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1.
Front Cardiovasc Med ; 9: 860322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548443

RESUMO

Objectives: To investigate the characteristics of patients with primary hypertension who had positive responses to the cold pressor test (CPT). Methods: This cross-sectional study was conducted between November 2018 to November 2019, and the CPT was performed in patients with primary hypertension in 48 hospitals. The demographic characteristics and complications were collected through a questionnaire and physical examinations. A 12-month follow-up was conducted to identify the occurrence of the following events: a) all-cause mortality; b) myocardial infarction; c) stroke; d) hospitalized for heart failure. Results: The CPT was positive in 30.7% of the patients. Compared with the negative CPT group, the positive CPT group was associated with a lower rate of blood pressure control, and was more likely to have a high salt diet, diabetes, hyperuricemia, left ventricular wall thickening, carotid plaques, coronary heart disease and heart failure. A high-salt diet (OR = 1.228, 95%CI: 1.037-1.456) was found to be correlated with the positive result of CPT. Among patients in the positive CPT group, those using diuretics had a significantly higher rate of blood pressure control than those not using diuretics (54.6 vs.42.6%, x2 = 6.756, P = 0.009). After a 12-month follow-up, the incidence of heart failure in the positive CPT group was significantly higher than that in the negative CPT group (7.35 vs.5.01%, x2 = 3.945, P = 0.047). Conclusions: Patients with positive responses to the CPT had lower rates of BP control and a high risk of heart failure, which may be related to their preference for a high-salt diet. The use of diuretics helps to better control blood pressure in those patients.

2.
BMC Biol ; 20(1): 105, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35550116

RESUMO

BACKGROUND: Metazoan guts are in permanent contact with microbial communities. However, the host mechanisms that have developed to manage the dynamic changes of these microorganisms and maintain homeostasis remain largely unknown. RESULTS: Serotonin (5-hydroxytryptamine [5-HT]) was found to modulate gut microbiome homeostasis via regulation of a dual oxidase (Duox) gene expression in both Bactrocera dorsalis and Aedes aegypti. The knockdown of the peripheral 5-HT biosynthetic gene phenylalanine hydroxylase (TPH) increased the expression of Duox and the activity of reactive oxygen species, leading to a decrease in the gut microbiome load. Moreover, the TPH knockdown reduced the relative abundance of the bacterial genera Serratia and Providencia, including the opportunistic pathogens, S. marcescens and P. alcalifaciens in B. dorsalis. Treatment with 5-hydroxytryptophan, a precursor of 5-HT synthesis, fully rescued the TPH knockdown-induced phenotype. CONCLUSIONS: The findings reveal the important contribution of 5-HT in regulating gut homeostasis, providing new insights into gut-microbe interactions in metazoans.

3.
Front Pharmacol ; 13: 888054, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571101

RESUMO

This study aimed to explore the effect of baicalein on the pharmacokinetics of cilostazol (CLZ) and its two metabolites 3,4-dehydro cilostazol (3,4-CLZ) and 4'-trans-hydroxy cilostazol (4'-CLZ) in rats using a newly established ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Ticagrelor was used as an internal standard (IS), then cilostazol and its two metabolites were separated by means of a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) using gradient elution method with 0.4 ml/min of flow rate. Acetonitrile as organic phase and water with 0.1% formic acid as aqueous phase constructed the mobile phase. Selective reaction monitoring (SRM) mode and positive ion mode were preferentially chosen to detect the analytes. Twelve SD rats were divided into two groups (n = 6) when CLZ was administered orally (10 mg/kg) with or without oral baicalein (80 mg/kg). The selectivity, linearity, recovery, accuracy, precision, matrix effect and stability of UPLC-MS/MS assay were satisfied with the standards of United States Food and Drug Administration guidelines. In control group, AUC0-∞ and Cmax of CLZ were 2,169.5 ± 363.1 ng/ml*h and 258.9 ± 82.6 ng/ml, respectively. The corresponding results were 3,767.6 ± 1,049.8 ng/ml*h and 308.6 ± 87.9 ng/ml for 3, 4-CLZ, 728.8 ± 189.9 ng/ml*h and 100.3 ± 51.3 ng/ml for 4'-CLZ, respectively. After combination with baicalein, AUC0-∞ and Cmax of CLZ were 1.48, 1.38 times higher than the controls. Additionally, AUC0-∞ and Cmax were separately decreased by 36.12 and 19.54% for 3,4-CLZ, 13.11 and 44.37% for 4'-CLZ. Baicalein obviously alters the pharmacokinetic parameters of CLZ, 3,4-CLZ and 4'-CLZ in rats. These results suggested that there was a potential drug-drug interaction between baicalein and CLZ. Therefore, it must raise the awareness when concomitant use of CLZ with baicalein, the dosage regimen of CLZ should be taken into consideration, if this result is confirmed in clinical studies.

4.
ACS Omega ; 7(18): 15326-15337, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35571814

RESUMO

In this paper, laminar combustion characteristics of methane/ammonia/air flames are numerically investigated using the Chemkin/Premix code. The initial temperature is set as 298 K; the initial pressures are set as 1, 2, 5, 10, and 20 atm; and the equivalence ratios are set as 0.8-1.6. Laminar burning velocity (LBV); adiabatic flame temperature (AFT); net heat release rate (NHRR); and the mole fractions of H, NH2, NO, NO2, and HCN at stoichiometric ratio are studied with ammonia (NH3) addition. Meanwhile, temperature sensitivity and rate of production (ROP) are analyzed. The results show that with the increase of the initial pressures, LBV decreases and AFT and NHRR increase. With the increase of ammonia doping ratios, LBV, AFT, and NHRR decrease. From temperature sensitivity analyses, the main reactions that promote temperature rise are R39 (H + O2 < = > O + OH), R100 (OH + CH3 < = > CH2(S) + H2O), R102 (OH + CO < = > H + CO2), and R122 (HO2 + CH3 < = > OH + CH3O). The main reactions that inhibit temperature rise are R53 (H + CH3(+M) < = > CH4(+M)), R36 (H + O2 + H2O < = > HO2 + H2O), and R46 (H + HO2 < = > O2 + H2). For the rate of production of the free radical pool, the trends of H and NO are consuming first and then producing, and the trends of NH2, NO2, and HCN are the opposite. The pathway from methane to carbon dioxide is CH4 → CH3 → CH3O → CH2O → HCO → CO → CO2, and the pathway from ammonia to nitrogen is NH3 → NH2 → NH/HNO → NO/NO2 → N2.

5.
J Geriatr Cardiol ; 19(4): 301-314, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35572216

RESUMO

BACKGROUND: Mutation in the titin gene (TTN) in left ventricular noncompaction (LVNC) has been reported with a highly heterogeneous prevalence, and the molecular mechanisms underlying the pathogenesis of TTN gene mutation are uncharacterized. In the present study, we identified a novel TTN mutation in a pedigree with LVNC and investigated the potential pathogenic mechanism by functional studies. METHODS: The whole-genome sequencing with linkage analysis was performed in a 3-generation family affected by autosomal dominant LVNC cardiomyopathy. The clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR/Cas9) technology was used to establish novel truncating mutation in TTN in a rat cardiomyoblast H9C2 cell line in vitro, in which functional studies were carried out and characterized in comparison to its wild-type counterpart. RESULTS: A novel truncating mutation TTN p. R2021X was identified as the only plausible disease-causing variant that segregated with disease among the five surviving affected individuals, with an interrogation of the entire genome excluding other potential causes. Quantitative reverse transcription-polymerase chain reaction and cellular immunofluorescence supported a haploinsufficient disease mechanism in titin truncation mutation cardiomyocytes. Further functional studies suggested mitochondrial abnormities in the presence of mutation, including decreased oxygen consumption rate, reduced adenosine triphosphate production, impaired activity of electron translation chain, and abnormal mitochondrial structure on electron microscopy. Impaired autophagy under electron microscopy accompanied with activation of the Akt-mTORC1 signaling pathway was observed in TTN p. R2021X truncation mutation cardiomyocytes. CONCLUSIONS: The TTN p. R2021X mutation has a function in the cause of a highly penetrant familial LVNC. These findings expand the spectrum of titin's roles in cardiomyopathies and provide novel insight into the molecular basis of titin-truncating variants-associated LVNC.

6.
Front Microbiol ; 13: 860288, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572690

RESUMO

Objective: This study aimed to develop a new rapid and simplified carbapenemase detection method (rsCDM) for detection and characterization of carbapenemase with 3-aminophenylboronic acid (APBA), ethylenediaminetetraacetic acid (EDTA), and cloxacillin (CLO) ß-lactamase inhibitors. Methods: A panel of 182 carbapenem-resistant Enterobacterales (CRE) strains with blaKPC (88), blaNDM (60), blaIMP (10), blaVIM (3), blaOXA-181 (5), blaKPC, and blaNDM (7), porin changes in combination with an extended-spectrum ß-lactamase (ESBL) (3) or AmpC hyper-production (6) and 43 carbapenem-susceptible Enterobacterales isolates were used to evaluate the performance of rsCDM and EDTA-carbapenem inactivation method (eCIM). Carbapenemase class was determined with specific inhibitors at 4, 6, and 18 h by rsCDM, and the difference between imipenem (IMI) and meropenem (MEM) disks was simultaneously compared. Results: The sensitivity of rsCDM using IMI was 97.1% at the three time points, with a specificity of 100%, independent of the culture duration. Similar to IPM, MEM disk also showed high sensitivity (97.1%) and specificity (100%) at 6 h. And the sensitivity of eCIM was 95.4% and the specificity was 100%. Based on a decision algorithm, the characterization number of IMI and MEM in KPC-producing isolates was 88 vs. 87, metallo-ß-lactamases (MBLs) was 73 vs. 72, KPC and NDM carbapenemase was 7 vs. 7 at 4 h, respectively. After 6 h, the category number changed insignificantly except for isolates with combined AmpC overproduction and porin changes, showing an increase in IMI (6) and MEM (2), and there was no difference in the results between 6 and 18 h for the two tablets. OXA-181-producing strains can't be distinguished by rsCDM. For eCIM, the characterization number in KPC-, OXA- 181-, and MBLs-producing strains was 88, 5, and 72, but it failed to detect multi-enzyme-producing isolates (KPC and NDM). Conclusion: rsCDM accurately discriminated carbapenemase within 4 h and could differentiate multi-enzyme (KPC and NDM) and AmpC in conjunction with porin changes strains. Hence, rsCDM represents a rapid, simple, easy readout, and accurate tool that can be used without any specialized equipment.

7.
Front Oncol ; 12: 874852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574363

RESUMO

Aim: Clinical utility of doxorubicin (DOX) is limited by its cardiotoxic side effect, and the underlying mechanism still needs to be fully elucidated. This research aimed to examine the role of (pro)renin receptor (PRR) in DOX-induced heart failure (HF) and its underlying mechanism. Main Methods: Sprague Dawley (SD) rats were injected with an accumulative dosage of DOX (15 mg/kg) to induce HF. Cardiac functions were detected by transthoracic echocardiography examination. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum were detected, and oxidative stress related injuries were evaluated. Furthermore, the mRNA expression of PRR gene and its related genes were detected by real-time PCR (RT-PCR), and protein levels of PRR, RAC1, NOX4 and NOX2 were determined by Western blot. Reactive oxygen species (ROS) were determined in DOX-treated rats or cells. Additionally, PRR and RAC1 were silenced with their respective siRNAs to validate the in vitro impacts of PRR/RAC1 on DOX-induced cardiotoxicity. Moreover, inhibitors of PRR and RAC1 were used to validate their effects in vivo. Key Findings: PRR and RAC1 expressions increased in DOX-induced HF. The levels of CK and LDH as well as oxidative stress indicators increased significantly after DOX treatment. Oxidative injury and apoptosis of cardiomyocytes were attenuated both in vivo and in vitro upon suppression of PRR or RAC1. Furthermore, the inhibition of PRR could significantly down-regulate the expressions of RAC1 and NOX4 but not that of NOX2, while the inhibition of RAC1 did not affect PRR. Significance: Our findings showed that PRR inhibition could weaken RAC1-NOX4 pathway and alleviate DOX-induced HF via decreasing ROS production, thereby suggesting a promising target for the treatment of DOX-induced HF.

8.
Ying Yong Sheng Tai Xue Bao ; 33(3): 671-676, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35524518

RESUMO

Clarifying the differences of maize yield and its stability under long-term no-tillage with different stover mulching amounts can provide theoretical and technical supports for establishing and evaluating long-term conservation tillage pattern and promoting grain production. Based on a long-term conservation tillage field experiment in the mollisol area of Northeast China since 2007, we analyzed the interannual variation, variation coefficient and stability of maize yield during 2013 and 2019 across five treatments, i.e., no-tillage stover-free mulching (NT0), no-tillage with 33% stover mulching (NT33), no-tillage with 67% stover mulching (NT67) and no-tillage with 100% stover mulching (NT100), with the traditional ridge cropping (RT) as the control. The results showed that compared with RT, long-term no-tillage with stover mulching treatments could increase maize yield. NT100 had the highest increasing rate of 11.4%, followed by NT67 and NT0, with the increasing rate of 11.0% and 10.4%, respectively. Maize yield exhibited a nonlinear relationship with the amount of stover mulch. The variation coefficient of maize yield under multi-year no-tillage with different stover mulching could be sorted as NT67NT0>NT100>RT>NT33, indicating that NT67 treatment could significantly reduce the interannual fluctuation of maize yield and had better sustainability of yield. No-tillage stover mulching significantly increased soil total carbon and total nitrogen contents, which were significantly positively correlated with maize yield. In conclusion, compared with traditional tillage, no-tillage stover mulching could increase maize yield and soil carbon and nitrogen contents. Appropriate stover mulching (NT67)had the potential to improve the stability and sustainability of maize yield.


Assuntos
Agricultura , Zea mays , Agricultura/métodos , Carbono , China , Nitrogênio/análise , Solo
9.
J Phys Chem Lett ; : 4434-4440, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35549269

RESUMO

Electrochemical CO2 reduction technology plays an important role in reducing CO2 into valuable chemical fuels. Therein, Cu-based catalysts show superior performance for producing high-value C2+ products. Here, we illustrate the ascendency of high-index facets of Cu catalysts in producing C2+ products and find that two kinds of sites favor C-C coupling on the surface. One is prone to adsorb the C-C coupling structure by spanning stepped coppers with different coordination numbers. The other is to embed the structure along two columns of Cu with similar characteristics through O and C adsorbed simultaneously. Within all research surfaces, the coupling energy barrier is lowest on the Cu(911) facet, which is consistent with the experiment. The less charged sites promote the stabilization of the CO-CO structure as determined by charge analysis. Furthermore, our results suggest that the high selectivity for C2+ products on a Cu surface could significantly come from the contribution of the high-index facet.

10.
J Ethnopharmacol ; 294: 115392, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35589019

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia procumbens L. is a traditional Chinese medicine, first recorded in "Shen Nong's Herbal Classic", for the treatment of lumbar pain and fever. As a widely distributed herb, it has also been documented in India, Nepal, and Malaysia. In "Tang Materia Medica", a famous medicinal book of Tang Dynasty in ancient China, it was first used to treat diseases associated with blood stasis. Blood stasis syndrome is closely related to thrombus formation and platelet aggregation. Although some compounds isolated from this plant have anti-platelet aggregation effects, the main chemical components and mechanism of J. procumbens in terms of these effects are little known. AIMS OF THE STUDY: Through in vivo and in vitro experiments, this studsy revealed the characteristic components and action mechanism of anti-platelet aggregation by J. procumbens from an overall perspective. MATERIALS AND METHODS: The effective crude extracts of the whole plant were screened via an in vitro anti-platelet aggregation test. After incubating these extracts with apheresis platelets, high affinity compounds were detected by HPLC-MS and regulatory genes were detected using gene chips. The effective components and potential target proteins were analyzed using computational docking technology. Furthermore, the compound with the strongest predicted activity was evaluated in vivo via an anti-thrombotic test. RESULTS: Integrin aⅡbß3, PKCα, PI3Kγ, and mitogen-activated protein kinase 14 were found to be potential targets. Justicidin B, tuberculatin, chinensinaphthol methyl ether, and neojusticin B were effective compounds that inhibited human platelet aggregation by suppressing Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways. Among the compounds that bind to platelets, justicidin B showed the strongest virtual binding force. The test of carotid artery thrombosis induced by ferric chloride in SD rats confirmed that justicidin B inhibited thrombus formation. CONCLUSION: Experimental investigation showed that arylnaphthalene lignan aglycones with one methylenedioxy group and two methoxy groups are effective components for anti-platelet aggregation by J. procumbens. These compounds inhibit Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways by suppressing the expression of genes such as ITGB3, PRKCA, PIK3CG, and MAPK14. These results reflected the characteristics of multi-component and multi-target synergistic treatment of Chinese medicine.

11.
Ecotoxicol Environ Saf ; 239: 113638, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35597142

RESUMO

Recently, concerns for species that sex differentiation is influenced by temperature in the context of global warming have increased because disrupted operational sex ratios could threaten population maintenance. In contrast, little attention has been given to the reproductive ability of populations that experienced elevated temperatures. In this study, we demonstrated that high temperature (HT) would decrease population size via three different aspects of reproductive ability for the first time. We show that, in a thermo-sensitive teleost yellow catfish, a short period of HT (+3 °C) exposure during the critical period of sex differentiation leads to a different percentage of masculinization of XX genotypic females (1-23%) in wet-lab and natural water bodies. Combining the results of gonadal appearance, histology, sperm parameters, and fertilization rate, we found that XX pseudo-males induced by HT display significantly discounted fertility and reproductive performance compared to XY normal males. We demonstrate that the survival of the XY genotype is lower than XX genotype under environmental stress, including HT, hypoxia, and parasite infection, and the differential survival seems unrelated to male-biased sexual size dimorphism. The mathematical model predicts that the phenotypic female percent will be stabilized at 50% and the population will be sustainably maintained when masculinizing force is less than 0.5, while HT will put the population in danger when the masculinizing force exceeds 0.5. However, when we combine the real-world data of reproductive ability and mathematic model, our results suggest the population size decreases and the long-term survival of the studied species are threatened under the projected pace of increasing temperature. These findings will be useful for understanding the long-term effects of increasing temperature on sex ratio, reproduction and population maintenance in teleost.

12.
Neurochem Res ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522367

RESUMO

Satellite glial cells (SGCs) tightly surround neurons and modulate sensory transmission in dorsal root ganglion (DRG). At present, the biological property of primary SGCs in culture deserves further investigation. To reveal the key factor for SGCs growth and survival, we examined the effects of different culture supplementations containing Dulbecco's Modified Eagle Medium (DMEM)/F12, DMEM high glucose (HG) or Neurobasal-A (NB). CCK-8 proliferation assay showed an increased proliferation of SGCs in DMEM/F12 and DMEM/HG, but not in NB medium. Bax, AnnexinV, and propidium iodide (PI) staining results showed that NB medium caused cell death and apoptosis. We showed that glutamine was over 2.5 mM in DMEM/F12 and DMEM/HG, whereas it was absence in NB medium. Interestingly, exogenous glutamine application significantly reversed the poor proliferation and cell death of SGCs in NB medium. These findings demonstrated that DMEM/F12 medium was optimal to get high-purity SGCs. Glutamine was the key molecule to maintain SGCs growth and survival in culture. Here, we provided a novel approach to get high-purity SGCs by changing the key component of culture medium. Our study shed a new light on understanding the biological property and modulation of glial cells of primary sensory ganglia.

13.
Front Endocrinol (Lausanne) ; 13: 856667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528007

RESUMO

Objective: To investigate the effect of BMI in male and/or female partners on embryo development and clinical pregnancy outcome during ART. Methods: Data of 11,130 cycles between January 2018 and December 2020 were retrospectively analyzed. They were divided into Group A, B, C, and D based on couples' BMI values, also were divided into Group I, II, III and IV in IVF cycles and Group i, ii, iii, and iv in ICSI cycles. After grouping, inter-group indicators comparisons and logistic regression analysis were performed. Results: In IVF cycles, CPR in Group I and Group III were higher than Group IV. In Group III, it was higher than Group II. The AR in Group IV was higher, but the LBR was lower than Group I, Group II, and Group III. Logistic regression analysis results suggested that AR in Group IV was higher than that in Group I in IVF cycles, whereas LBR was lower.In ICSI cycles, high-quality embryo rate in Group i and Group ii were both higher than that in Group iii and Group iv. The CPR in Group i was higher than Group ii and Group iv, and in Group iii was higher than Group ii and Group iv. The AR in Group i was lower than Group iii and Group iv, and AR in Group ii was lower than Group iv. LBR, in Group I it was higher than Group ii, Group iii, and Group iv. Logistic regression analysis results suggested CPR in Group ii was significantly lower than that in Group i. AR in Group iii was considerably higher than that in Group i. LBR in Group ii and Group iv were significantly lower than that in Group i. Conclusion: Female higher BMI was not conducive to the formation of high-quality embryos in ICSI cycle. Female and/or male BMI affected AR and LBR more than CPR not only in IVF cycles, but also in ICSI cycles.


Assuntos
Resultado da Gravidez , Injeções de Esperma Intracitoplásmicas , Índice de Massa Corporal , Desenvolvimento Embrionário , Feminino , Fertilização In Vitro/métodos , Humanos , Masculino , Gravidez , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/métodos
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(4): 423-427, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35527419

RESUMO

OBJECTIVES: To study the value of Silverman-Anderson score versus Downes score in predicting respiratory failure in full-term neonates. METHODS: The convenience sampling method was used to select the full-term neonates with lung diseases who were hospitalized in the neonatal intensive care unit from July 2020 to July 2021. According to the diagnostic criteria for neonatal respiratory failure, they were divided into a respiratory failure group (65 neonates) and a non-respiratory failure group (363 neonates). Silverman-Anderson score and Downes score were used for evaluation. The receiver operating characteristic analysis was used to compare the value of the two noninvasive scores in predicting respiratory failure in full-term neonates. RESULTS: Among the 428 full-term neonates, 65 (15.2%) had respiratory failure. The Silverman-Anderson score had a significantly shorter average time spent on evaluation than the Downes score [(90±8) seconds vs (150±13) seconds; P<0.001]. The respiratory failure group had significantly higher points in both the Silverman-Anderson and Downes scores than the non-respiratory failure group (P<0.001). The Silverman-Anderson score had an AUC of 0.876 for predicting respiratory failure, with a sensitivity of 0.908, a specificity of 0.694, and a Youden index of 0.602 at the optimal cut-off value of 4.50 points. The Downes score had an AUC of 0.918 for predicting respiratory failure, with a sensitivity of 0.723, a specificity of 0.953, and a Youden index of 0.676 at the optimal cut-off value of 6.00 points. The Downes score had significantly higher AUC for predicting respiratory failure than the Silverman-Anderson score (P=0.026). CONCLUSIONS: Both Silverman-Anderson and Downes scores can predict the risk of respiratory failure in full-term neonates. The Silverman-Anderson score requires a shorter time for evaluation, while the Downes score has higher prediction efficiency. It is recommended to use Downes score with higher prediction efficiency in general evaluation, and the Silverman-Anderson score requiring a shorter time for evaluation can be used in emergency.


Assuntos
Unidades de Terapia Intensiva Neonatal , Insuficiência Respiratória , Humanos , Recém-Nascido , Prognóstico , Curva ROC , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Fatores de Risco
15.
Plant Genome ; : e20216, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35535627

RESUMO

Mitogen-activated protein kinase (MAPK or MPK) cascades consist of three protein kinase components, MAPK kinase kinases (MAPKKKs), MAPK kinases (MKKs and MPKs), which are indispensable for various plant physiological processes. The functions of MAPK families have been extensively studied in maize (Zea mays L.) and other plant species, but little is known about MAPK families in the elite Chinese maize line Huangzaosi (hzs). In this study, we observed that overall performance of Huangzaosi was substantially better than that of B73 under drought conditions at the seedling and V16 stages with a favorable root/canopy ratio. In silico analyses identified 72, 10, and 24 MAPKKKs, MKKs, and MPKs, respectively, in Huangzaosi. Examinations of phylogenetic relationships among Arabidopsis thaliana (L.) Heynh., rice (Oryza sativa L.), and maize (lines B73 and hzs), gene structures, conserved protein motifs, and chromosomal locations revealed their evolutionary relationships. The basal gene expression levels and tissue specificities of all three MAPK families in hzs reflected the diversity in the MAPK functions related to growth and development. The quantitative real-time polymerase chain reaction (qPCR) assay indicated that certain MAPK genes with high basal expression levels in the primary and crown roots responded differentially to drought between B73 and hzs, suggesting that these genes may contribute to their distinct drought tolerance at different developmental stages. The important information regarding the evolution and expression of hzs MAPK family members generated in this study provides a new avenue for the better understanding on the regulatory mechanism of MAPK cascade in the core inbred line hzs, which may be useful to guide the development of new maize cultivars with desirable traits (e.g., drought resistance).

16.
Anal Chem ; 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35604850

RESUMO

Nanobodies, also known as VHHs, originate from the serum of Camelidae. Nanobodies have considerable advantages over conventional antibodies, including smaller size, more modifiable, and deeper tissue penetration, making them promising tools for immunotherapy and antibody-drug development. A high-throughput nanobody screening platform is critical to the rapid development of nanobodies. To date, droplet-based microfluidic systems have exhibited improved performance compared to the traditional phage display technology in terms of time and throughput. In realistic situations, however, it is difficult to directly apply the technology to the screening of nanobodies. Requirements of plasma cell enrichment and high cell viability, as well as a lack of related commercial reagents, are leading causes for impeding the development of novel methods. We overcame these obstacles by constructing a eukaryotic display system that secretes nanobodies utilizing homologous recombination and eukaryotic transformation technologies, and the significant advantages are that it is independent of primary cell viability and it does not require plasma cell enrichment in advance. Next, a signal capture system of "SA-beads + Biotin-antigen + nanobody-6 × His + fluorescence-labeled anti-6 × His (secondary antibody)" was designed for precise localization of the eukaryotic-expressed nanobodies in a droplet. Based on this innovation, we screened 293T cells expressing anti-PD-L1 nanobodies with a high positive rate of targeted cells (up to 99.8%). Then, single-cell transcriptomic profiling uncovered the intercellular heterogeneity and BCR sequence of target cells at a single-cell level. The complete complementarity determining region (CDR3) structure was obtained, which was totally consistent with the BCR reference. This study expanded the linkage between microfluidic technology and nanobody applications and also showed potential to accelerate the rapid transformation of nanobodies in the large-scale market.

17.
Bioorg Chem ; 126: 105859, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35605553

RESUMO

A series of novel pleuromutilin derivatives containing 4-aminothiophenol moieties have been designed and synthesized as promising antibacterial agents against Methicillin-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these semisynthetic derivatives against 4 strains of S. aureus (MRSA ATCC 43300, S. aureus ATCC 29213, S. aureus 144 and S. aureus AD3) was evaluated by the broth dilution method. Most of the synthesized derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). 12 Compounds possessed superior antibacterial activity against MRSA compared with valnemulin and retapamulin (MIC = 0.0625 µg/mL). Compounds 12, 16a, 16c and 19 exhibited the most effective antibacterial effect against MRSA (MIC = 0.015 µg/mL). Furthermore, the time-kill curves showed compounds 12 and 19 had a certain inhibitory effect against MRSA in vitro. Compounds 12 and 19 possessed longer PAE time (2.74 h and 3.11 h, respectively) than tiamulin (PAE = 2.04 h) against MRSA after exposure at 4 × MIC concentration for 2 h. Compounds 12 and 19 also displayed superior in vivo antibacterial efficacy (-1.20 log10 CFU/mL and -1.21 log10 CFU/mL, respectively) than tiamulin (-0.75 log10 CFU/mL) in reducing MRSA load in the mice thigh infection model. In addition, compound 19 had barely inhibitory effect on RAW 264.7 and 16HBE cells at 8 µg/mL. In molecular docking study, upon docking into the 50S ribosomal subunit, the binding free energy (ΔGb) of compound 12 and 19 was calculated to be -9.02 kcal/mol and -9.89 kcal/mol, respectively.

18.
Zhongguo Zhong Yao Za Zhi ; 47(8): 2200-2210, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35531737

RESUMO

Dachaihu Decoction is a classical Chinese herbal prescription that is effective in harmonizing lesser yang and purging internal accumulated heat. At present, it has been widely used in clinical practice, and the resulting outcomes are satisfactory. However, its quality indicators and action mechanism are still not clear. Therefore, this paper explored the efficacy markers of Dachaihu Decoction and its action mechanism based on literature mining, molecular biology, and network pharmacology, so as to better control its quality and ensure its clinical efficacy. The efficacy markers of Dachaihu Decoction were predicted and analyzed according to the "five principles" for Q-markers of Chinese herbs. Then the anti-inflammatory activity of the efficacy markers of Dachaihu Decoction was evaluated with Griess reagent after the establishment of RAW264.7 cell inflammation model in vitro with lipopolysaccharide(LPS). The potential targets of efficacy markers were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), ChEMBL, and SwissTargetPrediction, followed by the construction of the protein-protein interaction(PPI) network of the efficacy markers of Dachaihu Decoction. Topological, GO, and KEGG enrichment analysis was carried out to construct the "key target-signaling pathway-biological process" network, thus elucidating the action mechanism of the efficacy markers of Dachaihu Decoction. Saikosaponin B_2, baicalin, baicalein, wogonoside, neohesperidin, naringin, hesperidin, and paeoniflorin were considered as the potential efficacy markers of Dachaihu Decoction. The anti-inflammatory activity evaluation showed that the potential efficacy markers effectively inhibited the release of NO, exhibiting good anti-inflammatory activities. As demonstrated by network pharmacology, the efficacy markers of Dachaihu Decoction regulated the inflammatory response by acting on MAPK and NF-κB signaling pathways, the carbohydrate metabolism by HIF-1 and PI3 K-AKT signaling pathways, and the lipid metabolism by AMPK and PI3 K-AKT signaling pathways. This study discovered the efficacy markers of Dachaihu Decoction based on literature mining combined with molecular biological experiments and explored its action mechanism at the molecular level based on network pharmacology, which would provide reference for the quality control of Dachaihu Decoction and scientific basis for its clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Biomarcadores , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais
19.
Nutrients ; 14(9)2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35565922

RESUMO

Background: The role of meat and vegetable intake in the development of asthenozoospermia has been controversial, and the role of cooking methods for meat and vegetables in the association has yet to be determined. The present study aimed to illuminate the relationship between the consumption and cooking methods of meat and vegetables and the risk of asthenozoospermia. Methods: In this hospital-based case-control study, we enrolled 552 patients with asthenozoospermia and 585 healthy controls. Dietary information was assessed using a validated self-administered food frequency questionnaire. Asthenozoospermia was diagnosed according to the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Results: Participants in the highest tertile of total meat and unprocessed meat intake had a 44% and 39% lower risk of asthenozoospermia than those in the lowest tertile (OR = 0.56, 95% CI: 0.37, 0.87 and OR = 0.61, 95% CI: 0.40, 0.93), respectively. Participants with the highest processed meat consumption showed higher risk (OR = 1.44, 95% CI: 1.01, 2.06). Raw vegetable consumption was negatively associated with the risk of asthenozoospermia (OR = 0.67, 95% CI: 0.45, 0.98). The stir-frying cooking method for meat was associated with increased risk of asthenozoospermia (OR = 1.58, 95% CI: 1.02, 2.46). Conclusions: Intake of total meat, unprocessed meat, and raw vegetable may reduce asthenozoospermia risk, while higher consumption of processed meat may increase the risk. Cooking methods may play a role in these associations. These findings need to be confirmed in large and prospective cohort studies.

20.
Biochem Biophys Res Commun ; 613: 7-11, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35526489

RESUMO

The mitogen-activated protein kinase (MAPK), as a major member in MAPK cascade, has been shown to play an important role in plant development and growth. However, little is known about the function of MAPK in regulating cell wall synthesis/metabolism. In this study, we found that the l-arabinose content in mpk4 mutant was much higher compared to those in wild type, mpk3 and mpk6 mutants, whereas overexpressing MPK4 in Arabidopsis obviously decreased the l-arabinose content of cell wall. Furthermore, loss of function in MPK4 significantly decreased the expression of l-arabinose synthesis/metabolism-related gene MUR10, but did not affect the expressions of the other genes (MUR4, MUR5, UXT1 and ARAD1). Moreover, knock-out of MPK4 significantly decreased the cellulose content. These results suggest that MPK4 negatively regulates the l-arabinose synthesis of cell wall by likely modulating the expression of MUR10.

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