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1.
Signal Transduct Target Ther ; 7(1): 6, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34992208

RESUMO

Revascularization and angiogenesis, as substrates of sustained collateral circulation, play a crucial role in determining the severity and clinical outcome of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Developing an adjunct biomarker to help identify and monitor collateral status would aid stroke diagnosis and prognosis. To screen the potential biomarkers, proteomic analysis was performed in this study to identify those distinct plasma protein profiles in AIS due to LVO with different collateral status. Interestingly, we found that levels of Plasma Factor VII Activating Protease (FSAP) significantly increased in those AIS patients with poor collaterals, and were correlated with worse neurological outcome. Furtherly, both in vitro and in vivo models of ischemic stroke were used to explore pathological mechanisms of FSAP in endothelial dysfunction. We demonstrated that the FSAP inhibitor, high-molecular-weight hyaluronan (HMW-HA), enhanced the pro-angiogenic vascular factors, improved the integrity of brain blood barrier, and promoted newly formed cerebral microvessels in the ischemic penumbra, consequently improving neurological function. To elucidate the pathways that might contribute to revascularization during LVO, we applied transcriptomic analysis via unbiased RNA sequencing and showed that Wnt signaling was highly involved in FSAP mediated endothelial dysfunction. Notably, inhibition of Wnt5a largely reversed the protective effects from HMW-HA treatment, implying that FSAP might aggravate endothelial dysfunction and neurological deficits by regulating Wnt5a signaling. Therefore, FSAP may represent a potential biomarker for collateral status after LVO and a promising therapeutic target to be explored in the treatment of stroke.

2.
Nanomaterials (Basel) ; 12(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35010104

RESUMO

Copper thiocyanate (CuSCN) has been gradually utilized as the hole injection layer (HIL) within optoelectronic devices, owing to its high transparency in the visible range, moderate hole mobility, and desirable environmental stability. In this research, we demonstrate quantum dot light-emitting diodes (QLEDs) with high brightness and current efficiency by doping 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) in CuSCN as the HIL. The experimental results indicated a smoother surface of CuSCN upon F4TCNQ doping. The augmentation in hole mobility of CuSCN and carrier injection to reach balanced charge transport in QLEDs were confirmed. A maximum brightness of 169,230 cd m-2 and a current efficiency of 35.1 cd A-1 from the optimized device were received by adding 0.02 wt% of F4TCNQ in CuSCN, revealing promising use in light-emitting applications.

3.
Innovation (N Y) ; 3(1): 100191, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34977835

RESUMO

Doublecortin-like kinase 1 (DCLK1) is upregulated in many tumors and is a marker for tumor stem cells. Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy. However, the regulation of DCLK1 kinase activity is poorly understood, particularly the function of its autoinhibitory domain (AID), and, moreover, no physiological activators of DCLK1 have presently been reported. Here we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of DCLK1. The C-terminal AID functions to block the ATP-binding site and is competitive with ATP. HPCAL1 binds directly to the AID in a Ca2+-dependent manner, which releases the autoinhibition. We also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity upregulation. Our results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.

4.
Environ Pollut ; 292(Pt A): 118306, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34634401

RESUMO

Slaughter wastewater is an important and wide range of environmental issues, and even threaten human health through meat production. A high efficiency and stability microsphere-immobilized Bacillus velezensis strain was designed to remove organic matter and inhibit the growth of harmful bacteria in process of slaughter wastewater. Bacillus velezensis was immobilized on the surface of sodium alginate (SA)/Polyvinyl alcohol (PVA)/Nano Zinc Oxide (Nano-ZnO) microsphere with the adhesion to bio-carrier through direct physical adsorption. Results indicated that SA/PVA/ZnO and SA/ZnO microspheres could inhibit E.coli growth with adding 0.15 g/L nano-ZnO and not affect Bacillus velezensis strain, and the removal the chemical oxygen demand (COD) rates of SA/PVA/ZnO microsphere immobilized cells are 16.99%, followed by SA/ZnO (13.69%) and free bacteria (7.61%) from 50% concentration slaughter wastewater within 24 h at 37 °C, pH 7.0, and 120 rpm, a significant difference was found between the microsphere and control group. Moreover, when the processing time reaches 36 h, COD degradation of SA/PVA/ZnO microsphere is obviously higher than other groups (SA/PVA/ZnO:SA/ZnO:control vs 18.535 : 15.446: 10.812). Similar results were obtained from 30% concentration slaughter wastewater. Moreover, protein degradation assay was detected, and there are no significant difference (SA/PVA/ZnO:SA/ZnO:control vs 35.4 : 34.4: 36.0). The design of this strategy could greatly enhance the degradation efficiency, inhibit the growth of other bacteria and no effect on the activity of protease in slaughter wastewater. These findings suggested that the nano-ZnO hydrogel immobilization Bacillus velezensis system wastewater treatment is a valuable alternative method for the remediation of pollutants from slaughter wastewater with a novel and eco-friendly with low-cost investment as an advantage.


Assuntos
Óxido de Zinco , Bacillus , Humanos , Microesferas , Álcool de Polivinil , Águas Residuárias
5.
Mol Med Rep ; 25(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34738629

RESUMO

Modulating the biological status of endothelial progenitor cells (EPCs), such as function and survival, is essential for therapeutic angiogenesis in ischemic vascular disease environments. This study aimed to explore the role and molecular mechanisms underlying Netrin­1 in the viability and angiogenic function of EPCs. EPCs were isolated from the bone barrow of adult C57/BL6 mice. The apoptosis and various functions of EPCs were analyzed in vitro by manipulating the expression of Netrin­1. The TUNEL assay was performed to detect apoptotic EPCs. Cell migration and tube formation assays were performed to detect EPC function. Trypan blue staining was performed to detect cell viability. Western blot analysis was performed to detect the protein expression levels of Netrin­1, CD146 and apoptotic factors. Quantitative PCR analysis was performed to detect the expression levels of Netrin­1 receptors. The results demonstrated that treatment with exogenous Netrin­1 promoted EPC migration and tube formation, whereas transfection with small interfering (si)RNA targeting Netrin­1 exhibited the opposite effects. Exogenous Netrin­1 protected EPCs from hypoxia­induced apoptosis, whereas the interruption of endogenous Netrin­1 enhancement under hypoxia by Netrin­1­siRNA exacerbated the apoptosis of EPCs. Furthermore, CD146, one of the immunoglobulin receptors activated by Netrin­1, was screened for in the present study. Results demonstrated that CD146 did not participate in Netrin­1­promoted EPC function, but mediated the anti­apoptotic effects of Netrin­1 in EPCs. In conclusion, Netrin­1 enhanced the angiogenic function of EPCs and alleviated hypoxia­induced apoptosis, which was mediated by CD146. This biological function of Netrin­1 may provide a potential therapeutic option to promote EPCs for the treatment of ischemic vascular diseases.

6.
Gut ; 71(1): 176-184, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33408122

RESUMO

OBJECTIVE: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5. DESIGN: 191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR12) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed. RESULTS: The SVR12 rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR12 rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR12 rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR12 were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations. CONCLUSION: SOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Insuficiência Renal Crônica/complicações , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/classificação , Estudos Retrospectivos , Resposta Viral Sustentada , Adulto Jovem
7.
Sci Total Environ ; 806(Pt 2): 150705, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600988

RESUMO

In the coastal zones, numerous ecological shelterbelt projects were conducted to protect against natural hazards. However, it is still not fully understood whether phytoremediation with native legume Albizzia julibrissin plantation can improve saline soil structural development or microbial community structure. In this study, a field experiment was conducted to investigate the responses of rhizosphere soil salinity, nutrients, bacterial community, and aggregate structure to A. julibrissin plantation in a recently reclaimed area along Zhejiang coast, China. After ~3-year plantation, rhizosphere soil pH and EC reduced to 8.25 and 0.14 dS·m-1, respectively, belonging to non-saline soil. Meanwhile, total organic carbon (TOC), permanganate-oxidizable carbon (POXC), total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), and ammonium nitrogen (NH4+-N) were significantly increased in rhizosphere soil compared with bare land (P < 0.05). Consequently, rhizosphere soil had favorable habitat condition for copiotrophic bacterial taxa (e.g., Chloroflexi, Acidobacteria, and Bacteroidates), as well as high diversity, complex co-occurrence network, and catabolism related with nutrient cycling. The soil particle size of bare land was < 0.053 mm, while microaggregate (0.053-0.25 mm) and macroaggregate (0.25-2 mm) were formed in the rhizosphere and coupled with C accumulation and Fe removal. Soil aggregates were of great importance to soil fertility with more efficient bacterial network and biogeochemical cycles of nutrients. N-fixing Rhizobiales preferred to inhabit large soil particle and might primarily contribute to N accumulation. Generally, A. julibrissin was a suitable pioneer tree for mudflat reclamation projects, which effectively improved saline soil rhizosphere environment by reducing salinity, accumulating C and N, and promoting microbial community succession, as well as aggregate structure formation.


Assuntos
Albizzia , Fabaceae , Microbiota , Nitrogênio/análise , Nutrientes , Rizosfera , Solo , Microbiologia do Solo
8.
Zool Res ; 43(1): 40-51, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34821085

RESUMO

Mountain systems harbor an evolutionarily unique and exceptionally rich biodiversity, especially for amphibians. However, the associated elevational gradients and underlying mechanisms of amphibian diversity in most mountain systems remain poorly understood. Here, we explored amphibian phylogenetic and functional diversity along a 2 600 m elevational gradient on Mount Emei on the eastern margin of the Qinghai-Tibetan Plateau in southwestern China. We also assessed the relative importance of spatial (area) and environmental factors (temperature, precipitation, solar radiation, normalized difference vegetation index, and potential evapotranspiration) in shaping amphibian distribution and community structure. Results showed that the phylogenetic and functional diversities were unimodal with elevation, while the standardized effect size of phylogenetic and functional diversity increased linearly with elevation. Phylogenetic net relatedness, nearest taxon index, and functional net relatedness index all showed a positive to negative trend with elevation, indicating a shift from clustering to overdispersion and suggesting a potential change in key processes from environmental filtering to competitive exclusion. Overall, our results illustrate the importance of deterministic processes in structuring amphibian communities in subtropical mountains, with the dominant role potentially switching with elevation. This study provides insights into the underlying assembly mechanisms of mountain amphibians, integrating multidimensional diversity.


Assuntos
Altitude , Anfíbios , Distribuição Animal , Biodiversidade , Filogenia , Animais , China , Tibet
9.
New Phytol ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34854082

RESUMO

CaWRKY40 in pepper (Capsicum annuum) promotes immune responses to Ralstonia solanacearum infection (RSI) and to high-temperature, high-humidity (HTHH) stress, but how it interacts with upstream signaling components remains poorly understood. Herein, using approaches of reverse genetics, biochemical and molecular biology we functionally characterized the relationships among the WRKYGMK-containing WRKY protein CaWRKY27b, the calcium-dependent protein kinase CaCDPK29, and CaWRKY40 during pepper response to RSI or HTHH. Our data indicate that CaWRKY27b is upregulated and translocated from cytoplasm to the nucleus upon phosphorylation of Ser137 in the NLS by CaCDPK29. Using electrophoretic mobility shift assays and microscale thermophoresis, we observed that, due to the replacement of Q by M in the conserved WRKYGQK, CaWRKY27b in the nucleus failed to bind to W-boxes in the promoters of immunity- and thermotolerance-related marker genes. Instead, CaWRKY27B interacted with CaWRKY40 and promoted its binding and positive regulation of the tested marker genes including CaNPR1, CaDEF1 and CaHSP24. Notably, mutation of the WRKYGMK motif in CaWRKY27b to WRKYGQK restored the W-box binding ability. Our data thus suggest that CaWRKY27b is phosphorylated by CaCDPK29 and acts as transcriptional activator of CaWRKY40 during pepper response to RSI and HTHH.

10.
CRISPR J ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847728

RESUMO

The CRISPR-associated transposase system enables site-specific DNA integration on the genome independent of homologous recombination. Previous studies have demonstrated that the type V-K CRISPR-associated Tn7-like transposase system from Scytonema hofmanni and the type I-F system from Vibrio cholerae have strong target immunity like Tn7, and therefore two or more copies of the donor DNA would not be inserted into the same target location in theory. In this paper, we report that the type I-F system can insert multiple donor copies into one site, which was identified and confirmed by single-strain identification and high-throughput sequencing. This result is beneficial for our application of multicopy chromosomal integration by CRISPR-associated transposases, allowing more donor insertions into the chromosome. This unexpected result shows that the target immunity mechanism of this system has not been fully understood. Attention should be paid to the possibility of multiple insertions and their effects in related research.

11.
Sci Rep ; 11(1): 23473, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873250

RESUMO

The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

12.
Polymers (Basel) ; 13(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883773

RESUMO

The high price of petroleum, overconsumption of plastic products, recent climate change regulations, the lack of landfill spaces in addition to the ever-growing population are considered the driving forces for introducing sustainable biodegradable solutions for greener environment. Due to the harmful impact of petroleum waste plastics on human health, environment and ecosystems, societies have been moving towards the adoption of biodegradable natural based polymers whose conversion and consumption are environmentally friendly. Therefore, biodegradable biobased polymers such as poly(lactic acid) (PLA) and polyhydroxyalkanoates (PHAs) have gained a significant amount of attention in recent years. Nonetheless, some of the vital limitations to the broader use of these biopolymers are that they are less flexible and have less impact resistance when compared to petroleum-based plastics (e.g., polypropylene (PP), high-density polyethylene (HDPE) and polystyrene (PS)). Recent advances have shown that with appropriate modification methods-plasticizers and fillers, polymer blends and nanocomposites, such limitations of both polymers can be overcome. This work is meant to widen the applicability of both polymers by reviewing the available materials on these methods and their impacts with a focus on the mechanical properties. This literature investigation leads to the conclusion that both PLA and PHAs show strong candidacy in expanding their utilizations to potentially substitute petroleum-based plastics in various applications, including but not limited to, food, active packaging, surgical implants, dental, drug delivery, biomedical as well as antistatic and flame retardants applications.

13.
J Pharm Biomed Anal ; 209: 114515, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34894461

RESUMO

Toripalimab, a humanized IgG4 monoclonal antibody (mAb) against programmed death receptor-1, is being extensively studied to treat various malignancies. At present, there is no complete methodology reported for quantifying toripalimab, except for an electrochemiluminescence immunoassay (ECLIA) mentioned in several clinical studies. Therefore, a sensitive and robust ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to accurately detect toripalimab levels, compared with the ECLIA. Plasma samples were pretreated by a five-step process, encompassing denaturation, reduction, alkylation, enzymatic hydrolysis and quenching. And a unique, sensitive and stable enzymatic peptide (ASGYTFTDYEMHWVR) selected as surrogate of toripalimab was eluted and monitored by UPLC-MS/MS system with the linear range of 5.0375-201.5 µg/mL. After fully validated, the UPLC-MS/MS method was applied to determine 77 plasma samples from 29 patients in a phase I clinical trial, and compared with ECLIA based on 56 samples. Wilcoxon paired samples test showed toripalimab levels by UPLC-MS/MS were significantly higher than that by ECLIA (p < 0.001), though a strong correlation was observed (r = 0.96). Moreover, Passing-Bablok regression analysis exhibited constant and proportional biases: UPLC-MS/MS = 2.25 + 1.21 * ECLIA. This discrepancy could be mainly attributed to different forms determined: total mAb for UPLC-MS/MS and free mAb for ECLIA, respectively. As a result, this UPLC-MS/MS method may be complementary to ECLIA to monitor different forms of toripalimab. Beyond that, it can be easily modified to simultaneously quantitate multiple-analyte with a small volume of plasma.

14.
J Endocrinol Invest ; 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34865184

RESUMO

PURPOSE: Primary thyroid lymphoma (PTL) is a rare malignancy, and the literature is limited to small case series and case reports. This study aimed to assess the epidemiologic characteristics, survival, and prognostic factors of patients with PTL. METHODS: We analyzed 2215 PTL patients from the Surveillance, Epidemiology, and End Results database medical records, between 1983 and 2015, as the training cohort. We enrolled 105 patients from the Cancer Hospital, Chinese Academy of Medical Sciences, for the external validation cohort. The nomograms for predicting the 1-, 5-, and 10-year overall survival (OS) and lymphoma-specific survival (LSS) were constructed. RESULTS: PTL incidence steadily increased from 1977 to 1994, with an annual percentage change of 3.2% (95% confidence interval [CI]: 1.2-5.2, P < 0.05). The 1-, 5-, and 10-year OS and LSS rates were 84.66%, 71.61%, and 55.95%; and 90.5%, 85.7%, and 82.2%, respectively. Multivariate Cox regression analysis revealed that shorter OS association with age ≥ 60 years (hazard ratio [HR], 3.94; 95% CI 3.31-4.69; P < 0.001), unmarried status (HR, 1.55; 95% CI 1.37-1.75; P < 0.001), Ann Arbor stage III-IV (HR, 1.55; 95% CI 1.37-1.75; P = 0.020), diffuse large B-cell lymphoma (HR, 2.60; 95% CI 1.15-5.87; P = 0.022), and T cell non-Hodgkin lymphoma (HR, 3.53; 95% CI 1.12-11.10; P = 0.031). In the multivariate competing-risk analyzes, age, stages III-IV, year of diagnosis, surgery, radiation, chemotherapy, and histology were strongly predictive of PTL-specific risk of death. To estimate the 1-, 5-, and 10-year LSS and OS rates, respectively, nomograms were built. In the validation cohort, the results also confirmed the utility. CONCLUSIONS: This study presents the first prognostic model with an external validation that could help clinicians identify patients with high-risk PTL to improve their prognosis.

15.
Front Physiol ; 12: 740728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955875

RESUMO

In recent decade, pedelec has become one of the most popular transportation modes due to its effectiveness in reducing physical effort. The effects of using pedelec as an alternative mode of exercise were explored in previous studies. However, the effects of pedelec parameters were not quantified for the self-selected gear ratio, random riding speed, and varied road slopes, which restricted its application. Hence, this study aimed to evaluate the effects of gear ratio and assistive torque and to determine the optimum riding condition regarding physiological, biomechanical, and subjective responses of the rider. The riding tests consisted of simulated slope (1.0 vs. 2.5% grade), gear ratio (light vs. heavy), and assistive levels (0.5, 1, 1.5, and 2), and the tests were conducted in a randomized order. A total of 19 non-athletes completed the riding tests to evaluate physiological [metabolic equivalent of task (MET), heart rate, and gross efficiency (GE)], biomechanical [muscle activity (expressed as reference voluntary contraction, RVC) and power output], and subjective responses [rating of perceived exertion (RPE) and sense of comfort (SC)]. The test conditions induced moderate to vigorous intensities (3.7-7.4 METs, 58.5-80.3% of maximal heart rate, 11.1-29.5% of RVC rectus femoris activity, and 9.4-14.2 RPEs). The effects of gear ratio and assistive level on the physiological responses were significant. Riding with the heavy gear ratio showed advantages in METs and GE. For the optimum assistive level selection, low GE and limited improvement in subjective responses suggested the impact of low-power output conditions. Overall, for the health pedelec commuters, riding with 0.75 W/kg power output with 50 rpm cadence is recommended to obtain the moderate intensity (4.7 METs) and the advantages in GE and subjective feelings. Moreover, the findings can be applied to exercise intensity control and save battery energy effectively in varying riding conditions.

16.
Front Genet ; 12: 791778, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956333

RESUMO

Background: Primary biliary cholangitis (PBC) is an autoimmune disease and is often accompanied by thyroid dysfunction. Understanding the potential causal relationship between PBC and thyroid dysfunction is helpful to explore the pathogenesis of PBC and to develop strategies for the prevention and treatment of PBC and its complications. Methods: We used a two-sample Mendelian randomization (MR) method to estimate the potential causal effect of PBC on the risk of autoimmune thyroid disease (AITD), thyroid-stimulating hormone (TSH) and free thyroxine (FT4), hyperthyroidism, hypothyroidism, and thyroid cancer (TC) in the European population. We collected seven datasets of PBC and related traits to perform a series MR analysis and performed extensive sensitivity analyses to ensure the reliability of our results. Results: Using a sensitivity analysis, we found that PBC was a risk factor for AITD, TSH, hypothyroidism, and TC with odds ratio (OR) of 1.002 (95% CI: 1.000-1.005, p = 0.042), 1.016 (95% CI: 1.006-1.027, p = 0.002), 1.068 (95% CI: 1.022-1.115, p = 0.003), and 1.106 (95% CI: 1.019-1.120, p = 0.042), respectively. Interestingly, using reverse-direction MR analysis, we also found that AITD had a significant potential causal association with PBC with an OR of 0.021 (p = 5.10E-4) and that the other two had no significant causal relation on PBC. Conclusion: PBC causes thyroid dysfunction, specifically as AITD, mild hypothyroidism, and TC. The potential causal relationship between PBC and thyroid dysfunction provides a new direction for the etiology of PBC.

17.
PLoS Genet ; 17(12): e1009962, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34905536

RESUMO

TM2 domain containing (TM2D) proteins are conserved in metazoans and encoded by three separate genes in each model organism species that has been sequenced. Rare variants in TM2D3 are associated with Alzheimer's disease (AD) and its fly ortholog almondex is required for embryonic Notch signaling. However, the functions of this gene family remain elusive. We knocked-out all three TM2D genes (almondex, CG11103/amaretto, CG10795/biscotti) in Drosophila and found that they share the same maternal-effect neurogenic defect. Triple null animals are not phenotypically worse than single nulls, suggesting these genes function together. Overexpression of the most conserved region of the TM2D proteins acts as a potent inhibitor of Notch signaling at the γ-secretase cleavage step. Lastly, Almondex is detected in the brain and its loss causes shortened lifespan accompanied by progressive motor and electrophysiological defects. The functional links between all three TM2D genes are likely to be evolutionarily conserved, suggesting that this entire gene family may be involved in AD.

18.
Biom J ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34914842

RESUMO

Zeros in compositional data are very common and can be classified into rounded and essential zeros. The rounded zero refers to a small proportion or below detection limit value, while the essential zero refers to the complete absence of the component in the composition. In this article, we propose a new framework for analyzing compositional data with zero entries by introducing a stochastic representation. In particular, a new distribution, namely the Dirichlet composition distribution, is developed to accommodate the possible essential-zero feature in compositional data. We derive its distributional properties (e.g., its moments). The calculation of maximum likelihood estimates via the Expectation-Maximization (EM) algorithm will be proposed. The regression model based on the new Dirichlet composition distribution will be considered. Simulation studies are conducted to evaluate the performance of the proposed methodologies. Finally, our method is employed to analyze a dataset of fluorescence in situ hybridization (FISH) for chromosome detection.

19.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6149-6162, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951242

RESUMO

R2 R3-MYB transcription factors are ubiquitous in plants, playing a role in the regulation of plant growth, development, and secondary metabolism. In this paper, the R2 R3-MYB transcription factors were identified by bioinformatics analysis of the genomic data of Erigeron breviscapus, and their gene sequences, structures, physical and chemical properties were analyzed. The functions of R2 R3-MYB transcription factors were predicted by cluster analysis. Meanwhile, the expression patterns of R2 R3-MYB transcription factors in response to hormone treatments were analyzed. A total of 108 R2 R3-MYB transcription factors, named EbMYB1-EbMYB108, were identified from the genome of E. breviscapus. Most of the R2 R3-MYB genes carried 2-4 exons. The phylogenetic tree of MYBs in E. breviscapus and Arabidopsis thaliala was constructed, which classified 234 MYBs into 30 subfamilies. The MYBs in the five MYB subfamilies of A.thaliala were clustered into independent clades, and those in E. breviscapus were clustered into four clades. The transcriptome data showed that MYB genes were differentially expressed in different tissues of E. breviscapus and in response to the treatments with exogenous hormones such as ABA, SA, and GA for different time. The transcription of 13 R2 R3-MYB genes did not change significantly, and the expression patterns of some genes were up-regulated or down-regulated with the extension of hormone treatment time. This study provides a theoretical basis for revealing the mechanisms of R2 R3-MYB transcription factors in regulating the growth and development, stress(hormone) response, and active ingredient accumulation in E. breviscapus.


Assuntos
Erigeron , Genes myb , Proteínas de Plantas , Fatores de Transcrição , Erigeron/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Small Methods ; 5(8): e2100234, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34927876

RESUMO

Single-crystal nickel-rich cathode materials (SC-NRCMs) are the most promising candidates for next-generation power batteries which enable longer driving range and reliable safety. In this review, the outstanding advantages of SC-NRCMs are discussed systematically in aspects of structural and thermal stabilities. Particularly, the intergranular-crack-free morphology exhibits superior cycling performance and negligible parasitic reactions even under severe conditions. Besides, various synthetic methods are summarized and the relation between precursor, sintering process, and final single-crystal products are revealed, providing a full view of synthetic methods. Then, challenges of SC-NRCMs in fields of kinetics of lithium diffusion and the one particularly occurred at high voltage (intragranular cracks and aggravated parasitic reactions) are discussed. The corresponding mechanism and modifications are also referred. Through this review, it is aimed to highlight the magical morphology of SC-NRCMs for application perspective and provide a reference for following researchers.

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