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1.
Development ; 151(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38174902

RESUMO

To gain insight into the transcription programs activated during the formation of Drosophila larval structures, we carried out single cell RNA sequencing during two periods of Drosophila embryogenesis: stages 10-12, when most organs are first specified and initiate morphological and physiological specialization; and stages 13-16, when organs achieve their final mature architectures and begin to function. Our data confirm previous findings with regards to functional specialization of some organs - the salivary gland and trachea - and clarify the embryonic functions of another - the plasmatocytes. We also identify two early developmental trajectories in germ cells and uncover a potential role for proteolysis during germline stem cell specialization. We identify the likely cell type of origin for key components of the Drosophila matrisome and several commonly used Drosophila embryonic cell culture lines. Finally, we compare our findings with other recent related studies and with other modalities for identifying tissue-specific gene expression patterns. These data provide a useful community resource for identifying many new players in tissue-specific morphogenesis and functional specialization of developing organs.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Transcriptoma/genética , Organogênese , Proteínas de Drosophila/metabolismo , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento
2.
Am J Transplant ; 23(3): 336-352, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36695693

RESUMO

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.


Assuntos
Transplante de Fígado , MicroRNAs , Animais , Humanos , Ratos , Leucócitos Mononucleares/metabolismo , Macrófagos/metabolismo , MicroRNAs/genética , NF-kappa B/metabolismo , Pró-Colágeno/metabolismo , Pró-Colágeno/farmacologia
3.
Molecules ; 28(19)2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37836812

RESUMO

At present, phenolic acid derivatives and triazole derivatives have a good antifungal effect, which has attracted widespread attention. A series of novel phenolic acid triazole derivatives were synthesized, and their structures were characterized by IR, MS, NMR, and X-ray crystal diffraction. Compound methyl 4-(2-bromoethoxy)benzoate, methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate, 4-(2-(1H-1,2,4-triazol-1-yl)ethoxy)benzoic acid and 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)-3-methoxybenzoic acid crystallize in the monoclinic system with space group P21/n, the monoclinic system with space group P21, the monoclinic system with space group P21 and the orthorhombic system with space group Pca21, respectively. At a concentration of 100 µg/mL and 200 µg/mL, the antifungal activity against seven plant pathogen fungi was determined. Compound methyl 4-(2-bromoethoxy)benzoate has the best inhibitory effect on Rhizoctonia solani AG1, and the inhibitory rate reached 88.6% at 200 µg/mL. The inhibitory rates of compound methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate against Fusarium moniliforme and Sphaeropsis sapinea at a concentration of 200 µg/mL were 76.1% and 75.4%, respectively, which were better than that of carbendazim.

4.
Scand J Gastroenterol ; 57(9): 1066-1069, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35348416

RESUMO

OBJECTIVES: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication of liver cirrhosis. Both EncephalApp Stroop test (EncephalApp) and electronic number connection test-A (eNCT-A) are novel computerised psychometric tests for MHE screening. We aimed to compare the efficiency, convenience, accessibility, and acceptability of EncephalApp with that of eNCT-A for MHE screening in cirrhotic patients. METHODS: Ninety-five patients with hepatitis B-induced liver cirrhosis were included and respectively tested by the psychometric hepatic encephalopathy score (PHES), EncephalApp, and eNCT-A. Using PHES as the gold standard for MHE diagnosis, the efficiency of EncephalApp and eNCT-A for MHE screening were respectively analysed by the receiver operating characteristic (ROC) curve, and the areas under the ROC curve (AUROC) were compared. The convenience, accessibility, and acceptability of PHES, EncephalApp and eNCT-A were respectively evaluated by the 5-point Likert scale. RESULTS: Fifty-two (55%) of included cirrhotic patients were diagnosed with MHE. The EncephalApp had a sensitivity of 84.6%, a specificity of 74.4%, and an AUROC of 0.836. Meanwhile, the eNCT-A had a sensitivity of 78.8%, a specificity of 83.7%, and an AUROC of 0.845. No significant difference in AUROC was detected between the EncephalApp and eNCT-A (p = .453). Compared with the EncephalApp, the eNCT-A presented better convenience and higher acceptability in cirrhotic patients undergoing MHE screening (p = .019 and p < .001, respectively). CONCLUSIONS: As with the EncephalApp, the eNCT-A will be a potential home monitoring and point-of-care tool for cirrhotic patients at high risk of MHE.


Assuntos
Encefalopatia Hepática , Eletrônica , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/complicações , Psicometria , Teste de Stroop
5.
Inorg Chem ; 61(40): 16009-16019, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36153966

RESUMO

The functionalized design of metal-organic frameworks (MOFs) has been rapidly developed in the last 20 years, and its broad applicability has been demonstrated in many fields. MOFs with desired functions can be assembled using predesigned organic linkers with specific metal nodes, which possess the ordered functional sites and open structures. Although a large number of carboxylic acid junctions have been used to construct MOFs, it is still a great challenge to realize their multifunctionality. In particular, there is a relative lack of research on MOFs as direct photocatalysts, which require not only abundant active sites and open structures but also adsorption groups and effective electron-hole separation performance. To this end, MOFs constructed from the carboxylic acid ligands derived from lophine-based derivatives and copper ions were deliberately used as a photocatalyst, and then, their application in dye degradation and aromatic alcohol conversion was investigated. In addition, in combination with the abundant Lewis sites of copper ions and imidazole sites, the material shows not only the adsorption and separation of C2 series and dyes but also the application of dye degradation and conversion of aromatic alcohols under illumination conditions. The corresponding results fully illustrate that the MOF constructed by using lophine derivatives can be an effective way to prepare photocatalysts. The subsequent research ideas will focus on designing a series of MOFs constructed with multilinked moieties of lophine groups and exploring their application strategies in the field of photocatalysis.

6.
Molecules ; 27(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364410

RESUMO

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.


Assuntos
Chalcona , Chalconas , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Ratos , Animais , Glicemia , Diabetes Mellitus Experimental/patologia , 1-Desoxinojirimicina/farmacologia , 1-Desoxinojirimicina/uso terapêutico , Chalconas/farmacologia , Chalconas/uso terapêutico , Chalcona/farmacologia , Heterozigoto , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico
7.
BMC Cardiovasc Disord ; 20(1): 7, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918665

RESUMO

BACKGROUND: Previous clinical studies have suggested that trimethylamine-N-oxide (TMAO) could contribute to the development of atherosclerosis cardiovascular disease. However, the synthetic analysis in coronary heart disease (CHD) was not yet performed. We aimed to clarify the relationship between elevated plasma concentrations of TMAO and the incidence of major adverse cardiovascular events (MACE) in CHD patients. METHODS: Meta-analysis and dose-response analysis of hazard ratio data from prospective observational studies reporting on the association between TMAO plasma concentrations and the incidence of MACE in patients with CHD were conducted. RESULTS: Of the 2369 published articles identified in the search, seven papers, with data from nine cohort studies (10,301 patients), were included in the meta-analysis. Combined data showed that elevated plasma TMAO concentrations could increase 58% higher risk of MACE in patients with CHD (hazard ratios [HR]: 1.58; 95% confidence interval [CI] = 1.35-1.84, P = 0.000). For follow-up ≥ 1 year, it was associated with 62% higher risk of MACE in patients with longer-term than shorter-term (HR for follow-up ≥ 4 years: 1.96; 95% CI = 1.52-2.52 vs one to 3 years: 1.34; 95% CI = 1.26-1.43, P = 0.004). The dose-response analysis revealed a 'J' shaped association between TMAO concentration and the incidence of MACE (P = 0.033), with the concentration above 5.1 µmol/L being associated with HR of > 1. CONCLUSIONS: Elevated levels of TMAO are associated with an increased incidence of MACE in patients with CHD. TMAO concentration of 5.1 µmol/L may be a cut-off value for prognosis.


Assuntos
Doença das Coronárias/sangue , Metilaminas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Prognóstico , Regulação para Cima
8.
J Enzyme Inhib Med Chem ; 35(1): 1879-1890, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33003963

RESUMO

A series of novel N-alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC50 values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC50 = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43, 40, and 34 were all competitive inhibitors on α-glucosidase with Ki of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π-π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π-π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.


Assuntos
Glucosamina/análogos & derivados , Inibidores de Glicosídeo Hidrolases/síntese química , alfa-Glucosidases/metabolismo , 1-Desoxinojirimicina/síntese química , 1-Desoxinojirimicina/farmacocinética , Acarbose/farmacologia , Acarbose/normas , Compostos de Benzilideno/química , Glucosamina/síntese química , Glucosamina/farmacocinética , Inibidores de Glicosídeo Hidrolases/farmacocinética , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
9.
J Cell Physiol ; 233(10): 6630-6637, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29226948

RESUMO

MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and abnormal expression of miR-182-5p has been involved in many diseases. However, the role miR-182-5p in Atherosclerosis (AS) remains poorly understood. In our current investigation, an AS model was established by using oxidized low-density lipoprotein (ox-LDL) in RAW264.7 cells. miR-182-5p was markedly decreased in AS model dose-dependently and time-dependently. Additionally, CD36, oil-red staining levels, TC, and TG were inhibited by miR-182-5p mimics, meanwhile ROS levels, MDA, and cell apoptosis were also restrained with an enhancement of SOD activity. Consistently, opposite results were exhibited when miR-182-5p inhibitors were transfected into RAW264.7 cells. It is well known that toll-like receptor 4 (TLR4) is responsible for many inflammation diseases. By using bioinformatics analysis, TLR4 was indicated as a potential target of miR-182-5p. We observed TLR4 was activated in AS models and miR-182-5p could repress AS progression by targeting TLR4 in vitro. In conclusion, we uncovered that miR-182-5p played significant roles in AS through inhibiting oxidative stress and apoptosis via inactivating TLR4 expression.


Assuntos
Aterosclerose/genética , MicroRNAs/genética , Estresse Oxidativo/genética , Receptor 4 Toll-Like/genética , Animais , Apoptose/genética , Aterosclerose/patologia , Antígenos CD36/genética , Regulação da Expressão Gênica/genética , Humanos , Inflamação/genética , Inflamação/patologia , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Camundongos , Células RAW 264.7 , Transdução de Sinais/genética
10.
Zhongguo Zhong Yao Za Zhi ; 43(3): 484-492, 2018 Feb.
Artigo em Zh | MEDLINE | ID: mdl-29600612

RESUMO

The study is aimed to construct high quality Salvia miltiorrhiza cDNA library and obtain the SmJAZ8 gene of S. miltiorrhiza by yeast two-hybrid system. In this study, full-length cDNA was synthesized from roots, stems, leaves, flowers and hairy roots of S. miltiorrhiza. The full-length cDNA library was synthesized by SMART method and constructed with DSN homogenization technique. The results showed that the library capacity was 1.45×106, the recombination rate was 100%, and the average size of the insert was 500-2 000 bp. The recombinant vector of pDEST-pGADT7-SmJAZ8 was constructed and transformed into Y2HGold strain. The interaction protein was screened by yeast two-hybrid system. The DnaJ protein and UBQ protein were screened by yeast two-hybrid system. This study has successfully constructed a full-length cDNA library of S. miltiorrhiza, and laid the foundation for the follow-up study on functional gene screening and gene function of S. miltiorrhiza.


Assuntos
Proteínas Correpressoras/genética , Biblioteca Gênica , Proteínas de Plantas/genética , Salvia miltiorrhiza/genética , Técnicas do Sistema de Duplo-Híbrido , DNA Complementar
11.
J Hepatol ; 66(6): 1193-1204, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28192186

RESUMO

BACKGROUND & AIMS: Aberrant estrogen receptor-α (ERα) expression and signaling are implicated in the development of hepatocellular carcinoma (HCC), but its regulation in HCC remains enigmatic. Herein, we aimed to identify a new mechanism by which ERα signaling is regulated in HCC, which may lead to a potential new strategy for HCC therapy. METHODS: Expression levels of Erbin and ERα in human HCC samples were evaluated by immunohistochemistry. In vitro and in vivo experiments were used to assess the effect of Erbin and ERα signaling on HCC cell growth. Crosstalk between Erbin and ERα signaling was analyzed by molecular methods. Animal models of diethylnitrosamine (DEN) or DEN/CCl4-induced HCC in wild-type Erbin+/+ and mutant ErbinΔC/ΔC mice were observed. The regulatory effects of Erbin on tamoxifen treatment of HCC were evaluated in vitro and in vivo. RESULTS: Erbin inactivated ERα signaling to drive tumorigenesis of HCC, acting to enhance binding of Chip to ERα via its interaction with ERα and thereby promoting ubiquitination and degradation of ERα. Deletion of the PDZ domain of Erbin in ErbinΔC/ΔC mice, disrupted the interaction of Chip and ERα, increased the stability of ERα protein, and thus inhibited tumorigenesis of HCC. Silencing of Erbin effectively sensitized the response of HCC after tamoxifen treatment in vitro and in vivo. CONCLUSIONS: Our data uncovered an important role of Erbin in regulating HCC tumorigenesis through inactivating ERα-mediated tumor-suppressive signaling, suggesting a new strategy for tamoxifen therapy in HCC by targeting Erbin/ERα signaling axis. LAY SUMMARY: Erbin expression is significantly elevated in human hepatocellular carcinoma (HCC) tissue. This elevated expression of Erbin contributes to tumorigenesis of HCC by negatively regulating ERα signaling. However, restoring ERα signaling by inhibiting Erbin expression enhances the sensitivity of HCC cells to tamoxifen treatment, providing a new approach for tamoxifen treatment in HCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Receptor alfa de Estrogênio/metabolismo , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antineoplásicos Hormonais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Receptor alfa de Estrogênio/genética , Feminino , Inativação Gênica , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas Experimentais/etiologia , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Estabilidade Proteica , Fatores Sexuais , Tamoxifeno/uso terapêutico , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Regulação para Cima
12.
Neuropathology ; 35(1): 50-5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25112406

RESUMO

A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature.


Assuntos
Transformação Celular Neoplásica/patologia , Craniofaringioma/patologia , Neoplasias Hipofisárias/patologia , Adulto , Seguimentos , Humanos , Masculino
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 46(2): 258-62, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-25924441

RESUMO

OBJECTIVE: To determine risk factors associated with the prevalence of chronic obstructive pulmonary disease (COPD) in urban and rural populations in Chengdu. METHODS: A multistage random cluster sampling method was adopted to select participants from four communities in Chengdu. All residents aged 40-70 yr. were eligible to participate in this study, which involved a questionnaire survey, physical examination and portable spirometry. Those with airflow limitations were also given post-bronchodilator testing 15 min after inhalation of a dose of 200 microg salbutamol. We defined a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of less than 70% as COPD. Logistic regression models were performed to identify risk factors of COPD. RESULTS: Of a total of 1931 eligible participants, 1579 (81.77%) completed the questionnaire and spirometry. About 8.35% were identified with COPD: 7.69% in urban vs. 12.37% in rural (P<0.05). The prevalence of COPD increased with age (P<0.05) in the male and total populations. Rural COPD patients had a higher level of smoking rate and use of coal as fuel for cooking than their urban counterparts (P<0.05). But rural COPD patients had a lower level of BMI, waist circumference, literacy, and average household income per capita than their urban counterparts (P<0.05). The multivariate analysis showed that tobacco smoking index (pack-year), education, age and BMI were predictors of COPD for male patients; whereas, coal fuel usage, income and BMI were predictors of COPD for female patients. CONCLUSION: COPD prevalence is higher in rural areas than in urban Chengdu. Major risk factors of COPD include smoking, coal fuels and BMI.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , População Rural , População Urbana , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fumar , Espirometria , Inquéritos e Questionários
14.
Bioorg Med Chem ; 22(17): 4784-91, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25088549

RESUMO

Exploring small-molecule acetylcholinesterase (AChE) inhibitors to slow the breakdown of acetylcholine (Ach) represents the mainstream direction for Alzheimer's disease (AD) therapy. As the first acetylcholinesterase inhibitor approved for the clinical treatment of AD, tacrine has been widely used as a pharmacophore to design hybrid compounds in order to combine its potent AChE inhibition with other multi-target profiles. In present study, a series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as potent dual-site AChE inhibitors. Moreover, compound 1g was identified as the most potent candidate with about 2-fold higher potency (Ki=16.7nM) against human AChE and about 2-fold lower potency (Ki=16.1nM) against BChE than tacrine (Ki=35.7nM for AChE, Ki=8.7nM for BChE), respectively. In addition, some of the tacrine-coumarin hybrids showed simultaneous inhibitory effects against both Aß aggregation and ß-secretase. We therefore conclude that tacrine-coumarin hybrid is an interesting multifunctional lead for the AD drug discovery.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Peptídeos beta-Amiloides/antagonistas & inibidores , Inibidores da Colinesterase/farmacologia , Colinesterases/metabolismo , Cumarínicos/farmacologia , Inibidores Enzimáticos/farmacologia , Tacrina/farmacologia , Acetilcolinesterase/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Cumarínicos/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Tacrina/química
15.
bioRxiv ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38895453

RESUMO

Computational modelling of cell state transitions has been a great interest of many in the field of developmental biology, cancer biology and cell fate engineering because it enables performing perturbation experiments in silico more rapidly and cheaply than could be achieved in a wet lab. Recent advancements in single-cell RNA sequencing (scRNA-seq) allow the capture of high-resolution snapshots of cell states as they transition along temporal trajectories. Using these high-throughput datasets, we can train computational models to generate in silico 'synthetic' cells that faithfully mimic the temporal trajectories. Here we present OneSC, a platform that can simulate synthetic cells across developmental trajectories using systems of stochastic differential equations govern by a core transcription factors (TFs) regulatory network. Different from the current network inference methods, OneSC prioritizes on generating Boolean network that produces faithful cell state transitions and steady cell states that mimic real biological systems. Applying OneSC to real data, we inferred a core TF network using a mouse myeloid progenitor scRNA-seq dataset and showed that the dynamical simulations of that network generate synthetic single-cell expression profiles that faithfully recapitulate the four myeloid differentiation trajectories going into differentiated cell states (erythrocytes, megakaryocytes, granulocytes and monocytes). Finally, through the in-silico perturbations of the mouse myeloid progenitor core network, we showed that OneSC can accurately predict cell fate decision biases of TF perturbations that closely match with previous experimental observations.

16.
PLoS One ; 19(2): e0297287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315687

RESUMO

The seismic effects on sloped terrain, which are of paramount importance for engineering design and earthquake risk mitigation, have always been a central focus of earthquake engineering research. In this study, generalized geometric models of loess ridges at varying heights were created, and a three-dimensional nonlinear numerical model was established using FLAC3D. Seismic ground motion time histories at different frequencies and actual earthquake ground motion records were input into the model to analyze the peak acceleration amplification effects experienced by the surface of loess ridges when subjected to SV waves. The study's outcomes reveal that seismic amplification on the slopes of loess ridges is characterized by non-linearity with respect to slope height. Instead, it exhibits rhythmic variations, with the rate of change in these rhythms increasing in correspondence with the frequency of seismic motion and the height of the slope. Under low-intensity seismic motion, a linear increase in acceleration amplification is observed at the ridge's crest concerning the height of the loess ridge. However, under high-intensity seismic motion, the relationship between amplification and slope height becomes less significant. Typically, the peak acceleration at the ridge's crest is reported to be 1.5 to 2.5 times that observed at the slope's base. The amplification effect at the ridge's crest is more pronounced in the low-frequency and high-frequency segments when compared to the mid-frequency range. Conversely, significant amplification is observed in the high-frequency range in the lower sections of the slope near the base. It is further noted that the amplification effect at the ridge's crest displays distinct behavior at different frequencies, characterized by narrow frequency bands of maximum amplification, with peak amplification factors exceeding 10 in some cases. These research findings have practical significance and provide valuable references for engineering construction and seismic risk mitigation planning in loess regions.


Assuntos
Terremotos , Dinâmica não Linear , Matemática , Movimento (Física) , China
17.
Front Surg ; 11: 1371641, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425375

RESUMO

[This corrects the article DOI: 10.3389/fsurg.2022.939591.].

18.
World J Oncol ; 15(3): 521-525, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751705

RESUMO

Inflammatory myofibroblastic tumors (IMTs), which involve the proliferation of fibroblastic-myofibroblastic cells mixed with inflammatory infiltrates, are exceedingly rare in the extremities. There are no reported IMTs involving the sciatic nerve. This type of involvement may cause entrapment of the sciatic nerve, whose symptoms may mimic lumbar disc herniation (LDH), especially when it occurs in patients with lumbar degenerative disc disease. We describe the case of a 40-year-old male with lumbar degenerative disc disease accompanied by IMT involving the sciatic nerve whose symptoms mimicked LDH and posed a diagnostic challenge. We showed the course of the disease as well as the systematic imaging manifestations of IMTs involving the sciatic nerve and discussed their therapeutic management.

19.
J Oral Microbiol ; 16(1): 2334588, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550659

RESUMO

Background: Epidemiological evidence has confirmed that periodontitis is an essential and independent risk factor of chronic obstructive pulmonary disease (COPD). Porphyromonas gingivalis, a major pathogen implicated in periodontitis, may make a vital contribution to COPD progression. However, the specific effects and molecular mechanism of the link between P. gingivalis and COPD are not clear. Methods and Results: A COPD rat model was constructed by smoke exposure combined intratracheal instillation of E. coli-LPS, then P. gingivalis was introduced into the oral cavity of COPD rats. This research observed that lower lung function, more severe alveolar damage and inflammation occurred in COPD rats with P. gingivalis group. Meanwhile, P. gingivalis/gingipains could colonize the lung tissues and be enriched in bronchoalveolar lavage fluid (BALF) of COPD rats with P. gingivalis group, along with alterations in lung microbiota. Proteomic analysis suggested that Hsp90α/MLKL-meditated necroptosis pathway was up-regulated in P. gingivalis-induced COPD aggravation, the detection of Hsp90α and MLKL in serum and lung tissue verified that Hsp90α/MLKL was up-regulated. Conclusion: These results indicate that P. gingivalis could emigrate into the lungs, alter lung microbiota and lead to aggravation of COPD, which Hsp90α/MLKL might participate in.

20.
ACS Appl Mater Interfaces ; 16(1): 669-683, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38150676

RESUMO

Conventional photoresponsive materials have low photon utilization due to irregular distribution of photoactive groups, which severely limits the related real applications. Metal-organic frameworks (MOFs) can modulate the regular arrangement of functional groups to improve the electron transport paths and enhance the photon utilization, which provides strong support for the development of photoactive materials with excellent performance. In this work, one effective strategy for constructing a photoactive MOF had been developed via the utilization of Cd2+ and pyrazinoquinoxaline tetracarboxylic acid. The structural advantages of the Cd-MOF, such as a porous structure, abundant subject-object interaction sites, and a stable framework, ensure the prerequisite for various applications, while the better synergistic effect of Cd3 clusters and the pyrazinoquinoxaline derivative ensures efficient electron transfer efficiency. Therefore, by virtue of these structural advantages, the Cd-MOF can achieve fluorescence quenching detection for a variety of substrates, such as Fe3+, Cr2O72-, MnO4-, nitrofuran antibiotics, and TNP explosives, while fluorescence enhancement detection can be achieved for halogen ions, Cs+, Pb2+, and NO2-. In addition, the Cd-MOF can be used as a photocatalyst to successfully achieve the photocatalytic conversion of benzylamine to N-benzylbenzimidate under mild conditions. Thus, the Cd-MOF as a whole shows the possibility of application as a diverse fluorescence detection and photocatalyst and also illustrates the feasibility of preparing high-performance photoactive materials using the pyrazinoquinoxaline derivative.

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