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1.
Plant Cell Rep ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524479

RESUMO

KEY MESSAGE: We detected the genome-wide pattern of DNA methylation and its association with gene expression in sexual and asexual progenies of mature Robinia pseudoacacia trees. DNA methylation plays an important role in plant reproduction and development. Although some studies on sexual reproduction have been carried out in model plants, little is known about the dynamic changes in DNA methylation and their effect on gene expression in sexual and asexual progeny of woody plants. Here, through whole-genome bisulfite sequencing, we revealed DNA methylation patterns in the sexual and asexual progenies of mature Robinia pseudoacacia to understand the regulation of gene expression by DNA methylation in juvenile seedlings. An average of 53% CG, 34% CHG and 5% CHH contexts was methylated in the leaves of mature and juvenile individuals. The CHH methylation level of asexually propagated seedlings was significantly lower than that of seed-derived seedlings and mature trees. The intergenic regions had the highest methylation level. Analysis of differentially methylated regions (DMRs) showed that most of them were hypermethylated and located in the gene upstream and introns. A total of 24, 108 and 162 differentially expressed genes containing DMRs were identified in root sprouts (RSs), root cuttings (RCs) and seed-derived seedlings (SSs), respectively, and a large proportion of them showed hypermethylation. In addition, DMRs were enriched within GO subcategories including catalytic activity, metabolic process and cellular process. The results reveal widespread DNA methylation changes between mature plants and their progenies through sexual/asexual reproduction, which provides novel insights into DNA methylation reprogramming and the regulation of gene expression in woody plants.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34524637

RESUMO

The anaerobic digestion efficiency and methane production of straw was limited by its complex composition and structure. In this study, rice straw (RS), cellulose, and hemicellulose were used as raw materials to study biogas production performance and changes in the volatile fatty acids (VFAs). Further, microbial communities and genetic functions were analyzed separately for each material. The biogas production potential of RS, cellulose, and hemicellulose was different, with cumulative biogas production of 283.75, 412.50, and 620.64 mL/(g·VS), respectively. The methane content of the biogas produced from cellulose and hemicellulose was approximately 10% higher than that produced from RS after the methane content stabilized. The accumulation of VFAs occurred in the early stage of anaerobic digestion in all materials, and the cumulative amount of VFAs in both cellulose and hemicellulose was relatively higher than that in RS, and the accumulation time was 12 and 14 days longer, respectively. When anaerobic digestion progressed to a stable stage, Clostridium was the dominant bacterial genus in all three anaerobic digestion systems, and the abundance of Ruminofilibacter was higher during anaerobic digestion of RS. Genetically, anaerobic digestion of all raw materials proceeded mainly via aceticlastic methanogenesis, with similar functional components. The different performance of anaerobic digestion of RS, cellulose, and hemicellulose mainly comes from the difference of composition of raw materials. Increasing the accessibility of cellulose and hemicellulose in RS feedstock by pretreatment is an effective way to improve the efficiency of anaerobic digestion. Since the similar microbial community structure will be acclimated during anaerobic digestion, there is no need to adjust the initial inoculum when the accessibility of cellulose and hemicellulose changes.

3.
Cancer Biol Med ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491007

RESUMO

OBJECTIVE: Large volume radiological text data have been accumulated since the incorporation of electronic health record (EHR) systems in clinical practice. We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis. METHODS: Sonographic EHR data were obtained from the EHR database. Pathological reports were used as the gold standard for diagnosing thyroid cancer. We developed thyroid cancer diagnosis based on natural language processing (THCaDxNLP) to interpret unstructured sonographic text reports for thyroid cancer diagnosis. We used the area under the receiver operating characteristic curve (AUROC) as the primary metric to measure the performance of the THCaDxNLP. We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs. those without THCaDxNLP using 5 independent test sets. RESULTS: We obtained a total number of 788,129 sonographic radiological reports. The number of thyroid sonographic data points was 132,277, 18,400 of which were thyroid cancer patients. Among the 5 test sets, the numbers of patients per set were 439, 186, 82, 343, and 171. THCaDxNLP achieved high performance in identifying thyroid cancer patients (the AUROC ranged from 0.857-0.932). Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy (93.8% vs. 87.2%; one-sided t-test, adjusted P = 0.003), precision (92.5% vs. 86.0%; P = 0.018), and F1 metric (94.2% vs. 86.4%; P = 0.007). CONCLUSIONS: THCaDxNLP achieved a high AUROC for the identification of thyroid cancer, and improved the accuracy, sensitivity, and precision of thyroid ultrasound radiologists. This warrants further investigation of THCaDxNLP in prospective clinical trials.

4.
Nanoscale ; 13(35): 14900-14914, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533163

RESUMO

The cascade catalytic strategy could effectively enhance the antibacterial activity by regulating the production of hydroxyl radicals (˙OH) in the sites of bacterial infection. In this work, a ruthenium metal nanoframe (Ru NF) was successfully synthesized via the palladium template method. The cascade catalysis in the bacterial infection microenvironment was achieved by physically adsorbed natural glucose oxidase (GOx), and hyaluronic acid (HA) was coated on the outer layer of the system for locating the infection sites accurately. Eventually, a composite nano-catalyst (HA-Ru NFs/GOx) based on the ruthenium nanoframe was constructed, which exhibited excellent cascade catalytic activity and good biocompatibility. The prepared HA-Ru NFs/GOx enhances the antibacterial activity and inhibits bacterial regeneration through the outbreak of reactive oxygen species (ROS) caused by self-activating cascade reactions. In addition, in vivo experiments indicate that HA-Ru NFs/GOx could efficiently cause bacterial death and significantly promote wound healing/skin regeneration. Accordingly, ruthenium metal framework nanozymes could be used as an effective cascade catalytic platform to inhibit bacterial regeneration and promote wound healing, and have great potential as new antibacterial agents against antibiotic-resistant bacteria.


Assuntos
Infecções Bacterianas , Rutênio , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Catálise , Glucose Oxidase , Humanos
5.
Nature ; 597(7874): 77-81, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34471275

RESUMO

The amount of carbon stored in deadwood is equivalent to about 8 per cent of the global forest carbon stocks1. The decomposition of deadwood is largely governed by climate2-5 with decomposer groups-such as microorganisms and insects-contributing to variations in the decomposition rates2,6,7. At the global scale, the contribution of insects to the decomposition of deadwood and carbon release remains poorly understood7. Here we present a field experiment of wood decomposition across 55 forest sites and 6 continents. We find that the deadwood decomposition rates increase with temperature, and the strongest temperature effect is found at high precipitation levels. Precipitation affects the decomposition rates negatively at low temperatures and positively at high temperatures. As a net effect-including the direct consumption by insects and indirect effects through interactions with microorganisms-insects accelerate the decomposition in tropical forests (3.9% median mass loss per year). In temperate and boreal forests, we find weak positive and negative effects with a median mass loss of 0.9 per cent and -0.1 per cent per year, respectively. Furthermore, we apply the experimentally derived decomposition function to a global map of deadwood carbon synthesized from empirical and remote-sensing data, obtaining an estimate of 10.9 ± 3.2 petagram of carbon per year released from deadwood globally, with 93 per cent originating from tropical forests. Globally, the net effect of insects may account for 29 per cent of the carbon flux from deadwood, which suggests a functional importance of insects in the decomposition of deadwood and the carbon cycle.

6.
Medicine (Baltimore) ; 100(35): e27144, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477170

RESUMO

ABSTRACT: This study aimed to evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) and prostate-specific antigen (PSA) biomarkers in differentiating prostate cancer (PCa) and benign prostatic hyperplasia (BPH).A total of 43 cases of prostate diseases verified by pathology were enrolled in the present study. These cases were assigned to the BPH group (n = 20, 68.85±10.81 years old) and PCa group (n = 23, 74.13 ±â€Š7.37 years old). All patients underwent routine prostate magnetic resonance imaging and DKI examinations, and the mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA) values were calculated. Three serum indicators (PSA, free PSA [fPSA], and f/t PSA) were collected. We used univariate logistic regression to analyze the above quantitative parameters between the 2 groups, and the independent factors were further incorporated into the multivariate logistic regression model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacy of the single indicator and combined model.The difference in PSA, f/t PSA, MK, and FA between PCa and BPH was statistically significant (P < .05). The AUC for the combined model (f/t PSA, MK, and FA) of 0.972 (95% confidence interval [CI]: 0.928, 1.000) was higher than the AUC of 0.902 (95% CI: 0.801, 1.000) for f/t PSA, 0.833 (95% CI: 0.707, 0.958) for MK, and 0.807 (95% CI: 0.679, 0.934) for FA.The MK and FA values for DKI and f/t PSA effectively identify PCa and BPH, compared to the PSA indicators. Combining DKI and PSA derivatives can further improve the diagnosis efficiency and might help in the clinical setting.


Assuntos
Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos
7.
J Environ Manage ; 300: 113679, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509816

RESUMO

Extensive mineral exploitation activities in history have aggravated potential toxic elements (PTEs) contamination in agricultural soils in China. Comprehensive ecological risk assessment is of great significance to orientate the restoration of contaminated soils, especially for those with high background values and multiple sources. The study area is located in the major rice producing area of China. Historically, there was a silver mine and a lead-zinc mine in the area, which were successively closed during the investigation. The intensive mining activities caused serious PTEs pollution in the agricultural soils around the mining area. In this study, five PTEs (As, Cd, Cr, Hg and Pb) selected to assessed the potential of geoaccumulation index in assessing agricultural soil potential risk assessment by identifying ecological risk sources. 315 of soil samples collected in 2009, 2014, 2018 were comprehensively analyzed by single pollution index evaluation (single factor index, geoaccumulation index), comprehensive evaluation (Nemerow index, potential ecological risk index) and trend analysis. Single factor index analysis showed that geoaccumulation index considered the impact of natural diagenesis of background values and human activities on the environment, ensuring high evaluation accuracy comparing to other methods used in typical complex agricultural soils. The modified potential ecological risk index revealed that the high background area did not represent high risk area, which was consistent with the implementation effect of governance measures. This study can provide important insights for policymakers and environmental engineers to quantitatively recognize the soil pollution and the effectiveness of governance based on applicable and reasonable evaluation methods.

8.
Aging (Albany NY) ; 13(17): 21483-21496, 2021 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511433

RESUMO

2,5-dimethyl celecoxib (DMC), a close derivative of celecoxib, has also been reported to have anticancer effects. However, the effects and underlying molecular mechanisms of DMC with respect to nasopharyngeal carcinoma are still largely unknown. In this study, we present that DMC has displayed anticancer potency in nasopharyngeal carcinoma in vitro and in vivo. Mechanistically, we found DMC induced apoptosis and autophagy for anticancer therapy against nasopharyngeal carcinoma. Furthermore, DMC-induced autophagy could remarkably attenuate after the treatment of reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) and c-Jun N-terminal kinase (JNK) inhibitor SP600125 (SP). Taken together, these results suggested DMC induced apoptosis and autophagic death via activation of ROS/JNK axis in NPC cells, which providing us new insights into developing potential therapeutic agents for nasopharyngeal carcinoma patients.

9.
J Hazard Mater ; 423(Pt A): 126866, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34482079

RESUMO

Antibiotic resistant bacteria (ARB) and the antibiotic resistance genes (ARGs) dissemination via plasmid-mediated conjugation have attracted considerable attentions. In this research, sulfidated nanoscale zerovalent iron (S-nZVI)/peroxymonosulfate (PMS) and S-nZVI/peroxydisulfate (PDS) process were investigated to inactivate ARB (Escherichia coli DH5α with RP4 plasmid, Pseudomonas. HLS-6 contains sul1 and intI1 on genome DNA sequence). S-nZVI/PMS system showed higher efficiency than S-nZVI/PDS on ARB inactivation. Thus, the optimal condition 28 mg/L S-nZVI coupled with 153.7 mg/L (0.5 mM) PMS was applied to remove both intracellular ARGs (iARGs) and ARB. The oxidative damage of ARB cell was systemically studied by cell viability, intracellular Mg2+ levels, the changes of extracellular and internal structure, integrity of cell walls and membranes and enzymatic activities. S-nZVI/PMS effectively inactivated ARB (~7.32 log) within 15 min. These effects were greatly higher than those achieved individually. Moreover, removal efficiencies of iARGs sul1, intI1 and tetA were 1.52, 1.79 and 1.56 log, respectively. These results revealed that S-nZVI and PMS have a synergistic effect against ARB and iARGs. The regrowth assays illustrated that the ARB were effectively inactivated. By verifying the inhibitory impacts of S-nZVI/PMS treatment on conjugation transfer, this work highlights a promising alternative technique for inhibiting the horizontal gene transfer.

10.
J Phys Chem Lett ; : 8833-8840, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492184

RESUMO

Band structure is a cornerstone to understand the electronic properties of materials. Accurate band structure calculations using a high-level quantum chemistry theory can be computationally very expensive. It is promising to speed up such calculations with a quantum computer. In this study, we present a quantum algorithm for band structure calculations based on the equation-of-motion (EOM) theory. First, we introduce a new variational quantum eigensolver algorithm named ADAPT-C for ground-state quantum simulation of solids, where the wave function is built adaptively from a complete set of anti-Hermitian operators. Then, on top of the ADAPT-C ground state, quasiparticle energies and the band structure can be calculated using the EOM theory in a quantum-subspace-expansion style, where the projected excitation operators guarantee that the killer condition is satisfied. As a proof of principle, such an EOM-ADAPT-C protocol is used to calculate the band structures of silicon and diamond using a quantum computer simulator.

11.
J Travel Med ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34494100

RESUMO

BACKGROUND: We assessed the compliance with self-collection of stool smears on Whatman® FTA® Elute Card (FTA Card) and detection of travelers' diarrhea (TD) associated pathogens using a quantitative PCR assay (customized TaqMan® array card [TAC]), in a prospective, observational cohort of travelers. METHODS: Enrolled travelers documented symptoms on a travel diary and collected an FTA Card during a diarrheal episode, or at the end of travel if they remained asymptomatic. TAC testing was performed on FTA Cards from TD cases and 1:1 matched asymptomatic controls and 1:1 matched loose stool cases that did not meet TD criteria. Odds ratios (OR) were used to determine the association between detected pathogens and TD. RESULTS: 484 of 2456 (19.7%) travelers completed an illness diary and met TD criteria, and 257 (53.1%) collected an FTA Card during the TD episode. FTA Cards were stored for a median of 2 years at room temperature (IQR: 1-4 years) before extraction and testing. The overall TAC detection rate in TD cases was 58.8% (95%CI: 52.5-64.8). Enterotoxigenic E. coli was the most common pathogen in TD cases (26.8%) and 3.5% of samples were positive for norovirus. The odds of detecting TD-associated pathogens in 231 matched cases and asymptomatic controls was 5.4 (95% CI: 3.6-8.1) and 2.0 (95% CI:1.1-3.7) in 121 matched TD and loose stool cases (p < 0.05). Enteroaggregative E coli was the most common pathogen detected in asymptomatic controls and loose stool cases. Detection of diarrheagenic E coli, Shigella/enteroinvasive E coli (EIEC), and Campylobacter spp. was significantly associated with TD. CONCLUSIONS: FTA Cards are a useful adjunct to traditional stool collection methods for evaluating the pathogen-specific epidemiology of TD in austere environments. Qualitative detection of pathogens was associated with TD. Measures to improve compliance and quality of FTA Card collection with decreased storage duration may further optimize detection.

12.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34502280

RESUMO

Estrogen receptor alpha (ERα) is a ligand-dependent transcriptional factor in the nuclear receptor superfamily. Many structures of ERα bound with agonists and antagonists have been determined. However, the dynamic binding patterns of agonists and antagonists in the binding site of ERα remains unclear. Therefore, we performed molecular docking, molecular dynamics (MD) simulations, and quantum mechanical calculations to elucidate agonist and antagonist dynamic binding patterns in ERα. 17ß-estradiol (E2) and 4-hydroxytamoxifen (OHT) were docked in the ligand binding pockets of the agonist and antagonist bound ERα. The best complex conformations from molecular docking were subjected to 100 nanosecond MD simulations. Hierarchical clustering was conducted to group the structures in the trajectory from MD simulations. The representative structure from each cluster was selected to calculate the binding interaction energy value for elucidation of the dynamic binding patterns of agonists and antagonists in the binding site of ERα. The binding interaction energy analysis revealed that OHT binds ERα more tightly in the antagonist conformer, while E2 prefers the agonist conformer. The results may help identify ERα antagonists as drug candidates and facilitate risk assessment of chemicals through ER-mediated responses.

13.
Sci Rep ; 11(1): 18029, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504267

RESUMO

Southern corn rust is a destructive maize disease caused by Puccinia polysora Underw that can lead to severe yield losses. However, genomic information and microsatellite markers are currently unavailable for this disease. In this study, we generated a total of 27,295,216 high-quality cDNA sequence reads using Illumina sequencing technology. These reads were assembled into 17,496 unigenes with an average length of 1015 bp. The functional annotation indicated that 8113 (46.37%), 1933 (11.04%) and 5516 (31.52%) unigenes showed significant similarity to known proteins in the NCBI Nr, Nt and Swiss-Prot databases, respectively. In addition, 2921 (16.70%) unigenes were assigned to KEGG database categories; 4218 (24.11%), to KOG database categories; and 6,603 (37.74%), to GO database categories. Furthermore, we identified 8,798 potential SSRs among 6653 unigenes. A total of 9 polymorphic SSR markers were developed to evaluate the genetic diversity and population structure of 96 isolates collected from Guangdong Province in China. Clonal reproduction of P. polysora in Guangdong was dominant. The YJ (Yangjiang) population had the highest genotypic diversity and the greatest number of the multilocus genotypes, followed by the HY (Heyuan), HZ (Huizhou) and XY (Xinyi) populations. These results provide valuable information for the molecular genetic analysis of P. polysora and related species.

14.
Breast Cancer Res ; 23(1): 89, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488828

RESUMO

BACKGROUND: Telomere maintenance is crucial for the unlimited proliferation of cancer cells and essential for the "stemness" of multiple cancer cells. TAZ is more extensively expressed in triple negative breast cancers (TNBC) than in other types of breast cancers, and promotes proliferation, transformation and EMT of cancer cells. It was reported that TAZ renders breast cancer cells with cancer stem cell features. However, whether TAZ regulates telomeres is still unclear. In this study, we explored the roles of TAZ in the regulation of telomere maintenance in TNBC cells. METHODS: siRNA and shRNA was used to generate TAZ-depleted TNBC cell lines. qPCR and Southern analysis of terminal restriction fragments techniques were used to test telomere length. Co-immunoprecipitation, Western blotting, immunofluorescence, Luciferase reporter assay and Chromatin-IP were conducted to investigate the underlying mechanism. RESULTS: By knocking down the expression of TAZ in TNBC cells, we found, for the first time, that TAZ is essential for the maintenance of telomeres in TNBC cells. Moreover, loss of TAZ causes senescence phenotype of TNBC cells. The observed extremely shortened telomeres in late passages of TAZ knocked down cells correlate with an elevated hTERT expression, reductions of shelterin proteins, and an activated DNA damage response pathway. Our data also showed that depletion of TAZ results in overexpression of TERRAs, which are a group of telomeric repeat-containing RNAs and regulate telomere length and integrity. Furthermore, we discovered that TAZ maintains telomere length of TNBC cells likely by facilitating the expression of Rad51C, a crucial element of homologous recombination pathway that promotes telomere replication. CONCLUSIONS: This study supports the notion that TAZ is an oncogenic factor in TNBC, and further reveals a novel telomere-related pathway that is employed by TAZ to regulate TNBC.

15.
Zhongguo Zhen Jiu ; 41(9): 1055-9, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491658

RESUMO

OBJECTIVE: To analyze the literature of acupuncture and moxibustion for diseases in the recent 5 years, and discuss the spectrum and indications of acupuncture and moxibustion. METHODS: The literature on acupuncture and moxibustion for diseases in CNKI, Wanfang and VIP databases from January 1, 2015 to December 31, 2019 was searched, summarized and analyzed, and the disease spectrum was summarized. At the same time, the literature from 2015 to 2019 (group A), 1978 to 2005 (group B), and 1949 to 2005 (group C) was compared, and the indications of acupuncture and moxibustion therapy were summarized. RESULTS: There were 32 011 articles on acupuncture and moxibustion for diseases in the recent 5 years, including 377 kinds of indications. These indications can be mostly classified as neurology (9384), orthopedics and traumatology (7765), gastroenterology (3529) and obstetrics and gynecology (2283). The types of diseases were mostly gastroenterology (52 types), neurology (47 types), ophthalmology and otorhinolaryngology (47 types), and obstetrics and gynecology (42 types). The first-class indications of acupuncture and moxibustion therapy in the recent 5 years were hemiplegia, lumbar disc herniation, cervical spondylosis, knee osteoarthritis, insomnia, constipation and cerebrovascular diseases; the second-class were facial neuritis, shoulder pain and headache; the third-class were dysphagia, dysmenorrhea and depression; the forth-class were asthma, urinary retention, cerebral palsy, hypertension, dementia, side effects of radiotherapy and chemotherapy, infertility, allergic rhinitis, vertigo, shoulder-hand syndrome, diabetic neuropathy, herpes zoster, pain, hiccup, diarrhea, lumbar sprain and sciatica. CONCLUSION: Although the disease spectrum and indications of acupuncture and moxibustion therapy have changed to some extent in the recent 5 years, neurology and orthopedics and traumatology are still predominant, and the observation objects tend to transition from symptoms to diseases.


Assuntos
Terapia por Acupuntura , Acupuntura , Moxibustão , Bibliometria , Dismenorreia , Feminino , Humanos
16.
Can J Cardiol ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500006

RESUMO

BACKGROUND: Deleterious rare variants in genes encoding desmosome proteins have been identified as the essential basis of arrhythmogenic cardiomyopathy (ACM) and detected in dilated cardiomyopathy, but the relationship between deleterious rare desmosomal variants and hypertrophic cardiomyopathy (HCM) remains unknown. METHODS: Whole exome sequencing was performed in 1000 HCM patients and 761 non-HCM controls to search for deleterious rare variants in genes encoding desmosomal proteins including PKP2, JUP, DSC2, DSG2, and DSP. Clinical phenotypes were assessed in HCM patients, and patients with deleterious rare desmosomal variants underwent evaluation of ACM revised Task Force Criteria. RESULTS: A total of 27 deleterious rare desmosomal variants were present in 24 (2.4%) HCM patients and 5 (0.66%) controls. The variants were more prevalent in the HCM patients than in the controls (P=0.004). The majority of patients possessing deleterious rare desmosomal variants could not be diagnosed as ACM. Moreover, the patients with deleterious rare desmosomal variants possessed several distinctive clinical features comparing to patients without such variants, including a higher incidence of non-sustained ventricular tachycardia (29.2% vs. 4.5%, P<0.001), left bundle branch block (33.3% vs. 1.6%, P<0.001), and right ventricular involvement for an HCM phenotype (29.2% vs. 0.30%, P<0.001). CONCLUSIONS: We screened deleterious rare desmosomal variants in a large HCM case-control cohort, and found deleterious rare desmosomal variants can be relevant to HCM. Moreover, our data indicated deleterious rare desmosomal variants were associated with distinctive clinical features of HCM. These findings require validation in other HCM cohorts.

17.
Mol Pharmacol ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503976

RESUMO

Carboxylesterase 2 (CES2), an important metabolic enzyme, plays a critical role in drug biotransformation and lipid metabolism. Although CES2 is very important, few animal models have been generated to study its properties and functions. Rat Ces2 is similar to human CES2A-CES3A-CES4A gene cluster, with highly similar gene structure, function and substrate. In this report, CRISPR/Cas9 technology was firstly used to knock out rat Ces2a, a main subtype of Ces2 mostly distributed in liver and intestine. This model showed the absence of CES2A protein expression in liver. Further pharmacokinetic studies of diltiazem, a typical substrate of CES2A, confirmed the loss of function of CES2A both in vivo and in vitro. At the same time, the expression of CES2C and CES2J protein in liver decreased significantly. The body and liver weight of Ces2a knockout rats also increased, but the food intake did not change. Moreover, the deficiency of Ces2a led to obesity, insulin resistance and liver fat accumulation, which are consistent with the symptoms of nonalcoholic fatty liver disease (NAFLD). Therefore, this rat model is not only a powerful tool to study drug metabolism mediated by CES2, but also a good disease model to study NAFLD. Significance Statement Human CES2 plays a key role in the first-pass hydrolysis metabolism of most oral prodrugs as well as lipid metabolism. In this study, CRISPR/Cas9 technology was used to knock out Ces2a gene in rats for the first time. This model can be used not only in the study of drug metabolism and pharmacokinetics, but also as a disease model of NAFLD and other metabolic disorder.

18.
Clin Oral Investig ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515858

RESUMO

OBJECTIVES: Polyamidoamine (PAMAM) dendrimers have well-defined structures, with monodispersity and easily modified surface groups, and they have broad applications in biomedicine. In this study, phosphorylated PAMAM (P-PAMAM) dendrimers were synthesized based on the idea of mimicking the phosphorylated proteins of dentin non-collagenous proteins (DNCP). Then, proliferation and osteo/odontogenic differentiation effects of P-PAMAM on dental pulp stem cells (DPSCs) were investigated and were compared with DNCP. MATERIALS AND METHODS: P-PAMAM was synthesized via the Mannich-type reaction. DNCP were extracted directly from human dentin with ethylenediaminetetraacetic acid (EDTA) solution. Then, the conditioned medium of P-PAMAM and DNCP were prepared respectively and applied to DPSCs. Proliferation of P-PAMAM was investigated with CCK-8, flow cytometry, and EdU test. Osteo/odontogenic differentiation of P-PAMAM was analyzed using alkaline phosphatase activity and staining, RT-PCR, western blot, alizarin red staining, and immunofluorescence staining. RESULTS: Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed that PAMAM were successfully phosphorylated. Western blot verified that the extracted DNCP contained dentin-related proteins DSPP, OPN, and BMP2. In cell proliferation, there was no apparent difference between P-PAMAM, DNCP, and Control groups (P > 0.05). P-PAMAM and DNCP upregulated related genes and proteins expression (DSPP/DSPP, COL-1/COL-1, ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN) and matrix mineralization. Still, the potential was lower than that of DNCP (P < 0.05). CONCLUSIONS: P-PAMAM dendrimers, as a biomimetic analog of DNCP, promote osteo/odontogenic differentiation of DPSCs without influencing their proliferation at a low concentration. CLINICAL RELEVANCE: This preliminary study about P-PAMAM dendrimers is expected to provide a more convenient bioactive macromolecular material for the regeneration of the pulp-dentin complex.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34468743

RESUMO

BACKGROUND: High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions. METHODS: We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm. RESULTS: The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence. CONCLUSIONS: In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered.

20.
Genomics ; 113(6): 3696-3704, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520805

RESUMO

Clausena lansium (Lour.) Skeels (Rutaceae), recognized as wampee, is a widely distributed fruit tree which is utilized as a folk-medicine for treatment of several common diseases. However, the genomic information about this medicinally important species is still lacking. Therefore, we assembled the first genome of Clausena genus with a total length of 310.51 Mb and scaffold N50 of 2.24 Mb by using 10× Genomics technology. Further annotation revealed a total of 34,419 protein-coding genes, while repetitive elements covered 39.08% (121.36 Mb) of the genome. The Clausena and Citrus genus were found to diverge around 22 MYA, and also shared an ancient whole-genome triplication event with Vitis. Furthermore, multi-tissue transcriptomic analysis enabled the identification of genes involved in the synthesis of carbazole alkaloids. Altogether, these findings provided new insights into the genome evolution of Wampee species and highlighted the possible role of key genes involved in the carbazole alkaloids biosynthetic pathway.

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