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2.
Nucleic Acids Res ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33035345

RESUMO

N6-Methyladenosine (m6A) messenger RNA methylation is a well-known epitranscriptional regulatory mechanism affecting central biological processes, but its function in human cellular senescence remains uninvestigated. Here, we found that levels of both m6A RNA methylation and the methyltransferase METTL3 were reduced in prematurely senescent human mesenchymal stem cell (hMSC) models of progeroid syndromes. Transcriptional profiling of m6A modifications further identified MIS12, for which m6A modifications were reduced in both prematurely senescent hMSCs and METTL3-deficient hMSCs. Knockout of METTL3 accelerated hMSC senescence whereas overexpression of METTL3 rescued the senescent phenotypes. Mechanistically, loss of m6A modifications accelerated the turnover and decreased the expression of MIS12 mRNA while knockout of MIS12 accelerated cellular senescence. Furthermore, m6A reader IGF2BP2 was identified as a key player in recognizing and stabilizing m6A-modified MIS12 mRNA. Taken together, we discovered that METTL3 alleviates hMSC senescence through m6A modification-dependent stabilization of the MIS12 transcript, representing a novel epitranscriptional mechanism in premature stem cell senescence.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33016859

RESUMO

A novel Gram-stain-negative, strictly aerobic, rod-shaped, brick red-pigmented bacterium, designated R-22-1 c-1T, was isolated from water from Baiyang Lake, Hebei Province, PR China. The strain was able to grow at 20-30 °C (optimum, 30 °C) and pH 6-7 (optimum, pH 6) in Reasoner's 2A medium. 16S rRNA gene sequence and phylogenetic analyses of R-22-1 c-1T revealed closest relationships to Rufibacter immobilis MCC P1T (97.8 %), Rufibacter sediminis H-1T (97.9 %) and Rufibacter glacialis MDT1-10-3T (97.0 %), with other species of the genus Rufibacter showing less than 97.0 % sequence similarity. The predominant polar lipids were phosphatidylethanolamine, two unidentified aminophospholipids and three unidentified lipids. The major cellular fatty acids were iso-C15 : 0, C15 : 1 ω6c, C17 : 1 ω6c, anteiso-C15 : 0, summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B). The respiratory quinone was MK-7. The draft genome of R-22-1 c-1T was 5.6 Mbp in size, with a G+C content of 50.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization relatedness values between strain R-22-1 c-1T and related type strains were R. immobilis MCC P1T (77.2 and 21.8 %), R. sediminis H-1T (81.6 and 21.4 %) and R. tibetensis 1351T (78.5 and 22.9 %). Based on these phylogenetic, chemotaxonomic and genotypic results, strain R-22-1 c-1T represents a novel species in the genus Rufibacter, for which the name Rufibacter latericius sp. nov. is proposed. The type strain is R-22-1 c-1T (=CGMCC 1.13570T=KCTC 62781T).

4.
Theranostics ; 10(24): 10940-10956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042263

RESUMO

Background: Taxanes are frontline chemotherapeutic drugs for patients with triple-negative breast cancer (TNBC); however, chemoresistance reduces their effectiveness. We hypothesized that the molecular profiling of tumor samples before and after neoadjuvant chemotherapy (NAC) would help identify genes associated with drug resistance. Methods: We sequenced 10 samples by RNA-seq from 8 NAC patients with TNBC: 3 patients with a pathologic complete response (pCR) and the other 5 with non-pCR. Differentially expressed genes that predicted chemotherapy response were selected for in vitro functional screening via a small-scale siRNAs pool. The clinical and functional significance of the gene of interest in TNBC was further investigated in vitro and in vivo, and biochemical assays and imaging analysis were applied to study the mechanisms. Results: Synaptotagmin-like 4 (SYTL4), a Rab effector in vesicle transport, was identified as a leading functional candidate. High SYTL4 expression indicated a poor prognosis in multiple TNBC cohorts, specifically in taxane-treated TNBCs. SYTL4 was identified as a novel chemoresistant gene as validated in TNBC cells, a mouse model and patient-derived organoids. Mechanistically, downregulating SYTL4 stabilized the microtubule network and slowed down microtubule growth rate. Furthermore, SYTL4 colocalized with microtubules and interacted with microtubules through its middle region containing the linker and C2A domain. Finally, we found that SYTL4 was able to bind microtubules and inhibit the in vitro microtubule polymerization. Conclusion: SYTL4 is a novel chemoresistant gene in TNBC and its upregulation indicates poor prognosis in taxane-treated TNBC. Further, SYTL4 directly binds microtubules and decreases microtubule stability.

5.
RNA Biol ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991228

RESUMO

The pluripotency of embryonic stem cells (ESCs) is controlled by a multilayer regulatory network, of which the key factors include core pluripotency genes Oct4, Sox2 and Nanog, and multiple microRNAs (miRNAs). Recently, long noncoding RNAs (lncRNAs) have been discovered as a class of new regulators for ESCs, and some lncRNAs could function as competing endogenous RNAs (ceRNAs) to regulate mRNAs by competitively binding to miRNAs. Here, we identify mmu-miR-139-5p as a new regulator for Nanog by targeting Nanog 3' untranslated region (UTR) to repress Nanog expression in mouse ESCs and embryos. Such regulation could be released by an ESC-specifically expressed ceRNA named lnc-NAP. The expression of lnc-NAP is activated by OCT4, SOX2, as well as NANOG through promoter binding. Downregulation of lnc-NAP reduces Nanog abundance, which leads to decreased pluripotency of mouse ESCs and embryonic lethality. These results reveal lnc-NAP as a new regulator for Nanog in mouse ESCs, and uncover a feed-forward regulatory loop of Nanog through the participation of lnc-NAP.

6.
Sci Rep ; 10(1): 16007, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994418

RESUMO

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and Coronavirus disease (COVID-19) were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature particularly in female animals. Low levels of virus shedding and replication in tissues occurred in all three age groups. Notably, young tree shrews (6 months to 12 months) showed virus shedding at the earlier stage of infection than adult (2 years to 4 years) and old (5 years to 7 years) animals that had longer duration of virus shedding comparatively. Histopathological examine revealed that pulmonary abnormalities were the main changes but mild although slight lesions were also observed in other tissues. In summary, tree shrew is less susceptible to SARS-CoV-2 infection compared with the reported animal models and may not be a suitable animal for COVID-19 related researches. However, tree shrew may be a potential intermediate host of SARS-CoV-2 as an asymptomatic carrier.

7.
Biosens Bioelectron ; 169: 112567, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32947084

RESUMO

Self-powered flexible sensors play an increasingly important role in wearable and even implantable electronic devices. Silk protein is an ideal material for flexible sensors because of its terrific biocompatibility and controllable degradation rate. Here, we overcome the problem of mechanical flexibility and poor electrical conductivity of proteins, and develop a highly transparent, biocompatible, full-degradable and flexible triboelectric nanogenerator (Bio-TENG) for energy harvesting and wireless sensing. First, the mechanical flexibility of the silk protein film is greatly enhanced by the mesoscopic functionalization of regenerated silk fibroin (RSF) via adding glycerol and polyurethane (PU). Second, hollow silver nanofibers are constructed on the silk film to form an air-permeable, stretchable, biocompatible and degradable thin layer and utilized as friction electrode. The obtained Bio-TENG demonstrates high transparency (83% by one Ag gird layer), stretchability (Ɛ = 520%) and an instantaneous peak power density of 0.8 W m-2 that can drive wearable electronics. Besides, the Bio-TENG can work as artificial electronic skin for touch/pressure perception, and also for wirelessly controlling Internet of Things as a switch.

8.
J Reprod Immunol ; 142: 103192, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32950783

RESUMO

BACKGROUND: Neisseria gonorrhoeae (N.g) is Gram-negative bacteria and can lead to endometritis in female. Toll-like receptors regulate immune response in various diseases. However, the roles of TLR2 and TLR4 in. Neisseria gonorrhoeae-induced infection damage in human endometrial epithelia were investigated. METHODS: hEECs were infected with N.g (MOI 10 and 100) and cell viability and apoptosis were measured by CCK8 and flow cytometry assays in both infected groups with the uninfected normal hEECs as negative control. TLR2/TLR4 proteins were measured by ELISA method. Pro-inflammatory markers NLRP3, PGES (PGE2) and TNF-α were assessed by RT-qPCR (mRNA expression) and Elisa (protein concentrations). Transfection assays were performed to up- or down- regulate expression of TLR2 and TLR4 so as to study the functions of TLR2/TLR4 in. N.g-infected hEECs, followed by apoptosis and inflammation assessment. Similarly, we explored the interactions between TLR2/TLR4 and Nrf2/NF-κB/p65 by knocking down TLR2/TLR4 to detect the signaling and further regulating the signaling to evaluate TLR2/ TLR4, apoptosis and inflammation in cells. RESULTS: N.g suppressed cell viabilities and induced cell apoptosis and inflammation. TLR2/TLR4 downregulation inhibited the infection damage. Nrf2 was activated while NF-κB/p65 was depleted as TLR2/ TLR4 was knocked down. Activation of Nrf2 and inhibition of NF-κB resulted in decrease of TLR2/TLR4, which could retard apoptosis and inflammation induced by N.g infection. CONCLUSION: TLR2/TLR4 depletion could alleviate the N.g-infected hEECs via Nrf2/NF-kB signaling, suggesting that TLR2/TLR4 inhibitors might serve as a treatment to reduce N.g infection in human endometrial epithelia.

9.
Curr Eye Res ; : 1-5, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32985270

RESUMO

PURPOSE: To evaluate the effect of anterior migration of triamcinolone acetonide on intraocular pressure (IOP) elevation after posterior subtenon injection of triamcinolone acetonide (PSTA) for macular edema. METHODS: One hundred and ten eyes from 89 patients who received PSTA for macular edema were prospectively enrolled. The extent of anterior migration of triamcinolone acetonide was recorded immediately after the injection. If TA particles were visible in the subtenon space (or subconjunctival space), it was recorded as "anterior subtenon migration" (or "anterior subconjunctival migration"). The correlation between anterior migration of triamcinolone acetonide and severe IOP elevation, which was defined as an increase of 8 mm Hg or more in IOP, was evaluated. RESULTS: A total of 159 PSTAs were given to 110 eyes. After PSTA, anterior subtenon migration occurred in 70.4% and anterior subconjunctival migration occurred in 12.0% of injection. Severe IOP elevation occurred in 7.1% of those without anterior migration, in 25.9% of those with anterior subtenon migration, and in 31.6% of those with anterior subconjunctival migration after PSTA (P = .052). Compared to those without anterior migration of triamcinolone acetonide, the hazard ratio for severe IOP elevation was 3.307 in those with anterior subtenon migration (P = .12) and 5.289 in those with anterior subconjunctival migration (P = .042). CONCLUSIONS: Anterior migration of triamcinolone acetonide after PSTA predisposes eyes to severe IOP elevation. Careful injection to restrict the triamcinolone particle within the subtenon space and behind the equator may lower the rate of IOP elevation after PSTA.

10.
Inorg Chem ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869994

RESUMO

Deep-blue-light-emitting materials are urgently desired in high-performance organic light-emitting diodes (OLEDs) for full-color display and solid-state lighting applications. However, the development of stable and efficient deep-blue emitters remains a great challenge. Herein, a series of stable and efficient tetradentate Pd(II)-complex-based deep-blue emitters with rigid 5/6/6 metallocycles and no F atom were designed and synthesized. These deep-blue emitters employ various isoelectronic five-membered heteroaryl-ring-containing ligands to exhibit extremely narrow emission spectra peaking at 439-443 nm with a full width at half-maximum (fwhm) of only 22-38 nm in 2-methyltetrahydrofuran at room temperature. In particular, the design of an intramolecular hydrogen bond enabled the 1-phenyl-1,2,3-trazole-based Pd(II) complexes to achieve CIEy < 0.1 (0.069-0.078; CIE is Commission Internationale de L'Eclairage). Theoretical calculation and natural transition orbital analysis reveal that these deep-blue materials emit light exclusively from their ligand (carbazole)-centered (3LC) states. Moreover, the triplet excited-state property can be efficiently regulated through ligand modification with isoelectronic oxazole and thiazole rings or pyridine rings, resulting in sky-blue-to-yellow materials, which emit light originating from an admixture of metal-to-ligand charge-transfer (3MLCT) and intraligand charge-transfer states. The newly developed Pd(II) complexes are strongly emissive in various matrixes with a quantum efficiency of up to 51% and also highly thermally stable with a 5% weight-reduction temperature (ΔT5%) of up to 400 °C. Deep-blue OLEDs with CIEy < 0.1 employing Pd(II) complexes as emitters were successfully fabricated for the first time. This study demonstrates that the Pd(II) complexes can act as excellent phosphorescent light-emitting materials through rational molecular design and also provide a valuable method for the development of Pd(II)-complex-based efficient and stable deep-blue emitters.

12.
Exp Cell Res ; 396(1): 112242, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32866497

RESUMO

FAM122A is a housekeeping gene and highly conserved in mammals. More recently, we have demonstrated that FAM122A is essential for maintaining the growth of hepatocellular carcinoma cells, in which we unexpectedly found that FAM122A deletion increases γH2AX protein level, suggesting that FAM122A may participate in the regulation of DNA homeostasis or stability. In this study, we continued to investigate the potential role of FAM122A in DNA damage and/or repair. We found that CRISPR/Cas9-mediated FAM122A deletion enhances endogenous DNA damages in cancer cells but not in normal cells, demonstrating a significant increase in γH2AX protein and foci formation of γH2AX and 53BP1, as well as DNA breaks by comet assay. Further, we found that FAM122A deletion greatly increases TOP2α protein level, and significantly and specifically enhances TOP2 poisons (etoposide and doxorubicin)-induced DNA damage effects in cancer cells. Moreover, FAM122A is found to be interacted with TOP2α, instead of TOP2ß. However, FAM122A knockout doesn't affect the intracellular ROS levels and the process of DNA repair after removal of etoposide with short-term stimulation, suggesting that FAM122A deletion-enhanced DNA damage does not result from endogenous overproduction of ROS and/or impairment of DNA repair ability. Collectively, our study provides the first demonstration that FAM122A is critical for maintaining DNA stability probably by modulating TOP2α protein, and FAM122A deletion combined with TOP2-targeted drugs may represent a potential novel chemotherapeutic strategy for cancer patients.

13.
Immunobiology ; 225(5): 152006, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32962824

RESUMO

Psoriasis is a common chronic inflammatory disease with the prevalence rate of approximately 1-3 %. Currently, it is generally believed that the pathogenesis of psoriasis is a T-cell immune-mediated skin disease mediated by multiple genes and factors, and the interaction between keratinocytes and T cells. TEA domain family member 4 (TEAD4) is a transcription factor which regulates the expression of downstream genes in Hippo pathway and affects several biological processes, such as regulating cell differentiation and embryonic development. However, few studies have reported the role of TEAD4 in psoriasis and its possible regulatory mechanism. In this study, we found the expression level of TEAD4 in the skin of psoriasis was significantly higher than that of normal skin. In patients with the pathological keratinocytes, TEAD4 can transcriptionally regulate the expression of SERPINB3/4 and affect the secretion of chemokines, and the depletion of SERPINB3/4 inhibited the secretion of chemokines. In addition, the supernatant of keratinocytes of patients can significantly increase the migration ability of T cells, and the supernatant of T cells cultured by the supernatant of keratinocytes of patients can significantly enhance the proliferation ability of keratinocytes. Therefore, our results suggested that TEAD4 is a key regulatory factor in progression of psoriasis, and the crosstalk between keratinocytes and T cells mediated by TEAD4 plays a critical role in the psoriasis pathogenesis.

14.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3518-3524, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893539

RESUMO

To analyze the clinincal application characteristics of Xiyanping Injection in real world. The data of the patients came from the hospital information systerm(HIS) of 29 tertiary hospitals in China from 2006 to 2016. It included three parts about basic information, Western medicine diagnosis information, and doctor advice information. The exploration was conducted for the characteristics of the patients and disease distribution as well as the therapeutic regimen. Apriori algorithm was adopted to establish the models, and Clementing 12.0 was used for a correlation analysis of the comprehensive therapeutic regimen of Xiyanping Injection. There were 194 873 cases in the study. The male to female ratio was 1.44∶1. The median age was 4 years old. The median daily dosage was 200 mg. 46.68% of the patients were administered with 250-500 mg, and 33.07% were 50-100 mg one day. 47.08% of the patients were administered for 4-7 d, and 32.65% of the patients were 1-3 d. In the doctor advice information, the most frequently types of Western medicine, traditional Chinese medicine were mucilagin, heat-clearing agent. Second generation cephalosporins, third generation cephalosporins, compound penicillin were the most common types of antibiotic. Interferon, nucleoside and nucleotide, human immunoglobulin were the most common types of antiviral drug. The mining association rules results were analyzed, finding the application of Xiyanping Injection in severe infectious diseases. To improve respiratory symptoms, Xiyanping Injection treaments were Budesonide + Ipratropium Bromide + Ambroxol. To severe pulmonary infection, the treaments were Dopamine + Ambroxine. To severe hand, foot and mouth disease, the treatments were Namefen + Mannitol. To pulmonary heart failure, the treatments were Dobutamine + Heparin. Based on the results of the real world HIS, we could provide clinical application the idea, and a reference for further excavation of the applicable diseases of Xiyanping Injection.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Pré-Escolar , China , Feminino , Humanos , Injeções , Masculino , Medicina Tradicional Chinesa
15.
Phytochem Anal ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939882

RESUMO

INTRODUCTION: Chromones are the major constituents of agarwood and are considered to be directly related to its quality. Agarotetrol, a chromone derivative, is a Chinese Pharmacopoeia content detection index. However, comprehensive high-performance liquid chromatography (HPLC), quantitative analysis of multiple components by a single marker (QAMS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) analyses of this pharmacopeial plant material have never been performed. Moreover, reports regarding the separation and detection of multiple active 2-(2-phenylethyl)chromone analogues from this plant material are surprisingly scarce. OBJECTIVE: To establish a simple, reliable, and effective HPLC method utilising both diode array and MS detection for the simultaneous determination of multiple active chromone analogues in agarwood. METHODS: Four 2-(2-phenylethyl)chromones were isolated from methanol extracts of agarwood. After optimising the extraction, separation, and analytical conditions, validation of the developed analytical method indicated good linearity, satisfactory precision, and good recovery. On this basis, a method for the quantitative analysis of multiple components by a single marker was established. The four 2-(2-phenylethyl)chromones were identified by nuclear magnetic resonance spectroscopic analysis and UPLC coupled to electrospray ionisation quadrupole-time-of-flight MS. CONCLUSIONS: The behaviour of the chromones characterised by MS fragmentation indicated a loss of molecular CO and the formation of m/z 121 compounds by the cleavage of CH2 -CH2 bonds between the chromone and phenyl moieties. Three detection methods were successfully used in this study for agarwood detection, and this protocol may potentially be used as a tool for the quality control of agarwood.

16.
Eur J Hum Genet ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32884118

RESUMO

In this study, we performed a spinal muscular atrophy carrier screening investigation with NGS-based method. First, the validation for NGS-based method was implemented in 2255 samples using real-time PCR. The concordance between the NGS-based method and real-time PCR for the detection of SMA carrier and patient were up to 100%. Then, we applied this NGS-based method in 10,585 self-reported normal couples (34 Chinese ethnic groups from 5 provinces in South China) for SMA carrier screening. The overall carrier frequency was 1 in 73.8 (1.4%). It varied substantially between ethnic groups, highest in Dai ethnicity (4.3%), and no significant difference was found between five provinces. One couple was detected as carriers with an elevated risk of having an SMA affected baby. The distribution of SMN1:SMN2 genotype was also revealed in this study. Among the individuals with normal phenotype, the exon 7 copy-number ratio of SMN1 to SMN2 proved the gene conversion between them. With NGS-based method, we investigated SMA carrier status in Chinese population for the first time, and our results demonstrated that it is a promising alternative for SMA carrier screening and could provide data support and reference for future clinical application.

17.
J Adv Nurs ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32951241

RESUMO

AIM: This study aims to evaluate the safety and analgesic efficacy of pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by dressing change for perianal abscess. DESIGN: This protocol is a randomized, double-blind, placebo-controlled trial. METHODS: This study will be implemented in the Hospital of Traditional Chinese Medicine. Subjects enrolled in this study are hospitalized patients who suffered from moderate to severe pain due to dressing change after incision and drainage. Two hundred patients will be selected and randomly assigned to either an intervention or a control group. The intervention group will get routine pain treatment plus pre-mixed nitrous oxide/oxygen mixture treatment and the control group will be treated with routine pain management plus medical air treatment. All these patients, medical staff and investigators are blind to the nature of the gas in each cylinder, which is randomized. Data will be collected at baseline (T0), 5 min (T1) after the starting of intervention and 5 min post intervention (T2) for each group. The primary outcome is the level of pain relief at T1 and T2. The secondary outcomes cover physiological parameters, adverse events, satisfaction of patients and health professionals and the acceptance from patients. DISCUSSION: Results of this study will be discussed and the safety and effect of nitrous oxide/oxygen treatment of pain induced by dressing change will be proven. IMPACT: When the finding of this study has an active effect on the treatment of pain caused by dressing change, it may provide more options for nursing staff to choose nurse-led analgesia techniques and then improving the level and quality of pain care as well as patients' overall satisfaction with the Anorectal Department in China.

18.
Diab Vasc Dis Res ; 17(5): 1479164120953626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32951444

RESUMO

PURPOSE: This study was conducted to investigate the relation of HP infection to peripheral arterial stiffness and 10-year cardiovascular risk in diabetes mellitus (DM). METHODS: DM subjects who underwent the C13-breath test were enrolled and divided into DMHP+ and DMHP- groups. Peripheral arterial stiffness was measured using brachial to ankle pulse wave velocity (baPWV). Framingham score (FRS) and Chinese evaluation method of ischemic cardiovascular diseases (ICVD) were used to clarify 10-year cardiovascular risk. RESULTS: A total of 6767 subjects were included, baPWV and proportion of subjects with severe peripheral arterial stiffness were lower in DMHP- group than DMHP+ group (1556.68 ± 227.54 vs 2031.61 ± 525.48 cm/s, p < 0.01; 21.9% vs 62.7%, p < 0.01). Multivariate logistic regression analysis demonstrated that HP infection was independently associated with baPWV. Furthermore, cardiovascular risk score and the proportion of subjects with high risk were lower in DMHP- group than DMHP+ group (FRS: 12.09 ± 3.77 vs 13.91 ± 3.77, 17.2% vs 38.8%; ICVD: 8.56 ± 2.99 vs 10.22 ± 3.16, 43.9% vs 65.4%, with all p < 0.05). CONCLUSION: DM subjects with HP infection had more severe peripheral arterial stiffness compared those without HP infection, a higher cardiovascular risk score and 10-year cardiovascular risk stratification were observed in those subjects.

19.
Appl Environ Microbiol ; 86(20)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32769197

RESUMO

Thermomyces dupontii, a widely distributed thermophilic fungus, is an ideal organism for investigating the mechanism of thermophilic fungal adaptation to diverse environments. However, genetic analysis of this fungus is hindered by a lack of available and efficient gene-manipulating tools. In this study, two different Cas9 proteins from mesophilic and thermophilic bacteria, with in vivo expression of a single guide RNA (sgRNA) under the control of tRNAGly, were successfully adapted for genome editing in T. dupontii We demonstrated the feasibility of applying these two gene editing systems to edit one or two genes in T. dupontii The mesophilic CRISPR/Cas9 system displayed higher editing efficiency (50 to 86%) than the thermophilic CRISPR/Cas9 system (40 to 67%). However, the thermophilic CRISPR/Cas9 system was much less time-consuming than the mesophilic CRISPR/Cas9 system. Combining the CRISPR/Cas9 systems with homologous recombination, a constitutive promoter was precisely knocked in to activate a silent polyketide synthase-nonribosomal peptide synthase (PKS-NRPS) biosynthetic gene, leading to the production of extra metabolites that did not exist in the parental strains. Metabolic analysis of the generated biosynthetic gene mutants suggested that a key biosynthetic pathway existed for the biosynthesis of thermolides in T. dupontii, with the last two steps being different from those in the heterologous host Aspergillus Further analysis suggested that these biosynthetic genes might be involved in fungal mycelial growth, conidiation, and spore germination, as well as in fungal adaptation to osmotic, oxidative, and cell wall-perturbing agents.IMPORTANCE Thermomyces represents a unique ecological taxon in fungi, but a lack of flexible genetic tools has greatly hampered the study of gene function in this taxon. The biosynthesis of potent nematicidal thermolides in T. dupontii remains largely unknown. In this study, mesophilic and thermophilic CRISPR/Cas9 gene editing systems were successfully established for both disrupting and activating genes in T. dupontii In this study, a usable thermophilic CRISPR/Cas9 gene editing system derived from bacteria was constructed in thermophilic fungi. Chemical analysis of the mutants generated by these two gene editing systems identified the key biosynthetic genes and pathway for the biosynthesis of nematocidal thermolides in T. dupontii Phenotype analysis and chemical stress experiments revealed potential roles of secondary metabolites or their biosynthetic genes in fungal development and adaption to chemical stress conditions. These two genomic editing systems will not only accelerate investigations into the biosynthetic mechanisms of unique natural products and functions of cryptic genes in T. dupontii but also offer an example for setting up CRISPR/Cas9 systems in other thermophilic fungi.

20.
MedComm (Beijing) ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32838396

RESUMO

Clinicians have been faced with the challenge of differentiating between severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) infected pneumonia (NCP) and influenza A infected pneumonia (IAP), a seasonal disease that coincided with the outbreak. We aim to develop a machine-learning algorithm based on radiomics to distinguish NCP from IAP by texture analysis based on computed tomography (CT) imaging. Forty-one NCP and 37 IAP patients admitted from January to February 6, 2019 admitted to two hospitals in Wenzhou, China. All patients had undergone chest CT examination and blood routine tests prior to receiving medical treatment. NCP was diagnosed by real-time RT-PCR assays. Eight of 56 radiomic features extracted by LIFEx were selected by least absolute shrinkage and selection operator regression to develop a radiomics score and subsequently constructed into a nomogram to predict NCP with area under the operating characteristics curve of 0.87 (95% confidence interval: 0.77-0.93). The nomogram also showed excellent calibration with Hosmer-Lemeshow test yielding a nonsignificant statistic (P = .904). The novel nomogram may efficiently distinguish between NCP and IAP patients. The nomogram may be incorporated to existing diagnostic algorithm to effectively stratify suspected patients for SARS-CoV-2 pneumonia.

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