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1.
BMC Genomics ; 25(1): 443, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704563

RESUMO

BACKGROUND: The transcriptome and metabolome dissection of the skeletal muscle of high- and low- growing individuals from a crossbred population of the indigenous Chongming white goat and the Boer goat were performed to discover the potential functional differentially expressed genes (DEGs) and differential expression metabolites (DEMs). RESULTS: A total of 2812 DEGs were detected in 6 groups at three time stages (3,6,12 Month) in skeletal muscle using the RNA-seq method. A DEGs set containing seven muscle function related genes (TNNT1, TNNC1, TNNI1, MYBPC2, MYL2, MHY7, and CSRP3) was discovered, and their expression tended to increase as goat muscle development progressed. Seven DEGs (TNNT1, FABP3, TPM3, DES, PPP1R27, RCAN1, LMOD2) in the skeletal muscle of goats in the fast-growing and slow-growing groups was verified their expression difference by reverse transcription-quantitative polymerase chain reaction. Further, through the Liquid chromatography-mass spectrometry (LC-MS) approach, a total of 183 DEMs in various groups of the muscle samples and these DEMs such as Queuine and Keto-PGF1α, which demonstrated different abundance between the goat fast-growing group and slow-growing group. Through weighted correlation network analysis (WGCNA), the study correlated the DEGs with the DEMs and identified 4 DEGs modules associated with 18 metabolites. CONCLUSION: This study benefits to dissection candidate genes and regulatory networks related to goat meat production performance, and the joint analysis of transcriptomic and metabolomic data provided insights into the study of goat muscle development.


Assuntos
Cabras , Carne , Músculo Esquelético , Transcriptoma , Animais , Cabras/genética , Cabras/metabolismo , Músculo Esquelético/metabolismo , Carne/análise , Metabolômica , Perfilação da Expressão Gênica , Metaboloma
2.
Phys Chem Chem Phys ; 25(46): 31848-31868, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37968998

RESUMO

In this study, we employ the framework of first-principles density functional theory (DFT) computations to investigate the physical, electrical, bandgap and thermal conductivity of Cs2AgInCl6-CAIC (type I) and Cs2AgSbCl6-CASC (type II) using the GGA-PBE method. CAIC possesses a direct band gap energy of 1.812 eV, while CASC demonstrates an indirect band gap energy of 0.926 eV. The CAIC and CASC exhibit intriguingly reduced thermal conductivity, which can be attributed to the notable reduction in their respective Debye temperatures, measuring 182 K and 135 K, respectively. The Raman active modes computed under ambient conditions have been compared with real-world data, showing excellent agreement. The thermal conductivity values of CAIC and CASC compounds exhibit quantum mechanical characteristics, with values of 0.075 and 0.25 W m-1 K-1, respectively, at 300 K. It is foreseen that these outcomes will generate investigations concerning phosphors and diodes that rely on single emitters, with the aim of advancing lighting and display technologies in the forthcoming generations.

3.
Phys Chem Chem Phys ; 26(1): 635, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38058216

RESUMO

Correction for 'Structural, electronic, optical, elastic, thermodynamic and thermal transport properties of Cs2AgInCl6 and Cs2AgSbCl6 double perovskite semiconductors using a first-principles study' by Keqing Zhang et al., Phys. Chem. Chem. Phys., 2023, 25, 31848-31868, https://doi.org/10.1039/d3cp03795a.

4.
Environ Res ; 220: 115172, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584849

RESUMO

In alkaline soil, abundant carbonates will mobilize uranium (U) and increase its ecotoxicity, which is a serious threat to crop growth. However, the knowledge of U remediation in alkaline soils remains very limited. In this study, U-contaminated alkaline soil (tillage layer) was collected from the Ili mining area of Xinjiang, the soil remediation was carried out by using phosphorus (P) fertilizers of different solubility (including KH2PO4, Ca(H2PO4)2, CaHPO4, and Ca3(PO4)2), and the pathways and mechanisms of U passivation in the alkaline soil were revealed. The results showed that water-soluble P fertilizers, KH2PO4 and Ca(H2PO4)2, were highly effective at immobilizing U, and significantly reduced the bioavailability of soil U. The exchangeable U was reduced by 70.5 ± 0.1% (KH2PO4) and 68.2 ± 1.9% (Ca(H2PO4)2), which was converted into the Fe-Mn oxide-bound and residual phases. Pot experiments showed that soil remediation by KH2PO4 significantly promoted crop growth, especially for roots, and reduced U uptake in crops by 94.5 ± 1.0%. The immobilization of U by KH2PO4 could be attributed to the release of phosphate anions, which react with the uranyl ion (UO22+) forming a stable mineral of meta-ankoleite and enhancing the binding of UO22+ to the soil Fe-Mn oxides. In addition, KH2PO4 dissolution produces acidity and P fertilizer, which can reduce soil alkalinity and improve crop growth. The findings in this work demonstrate that a rational application of P fertilizer can effectively, conveniently, and cheaply remediate U contamination and improve crop yield and safety on alkaline farmland.


Assuntos
Poluentes do Solo , Urânio , Fósforo , Fertilizantes/análise , Poluentes do Solo/análise , Solo
5.
BMC Pediatr ; 23(1): 98, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36859289

RESUMO

BACKGROUND: Henoch-Schönlein purpura (HSP) is a common form of immunological vasculitis in children. Hemophilia A is a genetic disorder and characterized by spontaneous hemorrhage or prolonged bleeding due to factor VIII deficiency. Both diseases increase the risk of bleeding, but they have different mechanisms. How should we treat patients with both diseases? CASE PRESENTATION: An 8-year-old male with hemophilia A was diagnosed with HSP while receiving coagulation factor VIII replacement therapy in our hospital. Hematochezia occurred 6 days after the diagnosis of HSP. And he treated with coagulation FVIII, methylprednisolone and hemostatic drugs. CONCLUSIONS: There is no causal relationship between hemophilia A and HSP, but both diseases can cause bleeding. This child's hematochezia was caused by HSP, but hemophilia could not be ignored during the treatment. Our case report adds to the present body of knowledge about the treatment of HSP associated hematochezia in a child with hemophilia A.


Assuntos
Hemofilia A , Vasculite por IgA , Masculino , Humanos , Criança , Terapia de Reposição Hormonal , Hospitais , Hemorragia Gastrointestinal
6.
Gene Ther ; 29(6): 333-345, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34611321

RESUMO

Inverted terminal repeats (ITRs) are the only wild-type components retained in the genome of adeno-associated virus (AAV) vectors. To determine whether ITR modification is a viable approach for AAV vector engineering, we rationally deleted all CpG motifs in the ITR and examined whether CpG elimination compromises AAV-vector production and transduction. Modified ITRs were stable in the plasmid and maintained the CpG-free nature in purified vectors. Replacing the wild-type ITR with the CpG-free ITR did not affect vector genome encapsidation. However, the vector yield was decreased by approximately 3-fold due to reduced vector genome replication. To study the biological potency, we made micro-dystrophin (µDys) AAV vectors carrying either the wild-type ITR or the CpG-free ITR. We delivered the CpG-free µDys vector to one side of the tibialis anterior muscle of dystrophin-null mdx mice and the wild-type µDys vector to the contralateral side. Evaluation at four months after injection showed no difference in the vector genome copy number, microdystrophin expression, and muscle histology and force. Our results suggest that the complete elimination of the CpG motif in the ITR does not affect the biological activity of the AAV vector. CpG-free ITRs could be useful in engineering therapeutic AAV vectors.


Assuntos
Dependovirus , Vetores Genéticos , Animais , Dependovirus/genética , Distrofina/genética , Terapia Genética , Vetores Genéticos/genética , Camundongos , Camundongos Endogâmicos mdx
7.
J Sep Sci ; 44(1): 6-16, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32926765

RESUMO

As a liquid-liquid partition chromatography, counter-current chromatography has advantages in large sample loading capacity without irreversible adsorption, which has been widely applied in separation and purification fields. The main factors, including partition coefficient, two-phase solvent systems, apparatus, and operating parameters greatly affect the separation process of counter-current chromatography. To promote the applications of counter-current chromatography, it is essential to develop theoretical research to master the principles of counter-current chromatographic separations so as to achieve predictions before laborious trials. In this article, recent progress about separation prediction methods are reviewed from a point of the steady and unsteady state of the mass transfer process of counter-current chromatography and its mass transfer characteristics, and then it is divided into three aspects: prediction of partition coefficient, modeling the thermodynamic process of counter-current chromatography, and modeling the dynamic process of counter-current chromatography.

8.
Mol Med ; 25(1): 31, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266455

RESUMO

BACKGROUND: Delocalization of neuronal nitric oxide synthase (nNOS) from the sarcolemma leads to functional muscle ischemia. This contributes to the pathogenesis in cachexia, aging and muscular dystrophy. Mutations in the gene encoding dystrophin result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). In many BMD patients and DMD patients that have been converted to BMD by gene therapy, sarcolemmal nNOS is missing due to the lack of dystrophin nNOS-binding domain. METHODS: Dystrophin spectrin-like repeats 16 and 17 (R16/17) is the sarcolemmal nNOS localization domain. Here we explored whether R16/17 protein therapy can restore nNOS to the sarcolemma and prevent functional ischemia in transgenic mice which expressed an R16/17-deleted human micro-dystrophin gene in the dystrophic muscle. The palmitoylated R16/17.GFP fusion protein was conjugated to various cell-penetrating peptides and produced in the baculovirus-insect cell system. The best fusion protein was delivered to the transgenic mice and functional muscle ischemia was quantified. RESULTS: Among five candidate cell-penetrating peptides, the mutant HIV trans-acting activator of transcription (TAT) protein transduction domain (mTAT) was the best in transferring the R16/17.GFP protein to the muscle. Systemic delivery of the mTAT.R16/17.GFP protein to micro-dystrophin transgenic mice successfully restored sarcolemmal nNOS without inducing T cell infiltration. More importantly, R16/17 protein therapy effectively prevented treadmill challenge-induced force loss and improved muscle perfusion during contraction. CONCLUSIONS: Our results suggest that R16/17 protein delivery is a highly promising therapy for muscle diseases involving sarcolemmal nNOS delocalizaton.


Assuntos
Músculo Esquelético/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Sarcolema/metabolismo , Utrofina/metabolismo , Animais , Humanos , Camundongos , Camundongos Transgênicos , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/terapia , Mutação/genética , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo I/farmacologia , Ligação Proteica/genética , Sarcolema/genética , Sarcolema/patologia , Utrofina/genética
9.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4641-4647, 2019 Nov.
Artigo em Zh | MEDLINE | ID: mdl-31872659

RESUMO

This study aimed to establish characteristic chromatogram and content determination method for Chan Taoren formula granules,evaluate the production processes of Chan Taoren formula granules based on the correlation of characteristic chromatogram and the transfer rate of D-amygdalin,and clarify the key control points. The optimized analytical method was carried out on a Waters CORTECS C18 column(4. 6 mm×150 mm,2. 7 µm) with acetonitrile-0. 1% phosphoric acid aqueous solution as the mobile phase at a flow rate of 0. 6 m L·min-1. The detection wavelength was 207 nm,and the column temperature was 20 ℃ . As compared with the standard decoction of Chan Taoren,there were five characteristic peaks in the decoction pieces,extracts,concentrates,spray-dried powders and formula granules,basically consistent in relative retention time and peak pattern; in addition,the transfer rate of D-amygdalin from Chan Taoren pieces to the formula granules was within the transfer rate range of standard decoction. The average transfer rate of D-amygdalin was 56.65%,72.85%,94.58% and 99.29% respectively in the extraction,concentration,spray drying and granulation processes. Therefore,the factors affecting D-amygdalin in the extraction process were further studied. The results showed that D-amygdalin was easily converted to L-amygdalin in the water extraction process,leading to a low transfer rate of D-amygdalin in this process.D-amygdalin was unstable under alkaline conditions and prone to isomerization. Both liquid to solid ratio and extraction time had significant effects on the extraction rate of D-amygdalin. In this study,the key links in the production process of Chan Taoren formula granules was clarified based on the characteristic chromatogram and the quantity transmission of D-amygdalin,which provided a theoretical basis for production and quality control.


Assuntos
Amigdalina , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Controle de Qualidade , Água
10.
Hum Mol Genet ; 25(17): 3647-3653, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27378693

RESUMO

Dystrophin is a large sub-sarcolemmal protein. Its absence leads to Duchenne muscular dystrophy (DMD). Binding to the sarcolemma is essential for dystrophin to protect muscle from contraction-induced injury. It has long been thought that membrane binding of dystrophin depends on its cysteine-rich (CR) domain. Here, we provide in vivo evidence suggesting that dystrophin contains three additional membrane-binding domains including spectrin-like repeats (R)1-3, R10-12 and C-terminus (CT). To systematically study dystrophin membrane binding, we split full-length dystrophin into ten fragments and examined subcellular localizations of each fragment by adeno-associated virus-mediated gene transfer. In skeletal muscle, R1-3, CR domain and CT were exclusively localized at the sarcolemma. R10-12 showed both cytosolic and sarcolemmal localization. Importantly, the CR-independent membrane binding was conserved in murine and canine muscles. A critical function of the CR-mediated membrane interaction is the assembly of the dystrophin-associated glycoprotein complex (DGC). While R1-3 and R10-12 did not restore the DGC, surprisingly, CT alone was sufficient to establish the DGC at the sarcolemma. Additional studies suggest that R1-3 and CT also bind to the sarcolemma in the heart, though relatively weak. Taken together, our study provides the first conclusive in vivo evidence that dystrophin contains multiple independent membrane-binding domains. These structurally and functionally distinctive membrane-binding domains provide a molecular framework for dystrophin to function as a shock absorber and signaling hub. Our results not only shed critical light on dystrophin biology and DMD pathogenesis, but also provide a foundation for rationally engineering minimized dystrophins for DMD gene therapy.


Assuntos
Distrofina/química , Distrofina/metabolismo , Glicoproteínas/metabolismo , Distrofia Muscular Animal/metabolismo , Miocárdio/metabolismo , Animais , Sítios de Ligação , Sequência Conservada , Citosol/metabolismo , Cães , Distrofina/genética , Humanos , Camundongos , Camundongos Endogâmicos mdx , Domínios Proteicos , Sarcolema/metabolismo
11.
Hum Mol Genet ; 24(20): 5880-90, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26264580

RESUMO

The ultimate goal of muscular dystrophy gene therapy is to treat all muscles in the body. Global gene delivery was demonstrated in dystrophic mice more than a decade ago using adeno-associated virus (AAV). However, translation to affected large mammals has been challenging. The only reported attempt was performed in newborn Duchenne muscular dystrophy (DMD) dogs. Unfortunately, AAV injection resulted in growth delay, muscle atrophy and contracture. Here we report safe and bodywide AAV delivery in juvenile DMD dogs. Three ∼2-m-old affected dogs received intravenous injection of a tyrosine-engineered AAV-9 reporter or micro-dystrophin (µDys) vector at the doses of 1.92-6.24 × 10(14) viral genome particles/kg under transient or sustained immune suppression. DMD dogs tolerated injection well and their growth was not altered. Hematology and blood biochemistry were unremarkable. No adverse reactions were observed. Widespread muscle transduction was seen in skeletal muscle, the diaphragm and heart for at least 4 months (the end of the study). Nominal expression was detected in internal organs. Improvement in muscle histology was observed in µDys-treated dogs. In summary, systemic AAV gene transfer is safe and efficient in young adult dystrophic large mammals. This may translate to bodywide gene therapy in pediatric patients in the future.


Assuntos
Dependovirus/genética , Distrofina/genética , Terapia Genética/métodos , Músculo Esquelético , Distrofia Muscular de Duchenne/genética , Transdução Genética/métodos , Administração Intravenosa , Animais , Cães , Distrofina/uso terapêutico , Feminino , Vetores Genéticos , Masculino , Distrofia Muscular Animal/genética , Distrofia Muscular de Duchenne/terapia
12.
Hum Mol Genet ; 22(18): 3720-9, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23681067

RESUMO

Neuronal nitric oxide synthase (nNOS) membrane delocalization contributes to the pathogenesis of Duchenne muscular dystrophy (DMD) by promoting functional muscle ischemia and exacerbating muscle injury during exercise. We have previously shown that supra-physiological expression of nNOS-binding mini-dystrophin restores normal blood flow regulation and prevents functional ischemia in transgenic mdx mice, a DMD model. A critical next issue is whether systemic dual adeno-associated virus (AAV) gene therapy can restore nNOS-binding mini-dystrophin expression and mitigate muscle activity-related functional ischemia and injury. Here, we performed systemic gene transfer in mdx and mdx4cv mice using a pair of dual AAV vectors that expressed a 6 kb nNOS-binding mini-dystrophin gene. Vectors were packaged in tyrosine mutant AAV-9 and co-injected (5 × 10(12) viral genome particles/vector/mouse) via the tail vein to 1-month-old dystrophin-null mice. Four months later, we observed 30-50% mini-dystrophin positive myofibers in limb muscles. Treatment ameliorated histopathology, increased muscle force and protected against eccentric contraction-induced injury. Importantly, dual AAV therapy successfully prevented chronic exercise-induced muscle force drop. Doppler hemodynamic assay further showed that therapy attenuated adrenergic vasoconstriction in contracting muscle. Our results suggest that partial transduction can still ameliorate nNOS delocalization-associated functional deficiency. Further evaluation of nNOS binding mini-dystrophin dual AAV vectors is warranted in dystrophic dogs and eventually in human patients.


Assuntos
Dependovirus/genética , Distrofina/genética , Músculo Esquelético/lesões , Distrofia Muscular de Duchenne/terapia , Óxido Nítrico Sintase Tipo I/metabolismo , Condicionamento Físico Animal/efeitos adversos , Animais , Cães , Distrofina/metabolismo , Terapia Genética , Vetores Genéticos , Humanos , Isquemia/terapia , Masculino , Camundongos , Camundongos Transgênicos , Contração Muscular , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/patologia , Distrofia Muscular Animal/terapia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Sarcolema/enzimologia
13.
Mol Ther ; 21(4): 750-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23319056

RESUMO

Dystrophin deficiency results in lethal Duchenne muscular dystrophy (DMD). Substituting missing dystrophin with abbreviated microdystrophin has dramatically alleviated disease in mouse DMD models. Unfortunately, translation of microdystrophin therapy has been unsuccessful in dystrophic dogs, the only large mammalian model. Approximately 70% of the dystrophin-coding sequence is removed in microdystrophin. Intriguingly, loss of ≥50% dystrophin frequently results in severe disease in patients. To test whether the small gene size constitutes a fundamental design error for large mammalian muscle, we performed a comprehensive study using 22 dogs (8 normal and 14 dystrophic). We delivered the ΔR2-15/ΔR18-19/ΔR20-23/ΔC microdystrophin gene to eight extensor carpi ulnaris (ECU) muscles in six dystrophic dogs using Y713F tyrosine mutant adeno-associated virus (AAV)-9 (2.6 × 10(13) viral genome (vg) particles/muscle). Robust expression was observed 2 months later despite T-cell infiltration. Major components of the dystrophin-associated glycoprotein complex (DGC) were restored by microdystrophin. Treated muscle showed less inflammation, fibrosis, and calcification. Importantly, therapy significantly preserved muscle force under the stress of repeated cycles of eccentric contraction. Our results have established the proof-of-concept for microdystrophin therapy in dystrophic muscles of large mammals and set the stage for clinical trial in human patients.


Assuntos
Distrofina/metabolismo , Distrofia Muscular Animal/terapia , Distrofia Muscular de Duchenne/terapia , Animais , Western Blotting , Cães , Distrofina/genética , Técnicas de Transferência de Genes , Masculino , Camundongos , Distrofia Muscular Animal/metabolismo , Distrofia Muscular de Duchenne/metabolismo
14.
Nutrients ; 16(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732580

RESUMO

The dietary patterns of older adults, particularly in relation to meat, egg, and dairy (MED) consumption, significantly impact frailty, a state of heightened vulnerability to adverse health outcomes. This paper investigates the association between MED consumption and frailty among older Chinese adults, considering rural/urban disparities and gender differences. Analyzing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) spanning from 2008 to 2018, this study explores how MED consumption influences frailty levels over time. The results show that moderate MED consumption is associated with slower frailty progression, suggesting a protective effect against frailty among older adults. However, excessive MED consumption, particularly among rural residents and females, is linked to accelerated frailty progression. Urban residents and males report higher MED consumption levels, possibly due to their greater access to diverse food options and traditional dietary preferences. The findings underscore the complex interplay between dietary habits, demographic factors, and frailty outcomes. Understanding these dynamics is crucial for developing targeted interventions to mitigate frailty risk factors and promote healthy aging among Chinese older adults.


Assuntos
Dieta , Ovos , Fragilidade , Carne , População Rural , População Urbana , Humanos , Masculino , Feminino , Idoso , China/epidemiologia , População Rural/estatística & dados numéricos , Fragilidade/epidemiologia , População Urbana/estatística & dados numéricos , Dieta/estatística & dados numéricos , Estudos Longitudinais , Laticínios/estatística & dados numéricos , Idoso de 80 Anos ou mais , Fatores Sexuais , Idoso Fragilizado/estatística & dados numéricos , Comportamento Alimentar , População do Leste Asiático
15.
Microbiol Spectr ; 12(2): e0254223, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38149860

RESUMO

This study investigated resistance genes corresponding to the fosfomycin resistance phenotype in clinical isolate Providencia rettgeri W986, as well as characterizing the enzymatic activity of FosA11 and the genetic environment. Antimicrobial susceptibility testing was performed using the agar microdilution method based on the Clinical and Laboratory Standards Institute guidelines. The whole genomic sequence of Providencia rettgeri W986 was obtained using Illumina sequencing and the PacBio platform. The fosA-11 gene was amplified by PCR and cloned into the pUCP20 vector. The recombinant strain pCold1-fosA11-BL21 was expressed to extract the target protein, and absorbance photometry was applied for enzymatic parameter determination. Minimal inhibitory concentration (MIC) tests showed that W986 conferred fosfomycin resistance and was inhibited by phosphonoformate, thereby indicating the presence of a FosA protein. A novel resistance gene designated as fosA11 was identified by whole-genome sequencing and bioinformatics analysis, and it shared 54.41%-64.23% amino acid identity with known FosA proteins. Cloning fosA11 into Escherichia coli obtained a significant increase (32-fold) in the MIC with fosfomycin. Determination of the enzyme kinetics showed that FosA11 had a high catalytic effect on fosfomycin, with Km = 18 ± 4 and Kcat = 56.1 ± 3.2. We also found that fosA11 was located on the chromosome, but the difference in the GC content between the chromosome and fosA11 was dubious, and thus further investigation is required. In this study, we identified and characterized a novel fosfomycin inactivation enzyme called FosA11. The origin and prevalence of the fosA11 gene in other bacteria require further investigation.IMPORTANCEFosfomycin is an effective antimicrobial agent against Enterobacterales strains. However, the resistance rate of fosfomycin is increasing year by year. Therefore, it is necessary to study the deep molecular mechanism of bacterial resistance to fosfomycin. We identified a novel chromosomal fosfomycin glutathione S-transferase, FosA11 from Providencia rettgeri, which shares a very low identity (54.41%-64.23%) with the previously known FosA and exhibits highly efficient catalytic ability against fosfomycin. Analysis of the genetic context and origin of fosA11 displays that the gene and its surrounding environments are widely conserved in Providencia and no mobile elements are discovered, implying that FosA11 may be broadly important in the natural resistance to fosfomycin of Providencia species.


Assuntos
Fosfomicina , Fosfomicina/farmacologia , Providencia/genética , Antibacterianos/farmacologia , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Cromossomos
16.
Mol Ther Methods Clin Dev ; 32(2): 101268, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38911286

RESUMO

Excessive cytosolic calcium accumulation contributes to muscle degeneration in Duchenne muscular dystrophy (DMD). Sarco/endoplasmic reticulum calcium ATPase (SERCA) is a sarcoplasmic reticulum (SR) calcium pump that actively transports calcium from the cytosol into the SR. We previously showed that adeno-associated virus (AAV)-mediated SERCA2a therapy reduced cytosolic calcium overload and improved muscle and heart function in the murine DMD model. Here, we tested whether AAV SERCA2a therapy could ameliorate muscle disease in the canine DMD model. 7.83 × 1013 vector genome particles of the AAV vector were injected into the extensor carpi ulnaris (ECU) muscles of four juvenile affected dogs. Contralateral ECU muscles received excipient. Three months later, we observed widespread transgene expression and significantly increased SERCA2a levels in the AAV-injected muscles. Treatment improved SR calcium uptake, significantly reduced calpain activity, significantly improved contractile kinetics, and significantly enhanced resistance to eccentric contraction-induced force loss. Nonetheless, muscle histology was not improved. To evaluate the safety of AAV SERCA2a therapy, we delivered the vector to the ECU muscle of adult normal dogs. We achieved strong transgene expression without altering muscle histology and function. Our results suggest that AAV SERCA2a therapy has the potential to improve muscle performance in a dystrophic large mammal.

17.
Prim Care Diabetes ; 18(1): 97-103, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37993324

RESUMO

BACKGROUND: As meta-inflammation is a common feature for obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease and atherosclerosis, we have proposed a new concept, metabolic inflammatory syndrome (MIS), to cluster such diseases. We aimed to characterize MIS and explore its association with coronary heart disease (CHD) among T2D inpatients in China. METHODS: A total number of 8344 T2D participants were enrolled. Each component of MIS and metabolic syndrome (MS) was analyzed. Their association with the risk of CHD was assessed using a binary logistic analysis. RESULTS: Among the T2D inpatients, the detection rate of MIS was much higher than that of MS (93.6 % vs. 53.2 %). Among all the components of MIS and MS, carotid atherosclerosis (71.9 %) was most commonly detected, which increased with aging in subgroups. Surprisingly, the most common combination of MIS was with all 4 components in T2D patients, with a constituent ratio of 30.9 %. According to the odds ratios (ORs), MIS was a better predictor of CHD than MS, especially after adjustment for age, sex, smoking, and alcohol consumption (adjusted OR for MIS: 3.083; for MS: 1.515). The presence of more components of MIS was associated with a higher detection rate of CHD (P < 0.001). Among all the components of MIS and MS, carotid atherosclerosis best predicted the risk of CHD (adjusted OR: 1.787). CONCLUSIONS: MIS is an independent risk factor for CHD, with a bigger OR value than MS. Carotid atherosclerosis, with the highest detection rate, was the best individual predictor of CHD and thus a critical component of MIS. The concept of MIS represents the understanding of metabolic diseases from the perspective of holistic integrative medicine.


Assuntos
Doenças das Artérias Carótidas , Doença das Coronárias , Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Pacientes Internados , Fatores de Risco , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , China/epidemiologia
18.
Bioorg Med Chem Lett ; 23(9): 2679-82, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23511018

RESUMO

The anti hepatitis C virus (HCV) activity of (+)-lycoricidine (1) was evaluated for the first time in this letter, yielding an EC50 value of 0.55 nmol/mL and an selection index (SI) value of 12.72. Further studies indicated that 1 induced this effect by down-regulating host heat-stress cognate 70 (Hsc70) expression. In addition, 20 derivatives were designed and synthesised to investigate the basic structure-activity relationship (SAR) of the title compound. Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 (EC50=0.68 nmol/mL, SI=33.86), compound 2d (EC50=15 nmol/mL, SI=12) and compound 5 (EC50=33 nmol/mL, SI >10.91). Meanwhile, the experimental data suggest that the modification of certain groups of (+)-lycoricidine can reduce the cytotoxicity of the compounds.


Assuntos
Alcaloides de Amaryllidaceae/química , Antivirais/química , Proteínas de Choque Térmico HSC70/metabolismo , Hepacivirus/efeitos dos fármacos , Fenantridinas/química , Alcaloides de Amaryllidaceae/síntese química , Alcaloides de Amaryllidaceae/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSC70/antagonistas & inibidores , Humanos , Fenantridinas/síntese química , Fenantridinas/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade
19.
Res Aging ; 45(2): 221-238, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35485278

RESUMO

This study aims to examine whether adverse childhood experiences (ACEs) are associated with oral health conditions (denture use, difficulty in chewing, and edentulism) among middle-aged and older adults in China and if gender and adulthood education moderate the associations. Data were obtained from the 2014 and 2018 surveys from the China Health and Retirement Longitudinal Study (N = 17,091) and logistic regressions were carried out. Results show that childhood hunger (OR = 1.12), loneliness (OR = 1.10) and family relations (OR = 1.07) were significantly associated with higher odds of denture use and there were significant associations between hunger (OR = 1.16) and difficulty in chewing. For the female subsample, education significantly moderated the adverse effect of childhood hunger on denture use and difficulty in chewing. Findings suggest that ACEs have long-lasting impacts on oral health conditions in later life and adulthood education might offer critical resources for females, helping them buffer the detrimental health impacts of ACEs.


Assuntos
Experiências Adversas da Infância , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , Saúde Bucal , População do Leste Asiático , Escolaridade
20.
J Appl Gerontol ; 42(1): 111-120, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36204775

RESUMO

This study aims to examine the association between intergenerational support and self-rated health (SRH) levels using data collected from Chinese older adults residing in Honolulu, United States (N = 329). We also investigated the mediating role of resilience and the moderating role of gender in the association. We found that receiving emotional support was significantly and positively associated with better SRH for the whole sample. The positive effect of receiving emotional support on health was significant among older women only. In contrast, the beneficial effect of providing economic support on health was significant among older men only. We found that resilience significantly mediated the positive effect of received emotional support on SRH, and this effect was found for the whole sample and among older women. However, resilience did not mediate the positive effect of the economic support provided on SRH among older men.


Assuntos
População do Leste Asiático , Nível de Saúde , Masculino , Humanos , Feminino , Idoso , Povo Asiático
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