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1.
Nat Commun ; 12(1): 1341, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637716

RESUMO

Hypoxia-inducible factor-1 (HIF-1) is a master driver of glucose metabolism in cancer cells. Here, we demonstrate that a HIF-1α anti-sense lncRNA, HIFAL, is essential for maintaining and enhancing HIF-1α-mediated transactivation and glycolysis. Mechanistically, HIFAL recruits prolyl hydroxylase 3 (PHD3) to pyruvate kinase 2 (PKM2) to induce its prolyl hydroxylation and introduces the PKM2/PHD3 complex into the nucleus via binding with heterogeneous nuclear ribonucleoprotein F (hnRNPF) to enhance HIF-1α transactivation. Reciprocally, HIF-1α induces HIFAL transcription, which forms a positive feed-forward loop to maintain the transactivation activity of HIF-1α. Clinically, high HIFAL expression is associated with aggressive breast cancer phenotype and poor patient outcome. Furthermore, HIFAL overexpression promotes tumor growth in vivo, while targeting both HIFAL and HIF-1α significantly reduces their effect on cancer growth. Overall, our results indicate a critical regulatory role of HIFAL in HIF-1α-driven transactivation and glycolysis, identifying HIFAL as a therapeutic target for cancer treatment.

2.
Biosci Rep ; 41(3)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33605406

RESUMO

Acute radiation injury caused by high-dose radiation exposure severely impedes the application of radiotherapy in cancer management. To deeply understand the side effects of radiation on intestinal tract, an irradiation murine model was applied and evaluated. C57BL/6 mice were given 4 Gy non-myeloablative irradiation, 8 Gy myeloablative irradiation and non-irradiation (control), respectively. Results demonstrated that the 8 Gy myeloablative irradiations significantly damaged the gut barrier along with decreasing MECA32 and ZO-1. However, a slight increase in MECA32 and ZO-1 was detected in the 4 Gy non-myeloablative irradiations treatment from day 5 to day 10. Further, the irradiations affected the expression of P38 and JNK mitogen-activated protein kinase (MAPK) but not ERK1/2 MAPK signal pathway. Moreover, irradiation had adverse effects on hematopoietic system, altered the numbers and percentages of intestinal inflammatory cells. The IL-17/AhR had big increase in the gut of 4 Gy irradiation mice at day 10 compared with other groups. Both 8 Gy myeloablative and 4 Gy non-myeloablative irradiation disturbed the levels of short-chain fatty acids (SCFAs) in intestine. Meanwhile, high dosage of irradiation decreased the intestinal bacterial diversity and altered the community composition. Importantly, the fatty acids generating bacteria Bacteroidaceae and Ruminococcaceae played key roles in community distribution and SCFAs metabolism after irradiation. Collectively, the irradiation induced gut barrier damage with dosages dependent that led to the decreased p38 MAPK and increased JNK MAPK, unbalanced the mononuclear cells (MNCs) of gut, disturbed intestinal bacterial community and SCFAs level.

3.
Biomed Res Int ; 2021: 6638915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628799

RESUMO

Background: A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. Methods: The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. Results: QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues (P < 0.0001). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion (P < 0.05), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion (P < 0.05). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan-Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004) and overall survival (OS) times (P = 0.010) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS (P = 0.004) and OS times (P = 0.014) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

4.
Clin Rheumatol ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538925

RESUMO

OBJECTIVES: The objective was to identify the comorbidities of gout, to compare gender difference and independent factors of frequent gout attacks (> 20 times). METHOD: Demographic, clinical variables, self-reported comorbidities, and biochemical variables (i.e., initial serum uric acid (UA) and UA at visit) were collected in this cross-sectional study. Gout attack times were recorded as ≤ 5, 6-10, 11-20, and > 20. Adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to explore the association between selected risk factors and frequent gout attacks. RESULTS: Six hundred fifty-three gout patients with a mean age of 48.3 ± 15.8 years were included, 84.7% of whom were males. The median gout duration was 6.0 (3.0-12.0) years. The most common comorbidities involved hypertension (166, 25.4%), coronary artery disease (CAD) (67, 10.3%), chronic kidney disease (66, 10.1%), and hyperlipidemia (57, 8.7%). Abnormalities including nephrolithiasis (29.4%), hydronephrosis (3.2%), and gallstones (11.9%) were also found. Although female patients had a longer disease duration and more CAD, they had a lower level of UA, creatine, and C-reactive protein (CRP) but higher high-density lipoprotein cholesterol (HDL-C) (p < 0.05). A positive correlation between UA and triglycerides was found in females (p = 0.039). Patients with renal insufficiency or nephrolithiasis had longer disease duration and more gout attacks (p < 0.001). In multivariable regression analysis, only gout duration (OR = 7.89, p < 0.001) and UA (OR = 1.48, p < 0.001) was independent factors of frequent gout attacks. CONCLUSIONS: Comorbidity screening involving dyslipidemia is often neglected in gout patients. Gout duration and UA are the risk factors of frequent gout attacks. Key Points • Comorbidities can be overlooked if the screening for lipid levels, cardiovascular disease, and kidney disease is not completed. • There are differences in comorbidities and biochemical findings between male and female patients with gout. • Gout duration and serum uric acid level are independent risk factors of frequent gout attacks.

5.
Can J Ophthalmol ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33485841

RESUMO

OBJECTIVE: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China. METHODS: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed. RESULTS: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes. CONCLUSION: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33395249

RESUMO

It is difficult to achieve higher energy density with the existing system of lithium (Li)-ion batteries. As a powerful candidate, Li metal batteries are in the renaissance. Unfortunately, the uncontrolled growth process of Li dendrites has limited their actual application. Hence, inhibiting the formation and spread of Li dendrites has become an enormous challenge. Herein, a novel composite separator is developed with functionalized boron nitride nanosheet modification layer as a Li-ion regulator to regulate Li-ion fluxes. The composite separator contains abundant polar groups and nanoscale channels and could achieve uniform electrochemical deposition via the lithiophilic effect and shunting action. Under the synergy influence of the lithiophilic effect and shunting action, Li dendrites are effectively suppressed. As proof, the Li||Li symmetrical cells with composite separators can circulate steadily for a long time under high current densities (10 mA cm-2, 800 h). Moreover, the LiFePO4||Li full cells display excellent long cycling performance (82% retention after 800 cycles).

7.
Nucleic Acids Res ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33434272

RESUMO

Multiple driver genes in individual patient samples may cause resistance to individual drugs in precision medicine. However, current computational methods have not studied how to fill the gap between personalized driver gene identification and combinatorial drug discovery for individual patients. Here, we developed a novel structural network controllability-based personalized driver genes and combinatorial drug identification algorithm (CPGD), aiming to identify combinatorial drugs for an individual patient by targeting personalized driver genes from network controllability perspective. On two benchmark disease datasets (i.e. breast cancer and lung cancer datasets), performance of CPGD is superior to that of other state-of-the-art driver gene-focus methods in terms of discovery rate among prior-known clinical efficacious combinatorial drugs. Especially on breast cancer dataset, CPGD evaluated synergistic effect of pairwise drug combinations by measuring synergistic effect of their corresponding personalized driver gene modules, which are affected by a given targeting personalized driver gene set of drugs. The results showed that CPGD performs better than existing synergistic combinatorial strategies in identifying clinical efficacious paired combinatorial drugs. Furthermore, CPGD enhanced cancer subtyping by computationally providing personalized side effect signatures for individual patients. In addition, CPGD identified 90 drug combinations candidates from SARS-COV2 dataset as potential drug repurposing candidates for recently spreading COVID-19.

8.
Int J Biol Macromol ; 171: 17-27, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33412196

RESUMO

Herein, an effective adsorbent, 3D porous tubular network-structured citric acid-chitosan/Fe/polyethyleneimine beads (CCFPB) with multifunctional active groups and strong selectivity, was prepared for the selective removal of Cu2+ from simulated wastewater. Compared with pure chitosan beads (CB), the adsorption capacity of CCFPB for Cu2+ was increased by 127 mg g-1 (238%), and the adsorption equilibrium time was shortened by 480 min. The CCFPB showed porous surface and a novel 3D porous tubular network structure in interior, which were benefit to the diffusion of Cu2+ from surface to interior of the CCFPB and the shortening of adsorption equilibrium time. The common coexisting ions in the simulated wastewater had almost no effect on the adsorption of Cu2+ by CCFPB, and the adsorption was fast and reached equilibrium within 10 h. The adsorption process followed pseudo-second-order kinetics and the Langmuir isotherm model (qm = 240.9 mg g-1 for Cu2+). The adsorption mechanism of CCFPB for Cu2+ was mainly the synergistic interaction with amino, carboxyl, and hydroxyl groups. This strategy shows great potential for developing a variety of novel, highly active, and reusable immobilized functional beads materials for effective separation of Cu2+ from multi-ion wastewater.

9.
J Exp Clin Cancer Res ; 40(1): 47, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509226

RESUMO

BACKGROUND: Phosphatidylinositol-4-phosphate-binding protein GOLPH3L is overexpressed in human ductal carcinoma of the breast, and its expression levels correlate with the prognosis of breast cancer patients. However, the roles of GOLPH3L in breast tumorigenesis remain unclear. METHODS: We assessed the expression and biological function of GOLPH3L in breast cancer by combining bioinformatic prediction, metabolomics analysis and RNA-seq to determine the GOLPH3L-related pathways involved in tumorigenesis. Dual-luciferase reporter assay and coimmunoprecipitation (Co-IP) were used to explore the expression regulation mechanism of GOLPH3L. RESULTS: We demonstrated that knockdown of GOLPH3L in human breast cancer cells significantly suppressed their proliferation, survival, and migration and suppressed tumor growth in vivo, while overexpression of GOLPH3L promoted aggressive tumorigenic activities. We found that miRNA-1185-2-3p, the expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, is directly involved in suppressing the expression of GOLPH3L. Metabolomics microarray analysis and transcriptome sequencing analysis revealed that GOLPH3L promotes central carbon metabolism in breast cancer by stabilizing the p53 suppressor SERPINE1. CONCLUSIONS: In summary, we discovered a miRNA-GOLPH3L-SERPINE1 pathway that plays important roles in the metabolism of breast cancer and provides new therapeutic targets for human breast cancer.

10.
Carbohydr Polym ; 256: 117556, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33483059

RESUMO

Acute kidney injury (AKI) is a common and serious clinical syndrome of acute renal dysfunction in a short period. One of therapeutic interventions for AKI is to reduce ROS massively generated in the mitochondria and then ameliorate cell damage and apoptosis induced by oxidative stress. In this study, stepwise-targeting chitosan oligosaccharide, triphenyl phosphine-low molecular weight chitosan-curcumin (TPP-LMWC-CUR, TLC), was constructed for sepsis-induced AKI via removing excessive ROS in renal tubular epithelial cells. Benefiting from good water solubility and low molecular weight, TLC was rapidly and preferentially distributed in the renal tissues and then specifically internalized by tubular epithelium cells via interaction between Megalin receptor and LMWC. The intracellular TLC could further delivery CUR to mitochondria due to high buffering capacity of LMWC and delocalized positive charges of TPP. Both in vitro and in vivo pharmacodynamic results demonstrated the enhanced therapeutic effect of TLC in the treatment of AKI.

11.
Immunology ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33421118

RESUMO

Dendritic cells (DCs) play an important role in linking innate and adaptive immunity. DCs can sense endogenous and exogenous antigens and present those antigens to T cells to induce an immune response or immune tolerance. During activation, alternative splicing (AS) in DCs is dramatically changed to induce cytokine secretion and upregulation of surface marker expression. PTBP1, an RNA-binding protein, is essential in alternative splicing, but the function of PTBP1 in DCs is unknown. Here, we found that a specific deficiency of Ptbp1 in DCs could increase MHC II expression and perturb T-cell homeostasis without affecting DC development. Functionally, Ptbp1 deletion in DCs could enhance antitumour immunity and asthma exacerbation. Mechanistically, we found that Pkm alternative splicing and a subset of Ifn response genes could be regulated by PTBP1. These findings revealed the function of PTBP1 in DCs and indicated that PTBP1 might be a novel therapeutic target for antitumour treatment.

12.
J Dermatolog Treat ; 32(1): 90-94, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31084382

RESUMO

Background: Vitiligo is an acquired depigmentation skin disorder mainly caused by the destruction of melanocytes. There are many therapeutic options available for vitiligo, but the options are not uniformly effective.Objectives: This study aimed to explore the clinical effect of the autologous non-cultured epidermal cell suspension (NCES) technique in the treatment of patients with stable vitiligo.Methods: A retrospective study of before-after comparisons was undertaken with 41 patients with stable vitiligo who received treatment with the NCES technique. The percentage of repigmentation area was evaluated using image analysis of the appearance before and 6-9 months after operation.Results: A total of 41 patients (18 males and 23 females) with a duration of clinical stability for ranging from 1 to 10 years (mean 1.6 ± 1.9) were included. The mean age was 20.2 years (range, 8-50) and 4 (9.8%) were children under the age of 14 years. After 6-9 months of follow-up, 80.5% (33/41) of the patients showed good response; among these patients, 17.1% (7/41) showed complete or almost complete repigmentation. Interestingly, all 4 children showed very good response (more than 76% repigmentation). There were no significant differences in the efficacy of treatment between the different transplantation areas of the facial neck, trunk, and distal limbs and there were no adverse effects such as infection or scar formation.Limitation: This study included only a single center with a small sample size.Conclusions: Our study shows that the NCES technique has a high therapeutic effect, is safe for patients with stable vitiligo, and may be a very promising potential option for treating children.


Assuntos
Células Epidérmicas/transplante , Vitiligo/terapia , Adolescente , Adulto , Criança , Células Epidérmicas/citologia , Extremidades/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Estudos Retrospectivos , Tronco/patologia , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
13.
J Environ Manage ; 278(Pt 1): 111518, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33113397

RESUMO

Nowadays, nanoscale zero valent iron (nZVI) has been extensively applied for the decontamination of various pollutants, but passivation of nZVI severely affects its reactivity in use. In this study, ultrasound (US)-assisted catalytic reduction of Cr(VI) by an acid mine drainage based nZVI (AMD-nZVI) coupling with FeS2 system was systematically examined. Results show that the presence of FeS2 and US induced a synergistic enhancement of Cr(VI) removal by AMD-nZVI. Nearly 98% of Cr(VI) removal was achieved by AMD-nZVI/FeS2/US process within 60 min under optimal reaction conditions. Several coexisting substances with lower concentration including Pb(II), Ni(II), bisphenol A (BPA) and 2,4-diclorophenol (2,4-DCP) could be effectively removed in simultaneous manner with Cr(VI) removal. The inhibitory order of water matrix species on Cr(VI) removal was NO3- > PO43- > HCO3- > Ca2+ > Mg2+ > Cl-, and a serious suppression effect was induced by humic acid (HA). Addition of ethylene diamine tetra-acetic acid (EDTA) and citric acid (CA) could enhance Cr(VI) removal rate. An enhanced reaction mechanism was proposed, which involved the regeneration of more Fe2+ and H+ by AMD-nZVI/FeS2/US process, leading to the reduction of Cr(VI) by AMD-nZVI and FeS2 into Cr(III) species inculding Cr2O3 and Cr(OH)3. This study well demonstrates that AMD-nZVI/FeS2/US process is considered as a potential candidate for the remediation of Cr(VI) in real wasterwater.


Assuntos
Ferro , Poluentes Químicos da Água , Ácidos , Adsorção , Cromo/análise , Água , Poluentes Químicos da Água/análise
14.
Addict Biol ; 26(1): e12875, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031744

RESUMO

The development of opioid addiction involves DNA methylation. Accordingly, the DNA demethylation, induced by ten-eleven translocation (Tet) enzymes, may represent a novel approach to prevent opioid addiction. The present study examined the role of TET1 and TET3 in the development of morphine-seeking behavior in rats. We showed that 1 day of morphine self-administration (SA) training upregulated TET3 but not TET1 expression in the hippocampal CA1. With 7 days of morphine SA training, the expression of TET3 in the CA1 returned to the baseline level, while the TET1 expression was downregulated. No change of TET1 and TET3 in the nucleus accumbens shell was observed in morphine SA trained rats, or in the yoked morphine rats, or in rats trained for saccharin SA. Furthermore, we found that knocking down TET3 expression in the CA1 accelerated the acquisition of morphine SA, while overexpression of the catalytic domain of TET1 in the CA1 attenuated the acquisition. Together, these findings suggest that TET1 and TET3 in the CA1 are important epigenetic modulators involved in the morphine-seeking behavior and provide a new strategy in the treatment of opioid addiction.

15.
Sci Rep ; 10(1): 20902, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262384

RESUMO

We aimed to evaluate the application of external beam radiotherapy (EBRT) combined with californium-252 (252Cf) neutron intraluminal brachytherapy (NBT) in patients with local recurrent esophageal cancer after definitive chemoradiotherapy (CRT). Sixty-two patients with local recurrent esophageal squamous cell carcinoma after definitive CRT were retrospectively analyzed; 31 patients underwent NBT+EBRT, and 31 received EBRT alone. The response rate; 1-, 2-, and 3-year overall survival rates; and adverse event occurrence rates were compared between these two patient groups. The response rate was 83.87% (26/31) in the NBT+EBRT group and 67.74% (21/31) in the EBRT group (p < 0.001). The 1-, 2-, and 3-year overall survival rates were 80.6%, 32.3%, and 6.5%, respectively, in the EBRT group, with a median survival time of 18 months. The 1-, 2-, and 3-year overall survival rates were 83.8%, 41.9%, and 6.9%, respectively, in the NBT+EBRT group, with a median survival time of 19 months. The differences between the groups were not significant (p = 0.352). Regarding acute toxicity, no incidences of fistula or massive bleeding were observed during the treatment period. The incidences of severe and late complications were not significantly different between the two groups (p = 0.080). However, the causes of death for all patients differed between the groups. Our data indicate that 252Cf-NBT+EBRT produces favorable local control for patients with local recurrent esophageal cancer after CRT, with tolerable side effects.

16.
Ying Yong Sheng Tai Xue Bao ; 31(9): 3187-3193, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345520

RESUMO

To understand the status and dynamics of macrozoobenthos community in Sanmen Bay, we collected benthos samples by Agassiz trawl in November 2015, and February, May and August in 2016. The results showed that: 1) A total of 119 macrozoobenthos species were recorded, with main groups of fishes, crustaceans and molluscs, accounting for 79% of the total number of species. 2) The dominant species of macrozoobenthos throughout the year were Leptochela gracilis, Hyperacanthomysis longirostris and Amblychaeturichthys hexanema. The identity of dominant species changed significantly in different seasons. 3) The annual average biomass and density were 0.025 g·m-2 and 0.07 ind·m-2, respectively. 4) The Shannon's diversity index of macrozoobenthos in Sanmen Bay varied from 2.21 to 3.18, the Margalef's species richness index varied from 3.25 to 3.78, and the Pielou's evenness index varied from 0.53 to 0.79. Results from abundance-biomass curve analysis showed that the community was moderately disturbed in spring and winter, and slightly disturbed in summer and autumn. Results from Canonical correspondence analysis showed that water depth, temperature, salinity, and pH were the most important environmental factors affecting macrozoobenthos community.


Assuntos
Baías , Moluscos , Animais , Biodiversidade , China , Ecossistema , Peixes , Estações do Ano
17.
Artigo em Inglês | MEDLINE | ID: mdl-33331866

RESUMO

OBJECTIVE: Anti-Ro52 antibody often co-occurs with anti-Jo1 antibody in antisynthetase syndrome and their co-occurrence correlates with a more aggressive clinical phenotype and poorer prognosis. The strong association of anti-Ro52 antibody with anti-melanoma differentiation-associated protein-5 (anti-MDA5) antibody has been indicated in juvenile myositis. The aim of this study was to assess the clinical significance of anti-Ro52 antibody in a cohort of adult patients with anti-MDA5-positive clinically amyopathic dermatomyositis with interstitial lung disease (CADM-ILD). METHODS: We assessed a cohort of 83 consecutive patients with anti-MDA5-positive CADM-ILD. Anti-MDA5 antibodies and anti-Ro52 antibodies were detected in immunoblotting and semi-quantitatively analysed by densitometry. Clinical features and the 24 month survival were compared between anti-MDA5-positive patients with and without anti-Ro52 antibodies. RESULTS: Anti-Ro52 antibodies were found in 74.7% of anti-MDA5-positive CADM-ILD patients and were associated with an increased frequency of rapidly progressive interstitial lung disease (RP-ILD; 54.8% vs 23.8%; P = 0.014) and cutaneous ulcerations (27.4% vs 4.8%; P = 0.033). The cumulative 24 month survival rate tended to be lower in patients with anti-Ro52 antibodies than patients without (59.9% vs 85.7%; P = 0.051). The combination of anti-Ro52 antibody status and anti-MDA5 antibody levels further stratified patients' survival rates, showing that the survival rate of patients who were dual positive for anti-MDA5 antibody and anti-Ro52 antibody was significantly lower than patients with mild positive anti-MDA5 antibody alone (59.9% vs 100%; P = 0.019). CONCLUSION: Anti-Ro52 antibody is highly prevalent in anti-MDA5-positive CADM-ILD patients and their coexistence correlates with a subgroup of patients with more aggressive phenotypes. The combination of anti-MDA5 antibody levels and anti-Ro52 antibody status could help to predict patients' prognosis and guide risk-based therapy.

18.
Small ; : e2005433, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230977

RESUMO

The ideal bone repair material should firstly recognize and recruit osteoblast precursor cells to initiate the repair process, then promote the differentiation of osteoblasts and accelerate the mineralization of the extracellular matrix (ECM). Here, a bioinspired staged bone regeneration strategy which loads bone morphogenetic protein2 (BMP2 )-modified black phosphorus (BP@BMP2 ) nanosheets to a polylactic acid (PLLA) electrospun fibrous scaffold, with a combination of recruiting osteoblast precursor cells and biomineralization properties for bone regeneration, is constructed successfully by micro-sol electrospinning technique. BP, acting as carriers, can not only provide a negative surface and a strong BMP2 loading ability but can also promote biomineralization in a 3D manner on the electrospun fibrous scaffold, while the BMP2 is to target osteoblast precursor cells for recruitment and osteogenesis differentiation, which endows BP@BMP2 nanosheets with staged bone regeneration ability. Furthermore, the in vitro and in vivo data showed that the BP@BMP2 loaded electrospun fibrous scaffold have good biocompatibility and a strong osteogenesis ability resulting in rapid new bone tissue regeneration. Altogether, this newly developed bioinspired BMP2 -modified BP electrospun fiber with staged bone regeneration properties via recruiting osteoblast precursor cells to the bone injured site and accelerating biomineralization can be a promising approach in physiologic bone repair.

19.
J Environ Manage ; : 111583, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33187783

RESUMO

Greenhouse gasses (GHG) emission from the agricultural lands is a serious threat to the environment. Plants such as rice (Oryza sativa L.) that are cultivated in submerged conditions (paddy field) contribute up to 19% of CH4 emission from agricultural lands. Such plants have evolved lysigenous aerenchyma in their root system which facilitates the exchange of O2 and GHG between aerial parts of plant and rhizosphere. Currently, the regulation of GHG and O2 via aerenchyma formation is poorly understood in plants, especially in rice. Here, a reverse genetic approach was employed to reduce the aerenchyma formation by analyzing two mutants i.e., oslsd1.1-m12 and oslsd1.1-m51 generated by Tos17 and T-DNA insertion. The wild-type (WT) and the mutants were grown in paddy (flooded), non-paddy and hydroponic system to assess phenotypic traits including O2 diffusion, GHG emission and aerenchyma formation. The mutants exhibited significant reductions in several morphophysiological traits including 20-60% aerenchyma formation at various distances from the root apex, 25% root development, 50% diffusion of O2 and 27-36% emission of methane (CH4) as compared to WT. The differential effects of the oslsd1.1 mutants in aerenchyma-mediated CH4 mitigation were also evident in the diversity of (pmoA, mcrA) methanotrophs in the rhizosphere. Our results indicate the novel pathway in which reduced aerenchyma in rice is responsible for the mitigation of CH4, diffusion of O2 and the root growth in rice. Limited aerenchyma mediated approach to mitigate GHG specially CH4 mitigation in agriculture is helpful technique for sustainable development.

20.
J Foot Ankle Surg ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-33187902

RESUMO

We present a case of a 13-year-old female with severe varus deformity and limb discrepancy resulting from epiphyseal fracture. The preoperative tibial articular surface angle was 64.1°, and the affected tibia was 14 mm shorter than the contralateral tibia. She underwent a medial open osteotomy and fibular osteotomy with gradual distraction correction using Ilizarov fixator. The deformity was corrected at 3 months, and the external fixator was removed when bony union was achieved 6 months postoperatively. At 9 months after surgery, the patient could play basketball without feeling pain. At the last follow-up, namely 36 months after the operation, the American Orthopaedic Foot and Ankle Society hindfoot-ankle score was improved from 58 to 90, the patient was pain free, and the radiological measurements were nearly normal. Ilizarov fixator gradual distraction correction for distal tibial severe varus deformity is a safe and cost-effective method that can yield excellent radiological and clinical outcomes.

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