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Anthocyanin is one important nutrition composition in Tartary buckwheat (Fagopyrum tataricum) sprouts, a component missing in its seeds. Although anthocyanin biosynthesis requires light, the mechanism of light-induced anthocyanin accumulation in Tartary buckwheat is unclear. Here, comparative transcriptome analysis of Tartary buckwheat sprouts under light and dark treatments and biochemical approaches were performed to identify the roles of one B-box protein BBX22 and ELONGATED HYPOCOTYL 5 (HY5). The overexpression assay showed that FtHY5 and FtBBX22 could both promote anthocyanin synthesis in red-flower tobacco. Additionally, FtBBX22 associated with FtHY5 to form a complex that activates the transcription of MYB transcription factor genes FtMYB42 and FtDFR, leading to anthocyanin accumulation. These findings revealed the regulation mechanism of light-induced anthocyanin synthesis and provide excellent gene resources for breeding high-quality Tartary buckwheat.
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Antocianinas , Fagopyrum , Regulação da Expressão Gênica de Plantas , Luz , Proteínas de Plantas , Fatores de Transcrição , Fagopyrum/genética , Fagopyrum/metabolismo , Fagopyrum/crescimento & desenvolvimento , Fagopyrum/efeitos da radiação , Antocianinas/biossíntese , Antocianinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Perfilação da Expressão Gênica , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/crescimento & desenvolvimentoRESUMO
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.
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Antibacterianos , Biofilmes , Farmacorresistência Bacteriana Múltipla , Genoma Bacteriano , Filogenia , Salmonella typhimurium , Sequenciamento Completo do Genoma , Salmonella typhimurium/genética , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Biofilmes/efeitos dos fármacos , China , Genoma Bacteriano/genética , Plasmídeos/genética , Testes de Sensibilidade Microbiana , Humanos , Infecções por Salmonella/microbiologiaRESUMO
Photoplethysmography, a widely embraced tool for non-invasive blood pressure (BP) monitoring, has demonstrated potential in BP prediction, especially when machine learning techniques are involved. However, predictions with a singular model often fall short in terms of accuracy. In order to counter this issue, we propose an innovative ensemble model that utilizes Light Gradient Boosting Machine (LightGBM) as the base estimator for predicting systolic and diastolic BP. This study included 115 women and 104 men, with experimental results indicating mean absolute errors of 5.63 mmHg and 9.36 mmHg for diastolic and systolic BP, in line with level B and C standards set by the British Hypertension Society. Additionally, our research confronts data imbalance in medical research which can detrimentally affect classification. Here we demonstrate an effective use for the Synthetic Minority Over-sampling Technique (SMOTE) with three nearest neighbors for handling moderate imbalanced datasets. The application of this method outperformed other methods in the field, achieving an F1 score of 81.6% and an AUC value of 0.895, emphasizing the potential value of SMOTE for addressing imbalanced datasets in medical research.
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Purpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission. Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the bla KPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location. Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly ß-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including bla KPC-2, bla CTX-M-65, bla TEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0-13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital. Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of bla KPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.
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In real-time human-machine interaction (HMI) applications, hand gesture recognition (HGR) requires high accuracy with low latency. Surface electromyography (sEMG), a physiological electrical signal reflecting muscle activation, is extensively used in HMI. Recently, transient sEMG, generated during the gesture transitions, has been employed in HGR to achieve lower observational latency compared to steady-state sEMG. However, the use of long feature windows (up to 200 ms) still make it less desirable in low-latency HMI. In addition, most studies have relied on remote computing, where remote data processing and large data transfer result in high computation and network latency. In this paper, we proposed a method leveraging transient high density sEMG (HD-sEMG) and in-sensor computing to achieve low-latency HGR. An sEMG contrastive convolution network (sCCN) was proposed for HGR. The mean absolute value and its average integration were used to train the sCCN in a contrastive learning manner. In addition, all signal acquisition, data processing, and pattern recognition processes were deployed within designed sensor for in-sensor computing. Compared to the state-of-the-art study using multi-channel 200-ms transient sEMG, our proposed method achieved a comparable HGR accuracy of 0.963, and a 58% lower observational latency of only 84 ms. In-sensor computing realizes a 4 times lower computation latency of 3 ms, and significantly reduces the network latency to 2 ms. The proposed method offers a promising approach to achieving low-latency HGR without compromising accuracy. This facilitates real-time HMI in biomedical applications such as prostheses, exoskeletons, virtual reality, and video games.
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Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.
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Adenovírus Humanos , Anti-Inflamatórios , Antivirais , Indóis , Oximas , Replicação Viral , Indóis/farmacologia , Animais , Oximas/farmacologia , Humanos , Antivirais/farmacologia , Adenovírus Humanos/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Camundongos , Camundongos Transgênicos , Infecções por Adenovirus Humanos/tratamento farmacológico , Infecções por Adenovirus Humanos/virologia , Células A549 , Citocinas/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
The red panda (Ailurus fulgens) is a distinctive mammal known for its reliance on a diet primarily consisting of bamboo. The gut microbiota and overall health of animals are strongly influenced by diets and environments. Therefore, conducting research to explore the taxonomical and functional variances within the gut microbiota of red pandas exposed to various dietary and environmental conditions could shed light on the dynamic complexities of their microbial communities. In this study, normal fecal samples were obtained from red pandas residing in captive and semi-free environments under different dietary regimes and used for metabolomic, 16S rRNA, and metagenomic sequencing analysis, with the pandas classified into four distinct cohorts according to diet and environment. In addition, metagenomic sequencing was conducted on mucus fecal samples to elucidate potential etiological agents of disease. Results revealed an increased risk of gastrointestinal diseases in red pandas consuming bamboo shoots due to the heightened presence of pathogenic bacteria, although an increased presence of microbiota-derived tryptophan metabolites appeared to facilitate intestinal balance. The red pandas fed bamboo leaves also exhibited a decrease in gut microbial diversity, which may be attributed to the antibacterial flavonoids and lower protein levels in leaves. Notably, red pandas residing in semi-free environments demonstrated an enriched gut microbial diversity. Moreover, the occurrence of mucus secretion may be due to an increased presence of species associated with diarrhea and a reduced level of microbiota-derived tryptophan metabolites. In summary, our findings substantiate the influential role of diet and environment in modulating the gut microbiota of red pandas, offering potential implications for improved captive breeding practices.
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Ailuridae , Dieta , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Animais , Microbioma Gastrointestinal/fisiologia , Dieta/veterinária , Ailuridae/microbiologia , Fezes/microbiologia , RNA Ribossômico 16S/genética , Bactérias/classificação , Ração Animal/análise , Meio AmbienteRESUMO
Tartary buckwheat (Fagopyrum tataricum) is an important plant, utilized for both medicine and food. It has become a current research hotspot due to its rich content of flavonoids, which are beneficial for human health. Anthocyanins (ATs) and proanthocyanidins (PAs) are the two main kinds of flavonoid compounds in Tartary buckwheat, which participate in the pigmentation of some tissue as well as rendering resistance to many biotic and abiotic stresses. Additionally, Tartary buckwheat anthocyanins and PAs have many health benefits for humans and the plant itself. However, little is known about the regulation mechanism of the biosynthesis of anthocyanin and PA in Tartary buckwheat. In the present study, a bHLH transcription factor (TF) FtTT8 was characterized to be homologous with AtTT8 and phylogenetically close to bHLH proteins from other plant species. Subcellular location and yeast two-hybrid assays suggested that FtTT8 locates in the nucleus and plays a role as a transcription factor. Complementation analysis in Arabidopsis tt8 mutant showed that FtTT8 could not recover anthocyanin deficiency but could promote PAs accumulation. Overexpression of FtTT8 in red-flowering tobacco showed that FtTT8 inhibits anthocyanin biosynthesis and accelerates proanthocyanidin biosynthesis. QRT-PCR and yeast one-hybrid assay revealed that FtTT8 might bind to the promoter of NtUFGT and suppress its expression, while binding to the promoter of NtLAR and upregulating its expression in K326 tobacco. This displayed the bidirectional regulating function of FtTT8 that negatively regulates anthocyanin biosynthesis and positively regulates proanthocyanidin biosynthesis. The results provide new insights on TT8 in Tartary buckwheat, which is inconsistent with TT8 from other plant species, and FtTT8 might be a high-quality gene resource for Tartary buckwheat breeding.
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Arabidopsis , Fagopyrum , Proantocianidinas , Humanos , Antocianinas/metabolismo , Proantocianidinas/metabolismo , Fagopyrum/genética , Fagopyrum/metabolismo , Proteínas de Plantas/metabolismo , Filogenia , Melhoramento Vegetal , Flavonoides/metabolismo , Plantas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Arabidopsis/genéticaRESUMO
OBJECTIVES: To investigate the resistance mechanism of a Salmonella Typhimurium (S. Typhimurium) isolated from a faecal sample of an infant, which exhibited concurrent resistance to ceftriaxone, ciprofloxacin and azithromycin. METHODS: Antimicrobial susceptibility testing was performed by broth microdilution in two kinds of drug-sensitive plates. Antimicrobial resistance (AMR) genes were identified by whole genome sequencing and bioinformatics analysis. Genotyping of the strain was performed by multilocus sequence typing (MLST). Plasmid DNA was sequenced and analysed using plasmid bioinformatics tools. RESULTS: The SH11G993 strain was resistant to 28 antibiotics and carried 54 AMR genes. MLST results showed that the strain belonged to a rare genotype. The plasmid profile and plasmid sequencing showed that the strain carried two resistance plasmids. The pSH11G993-1 carried 14 AMR genes (especially co-harboured blaCMY-2, mphA and ermB) and a variety of insertion sequences, belonging to the IncC. The pSH11G993-2 carried 3 AMR genes and 9 virulence genes, belonging to the IncFIB-FII, forming a novel resistance and virulence co-harbouring plasmid. CONCLUSIONS: Our findings highlight that continuously monitor the changes in antibiotic resistance patterns and research on the resistance mechanisms in potential human pathogens are imperative.
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Azitromicina , Salmonella typhimurium , Humanos , Lactente , Salmonella typhimurium/genética , Azitromicina/farmacologia , Ceftriaxona/farmacologia , Ciprofloxacina/farmacologia , Sorogrupo , Tipagem de Sequências Multilocus , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Human adenovirus (HAdV) is a highly virulent respiratory pathogen that poses clinical challenges in terms of diagnostics and treatment. Currently, no effective therapeutic drugs or prophylactic vaccines are available for HAdV infections. One factor contributing to this deficiency is that existing animal models, including wild-type and single-receptor transgenic mice, are unsuitable for HAdV proliferation and pathology testing. In this study, a tri-receptor transgenic mouse model expressing the three best-characterized human cellular receptors for HAdV (hCAR, hCD46, and hDSG2) was generated and validated via analysis of transgene insertion, receptor mRNA expression, and protein abundance distribution. Following HAdV-7 infection, the tri-receptor mice exhibited high transcription levels at the early and late stages of the HAdV gene, as well as viral protein expression. Furthermore, the tri-receptor mice infected with HAdV exhibited dysregulated cytokine responses and multiple tissue lesions. This transgenic mouse model represents human HAdV infection and pathogenesis with more accuracy than any other reported animal model. As such, this model facilitates the comprehensive investigation of HAdV pathogenesis as well as the evaluation of potential vaccines and therapeutic modalities for HAdV.
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Infecções por Adenoviridae , Infecções por Adenovirus Humanos , Adenovírus Humanos , Camundongos , Animais , Humanos , Camundongos Transgênicos , Processamento de Proteína Pós-Traducional , Expressão Gênica , Modelos Animais de Doenças , Adenovírus Humanos/fisiologiaRESUMO
PURPOSE OF REVIEW: The emergence of globally resistant enteric Shigella and nontyphoidal Salmonella strains (NTS) has limited the selection of effective drugs, which has become a major challenge for the treatment of infections. The purpose of this review is to provide the current opinion on the antimicrobial-resistant enteric Shigella and nontyphoidal Salmonella . RECENT FINDINGS: Enteric Shigella and NTS are resistant to almost all classes of antimicrobials in recent years. Those with co-resistance to ciprofloxacin, azithromycin and ceftriaxone, the first-line antibiotics for the treatment of infectious diarrhoea have emerged worldwide. Some of them have caused interregional and international spread by travel, trade, MSM, and polluted water sources. Several strains have even developed resistance to colistin, the last-resort antibiotic used for treatment of multidrug-resistant Gram-negative bacteria infections. SUMMARY: The drug resistance of enteric Shigella and NTS is largely driven by the use of antibiotics and horizontal gene transfer of mobile genetic elements. These two species show various drug resistance patterns in different regions and serotypes. Hence treatment decisions for Shigella and Salmonella infections need to take into consideration prevalent antimicrobial drug resistance patterns. It is worth noting that the resistance genes such as blaCTX,mph, ermB , qnr and mcr , which can cause resistance to ciprofloxacin, cephalosporin, azithromycin and colistin are widespread because of transmission by IncFII, IncI1, IncI2 and IncB/O/K/Z plasmids. Therefore, continuous global monitoring of resistance in Shigella and Salmonella is imperative.
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Azitromicina , Shigella , Humanos , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Colistina , Shigella/genética , Salmonella/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêuticoRESUMO
Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10-8, we confirmed association of the FADS signal and found evidence of two additional signals (in DAGLA and BEST1) within 200 kb of the originally reported FADS signal. Outside of the FADS region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including TMX2, SLC29A2, ANKRD13D and POLD4, and spanning a > 9 Mb region on chromosome 11 (57.5 Mb ~ 67.1 Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a POLD4 missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations.
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Ácidos Graxos Ômega-6 , Estudo de Associação Genômica Ampla , Humanos , Negro ou Afro-Americano/genética , Genômica , Hispânico ou Latino/genética , BestrofinasRESUMO
Linoleic acid (LA) is a primary n-6 polyunsaturated fatty acid (PUFA), which is of interest to nutritional professionals as it has been associated with health outcomes. However, as some LA-rich foods offer protection against chronic diseases such as CVD (e.g., fatty fish), while others increase risk (e.g., red meat), the individual foods contributing to LA intake may be an important factor to consider. Therefore, this analysis sought to examine whether there are racial/ethnic differences in the proportion of overall LA intake accounted for by individual food groups, via a cross-sectional analysis of 3815 adults participating in the National Health and Nutrition Examination Survey (NHANES; 2017-2018 cycle). Separate multivariable linear regressions models specified the proportion of overall LA intake attributable to each of the nine food groups (dairy, eggs, fat, fish, fruits and vegetables, grains, meat, nuts, and sweets) as the outcome, and race/ethnicity as the predictor, with age, gender, and socioeconomic status (SES) as covariates, in order to estimate whether there were mean differences by race/ethnicity in the proportion of overall LA intake attributable to each of these foods seperately. After a Bonferroni correction for multiple testing, eggs, grains, fruits and vegetables, meat, and fish each accounted for a different proportion of overall LA intake according to racial/ethnic grouping (all p < 0.006 after a Bonferroni correction). These findings indicate the food sources of LA in the diet differ by race/ethnicity, and warrant future investigations into whether this plays a role in health disparities.
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Ingestão de Energia , Ácido Linoleico , Humanos , Animais , Inquéritos Nutricionais , Estudos Transversais , Etnicidade , Dieta , Frutas , VerdurasRESUMO
BACKGROUNDS: To observe the effect of using mild intraoperative hyperventilation on the incidence of postlaparoscopic shoulder pain (PLSP) in patients undergoing laparoscopic sleeve gastrectomy. METHODS: Eighty patients undergoing laparoscopic sleeve gastrectomy, aged 22 to 36 years, with American Society of Anesthesiologists grade I or II, were divided into 2 groups according to method of random number table. A mild hyperventilation was used in group A with controlling pressure of end-tidal carbon dioxide (PETCO2) of 30 to 33 mm Hg, while conventional ventilation was used in group B with PETCO2 35 to 40 mm Hg during the operation. The incidence and severity of PLSP, dosage of remedial analgesia and adverse reactions such as nausea and vomiting at 12, 24, 48, 72 hours and 1 week after surgery were recorded. Arterial blood gas was recorded before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery. RESULTS: Compared with 12, 24, 48, and 72 hours after operation, the incidence of PLSP at 1 week decreased significantly (P < .01). Compared with group B, the incidence of PLSP, pain score, and dosage of remedial analgesic at 12, 24,48, 72 hours, and 1 week after surgery were significantly decreased (P < .01). There was no significant difference between the 2 groups in arterial blood gas analysis before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery (P > .05). There were no significant difference of the occurrence of adverse reactions such as nausea and vomiting between the 2 groups within 1 week after surgery (P > .05). CONCLUSION: Mild hyperventilation can reduce the incidence and severity of PLSP after laparoscopic sleeve gastrectomy without increasing the associated adverse effects.
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Laparoscopia , Pneumoperitônio , Humanos , Dor de Ombro/epidemiologia , Dor de Ombro/etiologia , Dor de Ombro/prevenção & controle , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Pneumoperitônio/etiologia , Incidência , Hiperventilação/epidemiologia , Hiperventilação/complicações , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Vômito/etiologia , Náusea/etiologiaRESUMO
BACKGROUND: Genome-wide association studies have identified hundreds of loci associated with common vascular diseases, such as coronary artery disease, myocardial infarction, and hypertension. However, the lack of mechanistic insights for many GWAS loci limits their translation into the clinic. Among these loci with unknown functions is UFL1-four-and-a-half LIM (LIN-11, Isl-1, MEC-3) domain 5 (FHL5; chr6q16.1), which reached genome-wide significance in a recent coronary artery disease/ myocardial infarction GWAS meta-analysis. UFL1-FHL5 is also associated with several vascular diseases, consistent with the widespread pleiotropy observed for GWAS loci. METHODS: We apply a multimodal approach leveraging statistical fine-mapping, epigenomic profiling, and ex vivo analysis of human coronary artery tissues to implicate FHL5 as the top candidate causal gene. We unravel the molecular mechanisms of the cross-phenotype genetic associations through in vitro functional analyses and epigenomic profiling experiments in coronary artery smooth muscle cells. RESULTS: We prioritized FHL5 as the top candidate causal gene at the UFL1-FHL5 locus through expression quantitative trait locus colocalization methods. FHL5 gene expression was enriched in the smooth muscle cells and pericyte population in human artery tissues with coexpression network analyses supporting a functional role in regulating smooth muscle cell contraction. Unexpectedly, under procalcifying conditions, FHL5 overexpression promoted vascular calcification and dysregulated processes related to extracellular matrix organization and calcium handling. Lastly, by mapping FHL5 binding sites and inferring FHL5 target gene function using artery tissue gene regulatory network analyses, we highlight regulatory interactions between FHL5 and downstream coronary artery disease/myocardial infarction loci, such as FOXL1 and FN1 that have roles in vascular remodeling. CONCLUSIONS: Taken together, these studies provide mechanistic insights into the pleiotropic genetic associations of UFL1-FHL5. We show that FHL5 mediates vascular disease risk through transcriptional regulation of downstream vascular remodeling gene programs. These transacting mechanisms may explain a portion of the heritable risk for complex vascular diseases.
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Doença da Artéria Coronariana , Hipertensão , Infarto do Miocárdio , Humanos , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Estudo de Associação Genômica Ampla , Remodelação Vascular , Infarto do Miocárdio/metabolismo , Hipertensão/metabolismo , Miócitos de Músculo Liso/metabolismo , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Fatores de Transcrição/metabolismo , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismoRESUMO
The complete mitochondrial genome (mitogenome) of the soft coral Sinularia acuta Manuputty and van Ofwegen, 2007 was sequenced and annotated using Illumina next-generation sequencing (NGS). The mitogenome of S. acuta was 18,730 bp in length and consisted of 14 protein-coding genes (PCGs), two ribosomal RNA genes (rRNA), and only one transfer RNA gene (tRNA-Met). The base composition was 30.18% A, 16.46% C, 19.35% G, and 34.00% T, with a total A + T content of 64.19%. The phylogenetic analysis demonstrated a close evolutionary relationship among Sinularia acuta, Sinularia penghuensis, and Sinularia maxima.
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Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 x 10 - 8 , we confirmed association of the FADS signal and found evidence of two additional signals (in DAGLA and BEST1 ) within 200 kb of the originally reported FADS signal. Outside of the FADS region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including TMX2 , SLC29A2 , ANKRD13D and POLD4, and spanning a > 9 Mb region on chromosome 11 (57.5Mb ~ 67.1Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a POLD4 missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations.
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Persistent asymptomatic (PA) SARS-CoV-2 infections have been identified. The immune responses in these patients are unclear, and the development of effective treatments for these patients is needed. Here, we report a cohort of 23 PA cases carrying viral RNA for up to 191 days. PA cases displayed low levels of inflammatory and interferon response, weak antibody response, diminished circulating follicular helper T cells (cTfh), and inadequate specific CD4+ and CD8+ T-cell responses during infection, which is distinct from symptomatic infections and resembling impaired immune activation. Administration of a single dose of Ad5-nCoV vaccine to 10 of these PA cases elicited rapid and robust antibody responses as well as coordinated B-cell and cTfh responses, resulting in successful viral clearance. Vaccine-induced antibodies were able to neutralize various variants of concern and persisted for over 6 months, indicating long-term protection. Therefore, our study provides an insight into the immune status of PA infections and highlights vaccination as a potential treatment for prolonged SARS-CoV-2 infections.
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COVID-19 , Humanos , SARS-CoV-2 , Infecções Assintomáticas , Anticorpos AntiviraisRESUMO
The quality of the solid-electrolyte interphase is crucial for the performance of most battery chemistries, but its formation dynamics during operation are not well understood due to a lack of reliable operando characterization techniques. Herein, we report a dynamic, non-invasive, operando reflection interference microscope to enable the real-time imaging of the solid-electrolyte interphase during its formation and evolution processes with high sensitivity. The stratified structure of the solid-electrolyte interphase formed during four distinct steps includes the emergence of a permanent inner inorganic layer enriched in LiF, a transient assembly of an interfacial electrified double layer and a consequent emergence of a temporary outer organic-rich layer whose presence is reversible with electrochemical cycling. Reflection interference microscope imaging reveals an inverse correlation between the thicknesses of two interphasial subcomponents, implying that the permanent inorganic-rich inner layer dictates the organic-rich outer layer formation and lithium nucleation. The real-time visualization of solid-electrolyte interphase dynamics provides a powerful tool for the rational design of battery interphases.
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Application of microRNA-mediated mRNA expression in treatment of diverse cancers has been documented. The current study was explored to study the role of miR-217 in breast cancer (BC) progression and the related downstream factors. Clinical tissue samples, BC cell lines and the established xenograft models were prepared for ectopic expression and depletion experiments to discern the regulatory roles of miR-217-mediated NF1 in BC cell proliferation, metastasis and chemoresistance as well as tumorigenic ability of BC cells in nude mice. miR-217 was upregulated in BC, which was a predictor of poor prognosis of BC patients. NF1 could be targeted by miR-217. miR-217 promoted malignant characteristics of BC cells through enhancing ATF3-MMP13 interaction by inhibiting NF1. miR-217 repressed sensitivity against anti-cancer drugs by inducing autophagy of BC cells through the NF1/HSF1/ATG7 axis. Also, miR-217 could inhibit NF1 to facilitate tumorigenic ability of BC cells in vivo. Our study emphasized that miR-217 could potentially inhibit NF1 expression to activate the c-Jun, thus enhancing the expression and interaction of ATF3/MMP13 and promoting the malignant features of BC cells. Furthermore, miR-217 conferred chemoresistance on BC by enhancing BC cell autophagy, which was achieved by limiting NF1 expression to induce the HSF1/ATG7 pathway.