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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 802-808, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511169

RESUMO

OBJECTIVES: To study the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with susceptibility to bronchial asthma and glucocorticoid (GC) efficacy in children. METHODS: A total of 173 children with bronchial asthma who were hospitalized between June 2018 and December 2020 were selected as the observation group. The children received aerosol inhalation of GC for three consecutive months. A total of 178 healthy children who underwent physical examination during the same period were selected as the control group. PCR was used to detect the genotypes of the MTHFR C677T for the two groups. The differences in genotype distribution between the two groups were analyzed. Children with different genotypes in the observation group were compared in terms of immunoglobulin E (IgE), interleukin-8 (IL-8), leukotriene B4 (LTB4), lung function, and clinical outcome before and after treatment. RESULTS: TT genotype and T allele were significantly more frequent in the observation group than in the control group (P<0.001). TT/CT genotypes and T allele were independent risk factors for bronchial asthma (OR=6.615 and 7.055 respectively; P<0.001). After GC treatment, the children with CC, CT or TT genotypes experienced significantly decreased levels of IgE, IL-8, and LTB4 and significantly increased forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio (P<0.001). The children with TT genotype showed significantly lower levels of IL-8 and LTB4 than those with CC genotype, a significantly lower level of LTB4 than those with CT genotype, significantly higher FVC than those with CT genotype, and a significantly higher FEV1/FVC ratio than those with CC genotype (P<0.05). The children with TT genotype had better GC efficacy compared with those with CC genotype (P<0.05). TT genotype was an independent factor for good GC efficacy (OR=2.111, P=0.018). CONCLUSIONS: MTHFR gene polymorphism is associated with asthma susceptibility and GC efficacy in children. Children carrying TT/CT genotypes have a higher risk of developing asthma, and those with TT genotype are more sensitive to GC treatment.


Assuntos
Asma , Glucocorticoides , Alelos , Asma/tratamento farmacológico , Asma/genética , Criança , Predisposição Genética para Doença , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético
2.
Acta Pharmacol Sin ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522005

RESUMO

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

3.
Sci Rep ; 11(1): 18063, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508146

RESUMO

Current research on DNA storage usually focuses on the improvement of storage density by developing effective encoding and decoding schemes while lacking the consideration on the uncertainty in ultra-long-term data storage and retention. Consequently, the current DNA storage systems are often not self-contained, implying that they have to resort to external tools for the restoration of the stored DNA data. This may result in high risks in data loss since the required tools might not be available due to the high uncertainty in far future. To address this issue, we propose in this paper a self-contained DNA storage system that can bring self-explanatory to its stored data without relying on any external tool. To this end, we design a specific DNA file format whereby a separate storage scheme is developed to reduce the data redundancy while an effective indexing is designed for random read operations to the stored data file. We verified through experimental data that the proposed self-contained and self-explanatory method can not only get rid of the reliance on external tools for data restoration but also minimise the data redundancy brought about when the amount of data to be stored reaches a certain scale.

4.
Int J Biol Sci ; 17(13): 3413-3427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512156

RESUMO

Cardiovascular diseases (CVDs) caused by arteriosclerosis are the leading cause of death and disability worldwide. In the late stages of atherosclerosis, the atherosclerotic plaque gradually expands in the blood vessels, resulting in vascular stenosis. When the unstable plaque ruptures and falls off, it blocks the vessel causing vascular thrombosis, leading to strokes, myocardial infarctions, and a series of other serious diseases that endanger people's lives. Therefore, regulating plaque stability is the main means used to address the high mortality associated with CVDs. The progression of the atherosclerotic plaque is a complex integration of vascular cell apoptosis, lipid metabolism disorders, inflammatory cell infiltration, vascular smooth muscle cell migration, and neovascular infiltration. More recently, emerging evidence has demonstrated that non-coding RNAs (ncRNAs) play a significant role in regulating the pathophysiological process of atherosclerotic plaque formation by affecting the biological functions of the vasculature and its associated cells. The purpose of this paper is to comprehensively review the regulatory mechanisms involved in the susceptibility of atherosclerotic plaque rupture, discuss the limitations of current approaches to treat plaque instability, and highlight the potential clinical value of ncRNAs as novel diagnostic biomarkers and potential therapeutic strategies to improve plaque stability and reduce the risk of major cardiovascular events.

5.
Dalton Trans ; 50(35): 12287-12291, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519746

RESUMO

Solid-state phase transition materials have received extraordinary interest due to their rich physical properties, such as thermal, dielectric, and ferroelectric properties. Here, two In-based organic-inorganic hybrid compounds, (C6H5CH2CH2NH3)3[InBr5(H2O)] (1) and [(C3H7)4N][InCl4] (2), both display reversible phase transition and dielectric response. Differential scanning calorimetry measurements indicate that the phase transition temperatures (Tc) of 1 and 2 are 167 K and 351 K, respectively. Moreover, structural analyses disclose that the phase transition of 1 can be attributed to the order-disorder changes of phenethylammonium organic cations whereas the phase transition of 2 is caused by the order-disorder changes of [InCl4]- anions. The phase transitions of In-based organic-inorganic hybrid compounds can be driven by the order-disorder changes of cations or anions. Therefore, the system of In-based organic-inorganic hybrid compounds is very suitable for exploring organic-inorganic hybrid phase transition materials.

6.
J Clin Apher ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520046

RESUMO

There is still no optimal treatment for patients with severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis refractory to first-line therapy (including intravenous methylprednisolone [IVMP] and intravenous immunoglobulin [IVIG]). A small study has shown that immunoadsorption (IA) is effective in treating anti-NMDAR encephalitis. However, the effectiveness and safety of IA in the treatment of patients with refractory and severe anti-NMDAR encephalitis is not fully known. Four patients with severe anti-NMDAR encephalitis are reported, which were refractory to the first-line immunotherapy including IVMP and IVIG. Immunoadsorption is performed during the fulminant stage of disease, and the effectiveness and safety of IA are assessed. The modified Rankin Scale (mRS) is used to assess neurological conditions before and after IA. Four patients with the most severe form of anti-NMDAR encephalitis (two with teratoma and two with unknown origin) did not respond to one or more rounds of IVMP plus IVIG. They all required intensive care unit (ICU) support including long-term mechanical ventilation, and thus developed ICU-related complications. Gradual and steady improvement was observed after IA treatment. Except for mild hypotension in patient 1, no other adverse events were observed during IA. Two patients had good early overall recovery on discharge. The other two patients had a good outcome with mRS of 2 at the 12-month follow-up. This small case series suggests that IA may be an effective treatment option to accelerate the recovery of patients with severe and refractory anti-NMDAR encephalitis.

7.
Andrologia ; : e14239, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520070

RESUMO

This study was aimed to investigate the protective effects of Lepidium draba L. (L. draba) extract on oxymetholone (OM)-induced testicular injury in rat. Six groups of n = 5 adult male rats were used as; 1: control, 2: OM (5 mg/kg OM orally), 3, 4 and 5: L. draba extract (100, 200 and 400 mg kg-1  day-1 ) +OM (5 mg kg-1  day-1 OM) and 6:400 mg/kg/d L. draba extract for 30 days. Serum testosterone (T), follicle-stimulating hormone (FSH) and luteinising hormone (LH), inflammatory cytokines (IL-6, IL-10, TNF-α, IL-1ß), oxidative stress (OS) indicators [superoxide dismutase, catalase, glutathione peroxidase and nitric oxide (NO)], apoptotic related genes (Bcl-2, p53, caspase-3 (c3) and Bax) were investigated. OM significantly increased the serum levels of T, proinflammatory cytokines and pro-apoptotic genes expression. Also, it decreased LH and FSH, sperm viability, count and motility. L. draba extract especially could markedly normalise the serum levels of LH and FSH, and T, restore serum antioxidant enzymes and suppressed the pro-inflammatory cytokines. Also, germ cells apoptosis was inhibited against via downregulating the p53, c3, Bax and upregulating Bcl-2. It concluded that L. draba extract could protect the function and structure of testis against OM-induced testicular toxicity via its antioxidant and anti-inflammatory properties.

8.
Chempluschem ; 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34520133

RESUMO

The precise arrangement of single entity is a crucial objective of nanoscience and holds great promise in various fields such as biology and material science. In this work, we develop a "DNA framework-mediated geometric renormalization" (DFMGR) strategy to reassemble gold nanoparticles into specific geometric shapes on a 2-dimensional (2D) fluidic membrane interface. Cholesterol-modified AuNPs are randomly anchored on the supported lipid bilayer (SLB) via the cholesterol-lipid interaction. We demonstrate that AuNPs are laterally mobile on SLB and could be further rearranged into a specific geometric shape by DNA framework containing algebraically topological DNA arms. Using scanning electron microscope (SEM) imaging approach, simple geometric shapes, such as points assembled by monomers, line segments assembled by dimers, triangles assembled by trimers are visually presented. Interestingly, we found that the statistic angle (58.77°) and side length (12.21 nm) of triangles obtained from SEM images were both agreed well with the theoretical angle of 60° and side length of 12.58 nm. And the relative error of the angle calculated was as low as 0.33 %. These results indicated that the DFMGR strategy showed precise regulation ability for the AuNPs renormalization. We believe that DNA framework-mediated geometric renormalization strategy would be a powerful means for regulating ligand-receptor interactions in biosystems and for nanoparticle assembling in material science.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34501593

RESUMO

Wulungu Lake is a vital fishery area in Xinjiang. However, the concentration, enrichment rules, and sources of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the aquatic organisms, have rarely been investigated. The results suggest that the concentrations of As, Ni, Pb, and Zn were higher than those recommended by the national standards for edible fish in some species. Hg, Ni, Cu, Pb, Cr, and Zn in the fish were dependent on the concentration of trace metals in the water environment (p < 0.05). The body weights of the fish were significantly negatively correlated with only Hg (p < 0.05); however, their body lengths were significantly positively correlated with As, Cu, Zn, and Hg contents. Values of δ13C ‰ (δ15N ‰) for the entire fish food web was found to range from -19.9‰ (7.37‰) to -27.7‰ (15.9‰), indicating a wide range of trophic positions and energy sources. Based on the linear correlation, As, Cu, Cd, and Zn contents were positively correlated with δ15N (p < 0.05), and bioaccumulation was observed in the fish. The target hazard quotient (THQ) of all fish species was less than 1, indicating the absence of potential risks to human health.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34501686

RESUMO

The study results serve as a reminder for parents, children, and drivers to be alert to the danger of traffic crashes on Halloween. The aim of this study was to examine whether Halloween is associated with a higher incidence of traffic injuries and whether traffic injuries sustained on Halloween are more severe than those sustained on other days. The U.K. STATS19 database, including the data of all road traffic crashes occurring from 1990 to 2017, was employed. A total of 73,587 pediatric traffic casualties (involving pedestrians, cyclists, and moped riders) were included. Between 17:00 and 19:00 (17:00~18:59) on Halloween, the number of casualties was higher than that on other public holidays and usual days. The logistic regression model revealed that, between 17:00 and 18:00 (17:00~17:59), the risk of being killed or seriously injured on Halloween was 34.2% higher (odds ratio = 1.342; 95% CI = 1.065-1.692) than that on other days. Pediatric crashes occurring on Halloween are associated with a higher number of injuries and increased injury severity.

11.
Orthop Surg ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516043

RESUMO

OBJECTIVE: To investigate the curative effect of closed reduction and external fixation in the treatment of grade IV supination-external rotation fractures of the ankle joint. METHODS: Fifty-six patients treated with closed reduction and external fixation from February 2016 to March 2020 were included in this retrospective study, all with sprains. After receiving nerve block anesthesia, the patient underwent closed reduction under C-arm fluoroscopy, and the ankle joint was fixed in a dorsiflexion-inversion position with casting and splints after the end of the fracture met the reduction standard by fluoroscopy. One week and four weeks after the reduction treatment, oblique axial and coronal MR scans of the ankle joint were performed to determine the degree of injury and healing of the inferior tibiofibular syndesmosis; anteroposterior and lateral X-rays of the ankle joint (including the ankle acupoints) were regularly reviewed to observe the fracture alignment and healing. Combined with the images and physical examination, the patients were instructed to undergo ankle weight-bearing rehabilitation training when they met the clinical healing standard, and at the last follow-up, the Mazur ankle evaluation and grading system were used for evaluation. After the reduction, the images were evaluated according to the Leeds standard. The image healing of fracture was evaluated by callus growth criteria. RESULTS: The follow-up period of patients ranged from 11 to 58 months, with an average of 26.8 months. The clinical healing time was (8.51 ± 2.12) weeks. The excellent and good rating after reduction was 82.1%, and the excellent and good rating during clinical fracture healing was 73.2%, according to the Leeds imaging evaluation. According to the Mazur ankle evaluation and grading system, the excellent and good rating was 75.0%. Pairwise comparison of callus images at 4, 6 and 12 weeks showed statistically significant differences (P < 0.05), suggesting callus growth at different time periods. A total of 56 patients had anterior inferior tibial fibular ligament (AITFL) injuries (grade II-III), among which 11 patients had AITFL injuries combined with grade II injuries of the interosseous ligament (IOL) and 4 patients had AITFL injuries combined with grade III injuries of the IOL. CONCLUSIONS: Most of the patients with grade IV supination-external rotation fracture of the ankle joint had good prognosis after closed reduction and plaster combined with splint fixation. For patients with IOL injury who had poor prognosis, open reduction and internal fixation therapy is appropriate.

12.
Acad Radiol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481706

RESUMO

RATIONALE AND OBJECTIVES: To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. MATERIALS AND METHODS: IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. RESULTS: ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). CONCLUSION: These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

13.
Liver Transpl ; 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482616

RESUMO

OBJECTIVE: To explore the impact of the Kasai procedure (KP) and the length of native liver survival time (NLST) on outcomes of liver transplantation (LT). METHODS: Patients with biliary atresia (BA), who underwent LT in Beijing Friendship Hospital from January 2017 to December 2019, were enrolled and divided into non-KP (N-KP) and post-KP (P-KP) groups. The patients in the P-KP group were further divided into early failure (KP-EF) defined by NLST <1 year, medium failure (KP-MF; NLST 1-5 years), and late failure (KP-LF, NLST >5 years) subgroups. Clinical data at the baseline and during follow-up were collected. The inverse probability of treatment weighting method was used to evaluate the independent effect of KP and the length of NLST on clinical outcomes. RESULTS: Among 197 BA cases, N-KP group accounted for 43 (21.8%), KP-EF 71 (46.1%), KP-MF 59 (38.3%) and KP-LF 24 (15.6%) cases, respectively. Patients in the N-KP and KP-EF groups had the least growth and development, the worst liver function reserve, and the highest pediatric end-stage liver disease (PELD) score prior to LT (all p<0.001). The N-KP and KP-EF groups had significantly longer hospitalization and intensive care unit (ICU) stay post LT. Graft and overall-survival rates were both 93.0% in N-KP and 97.4% in P-KP groups, respectively. The mortality in P-KP groups was significantly lower compared to that of N-KP group with a hazard ratio (HR) of 0.2 (p=0.002). The risks of biliary and vascular complications and cytomegalovirus (CMV) infection post LT were significantly higher in KP-EF group than those in KP-MF and KP-LF groups (HR= 0.09, 0.16 and 0.27; all p<0.05). CONCLUSION: The KP significantly improves post LT overall survival. Patients with early native liver failure after KP have significantly higher risks for biliary and vascular complications and CMV infection.

14.
BMC Complement Med Ther ; 21(1): 217, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465313

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions. METHODS: We systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures. RESULTS: A total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min' walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting. CONCLUSIONS: The present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial.

15.
Allergol Immunopathol (Madr) ; 49(5): 16-24, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476917

RESUMO

OBJECTIVES: This study aimed to evaluate the efficacy of air purifier therapy for patients with allergic asthma. METHODS: Thirty-eight subjects were categorized under two groups namely treatment group and control group. All subjects were under 18 years of age and they had been clinically diagnosed with allergic asthma. The treatment group used high efficiency particulate air (HEPA) purifiers for six consecutive months, and the control group did not use the air filters. Particulate matter (PM) data and dust samples (from bedding and a static point) were collected from the subjects' bedrooms before they started using the air purifiers and each month thereafter. Simultaneously, the subjects were asked to complete a questionnaire for the Asthma Control Test (ACT) or Childhood Asthma Control Test (C-ACT). Fractional exhaled nitric oxide (FENO) tests were performed at the start and end of the study. The concentrations of Der p1 and Der f1 were measured in the dust samples. RESULTS: (1) After utilizing the air purifier, the concentrations of house dust mite (HDM) allergens (Der p1+ Der f1) in the dust samples decreased. In addition, the PMindoor/outdoor values significantly decreased. (2) The ACT and C-ACT scores in the treatment group maintained a steady significant upward trend. (3) At the end of the study, the FENO levels in both groups were lower, although the differences were not significant. CONCLUSIONS: It is witnessed that HEPA air purifiers can decrease indoor HDM allergen and PM levels and improve the quality of life for allergic asthma patients.

16.
Cell Res ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480124

RESUMO

Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the specific degradation of mother centriole-capping CP110 to promote cilia initiation remains unknown. Here, we find that autophagy is crucial for CP110 degradation at mother centrioles after serum starvation in MEF cells. We further identify NudC-like protein 2 (NudCL2) as a novel selective autophagy receptor at mother centrioles, which contains an LC3-interacting region (LIR) motif mediating the association of CP110 and the autophagosome marker LC3. Knockout of NudCL2 induces defects in the removal of CP110 from mother centrioles and ciliogenesis, which are rescued by wild-type NudCL2 but not its LIR motif mutant. Knockdown of CP110 significantly attenuates ciliogenesis defects in NudCL2-deficient cells. In addition, NudCL2 morphants exhibit ciliation-related phenotypes in zebrafish, which are reversed by wild-type NudCL2, but not its LIR motif mutant. Importantly, CP110 depletion significantly reverses these ciliary phenotypes in NudCL2 morphants. Taken together, our data suggest that NudCL2 functions as an autophagy receptor mediating the selective degradation of mother centriole-capping CP110 to promote ciliogenesis, which is indispensable for embryo development in vertebrates.

17.
Plant Cell ; 33(8): 2538-2561, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34467412

RESUMO

A 1D/2D genome-wide association study strategy was adopted to investigate the genetic systems underlying the reciprocal adaptation of rice (Oryza sativa) and its bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo) using the whole-genome sequencing and large-scale phenotyping data of 701 rice accessions and 23 diverse Xoo strains. Forty-seven Xoo virulence-related genes and 318 rice quantitative resistance genes (QR-genes) mainly located in 41 genomic regions, and genome-wide interactions between the detected virulence-related genes and QR genes were identified, including well-known resistance genes/virulence genes plus many previously uncharacterized ones. The relationship between rice and Xoo was characterized by strong differentiation among Xoo races corresponding to the subspecific differentiation of rice, by strong shifts toward increased resistance/virulence of rice/Xoo populations and by rich genetic diversity at the detected rice QR-genes and Xoo virulence genes, and by genome-wide interactions between many rice QR-genes and Xoo virulence genes in a multiple-to-multiple manner, presumably resulting either from direct protein-protein interactions or from genetic epistasis. The observed complex genetic interaction system between rice and Xoo likely exists in other crop-pathogen systems that would maintain high levels of diversity at their QR-loci/virulence-loci, resulting in dynamic coevolutionary consequences during their reciprocal adaptation.

18.
Prenat Diagn ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480803

RESUMO

OBJECTIVE: Investigate the chromosome status and transfer outcomes of embryos selected using routine "best morphology" IVF practices. METHOD: A prospective multi-center, non-selection cohort study involving patients undertaking IVF treatment. Study entry conditions were blastocyst biopsy, >1 embryo with chromosome analysis and frozen transfer of the best morphology embryo. Primary analyses were ßhCG positive, implantation, ongoing pregnancy and birth rates and pregnancy-stage progression failures. RESULTS: After transfer, embryo chromosome status was assigned and outcomes divided into two primary groups - euploids (n=135) and aneuploids (n=53). Compared to euploid embryo transfers, aneuploid embryos had significantly lower primary outcomes (+ßhCG: 67% vs 30%, P<0.0001; IR: 56% vs 19%, P<0.0001; ongoing week 12: 51% vs 9%,P<0.0001; and livebirths: 50% vs 8%, P<0.0001, respectively). Transfers were further subdivided into smaller groups according to their main chromosomal feature. Stage analysis showed higher failure rates for aneuploids to initiate a pregnancy (P<0.0001), higher subclinical miscarriage rate (P=0.0402) and higher clinical miscarriage rate (P=0.0038). CONCLUSION: Routine morphology-based embryo selection resulted in a high euploid selection rate but a significant number of aneuploid embryos were still inadvertently selected for transfer (28%) with the subsequent high failure rates for pregnancy initiation and progression having implications for appropriate patient management. This article is protected by copyright. All rights reserved.

19.
J Am Soc Nephrol ; 32(9): 2159-2174, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34465607

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous cysts originating from renal tubules and is associated with significant tubular epithelial cell proliferation. Focal adhesion kinase (FAK) promotes tumor growth by regulating multiple proliferative pathways. METHODS: We established the forskolin (FSK)-induced three-dimensional (3D) Madin-Darby Canine Kidney cystogenesis model and 8-bromoadenosine-3`,5`-cyclic monophosphate-stimulated cyst formation in ex vivo embryonic kidney culture. Cultured human renal cyst-lining cells (OX-161) and normal tubular epithelial cells were treated with FAK inhibitors or transfected with green fluorescent protein-tagged FAK mutant plasmids for proliferation study. Furthermore, we examined the role of FAK in two transgenic ADPKD animal models, the kidney-specific Pkd1 knockout and the collecting duct-specific Pkd1 knockout mouse models. RESULTS: FAK activity was significantly elevated in OX-161 cells and in two ADPKD mouse models. Inhibiting FAK activity reduced cell proliferation in OX-161 cells and prevented cyst growth in ex vivo and 3D cyst models. In tissue-specific Pkd1 knockout mouse models, FAK inhibitors retarded cyst development and mitigated renal function decline. Mechanically, FSK stimulated FAK activation in tubular epithelial cells, which was blocked by a protein kinase A (PKA) inhibitor. Inhibition of FAK activation by inhibitors or transfected cells with mutant FAK constructs interrupted FSK-mediated Src activation and upregulation of ERK and mTOR pathways. CONCLUSIONS: Our study demonstrates the critical involvement of FAK in renal cyst development, suggests that FAK is a potential therapeutic target in treating patients with ADPKD, and highlights the role of FAK in cAMP-PKA-regulated proliferation.

20.
J Phys Chem Lett ; : 8627-8636, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472339

RESUMO

By means of electrocatalytic tests, surface-science techniques and density functional theory, we unveil the physicochemical mechanisms ruling the electrocatalytic activity of recently discovered mitrofanovite (Pt3Te4) mineral. Mitrofanovite represents a very promising electrocatalyst candidate for energy-related applications, with a reduction of costs by 47% compared to pure Pt and superior robustness to CO poisoning. We show that Pt3Te4 is a weak topological metal with the Z2 invariant, exhibiting electrical conductivity (∼4 × 106 S/m) comparable with pure Pt. In hydrogen evolution reaction (HER), the electrode based on bulk Pt3Te4 shows a very small overpotential of 46 mV at 10 mA cm-2 and a Tafel slope of 36-49 mV dec-1 associated with the Volmer-Heyrovsky mechanism. The outstanding ambient stability of Pt3Te4 also provides durability of the electrode and long-term stability of its efficient catalytic performances.

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