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1.
Bioresour Technol ; 367: 128229, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36332864

RESUMO

A novel two-stage process comprising pre-denitrification and single-stage partial nitritation/anammox was developed to treat swine manure digestate with a constant nitrogen loading rate of 1.0 gN/L/d. As the influent NH4+-N concentration increased from 500 to 1500 mg/L, a nitrogen removal efficiency of 88 %-96 % and 5-day biochemical oxygen demand removal efficiency of 93 %-97 % were achieved. Owing to the high influent chemical oxygen demand (COD)/nitrates and nitrites (NOX) ratio of 8.2-9.2 and high COD utilization of denitrifying bacteria (DB), the NO2--N and NO3--N removal efficiencies in the denitrification reactor reached 96 %-99 % and 97 %-99 %, respectively. The contribution of anammox bacteria to nitrogen removal was 70.9 %-84.3 %, whereas that of DB was 11.7 %-18.3 %. The contributions of DB and ordinary heterotrophic organisms to COD removal were 19.5 %-49.3 % and 17.9 %-39 %, respectively. This study will help guide the anammox process in swine wastewater treatment.


Assuntos
Desnitrificação , Nitrogênio , Suínos , Animais , Esterco , Reatores Biológicos/microbiologia , Oxidação Anaeróbia da Amônia , Oxirredução , Bactérias , Águas Residuárias/microbiologia , Esgotos
2.
Front Neurol ; 13: 1017654, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341116

RESUMO

RhoGTPase regulators play a key role in the development of the nervous system, and their dysfunction can result in brain malformation and associated disorders. Several guanine nucleotide exchange factors (GEF) have been linked to neurodevelopmental disorders. In line with this, ARHGEF17 has been recently linked as a risk gene to intracranial aneurysms. Here we report siblings of a consanguineous Pakistani family with biallelic variants in the ARHGEF17 gene associated with a neurodevelopmental disorder with intellectual disability, speech delay and motor dysfunction but not aneurysms. Cranial MRI performed in one patient revealed generalized brain atrophy with an enlarged ventricular system, thin corpus callosum and microcephaly. Whole exome sequencing followed by Sanger sequencing in two of the affected individuals revealed a homozygous missense variant (g.11:73021307, c.1624C>T (NM_014786.4), p.R542W) in the ARHGEF17 gene. This variant is in a highly conserved DCLK1 phosphorylation consensus site (I/L/V/F/M]RRXX[pS/pT][I/L/M/V/F) of the protein. Our report expands the phenotypic spectrum of ARHGEF17 variants from increased intracranial aneurysm risk to neurodevelopmental disease and thereby add ARHGEF17 to the list of GEF genes involved in neurodevelopmental disorders.

3.
Bioinformatics ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36355452

RESUMO

MOTIVATION: Somatic mutation co-occurrence has been proven to have a profound effect on tumorigenesis. While some studies have been conducted on co-mutations, a centralized resource dedicated to co-mutations in cancer is still lacking. RESULTS: Using multi-omics data from over 30,000 subjects and 1,747 cancer cell lines, we present the Cancer co-mutation database (CoMutDB), the most comprehensive resource devoted to describing cancer co-mutations and their characteristics. AVAILABILITY: http://www.innovebioinfo.com/Database/CoMutDB/Home.php. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36350440

RESUMO

The rapid development of modern society has resulted in discharge of large, heavy metal quantities into wetlands that have been continuously accumulating, causing severe pollution. Dajiuhu, located in the Shennongjia Forest District of Hubei Province in China, is a wetland of significant value internationally, serving as a model wetland ecosystem with heightened scientific research value. In this study, 27 surface sediment samples from nine sub-lakes in Dajiuhu were collected in August 2020. The concentrations of Cd, Cr, Cu, Ni, Pb, and Zn in the sediments were determined. The heavy metal occurrence and speciation characteristics were analyzed by an improved BCR (European Community Bureau of Reference) extraction method. Four methods were used to evaluate heavy metals' pollution degree and ecological risk. The possible source of heavy metals was inferred using correlation analysis and principal component analysis. The heavy metal content in the lake sediments of Dajiuhu wetland was from the highest to the lowest concentration as follows: Zn [Formula: see text] Cr [Formula: see text] Ni [Formula: see text] Pb [Formula: see text] Cu [Formula: see text] Cd. The average Cd content exceeded the national nature reserve threshold values, while the other heavy metals measured were below their respective threshold values. However, due to the occurrence of Pb and Cd in different forms, they still pose certain pollution and ecological risk to the lake wetlands. On the other hand, Zn, Cr, Ni, and Cu do not pose an ecological risk in the lakes of the Dajiuhu wetland. The spatial distribution of heavy metal content in the nine sub-lakes did vary significantly. Regarding the heavy metal sources in the lake sediments, Ni, Cr, and Cu originate from natural factors, and Cd and Pb have mainly anthropogenic origins. In contrast, Zn has both natural and anthropogenic origins. This study provides further insights into the study of heavy metal pollution in lake wetlands. It provides a framework and a direction for managing heavy metal pollution in the Dajiuhu wetland.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36422777

RESUMO

Snow depth is an important parameter to characterize the characteristics of snow cover, and it is also one of the most sensitive response factors to regional climate change. However, the extent of snow depth variability and its driving mechanisms are still unknown in China. Therefore, in this study, we used the regression analysis, root-mean-square error analysis, anomalous year analysis, and correlation analysis methods to explore the spatiotemporal variation characteristics of snow depth in China from 1979 to 2019 based on the reanalysis snow depth dataset. The results show that (1) the snow distribution in China is obviously spatially heterogeneous, and the southeastern, western, and southern regions of the Qinghai-Tibet Plateau, northern Xinjiang, and northeastern China have high values of snow depth; (2) the high-value regions are also the sensitive regions for anomalous variations in snow depth in China; (3) in the past 41 years, the interannual variability of snow depth in China has shown a significantly decreasing trend, and the linear tendency of snow depth is - 0.093 cm/10 a (p < 0.01) and the snow depth in four seasons showed a decreasing trend (p < 0.05); and (4) the driving factors of snow heterogeneity are dissimilar in different regions and seasons. In temperate zones, average air temperature is the main factor affecting snow depth in cold temperature, mid temperature, and warm temperature zones; the maximum air temperature is the main factor affecting snow depth in mid temperate and warm temperate zones. Both the minimum air temperature and the average land-surface temperature are important factors affecting the snow depth in the cold temperate, mid temperate and warm temperate zones, and all passed the significance test of 0.01.

6.
BMC Geriatr ; 22(1): 880, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402966

RESUMO

OBJECTIVE: Community-acquired pneumonia (CAP) is associated with elevated morbidity and mortality, and it usually occurs in older adults. Our goal here was to assess the efficacies of muscle mass-related biomarkers, such as, aspartate transaminase/alanine transaminase (AST/ALT) and creatinine/cystatin C*100 (Cr/CysC*100), in predicting 1-, 2-, and 3-year mortalities of older CAP patients. METHODS: Design: Retrospective cohort study. SETTING AND PARTICIPANTS: A teaching hospital in western China. Hospitalized CAP patients, aged≥60 years. We separated patients into a high or low muscle mass group, according to the median AST/ALT and Cr/CysC*100, respectively. We acquired data from medical records and local government mortality databases, as well as telephonic interviews. We analyzed the association between low muscle mass (AST/ALT and Cr/CysC*100) and all-cause mortality at 1, 2, and 3 years in older patients with CAP. RESULTS: We enrolled 606 patients (58.58% male; median age: 81 years) for analysis. The 1-, 2-, and 3-year mortality in older patients with CAP in the low muscle mass group (AST/ALT) was higher than in the high muscle mass group (AST/ALT) (1-year: 51.16% vs. 36.96%, p < 0.001; 2-year: 54.46% vs. 41.25%, p = 0.001; 3-year: 54.79% vs. 42.9%, p = 0.003). Upon adjustment of potential confounding factors, we revealed, using cox regression analysis, that the low muscle mass group (AST/ALT) experienced enhanced mortality risk at the 1-, 2-, and 3-year follow-ups, compared to the high muscle mass group (AST/ALT) (1-year: hazard ratios (HR) = 1.46, 95% confidence interval (CI): 1.13-1.88; 2-year: HR = 1.39, 95% CI: 1.09-1.77; 3-year: HR = 1.35, 95% CI: 1.06-1.72). The 1-, 2-, and 3-year mortality of older CAP patients in the low muscle mass group (Cr/CysC*100) was also higher than the high muscle mass group (Cr/CysC*100) (1-year: 56.29% vs. 31.91%, p < 0.001; 2-year: 60.26% vs. 35.53%, p < 0.001; 3-year: 61.26% vs. 36.51%, p < 0.001). Compared to the high muscle mass group (Cr/CysC*100), the low muscle mass group (Cr/CysC*100) experienced enhanced mortality risk at the 1-, 2-, and 3-year follow ups (1-year: HR = 1.9, 95% CI: 1.46-2.48; 2-year: HR = 1.85, 95% CI: 1.44-2.39; 3-year: HR = 1.85, 95% CI: 1.44-2.37). CONCLUSIONS: Low muscle mass (AST/ALT and Cr/CysC*100) were associated with enhanced 1-, 2-, and 3-year mortality risk in older patients with CAP.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Infecções Comunitárias Adquiridas/diagnóstico , Pneumonia/diagnóstico , Biomarcadores , Músculos
7.
Cancer Res Commun ; 2(11): 1436-1448, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36407834

RESUMO

Melanoma brain metastasis (MBM) is linked to poor prognosis and low overall survival. We hypothesized that melanoma circulating tumor cells (CTCs) possess a gene signature significantly expressed and associated with MBM. Employing a multi-pronged approach, we provide first-time evidence identifying a common CTC gene signature for ribosomal protein large/small subunits (RPL/RPS) which associate with MBM onset and progression. Experimental strategies involved capturing, transcriptional profiling and interrogating CTCs, either directly isolated from blood of melanoma patients at distinct stages of MBM progression or from CTC-driven MBM in experimental animals. Second, we developed the first Magnetic Resonance Imaging (MRI) CTC-derived MBM xenograft model (MRI-MBM CDX) to discriminate MBM spatial and temporal growth, recreating MBM clinical presentation and progression. Third, we performed the comprehensive transcriptional profiling of MRI-MBM CDXs, along with longitudinal monitoring of CTCs from CDXs possessing/not possessing MBM. Our findings suggest that enhanced ribosomal protein content/ribogenesis may contribute to MBM onset. Since ribosome modifications drive tumor progression and metastatic development by remodeling CTC translational events, overexpression of the CTC RPL/RPS gene signature could be implicated in MBM development. Collectively, this study provides important insights for relevance of the CTC RPL/RPS gene signature in MBM, and identify potential targets for therapeutic intervention to improve patient care for melanoma patients diagnosed with or at high-risk of developing MBM.

8.
Org Lett ; 24(45): 8283-8288, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36331137

RESUMO

In this work, we successfully explored an unexpected dehydrogenation triggered by Pd/Cu-catalyzed C(sp3)-H arylation and intramolecular C-N coupling of amides to synthesize the bioactive 1,2-dihydroquinoline scaffold with good regioselectivity and good compatibility of functional groups. This strategy provides an alternative route to realize molecular complexity and diversity from simple and readily available molecules via multiple C-H bond activation. Preliminary mechanistic studies demonstrated that ß,γ-dehydrogenation is triggered by the arylation of the C(sp3)-H bond and the intramolecular C-N coupling.


Assuntos
Amidas , Paládio , Amidas/química , Paládio/química , Catálise , Estrutura Molecular
9.
mSphere ; : e0048722, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36374086

RESUMO

Ceftazidime-avibactam is an effective antibiotic combination of a ß-lactam and a ß-lactamase inhibitor against Klebsiella pneumoniae-carbapenemase (KPC)-producing Enterobacterales. Despite a relatively low resistance rate, reports of resistance to ceftazidime-avibactam mainly caused by the mutations in KPC have increased in recent years. Here, we report a ceftazidime-avibactam-resistant and carbapenem-susceptible Klebsiella pneumoniae strain carrying a novel KPC variant, KPC-112, which differs from KPC-2 by 4-amino-acid deletions at Ambler positions 166L/167E and 242G/243T. The isolate was identified as K. pneumoniae by a Vitek mass spectrometer (bioMérieux, France). The MICs of antimicrobial agents were determined using broth microdilution susceptibility method. The result showed that the isolate was resistant to ceftazidime-avibactam (MIC = >128 mg/L) but susceptible to imipenem (MIC = 0.5 mg/L), meropenem (MIC = 1 mg/L), and tigecycline (MIC = 2 mg/L). The carbapenemase genes were confirmed by PCR-based sequencing. Plasmid transformation assay showed that the blaKPC-112-positive transformant increased MICs of ceftazidime-avibactam, ceftazidime, and cefepime by at least 256-fold, 128-fold, and 128-fold, respectively, compared with the recipient Escherichia coli DH5α. According to the whole-genome sequencing analysis, many common resistance genes were identified, including blaKPC-112, blaOXA-1, blaCTX-M-15, blaTEM-1B, blaSHV-28, aac(6')Ib-cr, aac(3)-IId, qnrS1, catA2, catB4, and fosA6, and mutations of GyrA (GyrA-83F and GyrA-87A) and ParC (ParC-80I) were also found. Overall, our study highlights the importance of monitoring susceptibility during ceftazidime-avibactam treatment and accurate detection of KPC variants. IMPORTANCE Carbapenem-resistant Enterobacterales (CRE) are one of the most serious antimicrobial resistance problems in the world, listed as an "urgent" threat by the U.S. Centers for Disease Control and Prevention. Among CRE, K. pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-KP) has become a significant health threat due to its rapid transmissibility and high mortality. With the wider clinical use of ceftazidime-avibactam, reports of resistance have increased in recent years even though the overall resistance rate remains relatively low. Among the reported resistance mechanisms are mainly mutations derived from the blaKPC-2 or blaKPC-3 gene. Here, we describe the characterization of a ceftazidime-avibactam-resistant blaKPC-112-positive K. pneumoniae clinical isolate for the first time. A number of Enterobacteriaceae isolates producing these kinds of KPC variants might be missed by conventional antimicrobial susceptibility testing (AST) methods and lead to irrational drug use. So, this study of KPC-112 will help to establish the diversity of KPCs and remind researchers of the challenge of drug resistance and detection brought by the KPC variants.

10.
Inorg Chem ; 61(45): 17993-18001, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36330783

RESUMO

The involvement of the 2-phosphaethynolate anion species with ambident nucleophilic properties serves as an essential protocol for synthesizing oxygen-bound or phosphorus-bound complexes. This work mainly describes the synthesis and characterization of U, Th, and Ti phosphaethynolate complexes featuring a preferential O-coordination fashion. Among these complexes, the first examples of a Ti(IV)-OCP complex 3A, Th(IV)-OCP complex 3B, and U(IV)-OCP complex 3C were assembled by a salt metathesis reaction between M(TrapenTMS)(Cl) (M = Ti, Th, U) and NaOCP(dioxane)2.5 and were all crystallographically characterized. The structural similarity of this series of phosphaethynolate complexes allows us to compare the bonding properties of d- and f-block elements in the corresponding compounds. The well-established density functional theory (DFT) computational method was employed to explore the electronic structures and covalency in M-O bonding, and the results showed a consistent pattern. The calculation result showed that 2-phosphaethynolate complexes exhibited the covalency trend of U-O > Th-O > Ti-O due to the involvement of 5f orbitals.

11.
BMJ Open ; 12(11): e061657, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36343990

RESUMO

OBJECTIVE: Data are sparse on healthcare needs related to pregnancy among Chinese women with type 1 diabetes (T1D) or the gap between the needs and healthcare provision in China. We aimed to identify their needs and the gaps in pregnancy care provision. DESIGN: This is a qualitative, face-to-face, one-to-one in-depth interview study. We recruited our participants using a purposive sampling strategy. Semistructural outlines were used to guide the interviews. The interviews were digitally recorded, transcribed and analysed using a thematic framework method with NVivo V.10.0. SETTING: Guangdong Province in China. PARTICIPANTS: This study involved three key stakeholders of pregnancy care for women with T1D: 29 women with T1D of childbearing age (aged 18-50 years), 16 family members (husbands, parents and parents-in-law of women with T1D) and 35 relevant healthcare providers (HCPs). RESULTS: We found that women with T1D and the family members had a more pessimistic attitude towards pregnancy outcomes, which was different from the more positive view of HCPs. However, all three stakeholders shared the following perspectives regarding pregnancy-related care for women with T1D: (1) lack of knowledge and access to education, (2) lack of multidisciplinary cooperation, (3) education should be started earlier in adulthood, (3) positive role of peer support, and (4) hope for future training of HCPs for relevant knowledge and skills specified for T1D and pregnancy with T1D. CONCLUSIONS: An immense gap was identified between the needs of women with T1D regarding pregnancy-related care and current care provision in China. These findings suggest that education be provided to patients and HCPs, and the role of professional and multidisciplinary support should be enhanced to optimise pregnancy care for women with T1D in China.


Assuntos
Diabetes Mellitus Tipo 1 , Gravidez , Humanos , Feminino , Adulto , Diabetes Mellitus Tipo 1/terapia , Pesquisa Qualitativa , Cuidado Pré-Natal/métodos , Pessoal de Saúde/educação , China
13.
Atherosclerosis ; 362: 11-22, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36435092

RESUMO

BACKGROUND AND AIMS: Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1. We aim to interrogate the molecular basis of 6p24.1 containing rs6903956 risk alleles in endothelial disease biology. METHODS AND RESULTS: We generated induced pluripotent stem cells (iPSCs) from CAD patients (AA risk genotype at rs6903956) and non-CAD subjects (GG non-risk genotype at rs6903956). CRISPR-Cas9-based deletions (Δ63-89bp) on 6p24.1, including both rs6903956 and a short tandem repeat variant rs140361069 in linkage disequilibrium, were performed to generate isogenic iPSC-derived endothelial cells. Edited CAD endothelial cells, with removal of 'A' risk alleles, exhibited a global transcriptional downregulation of pathways relating to abnormal vascular physiology and activated endothelial processes. A CXC chemokine ligand on chromosome 10q11.21, CXCL12, was uncovered as a potential effector gene in CAD endothelial cells. Underlying this effect was the preferential inter-chromosomal interaction of 6p24.1 risk locus to a weak promoter of CXCL12, confirmed by chromatin conformation capture assays on our iPSC-derived endothelial cells. Functionally, risk genotypes AA/AG at rs6903956 were associated significantly with elevated levels of circulating damaged endothelial cells in CAD patients. Circulating endothelial cells isolated from patients with risk genotypes AA/AG were also found to have 10 folds higher CXCL12 transcript copies/cell than those with non-risk genotype GG. CONCLUSIONS: Our study reveals the trans-acting impact of 6p24.1 with another CAD locus on 10q11.21 and is associated with intensified endothelial injury.

14.
Biochem Pharmacol ; : 115350, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36435201

RESUMO

The pulmonary vascular remodeling (PVR), the pathological basis of pulmonary hypertension (PH), entails pulmonary artery smooth muscle cells (PASMCs) phenotypic switching, but appreciation of the underlying mechanisms is incomplete. Exosomes, a novel transfer machinery enabling delivery of its cargos to recipient cells, have been recently implicated in cardiovascular diseases including PH. The two critical questions of whether plasma-derived exosomes drive PASMCs phenotypic switching and what cargo the exosomes transport, however, remain unclear. Herein, by means of transmission electron microscopy and protein detection, we for the first time, characterized lectin like oxidized low-density lipoprotein receptor-1 (LOX-1) as a novel cargo of plasma-derived exosomes in PH. With LOX-1 knockout (Olr1-/-) rats-derived exosomes, we demonstrated that exosomal LOX-1 could be transferred into PASMCs and thus elicited cell phenotypic switching. Of importance, Olr1-/- rats exhibited no cell phenotypic switching and developed less severe PH, but administration of wild type rather than Olr1-/- exosomes to Olr1-/- rats recapitulated the phenotype of PH with robust PASMCs phenotypic switching. We also revealed that exosomal LOX-1 triggered PASMCs phenotypic switching, PVR and ultimately PH via ERK1/2-KLF4 signaling axis. This study has generated proof that plasma-derived exosomes confer PH by delivering LOX-1 into PASMCs. Hence, exosomal LOX-1 represents a novel exploitable target for PH prevention and treatment.

15.
Nitric Oxide ; 130: 12-21, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36417988

RESUMO

BACKGROUND: In the nasal cavity, nitric oxide (NO) is involved in many physiological functions, including antibacterial and antiviral activity, promotion of nasal mucociliary clearance, and regulation of blood vessel expansion in the nasal mucosa. We investigated the distribution of NO concentration in the nasal cavity of healthy individuals during breathing. METHODS: A three-dimensional numerical model of the nasal airway, including the bilateral maxillary sinuses, was created to simulate NO distribution in the nasal cavity during normal breathing. The effect of different nasal airflow velocities and NO concentrations in the maxillary sinus on NO distribution in the nasal cavity was evaluated. The NO concentration in the nasal exhalation of 50 healthy people in Dalian was measured using an NO analyzer, and the growth rate of the NO concentration in the nasal cavity was measured under breath-holding conditions. RESULTS: The distribution of NO concentration in the nasal cavity of healthy people during breathing was obtained from numerical simulation results. Lower the airflow rate, higher was the NO concentration and greater was the diffusion range in the nasal cavity. The NO concentration in the nasal cavity increased with an increase in its concentration in the maxillary sinus, indicating a linear relationship. The NO concentration in the nasal exhalation of healthy people in Dalian and the growth rate of the NO concentration in the nasal cavity under breath-holding conditions were obtained through experiments. The numerical results correspond with the experimental results. CONCLUSIONS: The NO entered the nasal cavity mainly by diffusion and followed the convection flow of the respiratory air in the nasal cavity. NO concentration in the nasal cavity was related to the respiratory airflow velocity and NO concentration in the maxillary sinus. During inspiration, NO was present only in the nasal airway posterior to the maxillary sinus ostium, whereas during exhalation, the exhaled NO diffusely distributed throughout the nasal cavity.

16.
Open Biol ; 12(11): 220066, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36382370

RESUMO

The histone H4 basic patch is critical for chromatin structure and regulation of the chromatin machinery. However, the biological roles of these positively charged residues and the mechanisms by which they regulate gene expression remain unclear. In this study, we used histone mutagenesis to investigate the physiological function and downstream regulatory genes of H4 residues R17 and R19 in Drosophila. We found all histone mutations including R17A/E/H and R19A/E/H (R17 and R19 of H4 are substituted by A, E and H respectively) result in a range of growth defects and abnormalities in chromosomal high-order structures, whereas R17E mutation is embryonic lethal. RNA-seq demonstrates that downregulated genes in both R17A and R19A show significant overlap and are enriched in development-related pathways. In addition, Western and cytological analyses showed that the R17A mutation resulted in a significant reduction in H4K16 acetylation and male offspring, implying that the R17 may be involved in male dosage compensation mechanisms. R19 mutation on the other hand strongly affect Gpp (Dot1 homologue in flies)-mediated H3K79 methylation, possibly through histone crosstalk. Together these results provide insights into the differential impacts of positive charges of H4 basic patch R17/R19 on regulation of gene transcription during developmental processes.


Assuntos
Cromatina , Histonas , Masculino , Animais , Histonas/metabolismo , Acetilação , Metilação , Processamento de Proteína Pós-Traducional
17.
Microbiol Spectr ; : e0171522, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36326536

RESUMO

To evaluate the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus and Enterococcus species isolates were collected as part of the China Antimicrobial Surveillance Network (CHINET) in 2019 to provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice. Antimicrobial susceptibility testing was performed using the CLSI broth microdilution reference method. Eravacycline was highly active against Staphylococcus and Enterococcus species isolates, proved by the MIC50/90: 0.06/0.125, 0.06/0.25, 0.06/0.25, 0.06/0.25, 0.125/0.5, 0.125/0.25, and 0.03/0.06 mg/L for Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, S. hominis, S. haemolyticus, Enterococcus faecalis, and E. faecium, respectively. S. aureus isolates tested were fully susceptible to tedizolid. Still, nonsusceptible isolates were found for E. faecalis (72/567 [12.7%]) and E. faecium (12/501 [2.4%]). Norvancomycin at 2 mg/L could inhibit 100% of Staphylococcus spp., while 1 mg/L of ceftaroline could inhibit 78.9% of MRSA and 99.9% of methicillin-susceptible S. aureus (MSSA) isolates. Additionally, nemonoxacin was also active against Staphylococcus and Enterococcus species isolates tested (shown by the following MIC90s and ranges, in milligrams per liter: 2 and ≤0.015 to 8 for MRSA, 0.25 and ≤0.015 to 4 for MSSA, 0.5 and ≤0.015 to 8 for S. epidermidis, and 4 and ≤0.015 to >32 for E. faecalis). In conclusion, both eravacycline and tedizolid were highly active against clinical isolates of Staphylococcus spp. and Enterococcus spp. recently collected across China. Nemonoxacin showed potent activity against Staphylococcus spp. and E. faecalis but limited activity against E. faecium. Norvancomycin and ceftaroline displayed highly potent activity against Staphylococcus spp. IMPORTANCE Antimicrobial resistance has become a severe threat to global public health. According to statistics, nearly 700,000 people die from bacterial infections worldwide (J. O'Neill, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations, 2014; C. Y. Chin, K. A. Tipton, M. Farokhyfar, E. M. Burd, et al., Nat Microbiol 3:563-569, 2018, https://doi.org/10.1038/s41564-018-0151-5). The number of bacterial infections is expected to climb to 10 million by 2050, showing that bacterial resistance has become a significant problem that cannot be ignored. It is crucial to develop new antimicrobial agents to combat antimicrobial-resistant bacteria. In this study, we evaluated the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus spp. and Enterococcus species isolates which were collected as part of CHINET in 2019. We believe that this study can provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice.

18.
Ther Clin Risk Manag ; 18: 879-887, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212049

RESUMO

Purpose: The present study aimed to investigate the differences in muscle size and shear wave speed (SWS) values of biceps brachii muscle (BBM) between stroke survivors and healthy controls. Methods: This study comprised 61 stroke survivors and 24 healthy subjects, examined at Guangzhou First People's Hospital within one year. Each participant underwent ultrasonic examinations for recording some specific measurement indicators, including muscle thickness, cross-sectional area (CSA), and shear wave speed (SWS) of BBM. The muscular tension of the paretic arm was scored using the modified Ashworth scale (MAS). These above-mentioned indexes were compared between stroke survivors and healthy controls. Also, the correlations among SWS and MAS scores were assessed. Results: When the lifting arm angle was set for 45°, the CSA and muscle thickness of BBM were obviously decreased in the paretic arms of stroke subjects compared to the non-paretic arms as well as the arms of healthy controls. Moreover, the paretic arms had obviously higher SWS than the non-paretic arms and the healthy arms at 45° or 90°. When the angles of paretic arms were lifted at 90° and 45°, respectively, a positive correlation was established between MAS and SWS. Conclusion: Ultrasonic examination assessing muscle thickness, CSA, and SWS of the BBM could be used as a means of assessment of the paretic arms of stroke survivors.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1601-1606, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36208273

RESUMO

OBJECTIVE: To investigate the clinical value of neutrophil CD64 index in hematological malignancies with pulmonary infection. METHODS: The cohort study method was used to retrospectively analyze the clinical data of 125 patients with hematological malignancies and pulmonary infections who were treated in The Third Affiliated Hospital of Soochow University. All the patients were divided into four stages according to the diagnosis and treatment process: non-infected stage (T1), the symptoms of infection had appeared before using antibiotics (T2), one week after anti-infective treatment (T3), and after stopping antibiotics (T4). CD64 index, C-reactive protein (CRP), blood cell count, and immune cell level were compared before and after infection (T1 vs T2), the correlation between CD64 index and other indicators were explored, the change trends of the significantly different indicators in the course of the disease were observed, and the diagnostic efficacy of CD64 index and CRP were compared. The surviving patients were followed up for whether reinfection occurred within 30 days after discharge, and the re-examination results of indices before discharge (in stage of T4) between reinfected and non-reinfected patients were compared to find the risk factors of reinfection. RESULTS: Before and after infection, the CD64 index, CRP, CD14+HLA-DR+, CD4+, and lymphocyte counts were significantly different (all P<0.05). There was a negative correlation of CD64 index with CD14+HLA-DR+ (r=-0.395, P<0.001), a negative correlation with CD3+ (r=-0.1.87, P=0.047), and a negative correlation with lymphocyte count (r=-0.230, P=0.006), while a positive correlation with CRP(r=0.313, P<0.001). The area under the curve of CD64 index, CRP, and CD64 index combined with CRP was 0.790 (95%CI: 0.711-0.868), 0.754(95%CI: 0.667-0.841), and 0.835(95%CI: 0.762-0.907), respectively; the sensitivity was 59.6%, 72.7%, and 74.7%, the specificity was 89.2%, 73.0%, and 78.4%, and the cut-off value was 0.488, 0.457, and 0.531, respectively. There were only two re-examination indexes showed significantly different before discharge between reinfected patients and non-reinfected patients: CD14+HLA-DR+ (F=8.524, P=0.004) and CD64 index (F=9.993, P=0.002). The increase of CD64 index was an independent risk factor for reinfection within 30 days after discharge from the hospital (HR=1.790, 95%CI: 1.343-2.386, P<0.001). CONCLUSION: CD64 index has diagnostic value in patients with hematological malignancies and pulmonary infection, and its specificity is higher than that of CRP. The combination of the two indicators can improve the diagnostic sensitivity. CD64 index has a predictive value for reinfection within 30 days after infection treatment.


Assuntos
Proteína C-Reativa , Neoplasias Hematológicas , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Biomarcadores , Proteína C-Reativa/metabolismo , Estudos de Coortes , Neoplasias Hematológicas/metabolismo , Humanos , Neutrófilos/química , Neutrófilos/metabolismo , Receptores de IgG/metabolismo , Reinfecção , Estudos Retrospectivos
20.
Front Public Health ; 10: 947225, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225770

RESUMO

Objective: This study aimed to examine the relationship between social support and its sub-domains and cognitive performance, and the association with cognitive impairment among older adults in China. Design: A cross-sectional study. Setting and participants: We included 865 community-based individuals aged 65 and above from Hubei province, China. Methods: The level of social support was evaluated using the social support rating scale (SSRC). The Mini-Mental State Examination was adopted to assess cognitive function, and its cut-offs were used to determine cognitive impairment among the participants. Multiple linear regression models and logistic regression models were used to estimate the ß and odds ratios (ORs) and their 95% CIs, respectively. Results: The participants were divided into quartiles 1-4 (Q1-Q4), according to the total scores of SSRC. After adjusting for sociodemographic characteristics, lifestyle factors, and history of diseases, for MMSE scores, compared to these in Q1, the ß of Q2-Q4 were -0.22 (-0.88, 0.43), 0.29 (-0.35, 0.94), and 0.86 (0.19, 1.53), respectively; For cognitive impairment, the ORs of Q2-Q4 were 1.21 (0.80, 1.82), 0.62 (0.40, 0.94), and 0.50 (0.32, 0.80), respectively. Considering SSRC scores as the continuous variable, per 1-unit increase, the ß was 0.05 (0.02, 0.09) for the cognitive score, and the OR was 0.95 (0.92, 0.98) for cognitive impairment. In addition, higher levels of both subjective support and support utilization were related to better MMSE performance and lower risks of cognitive impairment. Conclusion and implications: Among the older adults in China, as expected, there is a positive relationship between social support and cognitive performance, and high levels of social support, particularly in support utilization, were related to low risks of cognitive impairment. More social support should be provided in this population to improve cognitive function and reduce the risks of cognitive impairment.


Assuntos
Cognição , Apoio Social , Idoso , China/epidemiologia , Estudos Transversais , Eletrólitos , Humanos
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