory cues, including odorants, salts, temperature, and mechanical stimulations. Most of these forms of behavioral plasticity, such as adaptation, habituation, associative learning, and imprinting, are shared with other animals. The C. elegans nervous system is considerably tractable for experimental studies-its function can be characterized and manipulated with molecular genetic methods, its activity can be visualized and analyzed with imaging approaches, and the connectivity of its relatively small number of neurons are well described. Therefore, C. elegans provides an opportunity to study molecular, neuronal, and circuit mechanisms underlying behavioral plasticity that are either conserved in other animals or unique to this species. These findings reveal insights into how the nervous system interacts with the environmental cues to generate behavioral changes with adaptive values.
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Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in tumor diagnosis and therapy. However, a pyroptosis inducer based on PLNPs has not been reported yet. Herein, polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA: PP) modified biodegradable CaS:Eu2+ (CSE@PP) PLNPs are synthesized as a pyroptosis inducer for tumor immunotherapy for the first time. The synthesized CSE@PP possesses biowindow persistent luminescence (PersL) and pH-responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed to weak acid (pH < 6.5). During degradation within the tumor, CSE@PP constantly releases H2S and Ca2+ while its PersL gradually fades away. Thus, the PersL signal can self-monitor H2S and Ca2+ release. Furthermore, the released H2S and Ca2+ result in mitochondrial dysfunction and the inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase-1/GSDM-D dependent pyroptosis and subsequent antitumor immune responses. In a word, it is confirmed that CSE@PP can self-monitor H2S and Ca2+ release and pyroptosis-mediated tumor Immunotherapy. This work will facilitate biomedical applications of PLNPs and inspire pyroptosis-induced tumor immunotherapy.
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Introduction: Currently, the development of new antiviral drugs against COVID-19 remains of significant importance. In traditional Chinese medicine, the herb Euphorbia fischeriana Steud is often used for antiviral treatment, yet its therapeutic effect against the COVID-19 has been scarcely studied. Therefore, this study focuses on the roots of E. fischeriana Steud, exploring its chemical composition, antiviral activity against COVID-19, and the underlying basis of its antiviral activity. Methods: Isolation and purification of phytochemicals from E. fischeriana Steud. The elucidation of their configurations was achieved through a comprehensive suite of 1D and 2D NMR spectroscopic analyses as well as X-ray diffraction. Performed cytopathic effect assays of SARS-CoV-2 using Vero E6 cells. Used molecular docking to screen for small molecule ligands with binding to SARS-CoV-2 RdRp. Microscale thermophoresis (MST) was used to determine the dissociation constant Kd. Results: Ultimately, nine new ent-atisane-type diterpenoid compounds were isolated from E. fischeriana Steud, named Eupfisenoids A-I (compounds 1-9). The compound of 1 was established as a C-19-degraded ent-atisane-type diterpenoid. During the evaluation of these compounds for their antiviral activity against COVID-19, compound 1 exhibited significant antiviral activity. Furthermore, with the aid of computer virtual screening and microscale thermophoresis (MST) technology, it was found that this compound could directly bind to the RNA-dependent RNA polymerase (RdRp, NSP12) of the COVID-19, a key enzyme in virus replication. This suggests that the compound inhibits virus replication by targeting RdRp. Discussion: Through this research, not only has our understanding of the antiviral components and material basis of E. fischeriana Steud been enriched, but also the potential of atisane-type diterpenoid compounds as antiviral agents against COVID-19 has been discovered. The findings mentioned above will provide valuable insights for the development of drugs against COVID-19.
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OBJECTIVE: This retrospective longitudinal cohort study aimed to explore the best therapeutic regimen and treatment duration of cough variant asthma (CVA) in children. METHODS: A total of 314 children with CVA were divided into receive inhaled corticosteroids (ICS) combined with long-acting beta2-agonist (LABA) group, ICS combined with leukotriene receptor antagonists (LTRA) group, ICS monotherapy group and LTRA monotherapy group. All clinical data were statistically analyzed. Logistic regression model was used to compare the advantages and disadvantages of different treatment schemes at each follow-up time point and the best treatment scheme. The Cox proportional hazard regression model based on inverse probability weighting was used to compare the effects of different medication regimens on adverse outcomes with asthma recurrence or progression as the end point. RESULTS: (1) After comprehensive analysis, ICS + LABA group was the preferred control regimen for CVA within 8 weeks. After 8 weeks of diagnosis, the efficacy of ICS group or LTRA group was comparable to that of ICS + LABA group and ICS + LTRA group. (2) The ICS + LABA group showed a significant improvement in cough at an early stage, particularly at 4 weeks; the symptoms of ICS + LTRA and ICS groups were significantly improved at 36 weeks. The LTRA group alone showed significant improvement at 20 weeks. CONCLUSION: ICS + LABA, ICS + LTRA, ICS alone and LTRA alone can effectively treat CVA. ICS + LABA could improve the symptoms most quickly within 8 weeks after CVA diagnosis, followed by ICS + LATR group. After 8 weeks, it can be reduced to ICS alone to control CVA for at least 36 weeks based on the remission of symptoms in children.
Subject(s)
Adrenal Cortex Hormones , Anti-Asthmatic Agents , Asthma , Cough , Drug Therapy, Combination , Leukotriene Antagonists , Humans , Asthma/drug therapy , Cough/drug therapy , Retrospective Studies , Female , Male , Child , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Administration, Inhalation , Leukotriene Antagonists/therapeutic use , Leukotriene Antagonists/administration & dosage , Child, Preschool , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Longitudinal Studies , Adrenergic beta-2 Receptor Agonists/therapeutic use , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adolescent , Cough-Variant AsthmaABSTRACT
Exploring the complexity of the epithelial-to-mesenchymal transition (EMT) unveils a diversity of potential cell fates; however, the exact timing and mechanisms by which early cell states diverge into distinct EMT trajectories remain unclear. Studying these EMT trajectories through single-cell RNA sequencing is challenging due to the necessity of sacrificing cells for each measurement. In this study, we employed optimal-transport analysis to reconstruct the past trajectories of different cell fates during TGF-beta-induced EMT in the MCF10A cell line. Our analysis revealed three distinct trajectories leading to low EMT, partial EMT, and high EMT states. Cells along the partial EMT trajectory showed substantial variations in the EMT signature and exhibited pronounced stemness. Throughout this EMT trajectory, we observed a consistent downregulation of the EED and EZH2 genes. This finding was validated by recent inhibitor screens of EMT regulators and CRISPR screen studies. Moreover, we applied our analysis of early-phase differential gene expression to gene sets associated with stemness and proliferation, pinpointing ITGB4, LAMA3, and LAMB3 as genes differentially expressed in the initial stages of the partial versus high EMT trajectories. We also found that CENPF, CKS1B, and MKI67 showed significant upregulation in the high EMT trajectory. While the first group of genes aligns with findings from previous studies, our work uniquely pinpoints the precise timing of these upregulations. Finally, the identification of the latter group of genes sheds light on potential cell cycle targets for modulating EMT trajectories.
Subject(s)
Epithelial-Mesenchymal Transition , Single-Cell Analysis , Epithelial-Mesenchymal Transition/genetics , Humans , Single-Cell Analysis/methods , Cell Lineage/genetics , Transforming Growth Factor beta/metabolism , Enhancer of Zeste Homolog 2 Protein/metabolism , Enhancer of Zeste Homolog 2 Protein/geneticsABSTRACT
This study employs an optimized and environmentally friendly method to extract and purify chondroitin sulfate (CS) from bovine nasal cartilage using enzymatic hydrolysis, ethanol precipitation, and DEAE Sepharose Fast Flow column chromatography. The extracted CS, representing 44.67 % ± 0.0016 of the cartilage, has a molecular weight of 7.62 kDa. Characterization through UV, FT-IR, NMR spectroscopy, and 2-aminoacridone derivatization HPLC revealed a high content of sulfated disaccharides, particularly ΔDi4S (73.59 %) and ΔDi6S (20.61 %). Interaction studies with bovine serum albumin (BSA) using fluorescence spectroscopy and molecular docking confirmed a high-affinity, static quenching interaction with a single binding site, primarily mediated by van der Waals forces and hydrogen bonding. The interaction did not significantly alter the polarity or hydrophobicity of BSA aromatic amino acids. These findings provide a strong foundation for exploring the application of CS in tissue engineering and drug delivery systems, leveraging its unique interaction with BSA for targeted delivery and enhanced efficacy.
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OBJECTIVES: To describe the perceptions of telehealth services among lung cancer patients in rural areas of China, as well as to explore the potential of telemedicine to improve long-term health recovery at home for rural lung cancer patients. METHODS: A qualitative descriptive study design was used in this study and we conducted semi-structured interviews with 14 rural Chinese lung cancer patients between December 2022 and March 2023. Interview content was analyzed using Nvivo software and a framework analysis was performed using the Technology Acceptance Model to identify meaningful themes. RESULTS: Participants identified perceptual and technical factors related to perceived ease of use, benefits and drawbacks related to perceived usefulness, and facilitators and barriers related to intention to use. However, regional and disease features including literacy barriers, medical insurance condition, symptom burden, and rural cultural health seeking behavior conduct must be taken into account. CONCLUSIONS: Lung cancer patients in rural China believe that telehealth services could be an alternative solution for addressing health and care needs, but various aspects, such as user interface design, cost-effectiveness, and technological anxiety, need to be optimized. IMPLICATIONS FOR NURSING PRACTICE: More highly specialized nursing team, friendly telecare lung function modules, and media technology training courses should be developed for rural lung cancer patients to enhance the quality of their home care, meet their information needs and better control their disease progression.
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OBJECTIVE: To assess the genetic etiologies underlying agenesis of the corpus callosum (ACC) and its pregnancy outcomes in the era of next-generation sequencing. METHODS: A retrospective analysis was conducted on prospectively collected prenatal ACC cases in which amniocentesis was performed between January 2016 and December 2022. ACC was divided into non-isolated and isolated according to the presence or absence of ultrasound abnormalities. Chromosomal microarray analysis (CMA), karyotyping and exome sequencing (ES) were performed after genetic counseling. Pregnancy outcomes were assessed by pediatric neurosurgeons and were followed up by telephone through their parents. RESULTS: Sixty-eight fetuses with ACC were enrolled in this study. CMA detected eight cases with pathogenic copy number variants (CNVs) and all were non-isolated ACC, with a detection rate of 11.8% (8/68). Among the CMA abnormalities, the majority (6/8) were detectable by karyotyping. ES was performed in 26 cases with normal CMA, revealing pathogenic or likely pathogenic gene variations in 12 cases (46.2%, 12/26), involving L1CMA, SMARCB1, PPP2R1A, ARID1B, USP34, CDC42, NFIA and DCC genes. The detection rates of ES in isolated and non-isolated ACC were 40% (6/15) and 54.5% (6/11), respectively. After excluding cases where pregnancy was terminated (56 cases), there were 12 live births, ranging in age from 15 months to 7 years. Of these, 91.7% (11 out of 12) demonstrated normal neurodevelopmental outcomes. Specifically, all five cases with isolated ACC and negative ES results exhibited normal neurodevelopment. The remaining six cases with favorable outcomes were all isolated ACC, among which ES identified variants of DCC and USP34 gene in one each case. The other four cases were CMA-negative and declined ES. CONCLUSIONS: We highlight the efficacy of prenatal ES in determining the genetic etiology of ACC, whether isolated or not. Favorable neurodevelopmental outcomes were observed when ACC was isolated and with normal ES results.
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Casitas B-lymphoma proto-oncogene-b (Cbl-b) is a RING finger E3 ligase that has an important role in effector T cell function, acting as a negative regulator of T cell, natural killer (NK) cell, and B cell activation. A discovery effort toward Cbl-b inhibitors was pursued in which a generative AI design engine, REINVENT, was combined with a medicinal chemistry structure-based design to discover novel inhibitors of Cbl-b. Key to the success of this effort was the evolution of the "Design" phase of the Design-Make-Test-Analyze cycle to involve iterative rounds of an in silico structure-based drug design, strongly guided by physics-based affinity prediction and machine learning DMPK predictive models, prior to selection for synthesis. This led to the accelerated discovery of a potent series of carbamate Cbl-b inhibitors.
Subject(s)
Carbamates , Drug Design , Proto-Oncogene Mas , Proto-Oncogene Proteins c-cbl , Proto-Oncogene Proteins c-cbl/antagonists & inhibitors , Proto-Oncogene Proteins c-cbl/metabolism , Carbamates/chemistry , Carbamates/pharmacology , Carbamates/chemical synthesis , Humans , Structure-Activity Relationship , Models, Molecular , Artificial Intelligence , Drug Discovery , Adaptor Proteins, Signal TransducingABSTRACT
Purpose: To illustrate the characteristics of perforating scleral vessels in macular regions between mCNV eyes and contralateral eyes in unilateral mCNV patients. Methods: This was a retrospective study that included patients with unilateral naive mCNV. The study aimed to identify and analyze the distribution of perforating scleral vessels (PSVs) in the macular region of mCNV eyes and contralateral eyes. The central macular choroidal thicknesses (mChT) were measured using optical coherence tomography angiography (OCTA). The grades of myopic atrophic maculopathy (MAM) and macular myopic diffuse chorioretinal atrophy (DCA) were evaluated within groups. The number of PSVs and mChT were compared between contralateral and mCNV eyes based on the grade of DCA. The ROC curves were utilized to explore the diagnostic indexes for mCNV. Results: A total of 102 eyes from 51 patients with unilateral mCNV were included. There was no significance in the severity of MAM or the grade of DCA between mCNV eyes and contralateral eyes (p = 0.074, p = 0.054, respectively). The mean number of PSVs in mCNV eyes was fewer than the contralateral eyes [1.00 (1.00-2.00) vs. 2.00 (0.75-3.00), p = 0.030]. The mChT in mCNV eyes was thinner than the contralateral eyes [36.00 (25.00-53.75) µm vs. 46.00 (31.00-75.25) µm, p = 0.001]. The mean grade of DCA in mCNV eyes was higher than that in contralateral eyes [3.00 (3.00-3.00) vs. 3.00 (2.00-3.00), p = 0.004]. When DCA involved the macular region, there were more PSVs in contralateral eyes than in mCNV eyes [1.50 (1.00-2.00) vs. 2.00 (1.00-3.00), p = 0.042]. Similarly, when DCA involved the foveal region, there were more PSVs in contralateral eyes than in mCNV eyes [1.50 (1.00-2.00) vs. 3.00 (2.00-4.00), p = 0.004]. The grade of DCA and mChT were valuable factors for predicting mCNV eyes (AUC = 0.6566, p = 0.021; AUC = 0.6304, p = 0.029; respectively). When the extent of DCA exceeded the foveal region, the count of PSVs was a good diagnostic factor for predicting mCNV (AUC = 0.7430, p = 0.003). Conclusion: The mean amount of PSVs was significantly lower in the mCNV eyes compared to the contralateral eyes. When the extent of DCA exceeded the foveal region, the count of PSVs was a good diagnostic factor for predicting mCNV. Myopic eyes with a higher grade of DCA and a thinner mChT were more likely to develop mCNV.
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To investigate the relationship between microphysical and chemical characteristics of size-resolved fog droplets in different regional backgrounds, we conducted observational experiments in urban, mountainous, rainforest, and rural areas of China. Fog water samples across different diameter ranges (4-16 µm, 16-22 µm, and >22 µm) were collected, alongside fog droplet spectra data. Our findings reveal a close relationship between pH value, electrical conductivity (EC), total ion concentration (TIC) of droplets, and droplet sizes, with smaller droplets exhibiting stronger acidity and higher ion concentrations. Significant differences in chemical composition are observed across size ranges and regional backgrounds. Droplet number concentration (N) and liquid water content (LWC) distributions in different regional backgrounds are skewed, with peak diameters of LWC spectra similar to those of N spectra, yet overall spectral distributions varied significantly. Droplet number concentrations are highest in urban area, while large droplets contribute more to overall LWC in mountainous, rainforest, and rural areas. No direct evidence linked LWC or surface area (S) to LWC ratio to water-soluble ion concentrations of size-resolved fog droplets in different regional backgrounds. However, by adjusting the contributions of S and LWC proportions of different-sized droplets to the ion concentration proportions, we find that expanding the LWC proportion to 2.43 times and decreasing the S proportion to 0.2 times for large droplets, while decreasing the LWC ratio to 0.76 times for small droplets, provided a better explanation for the distribution of ion concentrations. This study advances our understanding of the intricate relationship between the microphysical and chemical characteristics of fog, helping to develop more robust and comprehensive models for fog prediction and management.
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PURPOSE: Primary biliary cirrhosis-idiopathic inflammatory myopathy (PBC-IIM) overlap syndrome (OS) is a rare condition in which cardiac involvement is observed. We aimed to characterize the clinical features and associated factors of PBC-IIM OS patients with cardiac involvement. METHODS: Patients with PBC-IIM OS that visited our hospital from January 1983 to December 2021 were enrolled. Clinical presentations and laboratory and imaging data were recorded. The clinical data of patients with and without cardiac involvement were compared. According to the first instance of a disease flare, prognostic factors were also studied. RESULTS: Thirty-four patients with PBC-IIM OS were enrolled. A total of 58.8% of patients presented with muscle weakness at disease onset, which primarily involved skeletal muscle (85.3%). Slight liver dysfunction was discovered in this OS cohort. In patients with cardiac involvement, palpitation (63.6%) and dyspnea (36.4%) were the most common onset symptoms. Arrhythmia was a vital manifestation in OS patients, in which half of OS patients had nonsustained ventricular tachycardia (50.0%, 11/22). Compared with noncardiac involvement, myalgia (4.5%, P=0.004) and fever (0.0%, P=0.011) were reported relatively rarely at disease onset in the group with cardiac involvement. The prognosis analysis showed that positivity for anti-Ro52 (HR=0.00, P=0.034) negatively correlated with relapse in OS patients. CONCLUSION: PBC-IIM OS has unique features. Typical clinical manifestations and early worsening cardiac indicators can be used to identify cardiac involvement and predict prognosis. Anti-Ro52 may have prognostic value for PBC-IIM OS.
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The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-ß. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.
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A facile copper-catalyzed [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with various electron-deficient alkenes to access structurally polyfunctionalized spiro-pyrrolidine-oxindole motifs has been developed. Under the catalytic system, the N-2,2,2-trifluoroethylisatin ketimines could be utilized to react with a series of exocyclic alkenes, including 2-acylamino acrylates, 3-methylene-ß-lactams, and sterically hindered cycloalkenes represented by cyclobutenone, to obtain a variety of densely functionalized spiro-pyrrolidine frameworks bearing an α-amino acid ester, ß-lactam, and cyclobutanone, respectively, in generally good yields with excellent diastereo- and enantioselectivities.
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Diabetic skin wound is a disturbing and rapidly evolving clinical issue. Here, we investigated how salvianolic acid B (Sal B) affected the diabetic wound healing process. Following Sal B administration, histopathological damage was investigated by H&E and Masson staining, and CD34, apoptosis and mitophagy markers were measured by immunofluorescence, immunohistochemistry, and western blotting. Migration, proliferation, and mitochondrial function of high glucose (HG) -induced HMEC-1 cells were measured. The effects of si-Parkin on endothelial cell migration, apoptosis and mitochondrial autophagy were examined. Sal B alleviated inflammatory cell infiltration and promoted angiogenesis in skin wound tissue. Apoptosis and mitophagy were ameliorated by Sal B in diabetic skin wound tissues and HG-induced HMEC-1 cells. Parkin inhibition impaired the migratorypromoted cell apoptosis and inhibited mitophagy of HMEC-1 cells. This finding demonstrated that Sal B promoted diabetic skin wound repair via Pink1/Parkin-mediated mitophagy, improved our understanding of the diabetic wound healing process.
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Pollution control and carbon emission reduction pose significant challenges for developing countries, and achieving synergistic reductions in pollution and carbon emissions (SRPCs) has emerged as the optimal choice. Digitization, a prevailing trend in the current era, presents new opportunities for realizing the SRPC. We utilize data from Chinese A-share listed companies from 2007 to 2022 to investigate the impact of corporate digital transformation on the SRPC. The research reveals the following. (1) Enterprise digital transformation significantly promotes the SRPC, a conclusion validated through a series of robustness tests. However, the SRPC resulting from digital transformation is characterized by weak synergy, which is primarily observed in the coordinated reduction in air pollution and carbon emissions. (2) This effect is notably stronger for companies near environmental regulatory authorities, those receiving government environmental subsidies, and state-owned enterprises (SOEs). (3) Enhancing managerial collaborative management capabilities, promoting corporate technological innovation capabilities, and alleviating financing pressure are the primary mechanisms at play. This research provides important policy and practical insights for promoting the SRPC in the context of digitization, fostering sustainable development.
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Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.