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1.
World J Otorhinolaryngol Head Neck Surg ; 10(2): 113-120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855290

RESUMO

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

2.
PLoS One ; 19(6): e0305105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861546

RESUMO

PURPOSE: Knee osteoarthritis (KOA) is a common disorder among middle and older individuals. Electroacupuncture and exercise are present as two popular physical therapies for the management of KOA, and both were demonstrated to produce considerable results. However, the clinical decision-making process between these therapeutic interventions remains challenging due to the limited evidence of distinctions in their respective effects. This study aims to evaluate the clinical effect and cost effectiveness of electroacupuncture versus exercise in patients with KOA. STUDY DESIGN AND METHODS: This is a randomized controlled trial in which 196 symptomatic KOA patients will be randomly assigned 1:1 either to the electroacupuncture group (n = 98) and the exercise group (n = 98). Patients in the electroacupuncture group will receive acupuncture with electric stimulation 3 times a week for 8 weeks, whereas patients in the exercise group will receive neuromuscular training twice a week for 8 weeks. Education concerning KOA management will be provided in both therapies. Co-primary outcomes include changes in numerical rating scale (NRS) and Knee injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) subscale from baseline at week 8. Secondary outcomes include KOOS Pain subscale, KOOS knee-related Quality of Life (QOL) subscale, Short Form 6 Dimensions (SF-6D), five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), Credibility/ Expectancy Questionnaire, Patient's global assessment (PGA), 30-second Chair Stand Test (30s-CST), 40m (4*10m) Fast Paced Walk Test (40m FPWT), and Daily Physical Activity level (DPA). DISCUSSION: The results of this study will provide evidence regarding differences between these 2 physical therapies in multiple aspects and will provide specific guidance for the development of treatments based on the needs of individual patients. TRIAL REGISTRATION: ChiCTR2300070376.


Assuntos
Eletroacupuntura , Terapia por Exercício , Osteoartrite do Joelho , Qualidade de Vida , Humanos , Osteoartrite do Joelho/terapia , Eletroacupuntura/métodos , Terapia por Exercício/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso , Atividades Cotidianas , Adulto , Exercício Físico
3.
Org Lett ; 26(20): 4200-4204, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38739265

RESUMO

Solvent-switchable and site-selective phosphorylation of imidazoles at the C2 or C5 position of the imidazole ring was achieved via 1,4-palladium migration. P-Chiral tert-butyl(aryl)phosphine oxides were cross-coupled to 1-(2-bromophenyl)-1H-imidazoles with high enantiospecificity, thereby leading to a novel class of chiral imidazole-based phosphine oxides. As proof of concept, reduction of an analogue yielded the corresponding P-chiral 2-phosphinyl imidazole ligand, which was shown to induce high enantioselectivity in the formation of axially chiral molecules synthesized via Pd-catalyzed Suzuki-Miyaura cross-coupling.

4.
Clin Rheumatol ; 43(6): 2061-2077, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38696115

RESUMO

OBJECTIVE: This study aimed to estimate and predict the burden of osteoarthritis (OA) and site-specific OA (hip, knee, hand, and others) from 1990 to 2030 and their attributable risk factors in China. METHOD: Data were obtained from the Global Burden of Diseases 2019. The burden was estimated by analyzing the trends of prevalence, incidence, and disability-adjusted life years (DALY). Population attributable risk (PAR) was calculated to assess the impact of high body mass index (BMI). The prediction from 2020 to 2030 was implemented by Bayesian age-period-cohort analysis. RESULTS: In China, prevalent cases, DALY, and incident cases of OA increased to 132.81 million, 4.72 million, and 10.68 million, respectively. Age-standardized rates (ASRs) of prevalence, DALYs, and incidence increased for OA and site-specific OA, especially for hip OA. Site-specific OA showed different susceptible peaking ages, and the burden for those over 50 years old became serious. Female preference existed in the trends for knee OA but not in those for hip, hand, and other OA. PARs of high BMI continued to increase, impacting knee OA more than hip OA and showing female preference. In the next decade, incident cases for OA and site-specific OA will continue to increase, despite that the ASR of OA incidence will decrease. CONCLUSIONS: OA and site-specific OA remain huge public health challenges in China. The burden of OA and site-specific OA is increasing, especially among people over 50 years old. Health education, exercise, and removing modifiable risk factors contribute to alleviate the growing burden. Key Points • In China, the burden of osteoarthritis and site-specific osteoarthritis (hip, knee, hand, and others) as well as the Risk Factor (high body mass index) increased greatly from 1990 to 2019. • It is estimated that incident cases for OA and site-specific OA will continue to increase, despite that the ASR of OA incidence will decrease.


Assuntos
Osteoartrite , Humanos , China/epidemiologia , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Masculino , Prevalência , Idoso , Osteoartrite/epidemiologia , Incidência , Adulto , Índice de Massa Corporal , Osteoartrite do Joelho/epidemiologia , Efeitos Psicossociais da Doença , Anos de Vida Ajustados por Deficiência , Adulto Jovem , Carga Global da Doença/tendências , Anos de Vida Ajustados por Qualidade de Vida , Adolescente , Osteoartrite do Quadril/epidemiologia , Idoso de 80 Anos ou mais , Teorema de Bayes
5.
Public Health Nurs ; 41(3): 617-625, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556918

RESUMO

OBJECTIVES: To investigate the factors associated with stress, resilience, coping styles, and emergency competencies when nurses are faced with a public health emergency. DESIGN: This study used a cross-sectional design. SAMPLE: Study data came from a survey of 646 nurses who were from a tertiary hospital in Southern China in March-June 2022. METHODS: Participants responded to self-report questionnaires through a web-based survey. Stress, resilience, emergency competencies, and response to public emergencies were assessed using the Perceived Stress Scale, Connor-Davidson Resilience Scale, the core competencies of nurses in public health emergencies, and a simplified coping style questionnaire. RESULTS: A total of 646 nurses participated in this study. Slightly over half of the participants were ≤30 years old, and almost all were female. Resilience, positive coping, and negative coping were positively correlated with emergency competencies. Multiple linear regression analysis demonstrated that resilience, working years, and participation in the treatment of infectious diseases were significant predictors of emergency competencies. CONCLUSION: The findings suggest that nurses require additional training in emergency management and clinical practice to enhance their emergency competencies. More interventions and social support should be provided to improve nurses' resilience and positive coping strategies when they encounter public health emergencies.


Assuntos
Emergências , Enfermeiras e Enfermeiros , Testes Psicológicos , Humanos , Feminino , Adulto , Masculino , Estudos Transversais , Autorrelato , Capacidades de Enfrentamento , Inquéritos e Questionários , Adaptação Psicológica , Resiliência Psicológica
6.
Proc Natl Acad Sci U S A ; 121(12): e2307309121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38489381

RESUMO

The organization of interphase chromosomes in a number of species is starting to emerge thanks to advances in a variety of experimental techniques. However, much less is known about the dynamics, especially in the functional states of chromatin. Some experiments have shown that the motility of individual loci in human interphase chromosome decreases during transcription and increases upon inhibiting transcription. This is a counterintuitive finding because it is thought that the active mechanical force (F) on the order of ten piconewtons, generated by RNA polymerase II (RNAPII) that is presumably transmitted to the gene-rich region of the chromatin, would render it more open, thus enhancing the mobility. We developed a minimal active copolymer model for interphase chromosomes to investigate how F affects the dynamical properties of chromatin. The movements of the loci in the gene-rich region are suppressed in an intermediate range of F and are enhanced at small F values, which has also been observed in experiments. In the intermediate F, the bond length between consecutive loci increases, becoming commensurate with the distance at the minimum of the attractive interaction between nonbonded loci. This results in a transient disorder-to-order transition, leading to a decreased mobility during transcription. Strikingly, the F-dependent change in the locus dynamics preserves the organization of the chromosome at [Formula: see text]. Transient ordering of the loci, which is not found in the polymers with random epigenetic profiles, in the gene-rich region might be a plausible mechanism for nucleating a dynamic network involving transcription factors, RNAPII, and chromatin.


Assuntos
Cromatina , Cromossomos Humanos , Humanos , Cromatina/genética , Fatores de Transcrição/genética , Interfase/genética , RNA Polimerase II/genética
7.
Elife ; 122024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502563

RESUMO

Compartment formation in interphase chromosomes is a result of spatial segregation between euchromatin and heterochromatin on a few megabase pairs (Mbp) scale. On the sub-Mbp scales, topologically associating domains (TADs) appear as interacting domains along the diagonal in the ensemble averaged Hi-C contact map. Hi-C experiments showed that most of the TADs vanish upon deleting cohesin, while the compartment structure is maintained, and perhaps even enhanced. However, closer inspection of the data reveals that a non-negligible fraction of TADs is preserved (P-TADs) after cohesin loss. Imaging experiments show that, at the single-cell level, TAD-like structures are present even without cohesin. To provide a structural basis for these findings, we first used polymer simulations to show that certain TADs with epigenetic switches across their boundaries survive after depletion of loops. More importantly, the three-dimensional structures show that many of the P-TADs have sharp physical boundaries. Informed by the simulations, we analyzed the Hi-C maps (with and without cohesin) in mouse liver and human colorectal carcinoma cell lines, which affirmed that epigenetic switches and physical boundaries (calculated using the predicted 3D structures using the data-driven HIPPS method that uses Hi-C as the input) explain the origin of the P-TADs. Single-cell structures display TAD-like features in the absence of cohesin that are remarkably similar to the findings in imaging experiments. Some P-TADs, with physical boundaries, are relevant to the retention of enhancer-promoter/promoter-promoter interactions. Overall, our study shows that preservation of a subset of TADs upon removing cohesin is a robust phenomenon that is valid across multiple cell lines.


Assuntos
Cromatina , Coesinas , Animais , Camundongos , Humanos , Cromossomos , Heterocromatina , Interfase
8.
Artigo em Inglês | MEDLINE | ID: mdl-38521736

RESUMO

OBJECTIVE: Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals. METHODS: Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks. RESULTS: At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group. CONCLUSION: These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level.

9.
Ying Yong Sheng Tai Xue Bao ; 35(2): 347-353, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523091

RESUMO

In recent years, PM2.5 pollution has become a most important source of air pollution. Prolonged exposure to high PM2.5 concentrations can give rise to severe health issues. Negative air ion (NAI) is an important indicator for measuring air quality, which is collectively known as the 'air vitamin'. However, the intricate and fluctuating meteorological conditions and vegetation types result in numerous uncertainties in the correlation between PM2.5 and NAI. In this study, we collected data on NAI, PM2.5, and meteorological elements through positioning observation during the period of June to September in 2019 and 2020 under the condition of relatively constant leaf area in Quercus variabilis forest, a typical forest in warm temperate zones. We investigated the spatiotemporal variation of PM2.5 and NAI under consistent meteorological conditions, established the correlation between PM2.5 and NAI, and explicated the impact mechanism of PM2.5 on NAI in natural conditions. The results showed that NAI decreased exponentially with the increases in natural PM2.5, with a significant negative correlation (y=1148.79x-0.123). The decrease rates of NAI in PM2.5 concentrations of 0-20, 20-40, 40-80, 80-100 and 100-120 µg·m-3 were 40.1%, 36.2%, 9.4%, 2.4%, 5.1% and 6.8%, respectively. Results of the sensitivity analysis showed that the PM2.5 concentration range of 0-40 µg·m-3 was the sensitive range that affected NAI. Our findings could provide a scientific basis for better understanding the response mechanisms of NAI to environmental factors.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Quercus , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/análise , Florestas , Monitoramento Ambiental/métodos , China
10.
Discov Oncol ; 15(1): 32, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329652

RESUMO

BACKGROUND: Solitary fibrous tumors (SFT) and meningiomas (MA) have similar clinical and radiographic presentations but require different treatment approaches and have different prognoses. This emphasizes the importance of a correct preoperative diagnosis of SFT versus MA. OBJECTIVE: In this study, investigated the differences in imaging characteristics between SFT and MA to improve the accuracy of preoperative imaging diagnosis of SFT. METHODS: The clinical and imaging data of 26 patients with SFT and 104 patients with MA who were pathologically diagnosed between August 2017 and December 2022, were retrospectively analyzed. The clinical and imaging differences between SFT and MA, as well as between the various pathological grades of SFT, were analyzed. RESULTS: Age, gender, cystic change, flow void phenomenon, yin-yang sign, lobulation, narrow base, tumor/cortex signal ratio (TCSR) > 1.0 in T1-weighted imaging (T1WI), TCSR ≥ 1.1 in T2-weighted imaging (T2WI), peritumoral edema, and absence of dural tail sign varied between SFT and MA. As per the receiver operating characteristic (ROC) curve analysis, TCSR > 1 in T1WI has the maximum diagnostic accuracy for SFT. Cranial or venous sinus invasion had a positive effect on SFT (Grade III, World Health Organization (WHO) grading). CONCLUSION: Among the many radiological and clinical distinctions between SFT and MA, TCSR ≥ 1 exhibits the highest predictive efficacy for SFT; while cranial or venous sinus invasion may be a predictor of WHO grade III SFT.

11.
Plant Divers ; 46(1): 70-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38343594

RESUMO

Here, we characterize the temporal and spatial dynamics of forest community structure and species diversity in a subtropical evergreen broad-leaved forest in China. We found that community structure in this forest changed over a 15-year period. Specifically, renewal and death of common species was large, with the renewal of individuals mainly concentrated within a few populations, especially those of Aidia canthioides and Cryptocarya concinna. The numbers of individual deaths for common species were concentrated in the small and mid-diameter level. The spatial distribution of community species diversity fluctuated in each monitoring period, showing a more dispersed diversity after the 15-year study period, and the coefficient of variation on quadrats increased. In 2010, the death and renewal of the community and the spatial variation of species diversity were different compared to other survey years. Extreme weather may have affected species regeneration and community stability in our subtropical monsoon evergreen broad-leaved forests. Our findings suggest that strengthening the monitoring and management of the forest community will help better understand the long- and short-term causes of dynamic fluctuations of community structure and species diversity, and reveal the factors that drive changes in community structure.

12.
Angew Chem Int Ed Engl ; 63(10): e202318516, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38241198

RESUMO

In this work, full-color and stable white organic afterglow materials with outstanding water, organic solvents, and temperature resistances have been developed for the first time by embedding the selected polycyclic aromatic hydrocarbons into melamine-formaldehyde polymer via solution polymerization. The afterglow quantum yields and lifetimes of the resulting polymer films were up to 22.7 % and 4.83 s, respectively, under ambient conditions. For the coronene-doped sample, its afterglow color could be linearly tuned between yellow and blue by adjusting the temperature, and it could still emit an intense blue afterglow with a lifetime of 0.68 s at 440 K. Moreover, the films showed a bright and stable white afterglow at 370 K with a lifetime of 2.80 s and maintained an excellent afterglow performance after soaking in water and organic solvents for more than 150 days. In addition, the application potential of the polymer films in information encryption and anti-counterfeiting was also demonstrated.

13.
Huan Jing Ke Xue ; 45(1): 323-334, 2024 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-38216482

RESUMO

The aim of this study was to explore the carbon storage potential of karst forest soils in the Lijiang River Basin, reveal the spatial pattern of soil organic carbon (SOC), investigate the contributions and pathways of each driving factor to the spatial distribution of soil organic carbon, and provide a scientific basis for assessing the carbon cycle function of karst forests in the region. We employed structural equation modeling (SEM) and correlation analysis to investigate the spatial distribution characteristics of forest soil organic carbon in different basin sections (upper, middle, and lower reaches) and soil layers at different depths of the Lijiang River. Additionally, the direct and indirect ratios of each factor were quantified. The results showed that the overall soil layer of karst forest soils in the Lijiang River Basin was shallow, and soil organic carbon was phenoconcentric. The distribution of soil organic carbon content in different watershed sections was upstream > downstream > midstream, and the distribution of readily oxidizable carbon (ROC) and dissolved organic carbon (DOC) was consistent, whereas the distribution of microbial biomass carbon (MBC) was upstream > midstream > downstream. The contribution of various biotic and abiotic factors to the spatial distribution of soil organic carbon in karst forests in the watershed was different, and their contributions were ranked in descending order as:soil physicochemical factors > soil organic carbon active fraction > sample elevation > sample species diversity, with the total effects of 1.148, 0.574, 0.284, and -0.013, respectively. Among them, the sample site elevation had only an indirect effect on soil organic carbon, and the soil organic carbon active fraction had only a direct effect on soil organic carbon. Among the driving factors, total soil nitrogen, soil oxidizable organic carbon, sample site species richness, and soil soluble organic carbon could be used as important predictors of soil organic carbon content in karst forests in the Lijiang River Basin. Therefore, it is necessary to establish an effective eco-environmental protection mechanism covering the whole Lijiang River Basin, to reduce and control the impact of anthropogenic disturbances (especially in the middle urban section of the Lijiang River Basin), and to enhance and protect the species diversity of karst forests in the basin in order to improve soil physicochemical properties, improve and enhance the content of the soil organic carbon active fraction, and enhance the soil organic carbon stocks of karst forests in the Lijiang River Basin through other effective ways, as well as to promote the enhancement of the regional forest carbon sink function.

14.
BMC Genomics ; 25(1): 92, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254015

RESUMO

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.


Assuntos
Antílopes , Animais , Antílopes/genética , Filogenia , Cabras/genética , Rearranjo Gênico , Cromossomos
15.
Inflammation ; 47(3): 1002-1014, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38279067

RESUMO

Rosacea is a chronic facial inflammatory skin disease that occurs with dysfunction of the immune system. Colchicine was reported to have anti-inflammatory properties. However, the impact of colchicine on rosacea remains unclear. In the present study, the phenotype of rosacea lesions was evaluated by the redness score, inflammatory biomarkers were analyzed by reverse transcription PCR (RT‒PCR), and the infiltration of inflammatory cells was assessed by IHC analysis and immunofluorescence in a rosacea-like mouse model. In vitro, RT‒PCR was used to identify the inflammatory factors that Toll-like receptor 2 (TLR2) agonist caused neutrophils to produce, and immunofluorescence and coimmunoprecipitation were used to identify putative signalling pathways. We found that skin erythema and histopathological alterations, as well as elevated proinflammatory factors (IL-1ß, IL-6, TNFα, CXCL2) and CAMP, were significantly ameliorated by colchicine treatment in LL37-induced rosacea-like mice. In addition, colchicine reduced the colocalization of TLR2 and neutrophils and the formation of neutrophil extracellular trap networks (NET) in mouse lesions. In neutrophils, colchicine markedly reduced TLR2 agonist-induced inflammatory biomarker expression, NET formation, and ROS production. Moreover, we found that LL37 could bind to TLR2 upon activation of TLR2 in neutrophils. Importantly, colchicine could repress the combination of TLR2 and LL37 in vivo. Finally, bioinformatics methods further validated the key molecules of neutrophil-related inflammation in rosacea, which is consistent with our experimental findings. Collectively, colchicine ameliorated rosacea-like dermatitis by regulating the neutrophil immune response activated by the TLR2 pathway, indicating that it could be an effective therapeutic option for patients with rosacea.


Assuntos
Colchicina , Neutrófilos , Rosácea , Transdução de Sinais , Receptor 2 Toll-Like , Rosácea/tratamento farmacológico , Rosácea/metabolismo , Receptor 2 Toll-Like/metabolismo , Animais , Colchicina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/imunologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Humanos , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Catelicidinas , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia
16.
J Genet Genomics ; 51(2): 197-207, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37164272

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic small vessel disease caused by mutations in the NOTCH3 gene. However, the pathogenesis of CADASIL remains unclear, and patients have limited treatment options. Here, we use human induced pluripotent stem cells (hiPSCs) generated from the peripheral blood mononuclear cells of a patient with CADASIL carrying a heterozygous NOTCH3 mutation (c.1261C>T, p.R421C) to develop a disease model. The correction efficiency of different adenine base editors (ABEs) is tested using the HEK293T-NOTCH3 reporter cell line. ABEmax is selected based on its higher efficiency and minimization of predicted off-target effects. Vascular smooth muscle cells (VSMCs) differentiated from CADASIL hiPSCs show NOTCH3 deposition and abnormal actin cytoskeleton structure, and the abnormalities are recovered in corrected hiPSC-derived VSMCs. Furthermore, CADASIL blood vessel organoids generated for in vivo modeling show altered expression of genes related to disease phenotypes, including the downregulation of cell adhesion, extracellular matrix organization, and vessel development. The dual adeno-associated virus (AAV) split-ABEmax system is applied to the genome editing of vascular organoids with an average editing efficiency of 8.82%. Collectively, we present potential genetic therapeutic strategies for patients with CADASIL using blood vessel organoids and the dual AAV split-ABEmax system.

17.
Chemosphere ; 349: 140799, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38052313

RESUMO

This study focuses on modeling air quality with an adaptive utilization of spatio-temporal information from multiple air quality monitoring stations under a multi-scale framework. To this end, it is necessary to consider different strategies to combine different methods to decompose the given series and to fuse multi-site information. Based on a systematic comparative analysis, we propose a novel multi-scale and multi-site modeling method named the multivariate empirical mode decomposition and spatial cosine-attention-based long short-term memory (MEMD-SCA-LSTM). The MEMD-SCA-LSTM first employs MEMD to decompose the multi-site air quality series into the scale-aligned components and then models the components at different scales. The high-frequency components are modeled by a novel SCA-LSTM, which employs LSTM with residual blocks to extract the temporal information and utilizes an attention mechanism based on the cosine similarity to adaptively extract interactions among different sites. Other relatively regular components are modeled by the LSTM. Empirical study on PM2.5 in Hong Kong has demonstrated the effectiveness of fusing multi-site information using the spatial attention (SA) mechanism under the multi-scale framework with MEMD. The proposed MEMD-SCA-LSTM can improve the one-day ahead modeling performance with the mean absolute error and the root mean square error reduced over 10%, compared to the baseline modeling methods. For the two-day and three-day ahead performance, the MEMD-SCA-LSTM is still the best one. Furthermore, by visualizing the attention weights, we illustrate that our proposed SCA-LSTM can overcome some limitations of the traditional attention mechanisms and that the attention weights exhibit more informative patterns which could be used to analysis the transport of air pollutant between sites. The proposed modeling method is a general method, which is feasible and applicable to other pollutants in other cities or regions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Material Particulado/análise , Monitoramento Ambiental/métodos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Cidades
18.
Pest Manag Sci ; 80(3): 1107-1117, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37862262

RESUMO

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.


Assuntos
Glutationa Transferase , Mariposas , ortoaminobenzoatos , Animais , Mariposas/genética , Larva , Glutationa
19.
Oncol Rep ; 51(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37997815

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation data shown in Fig. 2C on p. 333 had already appeared in previously published articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 331­337, 2018; DOI: 10.3892/or.2017.6099].


Assuntos
Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , Divisão Celular , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Melanoma Maligno Cutâneo
20.
Heliyon ; 9(12): e22800, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38089988

RESUMO

Our previous work has shown that activating PI3K/Akt/mTOR signaling pathway is involved in angiogenesis after ischemic stroke, and recent studies have revealed that astragaloside IV (AS-IV) exerts beneficial effects on cerebral protection after ischemic stroke. However, it is unclear whether the beneficial effects of AS-IV against ischemic stroke is related to angiogenesis and PI3K/Akt/mTOR signaling pathway. The aim of this study was to investigate the effects of AS-IV on angiogenesis and long-term neurological recovery after focal ischemic stroke as well as the underlying mechanisms. After mice model of distal middle cerebral artery occlusion (dMCAO), AS-IV was administered with low dose (10 mg/kg), medium dose (20 mg/kg) or high dose (40 mg/kg) once daily for 14 days. We report herein that AS-IV (20 mg/kg) significantly ameliorated long-term neurological recovery and attenuated histological damage, while promoting cerebral blood flow recovery in ischemic mice. Moreover, AS-IV administration enhanced microvessel density as well as astrocyte and pericyte coverage around microvessels in the peri-infarct cortex. In vitro, AS-IV promoted endothelial cells (ECs) proliferation and tube formation after oxygen-glucose deprivation (OGD), which was partially inhibited by the specific PI3K inhibitor LY294002. Finally, AS-IV increased the expression of vascular endothelial growth factor (VEGF) through activating the PI3K/AKT/mTOR signaling pathway in the process of promoting angiogenesis. These results suggested that AS-IV may promote angiogenesis after ischemic stroke through increasing the expression of VEGF via PI3K/Akt/mTOR pathway, which unveils novel therapeutic effects of AS-IV and suggests promising application of AS-IV in ischemic stroke.

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