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1.
Mol Med ; 26(1): 95, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054759

RESUMO

Pulmonary fibrosis arises from the repeated epithelial mild injuries and insufficient repair lead to over activation of fibroblasts and excessive deposition of extracellular matrix, which result in a mechanical stretched niche. However, increasing mechanical stress likely exists before the establishment of fibrosis since early micro injuries increase local vascular permeability and prompt cytoskeletal remodeling which alter cellular mechanical forces. It is noteworthy that COVID-19 patients with severe hypoxemia will receive mechanical ventilation as supportive treatment and subsequent pathology studies indicate lung fibrosis pattern. At advanced stages, mechanical stress originates mainly from the stiff matrix since boundaries between stiff and compliant parts of the tissue could generate mechanical stress. Therefore, mechanical stress has a significant role in the whole development process of pulmonary fibrosis. The alveoli are covered by abundant capillaries and function as the main gas exchange unit. Constantly subject to variety of damages, the alveolar epithelium injuries were recently recognized to play a vital role in the onset and development of idiopathic pulmonary fibrosis. In this review, we summarize the literature regarding the effects of mechanical stress on the fundamental cells constituting the alveoli in the process of pulmonary fibrosis, particularly on epithelial cells, capillary endothelial cells, fibroblasts, mast cells, macrophages and stem cells. Finally, we briefly review this issue from a more comprehensive perspective: the metabolic and epigenetic regulation.

2.
Sci Rep ; 10(1): 16615, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024203

RESUMO

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a highly virulent pathogen that causes Middle East Respiratory Syndrome (MERS). Anti-MERS-CoV antibodies play an integral role in the prevention and treatment against MERS-CoV infections. Bioactivity is a key quality attribute of therapeutic antibodies, and high accuracy and precision are required. The major methods for evaluating the antiviral effect of antiviral antibodies include neutralization assays using live viruses or pseudoviruses are highly variable. Recent studies have demonstrated that the antibody-dependent cellular cytotoxicity (ADCC) activity of antiviral antibodies is more consistent with the virus clearance effect in vivo than neutralization activity. However, no reports evaluating the ADCC activity of anti-MERS antibodies have been published to date. Here, we describe the development of a robust and reliable cell-based reporter gene assay for the determination of ADCC activity of anti-MERS antibodies using 293T/MERS cells stably expressing the spike protein of MERS-CoV (MERS-S) as target cells and the engineered Jurkat/NFAT-luc/FcγRIIIa stably expressing FcγRIIIA and NFAT reporter gene as effector cells. According to the ICH-Q2 analytical method guidelines, we carefully optimized the experimental conditions and assessed the performance of our assay. In addition, we found that the ADCC activity of afucosylated anti-MERS antibodies is higher than their fucosylated counterparts. The establishment of this ADCC determination system provides a novel method for evaluating the bioactivity of anti-MERS antibodies and improving ADCC activity through modification of N-glycosylation of the Fc segment.

3.
Clin Transl Sci ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030809

RESUMO

Ex vivo (EV)-derived megakaryocytes (MKs) have shown great promise as a substitute for platelets in transfusion medicine to alleviate a severe shortage of donor-platelets. Challenges remain that include poor efficiency, a limited scale of production, and undefined short-term storage conditions of EV-derived MKs. This study aims to develop a high-efficiency system for large-scale production of Good Manufacturing Practice (GMP)-grade MKs and determine the short-term storage condition for the MKs. A roller-bottle culture system was introduced to produce GMP-grade MKs from small-molecule/cytokine cocktail expanded hematopoietic stem cells. Various buffer systems and temperatures for the short-term storage of MKs were assessed by cell viability, biomarker expression, and DNA ploidy levels. MKs stored for 24 hours were transplanted into sublethally irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice to confirm their platelet-releasing and tissue-homing ability in vivo. A yield of ~ 2.5 × 104 CD41a+ /CD42b+ MKs with purity of ~ 80% was achieved from one original cord blood CD34+ cell. Compared with the static culture, the roller-bottle culture system significantly enhanced megakaryopoiesis, as shown by the cell size, DNA ploidy, and megakaryopoiesis-related gene expression. The optimal storage condition for the MKs was defined as normal saline with 10% human serum albumin at 22℃. Stored MKs were capable of rapidly producing functional platelets and largely distributing in the lungs of NOD/SCID mice. The novel development of efficient production and storage system for GMP-grade MKs represents a significant step toward application of these MKs in the clinic.

4.
Clin Cancer Res ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051308

RESUMO

PURPOSE: Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). EXPERIMENTAL DESIGN: Here, we developed a novel digital droplet PCR (ddPCR) assay, that incorporates features to improve sensitivity and allows for the simultaneous detection and longitudinal monitoring of two TERT promoter mutations (C228T and C250T) in cfDNA from the plasma of glioma patients. RESULTS: In baseline performance in tumor tissue, the assay had perfect concordance with an independently performed clinical pathology laboratory assessment of TERT promoter mutations in the same tumor samples (95% CI 94%-100%). Extending to matched plasma samples, we detected TERT mutations in both discovery and blinded multi-institution validation cohorts with an overall sensitivity of 62.5% (95% CI 52%-73%) and a specificity of 90% (95% CI 80%-96%) compared to the gold standard tumor tissue-based detection of TERT mutations. Upon longitudinal monitoring in 5 patients, we report that peripheral TERT mutant allele frequency reflects the clinical course of the disease with levels decreasing after surgical intervention and therapy and increasing with tumor progression. CONCLUSIONS: Our results demonstrate the feasibility of detecting circulating cfDNA TERT promoter mutations in glioma patients with clinically relevant sensitivity and specificity.

5.
J Emerg Nurs ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32962848

RESUMO

INTRODUCTION: Coronavirus disease emerged in Wuhan, China, on December 31, 2019, and spread rapidly worldwide. Few studies have described the nursing care provided to patients in isolation between suspicion of having the disease and a confirmed diagnosis. The purpose of this study was to describe the treatment of, and nursing care processes for, patients suspected, but not yet confirmed, of having coronavirus disease at 1 facility in Shanghai, China. METHODS: For this retrospective facility case review and patient health record study, data were collected on all patients with suspected coronavirus disease who were treated between January 22, 2020, and February 29, 2020, at 1 hospital. The facility's nursing care processes were described in detail. RESULTS: A total of 119 patients were suspected of having coronavirus disease on the basis of the screening criteria. Nine (7.6%) patients had confirmed coronavirus disease and were transferred to a higher level of care. The remaining 110 (92.4%) were treated and discharged. No cross-infection between patients and hospital staff or other patients was detected. The patients' symptoms included fever (n = 98, 82.4%), cough (n = 79, 66.4%), dizziness (n = 28, 23.5%), headache (n = 26, 21.8%), fatigue (n = 26, 21.8%), myalgia (n = 16, 13.4%), rhinorrhea (n = 6, 5.0%), diarrhea (n = 5, 4.2%), severe nasal congestion (n = 4, 3.4%), and dyspnea (n = 1, 0.8%). DISCUSSION: Coronavirus disease is very contagious. Nurses need to understand the symptoms and treatment of the disease as well as nursing procedures, and learn how to cut off transmission routes, control transmission sources, and use protective equipment correctly to prevent transmission of the disease within the hospital.

6.
Medicine (Baltimore) ; 99(38): e22221, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957360

RESUMO

The prognostic impact of incomplete revascularization (ICR) on patients underwent percutaneous coronary intervention (PCI) was vague. Our research aimed to objectify the level of ICR by residual SYNTAX score (rSS) and evaluate the impact of ICR on exercise tolerance.We enrolled 87 patients who completed cardiopulmonary exercise testing (CPET) within 12 months after PCI, retrospectively. According to rSS, patients were divided into rSS = 0 group, 0 < rSS ≤ 8 group, and rSS > 8 group. The CPET variables--including peak metabolic equivalent (METpeak), percentages of predicting value of METpeak (METpeak%pred), MET at anaerobic threshold (AT), peak oxygen uptake (VO2peak), percentages of predicting value of VO2peak (VO2peak%pred), VO2 at AT--were collected and compared.Among rSS = 0, 0 < rSS ≤ 8 and rSS > 8 groups, patients with higher rSS had progressively lower METpeak, METpeak%pred, VO2peak%pred, VO2 at AT, and MET at AT, which indicate reduced exercise tolerance. And further multiple comparisons showed that there were no statistically significant differences between rSS = 0 and 0 < rSS ≤ 8 groups, while the aforementioned CPET variables were significantly lower in rSS > 8 group compared with rSS = 0 group. Logistic regression analysis showed that rSS was an independent risk factor for reduced exercise tolerance.


Assuntos
Doença da Artéria Coronariana/cirurgia , Tolerância ao Exercício , Avaliação de Resultados em Cuidados de Saúde/métodos , Intervenção Coronária Percutânea , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32900877

RESUMO

BACKGROUND: Children born preterm are at high risk for autism spectrum disorder (ASD). However, there is still a lack of appropriate developmental markers. In this study, we aim to examine whether early mental performance trajectory is related to ASD outcome in the preterm population. METHODS: The population-based cohort included 414 very preterm survivors born between 2008 and 2014. After excluding children with severe neurosensory impairment, 319 children with available records of developmental quotients before age 2 years were enrolled. The trajectory of mental performance evaluated by using the Bayley Scales of Infant Development across 6, 12, and 24 months of age was analyzed with group-based trajectory modeling. At 5 years of age, the ASD diagnosis was established by using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. RESULTS: There were 29 children with ASD and 290 children without ASD. The mental performances from age 6 to 24 months could be classified into 3 trajectory patterns: low declining, high declining, and high stable, which corresponded to ASD prevalence at age 5 years of 35%, 9%, and 3%, respectively. ASD odds was 15 times higher in the low-declining group than in the high-stable group (odds ratio 15; 95% confidence interval 3.8-59; P < .001). Through the analysis of multinomial logistic regression, we found that male infants with longer exposure to oxygen therapy whose mothers had lower maternal education levels tended to follow the low-declining trajectory. CONCLUSIONS: The early-life mental trajectory patterns, by using the Bayley Scales of Infant Development, may lead to identification of vulnerable children born preterm for early ASD diagnosis and targeted intervention.


Assuntos
Transtorno do Espectro Autista , Desenvolvimento Infantil , Lactente Extremamente Prematuro , Fatores Etários , Transtorno do Espectro Autista/classificação , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/fisiopatologia , Pré-Escolar , Intervalos de Confiança , Diagnóstico Precoce , Escolaridade , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Razão de Chances , Oxigênio/uso terapêutico , Prevalência , Fatores Sexuais
8.
Mar Drugs ; 18(10)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992455

RESUMO

Ascomylactam A was reported for the first time as a new 13-membered-ring macrocyclic alkaloid in 2019 from the mangrove endophytic fungus Didymella sp. CYSK-4 from the South China Sea. The aim of our study was to delineate the effects of ascomylactam A (AsA) on lung cancer cells and explore the antitumor molecular mechanisms underlying of AsA. In vitro, AsA markedly inhibited the cell proliferation with half-maximal inhibitory concentration (IC50) values from 4 to 8 µM on six lung cancer cell lines, respectively. In vivo, AsA suppressed the tumor growth of A549, NCI-H460 and NCI-H1975 xenografts significantly in mice. Furthermore, by analyses of the soft agar colony formation, 5-ethynyl-20-deoxyuridine (EdU) assay, reactive oxygen species (ROS) imaging, flow cytometry and Western blotting, AsA demonstrated the ability to induce cell cycle arrest in G1 and G1/S phases by increasing ROS generation and decreasing of Akt activity. Conversely, ROS inhibitors and overexpression of Akt could decrease cell growth inhibition and cell cycle arrest induced by AsA. Therefore, we believe that AsA blocks the cell cycle via an ROS-dependent Akt/Cyclin D1/Rb signaling pathway, which consequently leads to the observed antitumor effect both in vitro and in vivo. Our results suggest a novel leading compound for antitumor drug development.

9.
J Microbiol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32997305

RESUMO

Human intestinal microbiota is affected by the exogenous microenvironment. This study aimed to determine the effects of cigarettes and alcohol on the gut microbiota of healthy men. In total, 116 healthy male subjects were enrolled and divided into four groups: non-smoking and non-drinking (Group A), smoking only (Group B), drinking only (Group C), and smoking and drinking combined (Group D). Fecal samples were collected and sequenced using 16S rRNA to analyze the microbial composition. Short-chain fatty acid (SCFAs) levels in feces were determined by gas chromatography. We found that cigarette and alcohol consumptions can alter overall composition of gut microbiota in healthy men. The relative abundances of phylum Bacteroidetes and Firmicutes and more than 40 genera were changed with cigarette and alcohol consumptions. SCFAs decreased with smoking and alcohol consumption. Multivariate analysis indicated that when compared with group A, group B/C/D had higher Bacteroides, and lower Phascolarctobacterium, Ruminococcaceae_UCG-002, Ruminococcaceae_UCG-003, and Ruminiclostridium_9 regardless of BMI and age. Additionally, the abundance of Bacteroides was positively correlated with the smoking pack-year (r = 0.207, p < 0.05), the abundance of predicted pathway of bacterial toxins (r = 0.3672, p < 0.001) and the level of carcinoembryonic antigen in host (r = 0.318, p < 0.01). Group D shared similar microbial construction with group B, but exerted differences far from group C with lower abundance of Haemophilus. These results demonstrated that cigarette and alcohol consumption separately affected the intestinal microbiota and function in healthy men; furthermore, the co-occurrence of cigarette and alcohol didn't exacerbate the dysbiosis and cigarette played the predominated role on the alteration.

10.
Annu Rev Cell Dev Biol ; 36: 141-164, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-32886535

RESUMO

Mitochondrial function depends on the efficient import of proteins synthesized in the cytosol. When cells experience stress, the efficiency and faithfulness of the mitochondrial protein import machinery are compromised, leading to homeostatic imbalances and damage to the organelle. Yeast Msp1 (mitochondrial sorting of proteins 1) and mammalian ATAD1 (ATPase family AAA domain-containing 1) are orthologous AAA proteins that, fueled by ATP hydrolysis, recognize and extract mislocalized membrane proteins from the outer mitochondrial membrane. Msp1 also extracts proteins that have become stuck in the import channel. The extracted proteins are targeted for proteasome-dependent degradation or, in the case of mistargeted tail-anchored proteins, are given another chance to be routed correctly. In addition, ATAD1 is implicated in the regulation of synaptic plasticity, mediating the release of neurotransmitter receptors from postsynaptic scaffolds to allow their trafficking. Here we discuss how structural and functional specialization imparts the unique properties that allow Msp1/ATAD1 ATPases to fulfill these diverse functions and also highlight outstanding questions in the field.

11.
J Phys Chem Lett ; : 6691-6696, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32787221

RESUMO

Electrochemical water splitting in alkaline media is an attractive way to produce the clear and renewable hydrogen fuel H2. In this work, we report a single-atom Fe1/NC catalyst, where the Fe-Nx moiety works as the active site, for high-efficiency alkaline hydrogen evolution reaction (HER). The Fe1/NC electrocatalyst exhibits a low overpotential of 111 mV at the current density of 10 mA cm-2, with a Tafel slope of 86.1 mV dec-1 in 1 M KOH solution. Operando X-ray absorption spectroscopy reveals that, under the working states, the Fe-support interaction weakened as the Fe-N coordination number and Fe oxidation state decreased. As such, the evolved single-atom Fe site with more d electrons provides a favorable structure for boosting HER performance. This work gives insight into the structural evolution of the active site under the alkaline HER and provides a strategy for the design of non-noble metal electrocatalysts.

12.
Environ Res ; 188: 109821, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32798945

RESUMO

The sharp increase in e-waste derived from great consumption of electronic products has become a potential global environmental challenge. Limited information is available about the potential detrimental impact of e-waste on aquatic organisms. The present study investigated the expression of detoxification-related genes and life-history parameter changes in Daphnia magna exposed to e-waste leachate, simultaneously integrating with the chemical analysis of typical pollutants from e-waste leachate. The study aims at assessing impacts of e-waste to aquatic invertebrates and providing insights into its toxic mechanisms. The results showed high concentration of heavy metals like Cu (1657.14 ± 259.3 µg g-1, DW) and persistent organic compounds like polybrominated diphenyl ethers (7831.32 ± 1273.86 ng g-1, DW) in stream sediments near e-waste dismantling areas. Chronic exposure to these pollutants can affect the growth and reproduction of D. magna, resulting in significant development retardation, decreased total egg production per female, and even smaller body size. Expression of some detoxification and reproduction-related genes including DappuHR96, CYP360a, P-gp, EcR, CYP314 and Vtg exhibited different response patterns depending on the e-waste leachate concentration. E-waste leachate may affect the expression of detoxification-related and growth and reproduction-related genes and disrupt the growth and reproduction processes of D. magna.

13.
Mol Cancer Res ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753474

RESUMO

Gastric cancer remains the third leading cause of cancer-related death, and tumor metastasis is the main risk factor for poor prognosis of patients with gastric cancer. Transcription factor EB (TFEB) is a MiT family member and has been found to drive tumorigenesis in a number of tissues, whereas few studies were focused on investigating its prometastasis role and mechanism in gastric cancer. Here, we found TFEB was upregulated in gastric cancer tissues compared with adjacent normal gastric epithelial tissues. IHC analysis from gastric cancer tissue microarray revealed that TFEB in gastric cancer was correlated with depth of tumor invasion, lymph node or distant metastasis, tumor tumor-node-metastasis stage, and overall survival. Gastric cancer cells with TFEB overexpression presented an increased cell migration or invasion, and epithelial-mesenchymal transition (EMT). Furthermore, gene correlation analysis and gene set enrichment analysis enriched Wnt/ß-catenin signaling pathway members in TFEB high-expression group, and the TOP/FOPflash assay verified the effect of TFEB on ß-catenin transcription activity. Besides, we found that TFEB could trigger the aggregation of ß-catenin in nucleus and activate its transcription, as well as facilitate the expression of Wnt/ß-catenin target genes and EMT-related markers, which could be reversed by the Wnt/ß-catenin inhibitor XAV-939. Collectively, TFEB enhances gastric cancer metastatic potential by activating Wnt/ß-catenin signaling pathway and may become a promising therapeutic target for gastric cancer metastasis. IMPLICATIONS: Overexpressed TFEB predicts a higher rate of metastasis and worse survival in patients with gastric cancer. Mechanistically, TFEB activates Wnt/ß-catenin signaling to fuel migratory and invasive activities of gastric cancer cells, as well as EMT.

14.
J Med Virol ; 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32779744

RESUMO

Coronavirus disease 2019 (COVID-19) has now spread all over the world. The National Health Commission of the People's Republic of China reported 78,439 cured and discharged cases, 4634 deaths, 83,462 confirmed cases and 760,818 close contacts as of June 25, 2020. Joint detection of nucleic acids and antibodies has become an important laboratory diagnostic for COVID-19 patients. Disease progression and infection stage can be established based on the biological characteristics of these tests. However, there have been few studies of the different infection stages of COVID-19. We conducted a retrospective analysis to explore the clinical characteristics of COVID-19 patients at different infection stages and to characterize the characteristics of specific serum antibodies at each stage. These data will provide a theoretical basis for clinical diagnosis and treatment. This article is protected by copyright. All rights reserved.

15.
Phys Rev Lett ; 125(4): 047202, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32794802

RESUMO

The weak interlayer coupling in van der Waals (vdW) magnets has confined their application to two dimensional (2D) spintronic devices. Here, we demonstrate that the interlayer coupling in a vdW magnet Fe_{3}GeTe_{2} (FGT) can be largely modulated by a protonic gate. With the increase of the protons intercalated among vdW layers, interlayer magnetic coupling increases. Because of the existence of antiferromagnetic layers in FGT nanoflakes, the increasing interlayer magnetic coupling induces exchange bias in protonated FGT nanoflakes. Most strikingly, a rarely seen zero-field cooled (ZFC) exchange bias with very large values (maximally up to 1.2 kOe) has been observed when higher positive voltages (V_{g}≥4.36 V) are applied to the protonic gate, which clearly demonstrates that a strong interlayer coupling is realized by proton intercalation. Such strong interlayer coupling will enable a wider range of applications for vdW magnets.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32830379

RESUMO

The recent isolation of 2D van der Waals magnetic materials has uncovered rich physics that often differs from the magnetic behavior of their bulk counterparts. However, the microscopic details of fundamental processes such as the initial magnetization or domain reversal, which govern the magnetic hysteresis, remain largely unknown in the ultrathin limit. Here a widefield nitrogen-vacancy (NV) microscope is employed to directly image these processes in few-layer flakes of the magnetic semiconductor vanadium triiodide (VI3 ). Complete and abrupt switching of most flakes is observed at fields Hc  ≈ 0.5-1 T (at 5 K) independent of thickness. The coercive field decreases as the temperature approaches the Curie temperature (Tc  ≈ 50 K); however, the switching remains abrupt. The initial magnetization process is then imaged, which reveals thickness-dependent domain wall depinning fields well below Hc . These results point to ultrathin VI3 being a nucleation-type hard ferromagnet, where the coercive field is set by the anisotropy-limited domain wall nucleation field. This work illustrates the power of widefield NV microscopy to investigate magnetization processes in van der Waals ferromagnets, which can be used to elucidate the origin of the hard ferromagnetic properties of other materials and explore field- and current-driven domain wall dynamics.

17.
Ann Palliat Med ; 9(4): 2393-2399, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32762232

RESUMO

When anti-PD-1 drugs target healthy tissues, it may cause immune-related adverse events (irAEs). Hematological toxicities and renal immune-related adverse reactions were rare; these events recorded were often clinically severe and life-threatening. In this study, we first reported on an elderly esophageal cancer (ESC) case of cytokine release syndrome (CRS) and irAEs induced by radiotherapy following anti-PD-1 drug treatment. A 69-year-old male patient with ESC was hospitalized on December 2, 2019, after three cycles of chemotherapy with docetaxel and nedaplatin accompanied by the addition of PD-1 inhibitor (Sintilimab). The chemotherapy scheme was interrupted due to the absence of any response. Instead, three-dimensional conformal radiotherapy (60 Gy/30 times, 5 times/week) was locally applied to treat the esophageal lesion. Typical CRS and irAEs, including mild diarrhea, intermittent low fever, and leukopenia, occurred after 6 times of radiotherapy, which was alleviated by symptomatic treatment. Such radiotherapy, however, encountered an unexpected early ending after 10 times with patient platelet level being significantly decreased to 31×109/L and the serum creatinine of the patients sharply increased from 78.4 to 609.5 µmol/L. CT scan presented scattered inflammation in both lung. It also showed that mediastinal lymph nodes and esophageal lesions were significantly reduced, and the patients received symptomatic treatment of glucocorticoids and other immunomodulators. The patient get discharged from the hospital after the combination treatment improved the irAEs symptoms. This paper showed the possibility of CRS and multiple-organ injuries as potential irAEs during radiotherapy following the anti-PD-1 therapy strategy and discussed the management of these adverse events (AEs).

18.
Sci Rep ; 10(1): 12783, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732884

RESUMO

Micro-exons are exons of very small size (usually 3-30 nts). Some micro-exons are alternatively spliced. Their functions, regulation and evolution are largely unknown. Here, we present an example of an alternatively spliced 3 bp micro-exon (micro-Ex8) in the homothorax (hth) gene in Drosophila. Hth is involved in many developmental processes. It contains a MH domain and a TALE-class homeodomain (HD). It binds to another homeodomain Exd via its MH domain to promote the nuclear import of the Hth-Exd complex and serve as a cofactor for Hox proteins. The MH and HD domains in Hth as well as the HTh-Exd interaction are highly conserved in evolution. The alternatively spliced micro-exon lies between the exons encoding the MH and HD domains. We provide clear proof that the micro-Ex8 is produced by alternative splicing from a 48 bp full-length exon 8 (FL-Ex8) and the micro-Ex8 is the first three nt is FL-Ex8. We found that the micro-Ex8 is the ancient form and the 3 + 48 organization of alternatively spliced overlapping exons only emerged in the Schizophora group of Diptera and is absolutely conserved in this group. We then used several strategies to test the in vivo function of the two types of isoforms and found that the micro-Ex8 and FL-Ex8 isoforms have largely overlapping functions but also have non-redundant functions that are tissue-specific, which supports their strong evolutionary conservation. Since the different combinations of protein interaction of Hth with Exd and/or Hox can have different DNA target specificity, our finding of alternatively spliced isoforms adds to the spectrum of structural and functional diversity under developmental regulation.

19.
Carbohydr Polym ; 246: 116483, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32747226

RESUMO

A new sequence of steam explosion (SE) with periodic peristalsis (PP) exploited to fractionate corn pericarp (CP), and its high solid cellulosic hydrolysis to increase sugar yield. In this investigation, the optimum SE-condition was 0.8 MPa/5 min., recovered around 12.62 % total sugars than untreated CP, whereas glucan and xylan digestibility reached around 97 % and 87 %, respectively. Besides that, the unground SECP conversion increased by 27.10 % glucan and 34.18 % xylan than the ground one. FE-SEM, FTIR, XRD results confirmed that SE significantly fractionated the amorphous substances that driven the increment of the crystallinity index. SE changed the functional groups without altering the lignin, and also the formation of degradations products was negligible and not detrimental to sugars conversion. An unpolluted SEPP enzymatic hydrolysis system at high solid loading (25 %) with compatible low cellulase dose (15 FPU g-1 solids) was beneficial to intensified sugars conversion.

20.
ACS Appl Mater Interfaces ; 12(38): 42449-42471, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32812741

RESUMO

In the current information age, the realization of memory devices with energy efficient design, high storage density, nonvolatility, fast access, and low cost is still a great challenge. As a promising technology to meet these stringent requirements, nonvolatile multistates memory (NMSM) has attracted lots of attention over the past years. Owing to the capability to store data in more than a single bit (0 or 1), the storage density is dramatically enhanced without scaling down the memory cell, making memory devices more efficient and less expensive. Multistates in a single cell also provide an unconventional in-memory computing platform beyond the Von Neumann architecture and enable neuromorphic computing with low power consumption. In this review, an in-depth perspective is presented on the recent progress and challenges on the device architectures, material innovation, working mechanisms of various types of NMSMs, including flash, magnetic random-access memory (MRAM), resistive random-access memory (RRAM), ferroelectric random-access memory (FeRAM), and phase-change memory (PCM). The intriguing properties and performance of these NMSMs, which are the key to realizing highly integrated memory hierarchy, are discussed and compared.

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