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1.
Org Lett ; 26(37): 7864-7868, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39250002

RESUMO

A hypervalent iodine-reagent-based C-H functionalization strategy was utilized to synthesize diaryl ethers. This method directly transforms various arenes into their corresponding diaryliodonium salts, followed by a C-O coupling reaction to produce structurally diverse diaryl ethers. The efficacy of this approach in the late-stage structural modifications of complex molecules was demonstrated.

2.
Zool Res ; 45(6): 1188-1200, 2024 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-39318126

RESUMO

As an essential transcriptional activator, PDX1 plays a crucial role in pancreatic development and ß-cell function. Mutations in the PDX1 gene may lead to type 4 maturity-onset diabetes of the young (MODY4) and neonatal diabetes mellitus. However, the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models. In this study, three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology, all of which succumbed shortly postpartum, exhibiting pancreatic agenesis. Notably, one tri-allelic PDX1-mutant cynomolgus macaque (designated as M4) developed a pancreas, whereas the two mono-allelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation. RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions, indicating developmental delay and PDX1 haploinsufficiency. A marked change in m6A methylation was identified in the M4 pancreas, confirmed through cultured PDX1-mutant islet organoids. Notably, overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids. This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.


Assuntos
Proteínas de Homeodomínio , Macaca fascicularis , Pâncreas , Transativadores , Animais , Macaca fascicularis/genética , Transativadores/genética , Transativadores/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Mutação , Metilação , Feminino , Pancreatopatias/genética , Pancreatopatias/veterinária , Masculino , Doenças dos Macacos/genética
3.
Huan Jing Ke Xue ; 45(9): 5431-5440, 2024 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-39323160

RESUMO

Soil aggregate stability and organic carbon (SOC) are important indicators of soil structure and quality and play a key role in the improvement of soil quality in temperate deserts. This study aimed to investigate the distribution patterns, stability of soil aggregates, and variation characteristics of the content of aggregate organic carbon in different grassland types in temperate deserts and their interrelationships. Four grassland types in a temperate desert (Kalidium foliatum type, Reaumuria songarica type, Salsola passerina type, and Sympegma regelii type) in the Longzhong Loess Plateau as research objects, and the soil aggregate particle size distribution characteristics were determined using the wet sieving method. The stability of soil aggregates was analyzed by calculating aggregate stability indicators and the contribution of aggregate particle size SOC to bulk soil SOC content. Correlation analysis, principal component analysis, and linear fitting equations were used to reveal the relationship between the soil aggregate content and aggregate particle size SOC and aggregate stability. The results showed that the content of >0.25 mm aggregates (R0.25), mean weight diameter (MWD), geometric mean diameter (GMD), and bulk soil SOC content in each soil layer (0-10, 10-20, and 20-30 cm) of the K. foliatum type grassland were significantly higher than that of the R. songarica type and S. regelii type (P<0.05). The SOC content of 0.053-0.25 mm and <0.053 mm particle size in each soil layer of the K. foliatum type grassland were significantly higher than that of the S. regelii type (P<0.05). Surface and subsurface soils (0-10 cm and 10-20 cm) had the significantly highest contribution of 0.25-2 mm particle size SOC to the bulk soil SOC content (P<0.05). Additionally, as the soil layer deepened, the R0.25, MWD, GMD, bulk soil, and aggregate SOC contents of the K. foliatum type grassland showed a tendency to increase first and then decrease, with the highest contents from 10-20 cm. Kalidium foliatum type grassland aggregate content was dominated by 0.25-2 mm aggregates, whereas the other three grassland types were dominated by 0.053-0.25 mm aggregates. In addition, bulk soil SOC content was significantly correlated with R0.25, MWD, GMD, and ELT (P<0.01), and the 0.25 mm aggregate was the critical size of positive and negative correlation. R0.25, MWD, GMD, and ELT values were the key factors influencing bulk soil SOC in grassland. The equation fitted to bulk soil SOC content, and GMD was the most suitable to describe the relationship between SOC content and the stability of soil aggregates. Therefore, compared with other grassland types, K. foliatum type grassland had a promoting effect on the soil aggregate stability and the improvement of soil quality.

4.
Clinics (Sao Paulo) ; 79: 100497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39284275

RESUMO

INTRODUCTION: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. METHOD: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. RESULTS: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. DISCUSSION: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.


Assuntos
Antifúngicos , Candida auris , Farmacorresistência Fúngica , Fluconazol , Humanos , Farmacorresistência Fúngica/genética , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Virulência/genética , Candida auris/genética , Candida auris/efeitos dos fármacos , Candida auris/patogenicidade , Testes de Sensibilidade Microbiana , Mutação , Pequim , Simulação de Acoplamento Molecular , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Sequenciamento Completo do Genoma , Ásia Meridional
5.
Free Radic Biol Med ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326683

RESUMO

BACKGROUND: Diabetic cognitive dysfunction (DCD) has attracted increased attention, but its precise mechanism remains to be explored. Oligodendrocytes form myelin sheaths that wrap around axons. Granzyme B (GZMB) can cause axonal degeneration of the central nervous system. However, the role of GZMB in diabetic cognitive dysfunction (DCD) has not been reported. This study aimed to investigate whether GZMB promotes demyelination and participates in DCD by regulating the endoplasmic reticulum stress function of oligodendrocytes METHODS: Streptozotocin was injected intraperitoneally to establish a diabetic model in C57BL/6 mice. The mice were randomly divided into four groups: control group, diabetic group, diabetic + SerpinA3N group, and diabetic + saline treatment group. We performed the Morris water maze test to assess the learning and memory abilities of the mice. An immunofluorescence assay was performed to detect the expression sites of GZMB and OLIG2 in the hippocampal CA1 region. Luxol Fast Blue staining and electron microscopy were performed to detect the myelin number and myelin plate densities. Immunohistochemistry was used to detect the expression levels of MBP and CNPase. Protein blotting was used to assess the expression levels of GZMB, PERK, p-PERK, eIF2α, p-eIF2α, NLRP3, Caspase-1, GSDMD-N, IL-1ß, and IL-18 as well as MBP and CNPase. RESULTS: The GZMB inhibitor SerpinA3N reduces escape latency and increases the traversing platforms and residence time in the target area, improving DCD in mice. It also reduces endoplasmic reticulum stress in hippocampal oligodendrocytes and focal prolapse, further promoting MBP and CNPase expression and reducing demyelination. CONCLUSIONS: Our findings suggest that inhibition of GZMB activity modulates oligodendrocyte endoplasmic reticulum stress and pyroptosis, reduces demyelination, and ameliorates diabetes-related cognitive impairment.

6.
Org Lett ; 26(38): 8028-8033, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39283295

RESUMO

Radical cascade cyclizations of N-cyanamide alkenes have been developed for the divergent synthesis of pyrroloquinazolinones bearing azido, alkenyl, and nitro groups by controlling the reaction conditions. The reaction temperature and the loading of the base play important roles in the different reaction pathways. These reactions are characterized by wide functional group compatibility and mild conditions.

7.
Org Biomol Chem ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291542

RESUMO

Treatment of alkyl α-(N-heteroaryl)-α-diazoacetates with alkylating reagents affords diazoacetate N-heteroarenium salts. These novel 'onium' diazo compounds are mostly yellow solids, displaying increased thermal and acid stability. Their tetrafluoroborates undergo rhodium catalyzed [2 + 1] and Doyle-Kirmse reactions under mild conditions, suggesting the N-quaternization an effective means of elimination of N-coordination caused catalyst toxicity.

8.
mBio ; : e0159024, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292005

RESUMO

Isw2 proteins, ubiquitous across eukaryotes, exhibit a propensity for DNA binding and exert dynamic influences on local chromosome condensation in an ATP-dependent fashion, thereby modulating the accessibility of neighboring genes to transcriptional machinery. Here, we report the deletion of a putative MoISW2 gene, yielding substantial ramifications on plant pathogenicity. Subsequent gene complementation and chromatin immunoprecipitation sequencing (ChIP-seq) analyses were conducted to delineate binding sites. RNA sequencing (RNA-seq) assays revealed discernible impacts on global gene regulation along chromosomes in both mutant and wild-type strains, with comparative analyses against 55 external RNA-seq data sets corroborating these findings. Notably, MoIsw2-mediated binding and activities delineate genomic loci characterized by pronounced gene expression variability proximal to MoIsw2 binding sites, juxtaposed with comparatively stable expression in surrounding regions. The contingent genes influenced by MoIsw2 activity predominantly encompass niche-determinant genes, including those encoding secreted proteins, secondary metabolites, and stress-responsive elements, alongside avirulence genes. Furthermore, our investigations unveil a spatial correlation between MoIsw2 binding motifs and known transposable elements (TEs), suggesting a potential interplay wherein TE transposition at these loci could modulate the transcriptional landscape of Magnaporthe oryzae in a strain-specific manner. Collectively, these findings position MoIsw2 as a plausible master regulator orchestrating the delicate equilibrium between genes vital for biomass proliferation, akin to housekeeping genes, and niche-specific determinants crucial for ecological adaptability. Stress-induced TE transposition, in conjunction with MoIsw2 activity, emerges as a putative mechanism fostering enhanced mutagenesis and accelerated evolution of niche-determinant genes relative to housekeeping counterparts.IMPORTANCEIsw2 proteins are conserved in plants, fungi, animals, and other eukaryotes. We show that a fungal Isw2 protein in the rice pathogen Magnaporthe oryzae binds to retrotransposon (RT) DNA motifs and affects the epigenetic gene expression landscape of the fungal genome. Mainly ecological niche determinant genes close to the binding motifs are affected. RT elements occur frequently in DNA between genes in most organisms. They move place and multiply in the genome, especially under physiological stress. We further discuss the Isw2 and RT combined activities as a possible sought-after mechanism that can cause biased mutation rates and faster evolution of genes necessary for reacting to abiotic and biotic challenges. The most important biotic challenges for plant pathogens are the ones from the host plants' innate immunity. The overall result of these combined activities will be an adaptation-directed evolution of niche-determinant genes.

9.
Biomark Res ; 12(1): 105, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289775

RESUMO

Methyltransferase-like protein is a ubiquitous enzyme-like protein in the human body, with binding domains for nucleic acids, proteins and other small molecules, and plays an important role in a variety of biological behaviours in normal organisms and diseases, characterised by the presence of a methyltransferase-like structural domain and a structurally conserved SAM-binding domain formed by the seven-stranded ß-fold structure in the center of the protein. With the deepening of research, the METTL protein family has been found to be abnormally expressed in a variety of tumor diseases, and the clarification of its relationship with tumor diseases can be used as a molecular therapeutic target and has an important role in the prognosis of tumors. In this paper, we review the structure, biological process, immunotherapy, drug-targeted therapy, and markers of the METTL protein family to provide new ideas for the diagnosis and treatment of tumors.

10.
Heliyon ; 10(18): e36203, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39309903

RESUMO

This paper presents a detailed analysis of a case initially misdiagnosed as Idiopathic Thrombocytopenic Purpura (ITP), which was later correctly identified as MYH9-related disease (MYH9-RD), a rare genetic disorder characterized by thrombocytopenia, large platelets, and Döhle-like inclusion bodies in neutrophils. Using advanced slide reading technology, our team identified hallmark features of MYH9-RD in the patient's blood samples, leading to genetic testing that confirmed a spontaneous mutation in the MYH9 gene. This report highlights the diagnostic journey, emphasizing the crucial role of recognizing specific hematologic signs to accurately diagnose MYH9-RD. By comparing our findings with existing literature, we highlight the genetic underpinnings and clinical manifestations of MYH9-RD, emphasizing the necessity for heightened awareness and diagnostic precision in clinical practice to prevent similar cases of misdiagnosis. This case demonstrates the importance of integrating genetic testing into routine diagnostic protocols for unexplained thrombocytopenia, paving the way for improved patient care and treatment outcomes.

11.
Physiol Mol Biol Plants ; 30(9): 1475-1491, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39310708

RESUMO

Melon (Cucumis melo L.) is a horticultural crop that is planted globally. Cucumis melo L. cv. Baogua is a typical melon that is suitable for studying fruit development because of its ability to adapt to different climatic conditions. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs longer than 200 nucleotides, which play important roles in a wide range of biological processes by regulating gene expression. In this study, the transcriptome of the Baogua melon was sequenced at three stages of the process of fruit development (14 days, 21 days, and 28 days) to study the role of lncRNAs in fruit development. The cis and trans lncRNAs were subsequently predicted and identified to determine their target genes. Notably, 1716 high-confidence lncRNAs were obtained in the three groups. A subsequent differential expression analysis of the lncRNAs between the three groups revealed 388 differentially expressed lncRNAs. A total of 11 genes were analyzed further to validate the transcriptome sequencing results. Interestingly, the MELO3C001376.2 and MSTRG.571.2 genes were found to be significantly (P < 0.05) downregulated in the fruits. This study provides a basis to better understand the functions and regulatory mechanisms of lncRNAs during the development of melon fruit.

12.
Proc Natl Acad Sci U S A ; 121(40): e2405117121, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39312657

RESUMO

Cholinergic neurons in the basal forebrain play a crucial role in regulating adult hippocampal neurogenesis (AHN). However, the circuit and molecular mechanisms underlying cholinergic modulation of AHN, especially the initial stages of this process related to the generation of newborn progeny from quiescent radial neural stem cells (rNSCs), remain unclear. Here, we report that stimulation of the cholinergic circuits projected from the diagonal band of Broca (DB) to the dentate gyrus (DG) neurogenic niche promotes proliferation and morphological development of rNSCs, resulting in increased neural stem/progenitor pool and rNSCs with longer radial processes and larger busy heads. Interestingly, DG granule cells (GCs) are required for DB-DG cholinergic circuit-dependent modulation of proliferation and morphogenesis of rNSCs. Furthermore, single-nucleus RNA sequencing of DG reveals cell type-specific transcriptional changes in response to cholinergic circuit stimulation, with GCs (among all the DG niche cells) exhibiting the most extensive transcriptional changes. Our findings shed light on how the DB-DG cholinergic circuits orchestrate the key niche components to support neurogenic function and morphogenesis of rNSCs at the circuit and molecular levels.


Assuntos
Neurônios Colinérgicos , Giro Denteado , Células-Tronco Neurais , Neurogênese , Animais , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Giro Denteado/metabolismo , Giro Denteado/citologia , Neurogênese/fisiologia , Neurônios Colinérgicos/metabolismo , Neurônios Colinérgicos/fisiologia , Camundongos , Proliferação de Células , Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/fisiologia , Células-Tronco Adultas/citologia , Morfogênese , Nicho de Células-Tronco/fisiologia , Masculino
13.
Anal Bioanal Chem ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316091

RESUMO

Exosome analysis plays pivotal roles in various physiological and pathological processes. Plasmonic scattering microscopy (PSM) has proven to be an excellent label-free imaging platform for exosome detection. However, accurately detecting images scattered from exosomes remains a challenging task due to noise interference. Herein, we proposed an image processing strategy based on a new blind super-resolution deep learning neural network, named ESRGAN-SE, to improve the resolution of exosome PSI images. This model can obtain super-resolution reconstructed images without increasing experimental complexity. The trained model can directly generate high-resolution plasma scattering images from low-resolution images collected in experiments. The results of experiments involving the detection of light scattered by exosomes showed that the proposed super-resolution detection method has strong generalizability and robustness. Moreover, ESRGAN-SE achieved excellent results of 35.52036, 0.09081, and 8.13176 in terms of three reference-free image quality assessment metrics, respectively. These results show that the proposed network can effectively reduce image information loss, enhance mutual information between pixels, and decrease feature differentiation. And, the single-image SNR evaluation score of 3.93078 also showed that the distinction between the target and the background was significant. The suggested model lays the foundation for a potentially successful approach to imaging analysis. This approach has the potential to greatly improve the accuracy and efficiency of exosome analysis, leading to more accurate cancer diagnosis and potentially improving patient outcomes.

14.
Sci Rep ; 14(1): 20787, 2024 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242661

RESUMO

Ferroptosis is an important pathological mechanism of chronic heart failure (CHF). This study aimed to investigate the protective mechanism of Astragaloside IV (AS-IV) on CHF rats by integrating bioinformatics and ferroptosis. CHF-related targets and ferroptosis-related targets were collected. After the intersection, the common targets were obtained. The PPI network of the common targets was constructed, and topological analysis of the network was carried out. The target with the highest topological parameter values was selected as the key target. The key target p53 was obtained through bioinformatics analysis, and its molecular docking model with AS-IV was obtained, as well as molecular dynamics simulation analysis. The rat models of CHF after myocardial infarction were established by ligation of left coronary artery and treated with AS-IV for 4 weeks. AS-IV treatment significantly improved cardiac function in CHF rats, improved cardiomyocyte morphology and myocardial fibrosis, reduced mitochondrial damage, decreased myocardial MDA and Fe2+ content, increased GSH content, inhibited the expression of p53 and p-p53, and up-regulated the expression of SLC7A11 and GPX4. In conclusion, AS-IV improved cardiac function in CHF rats, presumably by regulating p53/SLC7A11/GPX4 signaling pathway and inhibiting myocardial ferroptosis.


Assuntos
Biologia Computacional , Ferroptose , Insuficiência Cardíaca , Saponinas , Triterpenos , Animais , Ferroptose/efeitos dos fármacos , Triterpenos/farmacologia , Saponinas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Ratos , Biologia Computacional/métodos , Masculino , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Simulação de Acoplamento Molecular , Doença Crônica , Modelos Animais de Doenças , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Simulação de Dinâmica Molecular , Miocárdio/metabolismo , Miocárdio/patologia
15.
Acta Pharmacol Sin ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223367

RESUMO

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

16.
Inflammation ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39289212

RESUMO

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

18.
JMIR Perioper Med ; 7: e63076, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269754

RESUMO

BACKGROUND: Preoperative cardiac risk assessment is an integral part of preoperative evaluation; however, there is significant variation among providers, leading to inappropriate referrals for cardiology consultation or excessive low-value cardiac testing. We implemented a novel electronic medical record (EMR) form in our preoperative clinics to decrease variation. OBJECTIVE: This study aimed to investigate the impact of the EMR form on the preoperative utilization of cardiology consultation and cardiac diagnostic testing (echocardiograms, stress tests, and cardiac catheterization) and evaluate postoperative outcomes. METHODS: A retrospective cohort study was conducted. Patients who underwent outpatient preoperative evaluation prior to an elective surgery over 2 years were divided into 2 cohorts: from July 1, 2021, to June 30, 2022 (pre-EMR form implementation), and from July 1, 2022, to June 30, 2023 (post-EMR form implementation). Demographics, comorbidities, resource utilization, and surgical characteristics were analyzed. Propensity score matching was used to adjust for differences between the 2 cohorts. The primary outcomes were the utilization of preoperative cardiology consultation, cardiac testing, and 30-day postoperative major adverse cardiac events (MACE). RESULTS: A total of 25,484 patients met the inclusion criteria. Propensity score matching yielded 11,645 well-matched pairs. The post-EMR form, matched cohort had lower cardiology consultation (pre-EMR form: n=2698, 23.2% vs post-EMR form: n=2088, 17.9%; P<.001) and echocardiogram (pre-EMR form: n=808, 6.9% vs post-EMR form: n=591, 5.1%; P<.001) utilization. There were no significant differences in the 30-day postoperative outcomes, including MACE (all P>.05). While patients with "possible indications" for cardiology consultation had higher MACE rates, the consultations did not reduce MACE risk. Most algorithm end points, except for active cardiac conditions, had MACE rates <1%. CONCLUSIONS: In this cohort study, preoperative cardiac risk assessment using a novel EMR form was associated with a significant decrease in cardiology consultation and testing utilization, with no adverse impact on postoperative outcomes. Adopting this approach may assist perioperative medicine clinicians and anesthesiologists in efficiently decreasing unnecessary preoperative resource utilization without compromising patient safety or quality of care.

19.
Food Chem X ; 23: 101764, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39280217

RESUMO

This study used headspace solid-phase microextraction-gas chromatography-mass spectrometry and multivariate statistical analysis to comprehensively analyze the volatile components in Liupao tea samples throughout fermentation. In total, 1009 volatile organic compounds were detected and identified, including terpenoids, heterocyclic compounds, esters, ketones, hydrocarbons, alcohols, aromatics, and acids. Principal component and hierarchical cluster analyses, characterize the volatile components of Liupao tea samples were characterized at various fermentation stages. Orthogonal partial least squares discriminant analysis identified 248 differentiating compounds (VIP ≥ 1, P < 0.05, and |Log2FC| ≥ 1.0) during fermentation. K-means clustering analysis showed that 11 metabolites increased significantly throughout the fermentation process, whereas 31 metabolites decreased continuously. Annotation of these differential compounds revealed significant changes in sensory flavor characteristics in "green, sweet, fruity, floral, and woody" flavors. The results demonstrated significant variations in the volatile components of Liupao tea fermentation, along with notable changes in flavor characteristics.

20.
Virol J ; 21(1): 206, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223668

RESUMO

BACKGROUND: Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021-2022. METHODS: A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. RESULTS: The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). CONCLUSION: In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.


Assuntos
Vírus da Parainfluenza 1 Humana , Filogenia , Humanos , China/epidemiologia , Pré-Escolar , Criança , Vírus da Parainfluenza 1 Humana/genética , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Masculino , Feminino , Lactente , Adolescente , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Nasofaringe/virologia , Infecções por Respirovirus/epidemiologia , Infecções por Respirovirus/virologia , Recém-Nascido
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