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Proteinuria is a biomarker of kidney injury that typically results from glomerular and/or tubulointerstitial disease. Whereas kidney impairment with normal urinary protein excretion is usually less focused and understudied. We conducted a retrospective review of the renal histopathology of the patients with variable degrees of unexplained renal insufficiency but with normal range proteinuria between 2014 and 2024 of three university teaching hospitals in Shenzhen city of Southern China. Patients with kidney dysfunction of undetermined or uncertain etiology and with normal urinary protein excretion (defined by a 24hr urinary protein excretion < 150 mg or spot urinary protein to creatinine ratio [PCR] < 150 mg/g) were enrolled and analyzed. In a total of 2405 patients, 53 (2.2%) fulfilled the inclusion criteria (male/female 40/13, age 47.3 ± 14.3 years) with a mean eGFR of 46.6 ± 16.8 ml/min per 1.73 m2. Glomerular disease (GD) was the most frequent pathological finding identified in 23 (43.4%) patients, while 19 (35.8%) cases showed tubulointerstitial disease (TID) and 11 (20.8%) patients exhibited small vascular disease (SVD). Patients in the TID had the lowest mean eGFR and the highest numerical 24hr urinary protein excretion among the three groups. The incidence of acute kidney injury was significantly higher in TID than in other two groups. The patients in the SVD group had the highest fraction of underlying hypertension. Kidney dysfunction with normal range proteinuria may be related with, in descending order of probablity, glomerular, tubulointerstitial and small vascular diseases. Renal biopsies were proved useful in informing therapeutic choice, long-term management and in predicting prognosis in this setting.
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Rim , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , China/epidemiologia , Rim/patologia , Proteinúria , Taxa de Filtração Glomerular , Injúria Renal Aguda/patologia , Injúria Renal Aguda/etiologia , IdosoRESUMO
BACKGROUND: As a pivotal pathway of programmed cell death, necroptosis significantly contributes to the pathogenesis of respiratory disorders. However, its role in asthma is not yet fully elucidated. Therefore, this study aimed to identify markers associated with necroptosis, evaluate their functions in asthma, and explore potential therapeutic agents targeting necroptosis for the management of asthma. METHODS: Firstly, machine learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were utilized to identify necroptosis-related differentially expressed genes (NRDEGs) in asthma patients compared to healthy controls. Concurrently, the expression of NRDEGs was validated using external datasets, Western blot, and quantitative real-time polymerase chain reaction (qPCR). Secondly, the clinical relevance of NRDEGs was assessed through Receiver Operating Characteristic (ROC) curve analysis and correlation with clinical indicators. Thirdly, the relationship between NRDEGs and pulmonary immune cell infiltration, as well as the signaling interactions between different cells types, were analyzed through immune infiltration and single-cell analysis. Fourthly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), were conducted to elucidate the functional roles of NRDEGs. Finally, compounds targeting NRDEGs were screened, and their binding affinities were evaluated using molecular docking studies. RESULTS: In asthma, necroptosis is activated, leading to the identification of four NRDEGs: NLRP3, PYCARD, ALOX15, and VDAC3. Among these, NLRP3, PYCARD, and ALOX15 are upregulated, whereas VDAC3 is downregulated in asthma. Comprehensive clinical evaluations indicated that NRDEGs hold diagnostic value for asthma. Specifically, NLRP3 was inversely correlated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), while VDAC3 showed an inverse correlation with sputum neutrophils. Conversely, ALOX15 expression was positively correlated with fractional exhaled nitric oxide (FeNO) levels, as well as sputum eosinophils, blood eosinophils, and blood IgE levels. Subsequent immune infiltration analysis revealed associations between NRDEGs and activated dendritic cells, mast cells, and eosinophils. Single-cell RNA sequencing (scRNA-seq) further confirmed the communication signals between myeloid dendritic cells, fibroblasts, neutrophils, and helper T cells, predominantly related to fibrosis and immune-inflammatory responses. Pathway enrichment analysis demonstrated that NRDEGs are involved in ribosomal function, oxidative phosphorylation, and fatty acid metabolism. Finally, resveratrol and triptonide were identified as potential therapeutic agents targeting the proteins encoded by NRDEGs for asthma treatment. CONCLUSIONS: The necroptosis pathway is activated in asthma, with NRDEGs-namely PYCARD, NLRP3, ALOX15, and VDAC3-correlated with declines in lung function and airway inflammation. These genes serve as reliable predictors of asthma risk and are involved in the regulation of the immune-inflammatory microenvironment. Resveratrol and triptolide have been identified as promising therapeutic candidates due to their potential to target the proteins encoded by these genes.
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Acute kidney injury (AKI) is an important clinical syndrome characterised by a sudden decline in renal function, often accompanied by renal inflammation and tubular epithelial cell damage. It has been reported that inhibiting DNA methylation significantly suppress the progression of AKI. In the current study, we investigate the effect of the DNA methyltransferase (DNMT) inhibitor RG108 in cisplatin- and hypoxia-reoxygenation-induced AKI. The expression of kidney injury molecules and inflammatory factors was examined by immunofluorescence, Western blotting and Real-time PCR. The results demonstrated that RG108 treatment significantly reduced kidney inflammation and injury. Furthermore, RNA-seq analysis was performed to reveal the regulatory mechanism of RG108 in AKI. The expression of the FOS and JUN genes, which are downstream of the MAPK pathway, were significant increased in AKI. Meanwhile, the expression of FOS and JUN were both inhibited by RG108, which is similar to what we found treatment with a specific JNK inhibitor and a specific p38 MAPK inhibitor, and thus attenuated renal inflammation and injury. In conclusion, we suggest that RG108 inhibits P38 MAPK/FOS and JNK/JUN pathways and attenuates renal injury and inflammatory responses. In these results, RG108 may become a novel MAPK pathway inhibitor and a clinical candidate for the treatment of AKI.
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The locked segment is critical for determining the stability of locked segment-type landslides. Research indicates that the volume expansion point marks the transition from the secondary creep stage to the tertiary creep stage in a landslide's evolution, and also separates the stable crack growth stage from the unstable crack growth stage in the locked segment. Identifying the volume expansion point is essential for early warning and predicting locked segment-type landslides. A series of instruments (resistance strain gauges, acoustic emission system, piezoelectric acceleration sensors, etc.) were used to conduct physical model tests of the landslide with retaining-wall-like locked segment under external load on the landslide's trailing edge. The evolution process of this landslide was analyzed through changes in slope shape and stress response characteristics. The experimental results reveal the failure mechanism of the landslide with retaining-wall-like locked segment: the upper part of the landslide thrusts and slides, the middle part squeezes and uplifts, the retaining-wall-like locked segment produces a locking effect, and compression-shear fracture of the retaining-wall-like locked segment leads to landslide failure. Based on the deformation and acoustic emission characteristics of the locked segment, a method for identifying the volume expansion point was established. This point was used as the onset of acceleration point in the inverse velocity method to predict the failure time of the locked segment-type landslides, incorporating the three-stage creep model and Fukumoto's theory.
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In this study, we elucidated the chemical and biological inactivation mechanisms of peroxydisulfate (PDS) activated by UVA and Fe2+ (UVA/Fe2+/PDS) in wild-type antibiotic-resistant bacteria (ARB) isolated from a river in Inner Mongolia. Among the screened wild-type ARB, the relative abundance of unidentified Enterobacteriaceae, Stenotrophomonas, and Ralstonia was high. A ratio of 1:1 for Fe2+ and PDS under 18 W·m-2 UVA radiation (sunny days) completely inactivated the environmental ARB isolates. In the macro view of the inactivation process, Fe2+ first activates PDS rapidly, and later the UVA energy accumulated starts to activate PDS; HO⢠then becomes the main active species at a rate-limiting step. From a micro perspective, damage to the cell wall, intracellular proteins, inactivation of antioxidant enzymes, and genetic material degradation are the inactivation series of events by UVA/Fe2+/PDS, contributing to the 97.8 % inactivation of ARB at the initial stage. No regrowth of sublethal ARBs was observed. The transfer of tetracycline resistance genes from ARB to lab E. coli was evaluated by horizontal gene transfer (HGT), in which no HGT occurred when ARB was eliminated by UVA/Fe2+/PDS. Moreover, the sulfate and iron residuals in the effluents of treated water were lower than the drinking water standards. In summary, PDS, UVA, and Fe2+ activation effectively inactivated wild ARB with a low concentration of reagents, while inhibiting their regrowth and spread of resistance due to the contribution of intracellular inactivation pathways.
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To convert Na2SO4 into other high-value products (NaOH, H2SO4, and (NH4)2SO4), three types of cell configurations of electrodialysis (ED) were applied (three-compartment bipolar membrane ED (BMED), four-compartment ED metathesis (EDM) and five-compartment bipolar membrane ED multifunction (BMEDM)) and parameters such as average voltage variation, removal ratio of salt, product concentration, conversion rate, ion flux, and energy consumption were calculated and compared. The experimental results and calculations indicated that the overall performance of BMEDM was inferior to that of BMED and EDM. An industrial model was established, which indicated that the net profit from converting Na2SO4 using BMEDM was always higher than that from BMED and EDM. Based on the advantages of low investment (132 $) and energy cost (152 $/t Na2SO4), EDM was applicable to factories with a low output of Na2SO4 (production capacity <45%), whereas BMED (157.3 $/t Na2SO4) and BMED-5 (227.6 $/t Na2SO4) were applicable to factories with a high output of Na2SO4 (production capacity >45%) based on high net profits.
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BACKGROUND: In hepatocellular carcinoma (HCC) treatment, first-line targeted therapy in combination with immune checkpoint inhibitors (ICIs) has improved patient prognosis, but the 5-year survival rate is far from satisfactory. Studies have shown that the extracellular matrix (ECM) is an essential part of the tumour microenvironment (TME) and participates in the progression of malignant tumours. ECM remodelling can enhance matrix stiffness in cirrhosis patients, induce an immunosuppressive microenvironment network, and affect the efficacy of targeted therapies and ICIs for treating HCC. However, the exact mechanism is still unclear. METHODS: We downloaded data from public databases, selected differentially expressed ECM proteins associated with matrix stiffness, constructed and validated a prognostic model of HCC using Lasso Cox regression, and investigated the roles and mechanism of one of the ECM proteins, dynein light chain LC8-type 1 (DYNLL1), in HCC proliferation, migration, and apoptosis via in vitro experiments. RESULTS: In this study, the risk score of the matrix stiffness-related ECM protein model effectively predicted the prognosis of HCC patients. The high- and low-risk subgroups of the model also showed differences in immune cells, immune functions, and drug sensitivity. DYNLL1 promoted HCC cell progression and migration and inhibited HCC cell apoptosis through the Wnt/ß-catenin pathway in vitro. CONCLUSION: The expression of matrix stiffness-related ECM proteins could be an independent predictor of HCC prognosis. DYNLL1, an oncogenic gene in HCC, has the potential to be a new target for HCC treatment.
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Carcinoma Hepatocelular , Progressão da Doença , Matriz Extracelular , Neoplasias Hepáticas , Microambiente Tumoral , Via de Sinalização Wnt , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Matriz Extracelular/metabolismo , Prognóstico , Dineínas do Citoplasma/metabolismo , Dineínas do Citoplasma/genética , Proliferação de Células , Proteínas da Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , MasculinoRESUMO
BACKGROUND: Melasma is a therapeutically challenging hyperpigmented skin condition. Currently, there is a lack of in vivo observation regarding changes in melanin and dendritic melanocytes after laser treatment. OBJECTIVE: To investigate alterations in melanin and melanocytes in melasma before and after laser treatment using optical coherence tomography (OCT). METHODS: Eight female melasma patients were enrolled in Taiwan. Based on the baseline OCT scans, the patients were categorized into either epidermal-type or mixed-type melasma and were assigned different treatment protocols accordingly. Sequential OCT images were collected from melasma lesions and normal skin at baseline, Week 4 and Week 8. RESULTS: After 8 weeks of laser treatment, the mean Melasma Area Severity Index (MASI) score improved from 10.92 to 6.30. Results from OCT showed no significant changes in the normalized density, area, or intensity of melanin in both lesional and normal skin. At baseline, the mean length of dendritic melanocytes in the affected skin was 15% longer than those in normal skin; at Week 8, the mean length of lesional dendritic melanocytes became the same as those in normal skin. Additionally, the mean width of dendritic melanocytes decreased from being 4% wider to only 2% wider than those in normal skin. CONCLUSION: After 8 weeks of treatment, an improvement of MASI score was noted, mainly attributable to a reduction in lesional area. OCT showed no notable change regarding melanin, but a decrease in length and width of dendritic melanocytes was noted in the lesional skin of melasma patients.
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Awake-prone position combined with noninvasive ventilation or high-flow nasal cannula ventilation has been shown to be safe in the treatment of patients with moderate to severe ARDS and COVID-19, and may avoid intubation and reduce patient mortality. We conducted a cross-sectional study in a hospital to observe the effect of prone position on neurological patients with SARS-CoV-2. A total of 52 neurological patients with SARS-CoV-2 participated in the survey. Most patients (76.92%) had cerebrovascular disease combined with SARS-CoV-2. After prone position, the oxygen saturation increased by 3.25% ± 3.02%. The number of patients with an oxygen saturation of 95% or more increased by 28.85%. Among the 3 types of neurological diseases, the oxygen saturation improvement values in patients with encephalitis or encephalopathy was the greatest, and cerebrovascular disease was the least. Oxygen saturation improvements did not differ among delivery modes. Prone position nursing can improve the effect of oxygen therapy on patients with neurological diseases combined with SARS-CoV-2 infection. Prone position nursing can slow the need for advanced equipment such as ventilators during the COVID-19 pandemic.
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COVID-19 , Doenças do Sistema Nervoso , Humanos , COVID-19/terapia , COVID-19/complicações , Estudos Transversais , Decúbito Ventral , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doenças do Sistema Nervoso/terapia , Doenças do Sistema Nervoso/etiologia , SARS-CoV-2 , Adulto , Saturação de Oxigênio , Oxigenoterapia/métodos , Posicionamento do Paciente/métodosRESUMO
BACKGROUND: The most popular traditional Chinese exercise (TCE) techniques include Tai Chi, Yijinjing, Baduanjin, Wuqinxi, and Qigong. Exercise is advised as a primary treatment for knee osteoarthritis (KOA) according to clinical standards. According to several studies, TCE may be an effective way to help people with KOA manage their pain, stiffness, and physical function. Which TCE therapy is the most effective and whose particular usefulness is still debatable. The network meta-analysis (NMA) method is used in this study to evaluate and compare the effects of various TCE therapies on KOA patients. METHODS: We will search PubMed, Embase, Scopus, Cochrane Library, Web of Science, the China National Knowledge Infrastructure, Wanfang, the Chinese Scientific Journal Database (VIP), and the China Biology Medical Literature Database (CBM) for randomized controlled trials reporting TCE therapy for KOA patients published before October 25, 2023. The Stata 16.0 program will compare the effectiveness of various TCE therapies on KOA patients using conventional pairwise and NMA. RESULTS: The final 29 studies included 15 articles on Tai Chi, 7 articles on Baduanjin, 4 articles on Wuqinxi, and 3 articles on Yijinjing. Tai Chi was first for the effect sizes of VAS scores, WOMAC pain scores, and WOMAC available scores, while Baduanjin was ranked top for WOMAC stiffness scores. Research should continue to be conducted on the effect of Qigong on KOA intervention. CONCLUSIONS: This NMA will help determine the best TCE treatment for KOA and offer evidence-based bias for clinical decision-making.
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Terapia por Exercício , Osteoartrite do Joelho , Humanos , Terapia por Exercício/métodos , Medicina Tradicional Chinesa/métodos , Metanálise em Rede , Osteoartrite do Joelho/terapia , Qigong/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tai Chi Chuan/métodos , Resultado do TratamentoRESUMO
Sinonasal squamous cell carcinoma (SNSCC) is an aggressive cancer affecting the nasal and sinus regions, with its progression factors, particularly genetic ones, not yet fully understood. Here, we first conducted a retrospective study with 219 SNSCC patients to identify clinical factors affecting SNSCC prognosis. Additionally, we mined a vast literature dataset to uncover genetic factors associated with SNSCC progression. Based on this data, we constructed SNSCC prognosis pathways and performed a gene set enrichment analysis (GSEA). Clear operative margins were linked to a 73.5-86.3% improvement in overall survival and a 73.5-88.9% lower risk of recurrence. Nasal cavity-originated cases exhibited a 67.6-97.4% decrease in mortality and an 80.7-96.7% lower recurrence rate. Patients at T1-2 staging had a 65.0-80.6% reduced risk of death and recurrence compared to those at T3 stage. Additionally, we identified 53 genes associated with SNSCC, with 14 also implicated in primary tumor site, T stage, and operative margin. These genes, including EGFR, PIK3CA, ERBB2, PTEN, BCL2, BRAF, KRAS, and PRL, form a complex SNSCC-prognosis pathway and were significantly enriched in 42 KEGG pathways and Gene Ontology (GO) terms (FDR-corrected p-value < 0.001), influencing cell growth, apoptosis, and oncogenic signaling pathways. Our study suggests that three clinical parameters (operative margin type, primary tumor site, and T-stage) and 14 genetic factors may influence SNSCC prognosis post-surgery. These findings deepen our understanding of SNSCC and offer potential avenues to enhance its treatment and outcomes.
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Carcinoma de Células Escamosas , Humanos , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias dos Seios Paranasais/genética , Neoplasias dos Seios Paranasais/cirurgia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/mortalidade , Recidiva Local de Neoplasia/genética , Estadiamento de Neoplasias , Adulto , Idoso de 80 Anos ou mais , Regulação Neoplásica da Expressão GênicaRESUMO
Cytochrome P450 monooxygenases (P450s), a multifunctional protein superfamily, are one of three major classes of detoxification enzymes. However, the diversity and functions of P450 genes from pyrethroid-resistant populations of Anopheles sinensis have not been fully explored. In this study, P450 genes associated with pyrethroid resistance were systematically screened using RNA-seq in three field pyrethroid-resistant populations (AH-FR, CQ-FR, YN-FR) and one laboratory resistant strain (WX-LR) at developmental stages, tissues, and post blood-meal in comparison to the laboratory susceptible strain (WX-LS) in An. sinensis. Importantly, the expression of significantly upregulated P450s was verified using RT-qPCR, and the function of selected P450s in pyrethroid detoxification was determined with RNA interference using four laboratory pyrethroid-resistant strains (WX-LR, AH-LR, CQ-LR, YN-LR). Sixteen P450 genes were significantly upregulated in at least one field-resistant population, and 44 were significantly upregulated in different developmental stages, tissues or post blood-meal. A total of 19 P450s were selected to verify their association with pyrethroid resistance, and four of them (AsCYP6P3v1, AsCYP6P3v2, AsCYP9J10, and AsCYP9K1) demonstrated significant upregulation in laboratory pyrethroid-resistant strains using RT-qPCR. Knockdown of these four genes all significantly reduced pyrethroid resistance and increased the mortality by 57.19% (AsCYP6P3v1 and AsCYP6P3v2 knockdown group), 38.39% (AsCYP9K1 knockdown group) and 48.87% (AsCYP9J10 knockdown group) in An. sinensis by RNAi, which determined the pyrethroid detoxification function of these four genes. This study revealed the diversity of P450 genes and provided functional evidence for four P450s in pyrethroid detoxification in An. sinensis for the first time, which increases our understanding of the pyrethroid resistance mechanism, and is of potential value for pyrethroid resistance detection and surveillance.
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Assessing the functional traits and ecological stoichiometric characteristics of dominant species across different life forms within plant communities in karst environments and investigating the inherent connection between them can provide insights into how species adjust their functional attributes in response to habitat heterogeneity. This approach offers a more comprehensive understanding of ecosystem processes and functions in contrast to examination of the taxonomic diversity of species. This study examines the relationship between the functional characteristics of dominant species in plant communities of various life forms in karst environments, focusing on deciduous leaf-soil ecological stoichiometry. The investigation relies on community science surveys, as well as the determination and calculation of plant functional traits and ecological stoichiometries, in plant communities of various life forms in Guizhou (a province of China). The findings of our study revealed considerable variability in the functional trait characteristics of dominant species across different plant-community life forms. Specifically, strong positive correlations were observed among plant height (PLH), leaf area (LA), leaf dry matter content (LDMC), and specific leaf area (SLA) in the dominant species. Additionally, our results indicated no significant differences in leaf ecological stoichiometry among different life forms. However, we did observe significant differences and strong positive correlations between soil N:P, withered material C:N, and apomictic C:P. Furthermore, our study found that plant height (PLH), leaf area (LA), and specific leaf area (SLA) were particularly sensitive to the ecological stoichiometry of soil and apomixis. The results of our study suggest that the functional traits of diverse plant-community life forms in karst regions are capable of adapting to environmental changes through various expressions and survival strategies. The development of various plant-community life forms in karst areas is particularly vulnerable to phosphorus limitation, and the potential for litter decomposition and soil nutrient mineralization is comparatively weaker. The functional traits of various plant-community life forms in karst regions exhibit greater sensitivity to both the soil's C:N ratio and the C:N ratio of apomictic material. Habitat variations may influence the ecological stoichiometric characteristics of the plant leaf-apomictic soil continuum.
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We report herein that nickel-mediated trifluoromethylation of chlorinated and brominated phenol derivatives ClArOTs and BrArOTf gave chloro(bromo)trifluoromethylarenes through the chemoselective cleavage of Ar-O bonds. Furthermore, under similar reaction conditions, the chemoselective trifluoromethylation of Ar-Cl and Ar-Br bonds of ClArOPiv and BrArOTs was achieved to give trifluoromethylated phenol derivatives.
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Phytochemical investigation on the leaves of Tibetan Leucosceptrum canum, a Chinese medicinal herb, led to the isolation of seven new leucosceptrane sesterterpenoids (1-7) and five known analogs (8-12). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRMS), quantum chemistry computations, and single crystal X-ray crystallographic analysis were applied to elucidate their structures. Compounds 1-3 and 6 were the first examples of the leucosceptrane sesterterpenoids with rare C-2 oxidation. Compound 2 exhibited immunosuppressive activities via suppressing the secretion of cytokines IL-6 and TNF-α in LPS-induced macrophages RAW264.7 with IC50 values of 13.39 and 19.34 µM, respectively.
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Imunossupressores , Compostos Fitoquímicos , Folhas de Planta , Sesterterpenos , Camundongos , Animais , Células RAW 264.7 , Estrutura Molecular , Folhas de Planta/química , Imunossupressores/farmacologia , Imunossupressores/isolamento & purificação , Imunossupressores/química , Sesterterpenos/isolamento & purificação , Sesterterpenos/farmacologia , Sesterterpenos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , TibetRESUMO
Approximately two-thirds of patients with asthma, a common inflammatory airway disease, are thought to present with allergies. Probiotics and tryptophan metabolites are becoming increasingly important in treating allergic asthma. This study aimed to identify potential probiotic strains and tryptophan metabolites that could alleviate asthma symptoms. Based on in vitro fermentation experiments, we evaluated variations in probiotic capacity to metabolize tryptophan. Of the eight tested strains, Bifidobacterium animalis subsp. lactis CCFM1274 produced relatively high levels of indole-3-carboxaldehyde (I3C). A mouse model of allergic asthma was established by oral administration of ovalbumin (OVA) and was subjected to oral administration of probiotics. The results demonstrated that treatment with CCFM1274 reduced the tendency for body weight loss and mortality in OVA-induced asthmatic mice. Ingestion of CCFM1274 improved the infiltration of perivascular and peribronchial inflammatory cells in the lung sections stained with hematoxylin and eosin (H&E). This outcome was accompanied by a reduction in the serum levels of OVA-specific immunoglobulin E (OVA-sIgE) and in the levels of IL-10 and IL-17 in the bronchoalveolar lavage fluid (BALF). The linear discriminant analysis effect size (LEfSe) of the gut microbiota showed that CCFM1274 increased the relative abundance of Bifidobacterium. In conclusion, CCFM1274 remodeled intestinal tryptophan metabolism in mice and contributed to the improvement of allergic asthma.
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Asma , Bifidobacterium animalis , Microbioma Gastrointestinal , Camundongos Endogâmicos BALB C , Probióticos , Triptofano , Animais , Triptofano/metabolismo , Asma/tratamento farmacológico , Camundongos , Probióticos/farmacologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Ovalbumina , Modelos Animais de Doenças , Imunoglobulina E , Líquido da Lavagem Broncoalveolar/química , Intestinos/microbiologia , Humanos , Indóis/farmacologiaRESUMO
BACKGROUND: The level of the regulator of G-protein signaling 4-1 (RGS4-1) isoform, the longest RGS4 isoform, is significantly reduced in the dorsolateral prefrontal cortex (DLPFC) of people with schizophrenia. However, the mechanism behind this has not been clarified. The 3'untranslated regions (3'UTRs) are known to regulate the levels of their mRNA splice variants. METHODS: We constructed recombinant pmir-GLO vectors with a truncated 3' regulatory region of the RGS4 gene (3R1, 3R2, 3R3, 3R4, 3R5, and 3R6). The dual-luciferase reporter assay was conducted to find functional regions in HEK-293, SK-N-SH, and U87cells and then predicted miRNA binding to these regions. We performed a dual-luciferase reporter assay and a Western blot analysis after transiently transfecting the predicted miRNAs. RESULTS: The dual-luciferase reporter assay found that regions +401-+789, +789-+1152, and +1562-+1990 (with the last base of the termination codon being +1) might be functional regions. Hsa-miR-874-3p, associated with many psychiatric disorders, might target the +789-+1152 region in the 3'UTR of the RGS4 gene. In the dual-luciferase reporter assay, the hsa-miR-874-3p mimic, co-transfected with 3R1, down-regulated the relative fluorescence intensities. However, this was reversed when the hsa-miR-874-3p mimic was co-transfected with m3R1 (deletion of +853-+859). The hsa-miR-874-3p mimic significantly decreased the endogenous expression of the RGS4-1 isoform in HEK-293 cells. CONCLUSIONS: Hsa-miR-874-3p inhibits the expression of the RGS4-1 isoform by targeting +853-+859.
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Regiões 3' não Traduzidas , MicroRNAs , Isoformas de Proteínas , Proteínas RGS , Humanos , Proteínas RGS/genética , Proteínas RGS/metabolismo , MicroRNAs/genética , Células HEK293 , Isoformas de Proteínas/genética , Regiões 3' não Traduzidas/genética , Esquizofrenia/genética , Esquizofrenia/metabolismo , Córtex Pré-Frontal/metabolismo , Linhagem Celular TumoralRESUMO
In biological neural networks, it has been well recognized that a healthy brain exhibits 1/f noise patterns. However, in artificial neural networks that are increasingly matching or even out-performing human cognition, this phenomenon has yet to be established. In this work, we found that similar to that of their biological counterparts, 1/f noise exists in artificial neural networks when trained on time series classification tasks. Additionally, we found that the activations of the neurons are the closest to 1/f noise when the neurons are highly utilized. Conversely, if the network is too large and many neurons are underutilized, the neuron activations deviate from 1/f noise patterns toward that of white noise.
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Redes Neurais de Computação , Neurônios , Humanos , Neurônios/fisiologia , Modelos NeurológicosRESUMO
BACKGROUND AND OBJECTIVES: To analyze oncological and functional results of transoral minimally invasive surgery (TMIS) for supraglottic laryngeal carcinoma (SGLC), and investigate independent prognostic factors. METHODS: Seventy SGLC patients treated with TMIS were included. The overall survival (OS), recurrence-free survival (RFS), and postoperative functions were analyzed. RESULTS: Sixty-two patients were early-stage (Tis, T1, and T2) and eight patients were T3. Eleven patients received preoperative induction chemotherapy (IC). Sixty patients received transoral laser microsurgery (TLM), and 10 patients received transoral robotic surgery (TORS). Fifty-eight patients were scored Grade-1 by water swallow test, and 49 patients were scored Grade 0 by grade, roughness, breathiness, asthenia, strain. The 1, 3, and 5 year OS of all were 95.450%, 84.877%, and 78.026%, and RFS were 89.167%, 78.052%, and 75.451% respectively. Kaplan-Meier survival analysis showed N stage and clinical stage were associated with OS, smoking, clinical stage, surgical margins, and Ki-67 index were associated with RFS. There were no significant differences in preoperative IC or direct surgery, TLM, or TORS. Cox analyses showed smoking and surgical margins were independent prognosis factors for RFS. CONCLUSIONS: The positive margin, Ki-67 index ≥40% and P53(+)&Ki-67 index ≥40% are worse factors affecting recurrence for SGLC patients. Both smoking and surgical margins are independent prognostic factors affecting recurrence.
Assuntos
Neoplasias Laríngeas , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Robóticos/métodos , Estadiamento de Neoplasias , Terapia a Laser/métodos , Adulto , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Microcirurgia/métodos , Prognóstico , Estudos Retrospectivos , Cirurgia Endoscópica por Orifício Natural/métodos , Laringectomia/métodos , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Intervalo Livre de Doença , Estimativa de Kaplan-MeierRESUMO
Purpose: The effect of carotid artery stenting in patients with unilateral carotid artery stenosis on the retina and choroid was evaluated using swept-source optical coherence tomography angiography (SS-OCTA). Methods: SS-OCTA examination was conducted before stenting and 4 days and 3 months after stenting. The retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, superficial vascular complex (SVC), deep vascular complex (DVC), choroidal vascular volume (CVV), and choroidal vascular index were measured. Repeated-measures analysis of variance was performed to assess the impact of carotid artery stenting on optical coherence tomography angiography (OCTA) metrics. Results: At baseline, 303 eyes from 160 patients (61.82 ± 9.98 years; 85.29% males) were enrolled. SVC and DVC densities and CVV were lower in ipsilateral eyes (stenosed side) compared to contralateral eyes (all P < 0.05). Four days after stenting, a significant increase was seen in SVC density in ipsilateral eyes (P < 0.05) while a significant increase was seen in CVV in ipsilateral eyes and contralateral eyes (both P < 0.05). Three months after stenting (63 patients with 114 eyes), a significant decrease was seen in the GCIPL thickness of ipsilateral and contralateral eyes (all P < 0.001). Conclusions: Short term after carotid artery stenting, ipsilateral eyes showed a rapid and significant increase in SVC density and CVV. Translational Relevance: Optical coherence tomography (OCT)/OCTA measurements may have the potential to detect retinal and choroidal changes after stenting. Future research on the long-term effect of stenting on the retina and choroid will be guided by these findings.