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1.
Bioorg Chem ; 149: 107487, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38805910

RESUMO

The peel of Trichosanthes kirilowii Maxim, is considered one of the primary sources for Trichosanthis pericarpium in traditional Chinese medicine, exhibiting lipid-lowering properties. The impact on hyperlipidemia mice of the crude polysaccharide from the peel of T. Kirilowii (TRP) was investigated in this study. The findings revealed that TRP exhibited a significant improvement in hepatic lipid deposition. Moreover, it significantly decreased serum levels of TC, TG, and LDL-C, while concurrently increasing HDL-C. 16S rRNA amplicon sequencing technique revealed that TRP group exhibited an increased relative abundance of Actinobacteria, a down-regulated relative abundance of Ruminiclostridium, and an up-regulated relative abundance of Ileibacterium. Therefore, TRP might play a role in anti-hyperlipidemia through regulation of the intestinal milieu and enhancement of microbial equilibrium. Consequently, targeted fractionation of TRP resulted in the isolation of a homogeneous acidic polysaccharide termed TRP-1. The TRP-1 polysaccharide, with an average molecular weight of 1.00 × 104 Da, and was primarily composed of Rha, GlcA, GalA, Glc, Gal and Ara. TRP-1 possessed a backbone consisting of alternating connections between â†’ 6)-α-Galp-(1 â†’ 4)-α-Rhap-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ units and branched chain containing â†’ 6)-α-Glcp-(1→, 2,4)-ß-Glcp-(1, and â†’ 4)-α-GlapA-(1→. Both TRP and TRP-1 exhibited significant disruption of cholesterol micelles, highlighting their potential as lipid-lowering agents that effectively inhibit cholesterol absorption pathways.


Assuntos
Colesterol , Microbioma Gastrointestinal , Hiperlipidemias , Polissacarídeos , Trichosanthes , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Trichosanthes/química , Camundongos , Hiperlipidemias/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Colesterol/metabolismo , Colesterol/sangue , Hipolipemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/isolamento & purificação , Masculino , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga
2.
J Am Chem Soc ; 145(23): 12812-12822, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37249527

RESUMO

Life molecules' distributions in live systems construct the complex dynamic reaction networks, whereas it is still challenging to demonstrate the dynamic distributions of biomolecules in live systems. Herein, we proposed a dynamic analysis strategy via sequence-structure bispecific RNA with state-adjustable molecules to monitor the dynamic concentration and spatiotemporal localization of these biomolecules in live cells based on the new insight of fluorescent RNA (FLRNA) interactions and their mechanism of fluorescence enhancement. Typically, computer-based nucleic acid-molecular docking simulation and molecular theoretical calculation have been proposed to provide a simple and straightforward method for guiding the custom-design of FLRNA. Impressively, a novel FLRNA with sequence and structure bispecific RNA named as a structure-switching aptamer (SSA) was introduced to monitor the real-time concentration and spatiotemporal localization of biomolecules, contributing to a deeper insight of the dynamic monitoring and visualization of biomolecules in live systems.


Assuntos
Corantes Fluorescentes , RNA , RNA/química , Simulação de Acoplamento Molecular , Corantes Fluorescentes/química
3.
Analyst ; 147(10): 2156-2163, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35438693

RESUMO

A facile strategy has been reported to anchor silver nanoparticles (Ag NPs) onto three-dimensional reduced graphene oxide (3D rGO) via a green and simple method. An accurate and reliable electrochemical sensing platform based on Ag NPs/3D rGO was designed for the ultrasensitive detection of rifampicin (RIF). The morphology and features of Ag NPs/3D rGO were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Raman spectroscopy and electrochemical measurements. The interface of the modified electrode presented effective electrical activity for the analysis of RIF due to the large electrochemically active surface area and excellent electron transport ability. The sensor exhibited a good linear relationship in the range of 0.01 nM-45 µM and a low detection limit of 0.810 nM (S/N = 3). Crucially, the fabricated Ag NPs/3D rGO sensor was successfully utilized to assess RIF in human blood, drug and aquatic product samples. This sensing platform exhibited outstanding electrochemical performance for RIF detection and showed great potential application in clinical diagnosis, pharmaceutical and food-related fields.


Assuntos
Grafite , Nanopartículas Metálicas , Técnicas Eletroquímicas/métodos , Grafite/química , Humanos , Nanopartículas Metálicas/química , Rifampina , Prata/química
4.
Arch Virol ; 167(12): 2519-2528, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36083350

RESUMO

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.


Assuntos
COVID-19 , Vacinas de DNA , Animais , Humanos , Camundongos , Adjuvantes Imunológicos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Imunidade Celular , Camundongos Transgênicos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Vacinas de DNA/genética
5.
Int J Obes (Lond) ; 45(5): 1105-1113, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33627773

RESUMO

BACKGROUND: Childhood obesity is one of the most common and costly nutritional problems with high heritability. The genetic mechanism of childhood obesity remains unclear. Here, we conducted a transcriptome-wide association study (TWAS) to identify novel genes for childhood obesity. METHODS: By integrating the GWAS summary of childhood body mass index (BMI), we conducted TWAS analyses with pre-computed gene expression weights in 39 obesity priority tissues. The GWAS summary statistics of childhood BMI were derived from the early growth genetics consortium with 35,668 children from 20 studies. RESULTS: We identified 15 candidate genes for childhood BMI after Bonferroni corrections. The most significant gene, ADCY3, was identified in 13 tissues, including adipose, brain, and blood. Interestingly, eight genes were only identified in the specific tissue, such as FAIM2 in the brain (P = 2.04 × 10-7) and fat mass and obesity-associated gene (FTO) in the muscle (P = 1.93 × 10-8). Compared with the TWAS results of adult BMI, we found that one gene TUBA1B with predominant influence only on childhood BMI in the muscle (P = 1.12 × 10-7). We evaluated the candidate genes by querying public databases and identified 12 genes functionally related to obesity phenotypes, including nine differentially expressed genes during the differentiation of human preadipocyte cells. The remaining genes (FAM150B, KNOP1, and LMBR1L) were regarded as novel candidate genes for childhood BMI. CONCLUSIONS: Our study identified multiple candidate genes for childhood BMI, providing novel clues for understanding the genetic mechanism of childhood obesity.


Assuntos
Índice de Massa Corporal , Obesidade Infantil/genética , Transcriptoma , Adenilil Ciclases/genética , Criança , Citocinas/genética , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Receptores de Superfície Celular/genética , Tubulina (Proteína)/genética
6.
Microb Pathog ; 150: 104729, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33429053

RESUMO

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) cause a huge economic loss around the pig industry worldwide; the NADC30-like PRRSV have attracted much attention outbreaks in China in recent years. Recombination between PRRSV subtypes, point mutations, insertions and deletions that contribute to the emergence of new variants in the genome. In this study, the PRRSV-HB-16-China-2019 strain's full-length genomic sequence shares 93.0% nucleotide similarity to NADC30 PRRSV without any gene insertion. Compared with VR-2332, it has an NSP2 coding region that is different from NADC30, which has a discontinuous 206-aa (111-aa from position 323 to 433 and 95-aa from position 476 to 570) deletion. Compared with other NADC30-Like strains, it has a discontinuous 75-amino acid (75-aa from position 476 to 552) deletion, which was first reported. Notably, the strain, PRRSV-HB-16-China-2019, contained an addition a 1-aa deletion in ORF5 and a unique 3-nt deletion in 3'-UTR similar to NADC30, the strain is recombined between a NADC30-like strain and a vaccine strain named RespPRRS MLV(parental strain VR-2332). Our findings indicate that PRRSV-HB-16-China-2019 is a new NSP2-deletion NADC30-like strain with certain deletions and mutations. Our results show that the emergence of the new NADC30-like strain has increased the difficulty of PRRSV prevention in China.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , China , Variação Genética , Genoma Viral , Filogenia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Recombinação Genética , Suínos
7.
J Stroke Cerebrovasc Dis ; 30(5): 105673, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33631472

RESUMO

BACKGROUND: Whether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV). METHODS: This case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP. RESULTS: CSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P < .05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P < .001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1-3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (r2 = 0.308-0.340). In model 4, the nocturnal SBP fall rate was negatively correlated with CSVD (odds ratio [OR] = 0.871, 95% confidence interval [CI] = 0.804-0.943; P = .001), with r2 = 0.415 fitting the model. In model 5, the pattern of SBP dipping was significantly associated with CSVD, with non-dipper (OR = 8.389, 95%CI = 1.489-47.254; P = .016) and reverse dipper (OR = 27.008, 95%CI = 3.709-196.660; P = .001) having the highest risks of CSVD (r2 = 0.413). CONCLUSIONS: Lower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea , Sistema Cardiovascular/inervação , Doenças de Pequenos Vasos Cerebrais/etiologia , Ritmo Circadiano , Frequência Cardíaca , Hipertensão/fisiopatologia , Idoso , Monitorização Ambulatorial da Pressão Arterial , Estudos de Casos e Controles , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
8.
Anal Chem ; 92(12): 8046-8050, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32449350

RESUMO

In this work, well-ordered platinum (Pt) nanocubes (NCs), with precise control on the size and the spatial arrangement, are synthesized from a microemulsion overgrowth in a block copolymer (BC) nanotemplate. The nanovials on this self-assembled BC template serve as microreactors for the reduction of the HCl/H2PtCl6 precursor and direct the ordered periodic arrangement of the reduced Pt nanoparticles (NPs). As the content of HCl increases from 0% to 25%, the Pt NPs evolve from quasi-spheres to NCs, for which the density functional theory (DFT) computation reveals that the different adsorption energies of Cl and HCl dominate this morphology transition. For their potential application in fuel cells, the electrochemical catalysis of the Pt NCs demonstrates a 2.8-fold mass activity in contrast to the commercial JM 40% catalyst at the same Pt loading in ethanol oxidation reaction (EOR) and a good stability of 2.2% ECSA loss over 10 000 CV cycling.

9.
Int J Syst Evol Microbiol ; 67(8): 3099-3104, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28820117

RESUMO

A Gram-stain-negative, aerobic, non-motile, rod-shaped and non-spore-forming bacterium, designated EF23T, was isolated from rhizosphere soil of watermelon. Growth of strain EF23T was observed at 10-37 °C, at pH 5.0-9.0 and in the presence of 0-0.5 % (w/v) NaCl. Strain EF23T contained menaquinone 7 (MK-7) as the major isoprenoid quinone, and summed feature 3 (C16:1ω7c and/or iso-C15 : 0 2-OH), iso-C15 : 0, C16 : 0 and iso-C17 : 0 3-OH as the major fatty acids. Phosphatidylethanolamine was identified as the major polar lipid. The genomic DNA G+C content of strain EF23T was 43.7 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain EF23T was most closely related to Mucilaginibacter gossypii Gh-67T (98.9 % similarity) and Mucilaginibacter gossypiicola Gh-48T (97.6 %). DNA-DNA relatedness values between strain EF23T and M. gossypii KCTC 22380T and M. gossypiicola KCTC 22379T were 31.6 and 53.7 %. On the basis of the evidence presented in this polyphasic taxonomic study, strain EF23T is considered to represent a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter rubeus sp. nov. is proposed. The type strain is EF23T (=CGMCC 1.15913T=KCTC 52516T).


Assuntos
Bacteroidetes/classificação , Citrullus/microbiologia , Filogenia , Rizosfera , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
10.
Int J Syst Evol Microbiol ; 67(6): 1771-1776, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28598303

RESUMO

The Gram-reaction-negative, aerobic, white- to pale-yellow-coloured and rod-shaped bacterium with a single polar flagellum or a stalk, designated strain 7F14T, was isolated from rhizosphere soil of cultivated watermelon (Citrullus lanatus) collected from Hefei, China. Growth of strain 7F14T was observed at pH 6.0-9.0, 10-30 °C and in the presence of 0-1 % (w/v) NaCl. Cells were catalase-negative and oxidase-positive. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain 7F14T formed a phyletic lineage within the genus Caulobacter of the family Caulobacteraceae and showed the highest 16S rRNA gene sequence similarities to Caulobacter henricii ATCC 15253T (98.66 %), Caulobacter segnis ATCC 21756T (98.27 %), Caulobacter vibrioides CB51T (97.92 %) and Caulobacter flavus RHGG3T (97.44 %). The G+C content of the genomic DNA was 68.6 mol%. Strain 7F14T contained Q-10 as the sole ubiquinone and 11-methyl C18 : 1ω7c, C18 : 1ω7c, C16 : 0 and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH) as the major fatty acids. The polar lipids profile consisted of phosphatidylglycerol, an unknown phosphoglycolipid, five unknown glycolipids, an unknown phospholipid and three unknown lipids. DNA-DNA relatedness values to the most closely related type strains Caulobacter henricii DSM 4730T and Caulobacter segnis DSM 7131T were 26.0 and 19.7 %, respectively. Based on unique phenotypic traits, and phylogenetic, chemotaxonomic and DNA-DNA hybridization results, strain 7F14T should be classified as a representative of a novel species of the genus Caulobacter, for which the name Caulobacter rhizosphaerae sp. nov. is proposed. The type strain is 7F14T (=CGMCC 1.15915T=KCTC 52515T).


Assuntos
Caulobacter/classificação , Filogenia , Rizosfera , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Caulobacter/genética , Caulobacter/isolamento & purificação , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
11.
Int Immunopharmacol ; 135: 112304, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38776851

RESUMO

Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic acid (RA) as a prominent polyphenolic secondary metabolite derived from Rosmarinus officinalis modulates ACE2 in sepsis remains unclear, although its impact on ACE inhibition and septic-associated lung injury has been explored. The study investigated the ACE2 expression in lipopolysaccharide (LPS)-induced lungs in mice and BEAS2B cells. Additionally, molecular docking, protein-protein interaction (PPI) network analysis, and western blotting were employed to predict and evaluate the molecular mechanism of RA on LPS-induced ferroptosis in vivo and in vitro. LPS-induced glutathione peroxidase 4 (GPX4) downregulation, ACE/ACE2 imbalance, and alteration of frequency of breathing (BPM), minute volume (MV), and the expiratory flow at 50% expired volume (EF50) were reversed by captopril pretreatment in vitro and in vivo. RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement, and decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice. Molecular docking showed RA was able to interact with ACE and ACE2. Moreover, combined with different pharmacological inhibitors to block ACE and ferroptosis, RA still significantly inhibited inflammatory cytokines Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine 2 (CXCL2) levels, as well as improved lung function, and enhanced GPX4 expression. Particularly, the anti-ferroptosis effect of RA in LPS-induced septic ARDS is RAS-dependent.


Assuntos
Enzima de Conversão de Angiotensina 2 , Cinamatos , Depsídeos , Ferroptose , Lipopolissacarídeos , Síndrome do Desconforto Respiratório , Ácido Rosmarínico , Sepse , Animais , Depsídeos/uso terapêutico , Depsídeos/farmacologia , Ferroptose/efeitos dos fármacos , Cinamatos/uso terapêutico , Cinamatos/farmacologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Humanos , Camundongos , Masculino , Sepse/tratamento farmacológico , Enzima de Conversão de Angiotensina 2/metabolismo , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/metabolismo , Camundongos Endogâmicos C57BL , Brônquios/efeitos dos fármacos , Brônquios/patologia , Linhagem Celular , Captopril/farmacologia , Captopril/uso terapêutico , Modelos Animais de Doenças , Citocinas/metabolismo
12.
Heliyon ; 10(12): e32833, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975231

RESUMO

Background: Bronchobiliary fistulas (BBFs), primarily stemming from choledocholithiasis, present considerable diagnostic and treatment challenges. Their prolonged nature can lead to life-threatening situations without timely management, often complicated by lung abscesses. Case presentation: A 64-year-old man, presenting with fever, chills, and a cough initially misdiagnosed as a common cold, developed severe respiratory distress and delirium upon admission. Urgent intensive care unit (ICU) admission was prompted by a computed tomography (CT) scan revealing a right lung abscess. Enhanced CT scans and elevated bilirubin levels confirmed the biliary origin of the BBFs. Comprehensive treatment included laparoscopic partial hepatectomy, choledochojejunostomy, stone extraction, choledochoscopy, T-tube drainage, and BBFs closure. The patient was discharged with a T-tube. Follow-up CT after two months showed no recurrence. Conclusions: Managing BBFs, especially with concurrent lung abscesses in choledocholithiasis patients, remains challenging but feasible. Early diagnosis and intervention are crucial to improving survival rates and quality of life, highlighting the need for vigilance. This case underscores the importance of early detection and comprehensive treatment for successful outcomes in such complex conditions.

13.
Acta Pharm Sin B ; 14(3): 1441-1456, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38487002

RESUMO

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases, immune cell infiltration and protease-driven tissue damages. It is an urgent need to explore potential drug strategies for mitigating lung inflammation. Protease-activated receptor 2 (PAR2) as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction. However, it has been rarely reported about the role of PAR2 in lung inflammation. This study applied CRISPR-Cas9 system encoding Cas9 and sgRNA (pCas9-PAR2) for PAR2 knockout and fabricated an anionic human serum albumin-based nanoparticles to deliver pCas9-PAR2 with superior inflammation-targeting efficiency and stability (TAP/pCas9-PAR2). TAP/pCas9-PAR2 robustly facilitated pCas9-PAR2 to enter and transfect inflammatory cells, eliciting precise gene editing of PAR2 in vitro and in vivo. Importantly, PAR2 deficiency by TAP/pCas9-PAR2 effectively and safely promoted macrophage polarization, suppressed pro-inflammatory cytokine releases and alleviated acute lung inflammation, uncovering a novel value of PAR2. It also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/pCas9-PAR2 was mainly dependent on ERK-mediated NLRP3/IL-1ß and NO/iNOS signalling. Therefore, this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

14.
Insect Biochem Mol Biol ; 170: 104130, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38734116

RESUMO

Agmatine N-acetyltransferase (AgmNAT), which catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine, is a member of the GCN5-related N-acetyltransferase family. So far, knowledge of the physiological roles of AgmNAT in insects is limited. Here, we identified one gene encoding protein homologous to that of Drosophila AgmNAT using sequence information from an activity-verified Drosophila AgmNAT in a BLAST search of the Bactrocera dorsalis genome. We expressed and purified B. dorsalis AgmNAT in Escherichia coli and used the purified enzyme to define the substrate specificity for acyl-CoA and amine substrates. Our application of the screening strategy to BdorAgmNAT led to the identification of agmatine as the best amine substrate for this enzyme, with the highest kcat/Km value. We successfully obtained a BdorAgmNAT knockout strain based on a wild-type strain (WT) using the CRISPR/Cas9 technique. The ovary development of the BdorAgmNAT knockout mutants was delayed for 10 days compared with the WT specimens. Moreover, mutants had a much smaller mature ovary size and laid far fewer eggs than WT. Loss of function of BdorAgmNAT caused by RNAi with mature WT females did not affect their fecundity. These findings indicate that BdorAgmNAT is critical for oogenesis. Our data provide the first evidence for AgmNAT in regulating ovary development.


Assuntos
Acetiltransferases , Ovário , Tephritidae , Animais , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Ovário/enzimologia , Feminino , Tephritidae/genética , Tephritidae/enzimologia , Tephritidae/crescimento & desenvolvimento , Tephritidae/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Agmatina/metabolismo
15.
Nat Commun ; 15(1): 1683, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395938

RESUMO

Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.


Assuntos
Dipterocarpaceae , Genômica , Floresta Úmida , Genoma , Filogenia
16.
Front Oncol ; 13: 1310471, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38288109

RESUMO

With the increasing implementation of early lung cancer screening and the increasing emphasis on physical examinations, the early-stage lung cancer detection rate continues to rise. Visceral pleural invasion (VPI), which denotes the tumor's breach of the elastic layer or reaching the surface of the visceral pleura, stands as a pivotal factor that impacts the prognosis of patients with non-small cell lung cancer (NSCLC) and directly influences the pathological staging of early-stage cases. According to the latest 9th edition of the TNM staging system for NSCLC, even when the tumor diameter is less than 3 cm, the final T stage remains T2a if VPI is present. There is considerable controversy within the guidelines regarding treatment options for stage IB NSCLC, especially among patients exhibiting VPI. Moreover, the precise determination of VPI is important in guiding treatment selection and prognostic evaluation in individuals with NSCLC. This article aims to provide a comprehensive review of the current status and advancements in studies pertaining to stage IB NSCLC accompanied by VPI.

17.
Rev Sci Instrum ; 94(3): 033301, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37012737

RESUMO

Schottky diagnostics is an important measure for the debunched beam during the injection phase of the Xi'an Proton Application Facility (XiPAF). The existing capacitive Schottky pickup has a relatively low sensitivity and a poor signal-to-noise ratio for the low-intensity beam. A resonant Schottky pickup based on the principle of a reentrant cavity is proposed. The effects of cavity geometric parameters on cavity properties are systematically studied. A prototype was built and tested to validate the simulation results. The prototype has a resonance frequency of 24.23 MHz, a Q value of 635, and a shunt impedance of 19.75 kΩ. The resonant Schottky pickup has the capability to detect as few as 2.3 × 106 protons with an energy of 7 MeV and a momentum spread of about 1% at the injection phase of XiPAF. The sensitivity is two orders of magnitude higher than the existing capacitive pickup.

18.
Int J Rheum Dis ; 26(7): 1350-1357, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37222184

RESUMO

BACKGROUND: Gastrointestinal tract surgeries could disrupt the microbiome and simultaneously cause trauma, which may result in psoriasis. OBJECTIVE: To examine associations between gastrointestinal tract surgeries and newly diagnosed psoriasis. METHODS: This nested case-control study included patients with newly diagnosed psoriasis from 2005 to 2013, retrieved from the Taiwan National Health Insurance Research Database. We retrospectively (5 years from the index date) determined whether the patients had undergone gastrointestinal tract surgery. RESULTS: We identified 16 655 patients with newly diagnosed psoriasis and matched 33 310 individuals as the control group. The population was stratified by age and sex. There was no association between age and psoriasis (<20 years: adjusted odds ratio [aOR] 0.80, 95% confidence interval [CI] 0.52-1.24; 20-39 years: aOR 1.09, 95% CI 0.79-1.51; 40-59 years: aOR 0.89, 95% CI 0.57-1.39; ≥60 years: aOR 0.82, 95% CI 0.54-1.26). Similar findings were obtained by sex, with no differences among men (aOR 0.90, 95% CI 0.69-1.17) and women (aOR 0.96, 95% CI 0.71-1.29). CONCLUSION: Our study indicates that gastrointestinal surgeries have limited age- and sex-related effects on psoriasis. These findings provide new insights into the risk of developing psoriasis.


Assuntos
Psoríase , Masculino , Humanos , Feminino , Estudos de Casos e Controles , Estudos Retrospectivos , Psoríase/diagnóstico , Psoríase/epidemiologia , Trato Gastrointestinal , Taiwan/epidemiologia , Fatores de Risco
19.
Ecol Evol ; 13(3): e9886, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36919019

RESUMO

In the Flora of China account of Saxifraga mengtzeana Engl. & Irmsch., eight synonyms were attributed to it and one variant, recognized as Saxifraga epiphylla Gornall & Ohba, was split from it. This study reevaluates the taxonomic status of some of the synonyms and of the segregated species in light of new evidence presented here. Morphological and molecular evidence demonstrate that collections from northwestern Yunnan and Sichuan are genetically differentiated from those in southeastern Yunnan and neighboring Guangxi. Observations in the field and in cultivation show that the peltate petiole attachment diagnostic of S. mengtzeana var. peltifolia Engl. & Irmsch. is developmentally labile. Similar observations combined with molecular data show that viviparous phenotypes, formerly treated as S. epiphylla, although largely under genetic control, occur sporadically throughout the ranges of both northern and southern taxa. Collections from northwestern Yunnan and Sichuan are best recognized as Saxifraga geifolia Balf.f., whereas those from southeastern Yunnan and neighboring Guangxi are S. mengtzeana. Peltate-leaved variants of the latter are given no status and are relegated to complete synonymy. Viviparous phenotypes of S. mengtzeana and S. geifolia are recognized at the rank of forma.

20.
Int J Biol Macromol ; 251: 126192, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37558038

RESUMO

Here, highly sensitive blueberry anthocyanin (BBA)-induced intelligent indicating films were fabricated by incorporating a novel composite ingredient, diatomite (DA), into a matrix of konjac glucomannan (KGM), carrageenan (CAR) and BBA. We systematically investigated the effects of introducing DA and BBA on the structure, physical properties, colorimetric response, and practical application of the KGM/CAR film. Our findings revealed that the DA particles and BBA were well-distributed in the KGM/CAR matrix through hydrogen bonding interactions. This distribution significantly improved tensile strength, surface hydrophobicity, thermal stability, and barrier properties of the KGM/CAR film. Notably, the KGM/CAR-based intelligent film loaded with 6 % DA exhibited the most optimal properties. Furthermore, DA exhibited a hierarchical porous structure, enabling the KGM/CAR film to detect volatile amines with heightened sensitivity. When applied to monitor shrimp spoilage in transparent plastic packaging, the color of the composite film underwent remarkable changes from bright pink to bluish violet. These color changes correlated well with the total volatile basic nitrogen (TVB-N) and pH changes in the shrimp, as determined by standard laboratory procedures. Our work presents a promising approach to the development of high-performance and intelligent food packaging materials. These materials hold great potential for practical applications in the field of food packaging.

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