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1.
J Cell Physiol ; 239(4): e31189, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38219074

RESUMO

Joubert syndrome (JBTS) is a systematic developmental disorder mainly characterized by a pathognomonic mid-hindbrain malformation. All known JBTS-associated genes encode proteins involved in the function of antenna-like cellular organelle, primary cilium, which plays essential roles in cellular signal transduction and development. Here, we identified four unreported variants in ARL13B in two patients with the classical features of JBTS. ARL13B is a member of the Ras GTPase family and functions in ciliogenesis and cilia-related signaling. The two missense variants in ARL13B harbored the substitutions of amino acids at evolutionarily conserved positions. Using model cell lines, we found that the accumulations of the missense variants in cilia were impaired and the variants showed attenuated functions in ciliogenesis or the trafficking of INPP5E. Overall, these findings expanded the ARL13B pathogenetic variant spectrum of JBTS.


Assuntos
Fatores de Ribosilação do ADP , Anormalidades Múltiplas , Cerebelo , Anormalidades do Olho , Doenças Renais Císticas , Retina , Humanos , Anormalidades Múltiplas/genética , Fatores de Ribosilação do ADP/genética , Fatores de Ribosilação do ADP/metabolismo , Cerebelo/anormalidades , Cílios/genética , Anormalidades do Olho/genética , Anormalidades do Olho/metabolismo , Anormalidades do Olho/patologia , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Doenças Renais Císticas/patologia , Monoéster Fosfórico Hidrolases/metabolismo , Retina/metabolismo , Retina/anormalidades , Masculino , Feminino , Lactente
2.
Small ; : e2400142, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38676334

RESUMO

Complex temporal molecular signals play a pivotal role in the intricate biological pathways of living organisms, and cells exhibit the ability to transmit and receive information by intricately managing the temporal dynamics of their signaling molecules. Although biomimetic molecular networks are successfully engineered outside of cells, the capacity to precisely manipulate temporal behaviors remains limited. In this study, the catalysis activity of isothermal DNA polymerase (DNAP) through combined use of molecular dynamics simulation analysis and fluorescence assays is first characterized. DNAP-driven delay in signal strand release ranged from 100 to 102 min, which is achieved through new strategies including the introduction of primer overhangs, utilization of inhibitory reagents, and alteration of DNA template lengths. The results provide a deeper insight into the underlying mechanisms of temporal control DNAP-mediated primer extension and DNA strand displacement reactions. Then, the regulated DNAP catalysis reactions are applied in temporal modulation of downstream DNA-involved reactions, the establishment of dynamic molecular signals, and the generation of barcodes for multiplexed detection of target genes. The utility of DNAP-based signal delay as a dynamic DNA nanotechnology extends beyond theoretical concepts and achieves practical applications in the fields of cell-free synthetic biology and bionic sensing.

3.
Biomacromolecules ; 25(4): 2587-2596, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38527924

RESUMO

In response to increasing antibiotic resistance and the pressing demand for safer infected wound care, probiotics have emerged as promising bioactive agents. To address the challenges associated with the safe and efficient application of probiotics, this study successfully loaded metabolites from Lacticaseibacillus rhamnosus GG (LGG) into a gelatin cross-linked macromolecular network by an in situ blending and photopolymerization method. The obtained LM-GelMA possesses injectability and autonomous healing capabilities. Importantly, the incorporation of LGG metabolites endows LM-GelMA with excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, while maintaining good biocompatibility. In vivo assessments revealed that LM-GelMA can accelerate wound healing by mitigating infections induced by pathogenic bacteria. This is accompanied by a reduction in the expression of key proinflammatory cytokines such as TNF-α, IL-6, VEGFR2, and TGF-ß, leading to increased re-epithelialization and collagen formation. Moreover, microbiological analysis confirmed that LM-GelMA can modulate the abundance of beneficial wound microbiota at family and genus levels. This study provides a facile strategy and insights into the functional design of hydrogels from the perspective of wound microenvironment regulation.


Assuntos
Lacticaseibacillus rhamnosus , Cicatrização , Antibacterianos/farmacologia , Citocinas , Escherichia coli , Hidrogéis/farmacologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-38838049

RESUMO

OBJECTIVE: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. MATERIALS AND METHODS: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. RESULTS: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). CONCLUSION: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(2): 129-133, 2024 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-38311548

RESUMO

OBJECTIVE: To explore the genetic basis of eighteen patients with Tetrahydrobiopterin deficiency (BH4D) from Gansu Province. METHODS: Eighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing. RESULTS: All of the thirty-six alleles of the eighteen patients were successfully determined by molecular genetic testing. Sixteen patients were found to harbor variants of the PTS gene, and two had harbored variants of the QDPR gene. Ten variants were detected in the PTS gene, with the most common ones being c.259C>T (34.38%) and c.286G>A (15.63%). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.259C>T was classified as a pathogenic variant, whilst the c.286G>A, c.166G>A, c.200C>T, c.272A>G, c.402A>C, c.421G>T, c.84_291A>G and c.317C>T were classified as likely pathogenic variants. A novel c.289_290insCTT variant was classified as likely pathogenic (PM1+PM2_Supporting+PM3+PP3+PP4). The two variants (c.478C>T and c.665C>T) detected in the QDPR gene were both classified as variants of uncertain significance (PM1+PM2_Supporting+PP3+PP4). CONCLUSION: Genetic testing has clarified the pathogenic variants in these BH4D patients, which has enabled timely and accurate clinical intervention and treatment, and provided a reference for genetic counseling and reproductive guidance for their families.


Assuntos
Fenilcetonúrias , Criança , Humanos , Alelos , Fenilcetonúrias/genética , Família , Aconselhamento Genético , Testes Genéticos , Mutação
6.
Am J Physiol Cell Physiol ; 324(1): C133-C141, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36440855

RESUMO

Stress causes a rapid spike in norepinephrine (NE) levels, leading to gastrointestinal dysfunction. NE reduces the expression of tight junctions (TJs) and aggravates intestinal mucosal damage, but the regulatory mechanism is still unclear. The present study aimed to investigate the molecular mechanisms underlying the regulation of stress-associated duodenal hyperpermeability by NE. Fluorescein isothiocyanate-dextran permeability, transepithelial resistance, immunofluorescence, Western blot, and high-performance liquid chromatography analysis were used in water-immersion restraint stress (WIRS) rats in this study. The results indicate that the duodenal permeability, degradation of TJs, mucosal NE, and ß2-adrenergic receptor (ß2-AR) increased in WIRS rats. The duodenal intracellular cyclic adenosine monophosphate levels were decreased, whereas the expression of ß-arrestin 2 negatively regulates G protein-coupled receptors signaling, was significantly increased. Src recruitment was mediated by ß-arrestin; thus, the levels of Src kinase activation were enhanced in WIRS rats. NE depletion, ß2-AR, or ß-arrestin 2 blockade significantly decreased mucosal permeability and increased TJs expression, suggesting improved mucosal barrier function. Moreover, NE induced an increased duodenal permeability of normal rats with activated ß-arrestin 2/Src signaling, which was significantly inhibited by ß2-AR blockade. The present findings demonstrate that the enhanced NE induced an increased duodenal permeability in WIRS rats through the activated ß2-AR/ß-arrestin 2/Src pathway. This study provides novel insight into the molecular mechanism underlying the regulation of NE on the duodenal mucosal barrier and a new target for treating duodenal ulcers induced by stress.


Assuntos
Duodeno , Norepinefrina , Animais , Ratos , beta-Arrestina 2/genética , beta-Arrestina 2/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Transdução de Sinais , Água/metabolismo , Estresse Fisiológico , Duodeno/patologia , Duodeno/fisiologia
7.
Small ; : e2307115, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38059744

RESUMO

The imbalance of charge injection is considered to be a major factor that limits the device performance of cadmium-free quantum-dot light-emitting diodes (QLEDs). In this work, high-performance cadmium-free Cu─In─Zn─S(CIZS)-based QLEDs are designed and fabricated through tailoring interfacial energy level alignment and improving the balance of charge injection. This is achieved by introducing a bilayered hole-injection layer (HIL) of Cu-doped NiOx (Cu─NiOx )/Poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS). High-quality Cu─NiOx film is prepared through a novel and straightforward sol-gel procedure. Multiple experimental characterizations and theoretical calculations show that the incorporation of Cu2+ ions can regulate the energy level structure of NiOx and enhance the hole mobility. The state-of-art CIZS-based QLEDs with Cu─NiOx /PEDOT:PSS bilayered HIL exhibit the maximum external quantum efficiency of 6.04% and half-life time of 48 min, which is 1.3 times and four times of the device with only PEDOT:PSS HIL. The work provides a new pathway for developing high-performance cadmium-free QLEDs.

8.
Ann Clin Microbiol Antimicrob ; 22(1): 51, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386463

RESUMO

OBJECTIVES: Pseudomonas aeruginosa has intrinsic antibiotic resistance and the strong ability to acquire additional resistance genes. However, a limited number of investigations provide detailed modular structure dissection and evolutionary analysis of accessory genetic elements (AGEs) and associated resistance genes (ARGs) in P. aeruginosa isolates. The objective of this study is to reveal the prevalence and transmission characteristics of ARGs by epidemiological investigation and bioinformatics analysis of AGEs of P. aeruginosa isolates taken from a Chinese hospital. METHODS: Draft-genome sequencing was conducted for P. aeruginosa clinical isolates (n = 48) collected from a single Chinese hospital between 2019 and 2021. The clones of P. aeruginosa isolates, type 3 secretion system (T3SS)-related virulotypes, and the resistance spectrum were identified using multilocus sequence typing (MLST), polymerase chain reaction (PCR), and antimicrobial susceptibility tests. In addition, 17 of the 48 isolates were fully sequenced. An extensive modular structure dissection and genetic comparison was applied to AGEs of the 17 sequenced P. aeruginosa isolates. RESULTS: From the draft-genome sequencing, 13 STs were identified, showing high genetic diversity. BLAST search and PCR detection of T3SS genes (exoT, exoY, exoS, and exoU) revealed that the exoS+/exoU- virulotype dominated. At least 69 kinds of acquired ARGs, involved in resistance to 10 different categories of antimicrobials, were identified in the 48 P. aeruginosa isolates. Detailed genetic dissection and sequence comparisons were applied to 25 AGEs from the 17 isolates, together with five additional prototype AGEs from GenBank. These 30 AGEs were classified into five groups -- integrative and conjugative elements (ICEs), unit transposons, IncpPBL16 plasmids, Incp60512-IMP plasmids, and IncpPA7790 plasmids. CONCLUSION: This study provides a broad-scale and deeper genomics understanding of P. aeruginosa isolates taken from a single Chinese hospital. The isolates collected are characterized by high genetic diversity, high virulence, and multiple drug resistance. The AGEs in P. aeruginosa chromosomes and plasmids, as important genetic platforms for the spread of ARGs, contribute to enhancing the adaptability of P. aeruginosa in hospital settings.


Assuntos
Anti-Infecciosos , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/genética , Antibacterianos/farmacologia , Tipagem de Sequências Multilocus , Farmacorresistência Bacteriana/genética , Produtos Finais de Glicação Avançada
9.
BMC Womens Health ; 23(1): 248, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37161406

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. RESULTS: Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. CONCLUSIONS: Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Adulto Jovem , População Negra , Vasos Coronários , Obesidade/complicações , Obesidade/epidemiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Estudos Prospectivos , Autorrelato , Fatores de Risco de Doenças Cardíacas , Negro ou Afro-Americano , Brancos , Adulto
10.
BMC Public Health ; 23(1): 1689, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658310

RESUMO

BACKGROUND: The weight-adjusted waist index (WWI) is a new measure of obesity, and this study aimed to determine the association between the WWI and stroke. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 2011-2020 dataset, cross-sectional data from 23,389 participants were analysed. The correlation between the WWI and stroke was investigated through multivariate logistic regression and smoothing curve fitting. Subgroup analysis and interaction tests were also carried out. RESULTS: The research involved 23,389 participants, of whom 893 (3.82%) had a stroke. The fully adjusted model revealed a positive correlation between the WWI and stroke [1.25 (1.05, 1.48)]. Individuals who were in the highest quartile of WWI exhibited a 62% higher likelihood of experiencing a stroke than those in the lowest quartile [1.62 (1.06, 2.48)]. Subgroup analysis and interaction tests revealed that this positive correlation was similar in different population settings (all P for interaction > 0.05). CONCLUSION: A higher WWI was associated with a higher prevalence of stroke. The results of this study underscore the value of the WWI in stroke prevention and management.


Assuntos
Acidente Vascular Cerebral , Humanos , Estudos Transversais , Inquéritos Nutricionais , Acidente Vascular Cerebral/epidemiologia , Obesidade/epidemiologia , Probabilidade
11.
Proc Natl Acad Sci U S A ; 117(26): 14667-14675, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32532923

RESUMO

Many natural materials possess built-in structural variation, endowing them with superior performance. However, it is challenging to realize programmable structural variation in self-assembled synthetic materials since self-assembly processes usually generate uniform and ordered structures. Here, we report the formation of asymmetric microribbons composed of directionally self-assembled two-dimensional nanoflakes in a polymeric matrix during three-dimensional direct-ink printing. The printed ribbons with embedded structural variations show site-specific variance in their mechanical properties. Remarkably, the ribbons can spontaneously transform into ultrastretchable springs with controllable helical architecture upon stimulation. Such springs also exhibit superior nanoscale transport behavior as nanofluidic ionic conductors under even ultralarge tensile strains (>1,000%). Furthermore, to show possible real-world uses of such materials, we demonstrate in vivo neural recording and stimulation using such springs in a bullfrog animal model. Thus, such springs can be used as neural electrodes compatible with soft and dynamic biological tissues.


Assuntos
Neuroestimuladores Implantáveis , Microtecnologia/instrumentação , Nanoestruturas , Impressão Tridimensional , Animais , Anuros , Elasticidade , Grafite/química , Íons/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Neurofisiologia/instrumentação , Nervo Isquiático/fisiologia
12.
J Assist Reprod Genet ; 40(5): 1147-1161, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36930359

RESUMO

PURPOSE: The objective of this study was to investigate the key glycolysis-related genes linked to immune cell infiltration in endometriosis and to develop a new endometriosis (EMS) predictive model. METHODS: A training set and a test set were created from the Gene Expression Omnibus (GEO) public database. We identified five glycolysis-related genes using least absolute shrinkage and selection operator (LASSO) regression and the random forest method. Then, we developed and tested a prediction model for EMS diagnosis. The CIBERSORT method was used to compare the infiltration of 22 different immune cells. We examined the relationship between key glycolysis-related genes and immune factors in the eutopic endometrium of women with endometriosis. In addition, Gene Ontology (GO)-based semantic similarity and logistic regression model analyses were used to investigate core genes. Reverse real-time quantitative PCR (RT-qPCR) of 5 target genes was analysed. RESULTS: The five glycolysis-related hub genes (CHPF, CITED2, GPC3, PDK3, ADH6) were used to establish a predictive model for EMS. In the training and test sets, the area under the curve (AUC) of the receiver operating characteristic curve (ROC) prediction model was 0.777, 0.824, and 0.774. Additionally, there was a remarkable difference in the immune environment between the EMS and control groups. Eventually, the five target genes were verified by RT-qPCR. CONCLUSION: The glycolysis-immune-based predictive model was established to forecast EMS patients' diagnosis, and a detailed comprehension of the interactions between endometriosis, glycolysis, and the immune system may be vital for the recognition of potential novel therapeutic approaches and targets for EMS patients.


Assuntos
Endometriose , Humanos , Feminino , Endometriose/diagnóstico , Endometriose/genética , Aprendizado de Máquina , Área Sob a Curva , Grupos Controle , Glicólise/genética , Glipicanas , Proteínas Repressoras , Transativadores
13.
Microb Pathog ; 169: 105659, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35760284

RESUMO

Biofilms formed by Yersinia pestis are able to attach to and block flea's proventriculus, which stimulates the transmission of this pathogen from fleas to mammals. In this study, we found that Nlp (YP1143) enhanced biofilm formation by Y. pestis and had regulatory effects on biofilm-associated genes at the transcriptional level. Phenotypic assays, including colony morphology assay, crystal violet staining, and Caenorhabditis elegans biofilm assay, disclosed that Nlp strongly promoted biofilm formation by Y. pestis. Further gene regulation assays showed that Nlp stimulated the expression of hmsHFRS, hmsCDE and hmsB, while had no regulatory effect on the expression of hmsT and hmsP at the transcriptional level. These findings promoted us to gain more understanding of the complex regulatory circuits controlling biofilm formation by Y. pestis.


Assuntos
Peste , Yersinia pestis , Animais , Arvicolinae/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Regulação Bacteriana da Expressão Gênica , Yersinia pestis/metabolismo
14.
Opt Lett ; 47(11): 2722-2725, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35648914

RESUMO

A high color rendering index (CRI) and stable spectra under different voltages are important parameters for large-area planar light sources. However, the spectrum of most electroluminescent white light-emitting diodes (el-WLEDs) with a single emissive layer (EML) varies with a changing voltage. Herein, an el-WLED is fabricated based on Cd-free Cu-In-Zn-S (CIZS)/ZnS nanocrystals (NCs) and poly [(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(p-butylphenyl))diphenylamine)] (TFB) as double EMLs, which exhibit white-light emission with a high CRI value of 91 and commission internationale de l'éclairage (CIE) color coordinates of (0.33, 0.33). Meanwhile, it has a stable spectrum under voltage up to 7 V and a maximum luminance up to 679 cd/m2 with a low turn-on voltage of 2.2 V. This work provides a foundation for Cd-free el-WLEDs with high CRI and stable spectra.

15.
Nat Chem Biol ; 16(11): 1170-1178, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32778845

RESUMO

The RAF family kinases function in the RAS-ERK pathway to transmit signals from activated RAS to the downstream kinases MEK and ERK. This pathway regulates cell proliferation, differentiation and survival, enabling mutations in RAS and RAF to act as potent drivers of human cancers. Drugs targeting the prevalent oncogenic mutant BRAF(V600E) have shown great efficacy in the clinic, but long-term effectiveness is limited by resistance mechanisms that often exploit the dimerization-dependent process by which RAF kinases are activated. Here, we investigated a proteolysis-targeting chimera (PROTAC) approach to BRAF inhibition. The most effective PROTAC, termed P4B, displayed superior specificity and inhibitory properties relative to non-PROTAC controls in BRAF(V600E) cell lines. In addition, P4B displayed utility in cell lines harboring alternative BRAF mutations that impart resistance to conventional BRAF inhibitors. This work provides a proof of concept for a substitute to conventional chemical inhibition to therapeutically constrain oncogenic BRAF.


Assuntos
Antineoplásicos , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas B-raf , Talidomida , Ubiquitina , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Resistencia a Medicamentos Antineoplásicos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Modelos Moleculares , Estrutura Molecular , Terapia de Alvo Molecular , Mutação , Fosforilação/efeitos dos fármacos , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , Proteólise , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Transdução de Sinais , Relação Estrutura-Atividade , Talidomida/análogos & derivados , Talidomida/química , Ubiquitina/química
16.
Brain Behav Immun ; 102: 11-22, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35143877

RESUMO

Gut microbiome disturbances have been widely implicated in major depressive disorder (MDD), although the identity of causal microbial species and the underlying mechanisms are yet to be fully elucidated. Here we show that Bacteroides species enriched in the gut microbiome from MDD patients differentially impact the susceptibility to depressive behaviors. Transplantation of fecal microbiome from MDD patients into antibiotic-treated mice induced anxiety and despair-like behavior and impaired hippocampal neurogenesis. Colonization of Bacteroides fragilis, Bacteroides uniformis, and, to a lesser extent, Bacteroides caccae, but not Bacteroides ovatus, recapitulated the negative effects of MDD microbiome on behavior and neurogenesis. The varying impacts of Bacteroides species were partially explained by differential alternations of tryptophan pathway metabolites and neurotransmitters along the gut-brain axis. Notably, an intensified depletion of cerebral serotonin concurred with the enhanced susceptibility to depression. Together, these findings identify select Bacteroidetes species that contribute to depression susceptibility in mice by metabolic regulation along the gut-brain axis.


Assuntos
Transtorno Depressivo Maior , Microbioma Gastrointestinal , Animais , Bacteroides , Encéfalo/metabolismo , Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Microbioma Gastrointestinal/fisiologia , Humanos , Camundongos
17.
Ann Clin Microbiol Antimicrob ; 21(1): 10, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264204

RESUMO

BACKGROUND: The carbapenem-resistance genes blaVIM are widely disseminated in Pseudomonas, and frequently harbored within class 1 integrons that reside within various mobile genetic elements (MGEs). However, there are few reports on detailed genetic dissection of blaVIM-carrying MGEs in Pseudomonas. METHODS: This study presented the complete sequences of five blaVIM-2/-4-carrying MGEs, including two plasmids, two chromosomal integrative and mobilizable elements (IMEs), and one chromosomal integrative and conjugative element (ICE) from five different Pseudomonas isolates. RESULTS: The two plasmids were assigned to a novel incompatibility (Inc) group IncpSTY, which included only seven available plasmids with determined complete sequences and could be further divided into three subgroups IncpSTY-1/2/3. A detailed sequence comparison was then applied to a collection of 15 MGEs belonging to four different groups: three representative IncpSTY plasmids, two Tn6916-related IMEs, two Tn6918-related IMEs, and eight Tn6417-related ICEs and ten of these 15 MGEs were first time identified. At least 22 genes involving resistance to seven different categories of antibiotics and heavy metals were identified within these 15 MGEs, and most of these resistance genes were located within the accessory modules integrated as exogenous DNA regions into these MGEs. Especially, eleven of these 15 MGEs carried the blaVIM genes, which were located within 11 different concise class 1 integrons. CONCLUSION: These blaVIM-carrying integrons were further integrated into the above plasmids, IMEs/ICEs with intercellular mobility. These MGEs could transfer between Pseudomonas isolates, which resulted in the accumulation and spread of blaVIM among Pseudomonas and thus was helpful for the bacteria to survival from the stress of antibiotics. Data presented here provided a deeper insight into the genetic diversification and evolution of VIM-encoding MGEs in Pseudomonas.


Assuntos
Conjugação Genética , Integrons , Plasmídeos , Pseudomonas , beta-Lactamases , Antibacterianos/farmacologia , Cromossomos Bacterianos , Integrons/genética , Plasmídeos/genética , Pseudomonas/efeitos dos fármacos , Pseudomonas/genética , beta-Lactamases/genética
18.
J Clin Periodontol ; 49(2): 177-187, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34866208

RESUMO

AIM: To determine whether collagen membrane (CM) fixation enhances guided bone regeneration in standardized defects. MATERIALS AND METHODS: Four 8-mm-diameter defects were surgically made in eight rabbit calvaria, and randomly allocated into four groups: control (empty), unfixed-CM, fixed-CM, and unfixed-CM with bone graft (BG + CM) (positive control). After 1- and 4-week healing periods, the animals were sacrificed and quantitative reverse transcription polymerase chain reaction, micro-computed tomography, and histological outcomes were assessed. RESULTS: At week 1, the expression levels of BMP-2, FGF-2, VEGF, and osteocalcin were significantly higher in the fixed-CM group than in the unfixed-CM and control groups (p < .05). Conversely, cathepsin-K was significantly expressed in the unfixed-CM group. No significant differences in expression markers were observed between the fixed-CM and BG + CM groups (p > .05). At week 4, new bone formation was significantly higher in the fixed-CM group than the unfixed-CM and control groups (p < .05), but similar to the BG + CM group (p > .05). CONCLUSIONS: CM fixation enhances the expression of osteogenic factors similar to BG + CM, leading to significantly more new bone formation. This suggests that the osteogenic potential is greater when membranes are fixed, thereby limiting the necessity of membrane-supporting materials to enhance bone formation.


Assuntos
Regeneração Óssea , Membranas Artificiais , Animais , Coelhos , Transplante Ósseo/métodos , Crânio/cirurgia , Microtomografia por Raio-X
19.
Small ; 17(40): e2008079, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34142431

RESUMO

Biomass-derived carbon materials (BCMs) are encountering the most flourishing moment because of their versatile properties and wide potential applications. Numerous BCMs, including 0D carbon spheres and dots, 1D carbon fibers and tubes, 2D carbon sheets, 3D carbon aerogel, and hierarchical carbon materials have been prepared. At the same time, their structure-property relationship and applications have been widely studied. This paper aims to present a review on the recent advances in the controllable preparation and potential applications of BCMs, providing a reference for future work. First, the chemical compositions of typical biomass and their thermal degradation mechanisms are presented. Then, the typical preparation methods of BCMs are summarized and the relevant structural management rules are discussed. Besides, the strategies for improving the structural diversity of BCMs are also presented and discussed. Furthermore, the applications of BCMs in energy, sensing, environment, and other areas are reviewed. Finally, the remaining challenges and opportunities in the field of BCMs are discussed.


Assuntos
Carbono , Biomassa
20.
Small ; 17(19): e2100066, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33792159

RESUMO

Natural materials, such as silk, nacre, and bone, possess superior mechanical properties which are derived from their unique hierarchical structures. Individual carbon nanotubes (CNTs) are considered as one of the strongest materials. However, macroscopic CNT fibers usually have breaking strength far below that of individual CNTs. In this work, by mimicking the structure of natural silk fibers, strong and stiff CNT fibers are prepared by infiltrating silk fibroin (SF) into CNT fibers. There are abundant hydrogen bonds in SF, contributing to the enhanced interactions between neighboring CNTs. Glycerol is selected to promote the formation of ß-sheet conformation in SF, leading to further enhanced strength and modulus. Remarkably, the SF infiltrated CNT fibers show breaking strength of 1023 MPa, toughness of 10.3 MJ m-3 , and Young's modulus of 81.3 GPa, which are 250%, 132%, and 442% of the pristine CNT fibers. The structure of the SF and the interactions between CNTs and SF are studied via Fourier transformed infrared spectroscopy and molecular dynamics simulation. Mimicking the hierarchical structures of natural silk fibers and enhance the interfacial load transfer by infiltrating SF are effective for reinforcing CNT fibers, which may be useful in the design and preparation of other structural materials.


Assuntos
Fibroínas , Nanotubos de Carbono , Biomimética , Fibra de Carbono , Seda
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