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1.
Bioinformatics ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643666

RESUMO

MOTIVATION: The acid dissociation constant (pKa) is a critical parameter to reflect the ionization ability of chemical compounds and is widely applied in a variety of industries. However, the experimental determination of pKa is intricate and time-consuming, especially for the exact determination of micro pKa information at the atomic level. Hence, a fast and accurate prediction of pKa values of chemical compounds is of broad interest. RESULTS: Here, we compiled a large scale pKa dataset containing 16595 compounds with 17489 pKa values. Based on this dataset, a novel pK a prediction model, named Graph-pKa, was established using graph neural networks. Graph-pKa performed well on the prediction of macro pK a values, with a mean absolute error around 0.55 and a coefficient of determination around 0.92 on the test dataset. Furthermore, combining multi-instance learning, Graph-pKa was also able to automatically deconvolute the predicted macro pKa into discrete micro pK a values. AVAILABILITY: The Graph-pK a model is now freely accessible via a web-based interface (https://pka.simm.ac.cn/). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

2.
J Am Chem Soc ; 143(40): 16320-16325, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34596399

RESUMO

Due to the lack of genetically encoded probes for fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR), its utility for probing eukaryotic membrane protein dynamics is limited. Here we report an efficient method for the genetic incorporation of an unnatural amino acid (UAA), 3'-trifluoromenthyl-phenylalanine (mtfF), into cannabinoid receptor 1 (CB1) in the Baculovirus Expression System. The probe can be inserted at any environmentally sensitive site, while causing minimal structural perturbation to the target protein. Using 19F NMR and X-ray crystallography methods, we discovered that the allosteric modulator Org27569 and agonists synergistically stabilize a previously unrecognized pre-active state. An allosteric modulation model is proposed to explain Org27569's distinct behavior. We demonstrate that our site-specific 19F NMR labeling method is a powerful tool in decoding the mechanism of GPCR allosteric modulation. This new method should be broadly applicable for uncovering conformational states for many important eukaryotic membrane proteins.

4.
Am J Hypertens ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618887

RESUMO

BACKGROUND: Previous studies have shown that hydrogen (H2) can antagonize the fibrosis of various organs. We investigated whether hydrogen-rich saline (HRS) can attenuate myocardial fibrosis in spontaneously hypertensive rats (SHR) and clarified the mechanisms involved. METHODS: We examined the effect of HRS and pirfenidone (PFD) on myocardial fibrosis in SHR. Systolic blood pressure, left ventricular mass index (LVMI) and heart weight index (HWI) were measured, Masson trichrome staining was performed. We assessed the role of superoxide dismutase (SOD), malondialdehyde (MDA), Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, and tissue inhibitors of metalloproteinases (TIMPs) in myocardium. We detected the concentrations of procollagen type-I C-terminal propeptide (PICP), procollagen type-III N-terminal propeptide (PIIINP), and angiotensin II (AngII) in rat serum. Furthermore, the relative protein levels of the TGFß/Smad pathway were tested. RESULTS: We discovered that HRS decreases LVMI (P<0.05) and HWI(P<0.05) in vivo. Compared to model group, HRS decreases the level of collagen volume fraction(P<0.0001), collagen I(P<0.001), and collagen III(P<0.001) in myocardium, and Ang II(P<0.05), PICP(P<0.001), and PIIINP(P<0.05) in serum. In addition, HRS down-regulates the expression of MDA(P<0.01), α-SMA(P<0.05), and TIMPs(P<0.05), and increased SOD(P<0.05). Furthermore, HRS down-regulated the expression levels of TGF-ß1(P<0.0001), Smad3(P<0.0001), and Smad2/3(P<0.001), but had no effect on Smad7 expression(P>0.05). PFD had similar effect compared with HRS and control group. CONCLUSIONS: HRS reduced oxidative stress and improved myocardial collagen content, which may be related to inhibition of the TGF-ß signaling pathway.This suggests that HRS is an effective therapeutic strategy for myocardial fibrosis.

5.
J Hazard Mater ; 424(Pt B): 127480, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34666293

RESUMO

Signal amplification provides an effective way to improve detection performance. Herein, an ultrasensitive electrochemiluminescence (ECL) aptasensor for Pb2+ detection was developed based on a dual signal-amplification strategy of the abscission of a quencher and the generation of a G-quadruplex by one-step and simultaneous way. Nitrogen-doped carbon quantum dots linked with complementary DNA (cDNA-NCQDs) at the sensing interface was applied as the quencher of a tris(4,4'-dicarboxylic acid-2,2'-bipyridyl)ruthenium(II) (Ru(dcbpy)32+)/tripropylamine system to minimize the ECL signal due to the intermolecular hydrogen bond-induced energy-transfer process. Upon the addition of Pb2+, its specific binding with the aptamer triggered the abscission of cDNA-NCQDs, accompanied by the formation of G-quadruplex on the surface of the electrode, both of which amplified the intensity of the light emission. The ECL amplification efficiency induced by the above two mechanisms (78.6%) was valuably greater than that of their sum value (69.3%). This synergistic effect resulted in high detection sensitivity of the ECL aptasensor, which allowed to thereby obtain Pb2+ measurements in the range of 1 fM - 10 nM with an ultra-low detection limit of 0.19 fM. The Pb2+-mediated synergistic signal-amplification ECL strategy can provide a new approach for integrating various amplification strategies.

6.
J Phys Chem Lett ; : 10333-10338, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664963

RESUMO

A hydrogenated amorphous carbon (a-C:H) film shows an ultralow friction coefficient (COF, lower than 0.01); however, its wear life is short in vacuum, and the mechanisms are still not well-understood. This study demonstrates the vacuum tribological behaviors of the a-C:H film can be regulated by interfacial activity. The strong interfacial activity induced continuous transfer of carbon from the film to counterface, causing the formation of a porous transfer film and severe wear of the a-C:H film. Interestingly, weak interfacial activity is beneficial to form spherical-like carbon at the sliding interface, which shields the interaction of dangling bonds and contributes to lower COF and wear of film. Notably, the catalytic nature of Au induced perfect graphene nanoscrolls around Au nanoparticles at the sliding interface, achieving ultralong vacuum wear life. This Letter unifies the understanding of vacuum tribological properties of a-C:H film and provides new insight for prolonging the life of carbon films in vacuum.

7.
Environ Microbiol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34472190

RESUMO

Magnaporthe oryzae is an important plant pathogen that causes rice blast. Hse1 and Vps27 are components of ESCRT-0 involved in the multivesicular body (MVB) sorting pathway and biogenesis. To date, the biological functions of ESCRT-0 in M. oryzae have not been determined. In this study, we identified and characterized Hse1 and Vps27 in M. oryzae. Disruption of MoHse1 and MoVps27 caused pleiotropic defects in growth, conidiation, sexual development and pathogenicity, thereby resulting in loss of virulence in rice and barley leaves. Disruption of MoHse1 and MoVps27 triggered increased lipidation of MoAtg8 and degradation of GFP-MoAtg8, indicating that ESCRT-0 is involved in the regulation of autophagy. ESCRT-0 was determined to interact with coat protein complex II (COPII), a regulator functioning in homeostasis of the endoplasmic reticulum (ER homeostasis), and disruption of MoHse1 and MoVps27 also blocked activation of the unfolded protein response (UPR) and autophagy of the endoplasmic reticulum (ER-phagy). Overall, our results indicate that ESCRT-0 plays critical roles in regulating fungal development, virulence, autophagy and ER-phagy in M. oryzae.

8.
Sci Rep ; 11(1): 19293, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588566

RESUMO

It is widely acknowledged that efficiency of pediatric critical care transport plays a vital role in treatment of critically-ill children. In developing countries, most critically-ill children were transported by ambulance, and a few by air, such as a helicopter or fixed airplane. High-speed train (HST) transport may be a potential choice for critically-ill children to a tertiary medical center for further therapy. This is a single-center, retrospective cohort study from June 01, 2016 to June 30, 2019. All the patients transported to the Pediatric Intensive Care Unit (PICU) of PLA general hospital were divided into two groups, HST group and ambulance group. The propensity score matching method was performed for the comparison between the two groups. Finally, a 2:1 patient matching was performed using the nearest-neighbor matching method without replacement. The primary outcome was hospital mortality. Secondary outcomes included duration of transport, transport cost, hospital stay, and hospitalization cost. A total of 509 critically-ill children were transported and admitted. Of them, 40 patients were transported by HST, and 469 by ambulance. The hospital mortality showed no difference between the two groups (p > 0.05). The transport distance in the HST group was longer than that in the ambulance group (1894.5 ± 907.09 vs. 902.66 ± 735.74, p < 0.001). However, compared to the HST group, the duration of transport time by ambulance was significantly longer (p < 0.001). No difference in vital signs, blood gas analysis, and critical illness score between groups at admission was noted (p > 0.05). There was no death during the transport. There was no difference between groups regarding the transport cost, hospital stays, and hospitalization cost (p > 0.05). High-quality tertiary medical centers are usually located in megacities. HST transport network for critically-ill children could be established to cover most regions of the country. Without increasing financial burden, HST medical transport can be a potentially promising option to improve the outcomes of critically-ill children in developing countries with developed HST network.Clinical Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx (chiCTR.gov; Identifier: ChiCTR2000032306).

9.
Analyst ; 146(20): 6170-6177, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34522939

RESUMO

Triphenyltin chloride (TPhT) is an organotin compound that causes intensive toxicological risk to the environment and humans. A detection method with high sensitivity and stability is therefore desired to better detect TPhT. In this study, a novel SERS substrate was prepared by sputtering an ultra-thin Au layer on a honeycomb-like silver nanoarray fabricated via the nanosphere lithography method. The ultra-thin Au layer was formed by sputtering the intermittent Au nanoparticles on the silver nanoarray, resulting in bimetallic coupling with dramatically increased hotspots and extremely high SERS enhancement with an analytical enhancement factor (AEF) of 6.08 × 109 using Rhodamine 6G (R6G) as the probe molecule. Based on density functional theory (DFT) simulations, the Raman characteristic peaks of TPhT at 999 cm-1 and 655 cm-1 were selected for TPhT detection. The AEF of the SERS substrate HC5-AgAu was calculated to be 3.38 × 106 with the detection concentration of TPhT down to 10-10 M. The as-prepared honeycomb-like silver-gold bimetallic SERS substrate demonstrated great stability and sensitivity for TPhT detection, which might also be applied in monitoring many other environmental pollutants.


Assuntos
Ouro , Nanopartículas Metálicas , Humanos , Compostos Orgânicos de Estanho , Prata , Análise Espectral Raman
10.
J Med Chem ; 64(19): 14011-14027, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34533311

RESUMO

Artificial intelligence (AI) is booming. Among various AI approaches, generative models have received much attention in recent years. Inspired by these successes, researchers are now applying generative model techniques to de novo drug design, which has been considered as the "holy grail" of drug discovery. In this Perspective, we first focus on describing models such as recurrent neural network, autoencoder, generative adversarial network, transformer, and hybrid models with reinforcement learning. Next, we summarize the applications of generative models to drug design, including generating various compounds to expand the compound library and designing compounds with specific properties, and we also list a few publicly available molecular design tools based on generative models which can be used directly to generate molecules. In addition, we also introduce current benchmarks and metrics frequently used for generative models. Finally, we discuss the challenges and prospects of using generative models to aid drug design.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34388097

RESUMO

Central precocious puberty (CPP) is the most common type of precocious puberty and has a significant effect on children. A gonadotropin-releasing hormone (GnRH)-stimulation test is the gold standard for confirming CPP. This test, however, is costly and unpleasant for patients. Therefore, it is critical to developing alternative methods for CPP diagnosis in order to alleviate patient suffering. This study aims to develop an artificial intelligence (AI) diagnostic system for predicting response to the GnRH-stimulation test using data from laboratory tests, electronic health records (EHRs), and pelvic ultrasonography and left-hand radiography reports. The challenges are in integrating these mul-timodal features into a comprehensive deep learning model in order to achieve an accurate diagnosis while also accounting for the missing or incomplete modalities. To begin, we developed a dynamic multimodal variational autoencoder (DMVAE) that can exploit intrinsic correlations between different modalities to im-pute features for missing modalities. Next, we combined features from all modalities to predict the outcome of a CPP diagnosis. The experimental results (AUROC 0.9086) demonstrate that our DMVAE model is superior to standard methods. Additionally, we showed that by setting appropriate operating thresholds, clinicians could diagnose about two-thirds of patients with confidence (1.0 specificity). Only about one-third of patients require confirmation of their diagnoses using GnRH (or GnRH analog)-stimulation tests. To interpret the results, we implemented an explainer Shapley additive explanation (SHAP) to analyze the local and global feature attributions.

12.
Nat Commun ; 12(1): 4876, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385436

RESUMO

While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.


Assuntos
Técnicas Biossensoriais/instrumentação , Medicina de Precisão/instrumentação , Têxteis , Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio/instrumentação , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , COVID-19/prevenção & controle , COVID-19/virologia , Desenho de Equipamento , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Medicina de Precisão/métodos , SARS-CoV-2/fisiologia , Suor/fisiologia
13.
J Fungi (Basel) ; 7(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34436214

RESUMO

Increasing evidence suggests that the endophytic fungus Piriformospora indica helps plants overcome various abiotic stresses, especially heavy metals. However, the mechanism of heavy metal tolerance has not yet been elucidated. Here, the role of P. indica in alleviating cadmium (Cd) toxicities in tobacco was investigated. It was found that P. indica improved Cd tolerance to tobacco, increasing Cd accumulation in roots but decreasing Cd accumulation in leaves. The colonization of P. indica altered the subcellular repartition of Cd, increasing the Cd proportion in cell walls while reducing the Cd proportion in membrane/organelle and soluble fractions. During Cd stress, P. indica significantly enhanced the peroxidase (POD) activity and glutathione (GSH) content in tobacco. The spatial distribution of GSH was further visualized by Raman spectroscopy, showing that GSH was distributed in the cortex of P. indica-inoculated roots while in the epidermis of the control roots. A LC-MS/MS-based label-free quantitative technique evaluated the differential proteomics of P. indica treatment vs. control plants under Cd stress. The expressions of peroxidase, glutathione synthase, and photosynthesis-related proteins were significantly upregulated. This study provided extensive evidence for how P. indica enhances Cd tolerance in tobacco at physiological, cytological, and protein levels.

14.
Front Immunol ; 12: 707287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394108

RESUMO

Background: The outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection. Methods: To further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents. Results: We explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-α. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone. Conclusions: This study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/patologia , Biologia Computacional/métodos , Dengue/tratamento farmacológico , Dengue/patologia , Mapas de Interação de Proteínas/fisiologia , Antivirais/uso terapêutico , Quimiocina CCL2/metabolismo , Coinfecção , Vírus da Dengue/efeitos dos fármacos , Dexametasona/uso terapêutico , Regulação da Expressão Gênica/genética , Genisteína/uso terapêutico , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Pulmão/metabolismo , Resveratrol/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Transdução de Sinais
15.
Medicine (Baltimore) ; 100(29): e26491, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398005

RESUMO

ABSTRACT: Hepatocellular carcinoma (HCC) is 1 of the deadliest malignancies worldwide. Despite significant advances in diagnosis and treatment, the mortality rate from HCC persists at a substantial level. Construction of a prognostic model that can reliably predict HCC patients' overall survival is urgently needed.Two RNA-seq dataset (the Cancer Genome Atlas and International Cancer Genome Consortium) and 1 microarray dataset (GSE14520) were included in our study. RNA-binding proteins (RBPs) in HCC patients was examined by differentially expressed genes analysis, functional enrichment analysis and protein-protein interaction network analysis. Subsequently, the Cancer Genome Atlas dataset was randomly divided into training and testing cohort with a prognostic model developed in the training cohort. In order to evaluate the prognostic value of the model, a comprehensive survival assessment was conducted.Five RBPs (ribosomal protein L10-like, enhancer of zeste homolog 2 (EZH2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), zinc finger protein 239, interferon-induced protein with tetratricopeptide repeats 1) were used to construct the model. The model accurately predicted the prognosis of liver cancer patients in both the training cohort and validation cohort. HCC patients could be assigned into a high-risk group and a low-risk group by this model, and the overall survival of these 2 groups was significantly different (P  < .05). Furthermore, the risk scores obtained by this model were highly correlated with immune cell infiltration.The prognostic model helps to identify HCC patients at high risk of mortality, which optimizes decision-making for individualized treatment.


Assuntos
Carcinoma Hepatocelular/complicações , Prognóstico , Proteínas com Motivo de Reconhecimento de RNA/análise , Área Sob a Curva , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco/métodos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos , Análise de Sobrevida
16.
Medicine (Baltimore) ; 100(34): e26967, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449462

RESUMO

ABSTRACT: Alzheimer disease (AD) and sporadic cerebral small vessel disease (CSVD) are common cognitive disorders. Both AD and CSVD have mental symptoms including chronic progressive cognitive impairment, dysfunction, and behavioral abnormalities. However, the differences on the cognitive dysfunction of AD and CSVD remain unclear. It is necessary to elucidate the cognitive dysfunction differences of AD and CSVD, and to identify the potential risk factors.AD or sporadic CSVD patients treated in our hospital from December 1, 2018 to May 31, 2019 were included. And we selected healthy participants as controls. The mini-mental state examination and Montreal Cognitive Assessment Scale were used for neuropsychological assessment, and related medical information were collected and compared.A total of 190 patients were included. The total mini-mental state examination scores in AD, CSVD group were significantly less than that of control group, there were significant differences in the domains of directional ability, attention and computing ability, delayed recall, and visual perception (all P < .05); the total Montreal Cognitive Assessment Scale scores in AD, CSVD group were significantly less than that of control group. There were significant differences in the domains of visual space and execution, immediate remember, attention and computing ability, language, delayed recall, and directional ability (all P < .05); diabetes was a risk factor both for AD (hazard ratio = 1.63, 95% confidence interval: 1.35-1.97) and CSVD (hazard ratio = 1.15, 95% confidence interval: 1.08-1.27).The cognitive dysfunctions of AD are difference to that of CSVD patients, and diabetes is the risk factor both for AD and CSVD, future studies are needed to further identify the prevention and treatment of AD and CSVD.


Assuntos
Doença de Alzheimer/complicações , Doenças de Pequenos Vasos Cerebrais/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Idoso , Comorbidade , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes de Estado Mental e Demência , Testes Neuropsicológicos
17.
Curr Med Sci ; 41(4): 712-721, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403096

RESUMO

OBJECTIVE: Atherosclerosis (AS), a chronic inflammatory disease, is the basis of cardiovascular disease (CVD). Although the treatment has been greatly improved, AS still imposes a large burden on human health and the medical system, and we still need to further study its pathogenesis. As a novel biomolecule, transfer RNA-derived fragments (tRFs) play a key role in the progression of various disease. However, whether tRFs contribute to atherosclerosis pathogenesis remains unexplored. METHODS: With deep sequencing technology, the change of tRFs expression profiles in patients with AS compared to healthy control group was identified. The accuracy of the sequencing data was validated using RT qPCR. Subsequently, we predicted the potential target genes of tRFs by online miRNA target prediction algorithms. The potential functions of tRFs were evaluated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS: There were 13 tRFs differentially expressed between patients with AS and healthy controls, of which 2 were up-regulated and 11 were down-regulated. Validation by RT-qPCR analysis confirmed the sequencing results, and tRF-Gly-GCC-009 was highly up-regulated in the AS group based on the results of sequencing which was confirmed by RT-qPCR analysis. Furthermore, GO enrichment and KEGG pathway analyses indicated that 10 signaling pathways were related to tRF-Gly-GCC-009. These pathways might be physiopathological fundamentals of AS, mainly involving in Apelin signaling, Notch signaling and calcium signaling. CONCLUSION: The results of our study provide important novel insight into the underlying pathogenesis and demonstrate that tRFs might be potential biomarkers and therapeutic targets for AS in the future.

18.
Br J Haematol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34405393

RESUMO

Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non-high-risk APL and received all-trans retinoic acid (ATRA) plus arsenic as front-line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar-indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow-up of 53·6 (24·3-85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML-RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5-year cumulative incidence of relapse, event-free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse.

19.
Biotechnol Lett ; 43(10): 2045-2052, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34390483

RESUMO

OBJECTIVE: To investigate the protoplast preparation and transformation system of endophytic fungus Falciphora oryzae. RESULTS: F. oryzae strain obtained higher protoplast yield and effective transformation when treated with enzyme digestion solution containing 0.9 M KCl solution and 10 mg mL-1 glucanase at 30 °C with shaking at 80 rpm for 2-3 h. When the protoplasts were plated on a regenerations-agar medium containing 1 M sucrose, the re-growth rate of protoplasts was the highest. We successfully acquired green fluorescent protein-expressing transformants by transforming the pKD6-GFP vector into protoplasts. Further, the GFP expression in fungal hyphae possessed good stability and intensity during symbiosis in rice roots. CONCLUSIONS: This study provided a protoplast transformation system of F. oryzae, creating opportunities for future genetic research in other endophytic fungi.

20.
Int J Pharm ; 607: 120971, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34363915

RESUMO

The co-amorphous (CAM) technology has attracted extensive attention in recent years because it can improve the solubility and provide a formulation strategy for fixed dose combination for poorly water-soluble drugs. Atorvastatin (ATR) is a poorly water-soluble drug and it has strong anti-hyperlipidemia activity, and it is usually used in combination with lisinopril (LNP), an anti-hypertension drug. The aim of this study is to test the feasibility to develop ATR/LNP co-amorphous formulation using a cryo-milling method. The solid-state behaviors of the CAM systems were characterized by polarizing light microscopy, differential scanning calorimetry and powder X-ray diffraction. The molecular interaction between ATR and LNP was confirmed by the analysis of glass transition temperature and Fourier transform infrared spectroscopy. Compared with crystalline ATR and neat amorphous ATR, the CAM systems showed significantly increased in vitro dissolution and intrinsic dissolution rate of ATR, because LNP enhanced the supersaturation maintenance of ATR and inhibited its solution-mediated recrystallization to a certain extent.


Assuntos
Lisinopril , Atorvastatina , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Estabilidade de Medicamentos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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