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1.
Sci Transl Med ; 13(580)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568520

RESUMO

Among the pleotropic roles of transforming growth factor-ß (TGFß) signaling in cancer, its impact on genomic stability is least understood. Inhibition of TGFß signaling increases use of alternative end joining (alt-EJ), an error-prone DNA repair process that typically functions as a "backup" pathway if double-strand break repair by homologous recombination or nonhomologous end joining is compromised. However, the consequences of this functional relationship on therapeutic vulnerability in human cancer remain unknown. Here, we show that TGFß broadly controls the DNA damage response and suppresses alt-EJ genes that are associated with genomic instability. Mechanistically based TGFß and alt-EJ gene expression signatures were anticorrelated in glioblastoma, squamous cell lung cancer, and serous ovarian cancer. Consistent with error-prone repair, more of the genome was altered in tumors classified as low TGFß and high alt-EJ, and the corresponding patients had better outcomes. Pan-cancer analysis of solid neoplasms revealed that alt-EJ genes were coordinately expressed and anticorrelated with TGFß competency in 16 of 17 cancer types tested. Moreover, regardless of cancer type, tumors classified as low TGFß and high alt-EJ were characterized by an insertion-deletion mutation signature containing short microhomologies and were more sensitive to genotoxic therapy. Collectively, experimental studies revealed that loss or inhibition of TGFß signaling compromises the DNA damage response, resulting in ineffective repair by alt-EJ. Translation of this mechanistic relationship into gene expression signatures identified a robust anticorrelation that predicts response to genotoxic therapies, thereby expanding the potential therapeutic scope of TGFß biology.

2.
Mol Ecol Resour ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609314

RESUMO

Sex determination systems in plants can involve either female or male heterogamety (ZW or XY, respectively). Here we used Illumina short reads, Oxford Nanopore Technologies (ONT) long reads, and Hi-C reads to assemble the first chromosome-scale genome of a female willow tree (Salix dunnii), and to predict genes using transcriptome sequences and available databases. The final genome sequence of 328 Mb in total was assembled in 29 scaffolds, and includes 31,501 predicted genes. Analyses of short-read sequence data that included female and male plants suggested a male heterogametic sex determining factor on chromosome 7, implying that, unlike the female heterogamety of most species in the genus Salix, male heterogamety evolved in the subgenus Salix. The S. dunnii sex-linked region occupies about 3.21 Mb of chromosome 7 in females (representing its position in the X chromosome), probably within a pericentromeric region. Our data suggest that this region is enriched for transposable element insertions, and about one third of its 124 protein-coding genes were gained via duplications from other genome regions. We detect purifying selection on the genes that were ancestrally present in the region, though some have been lost. Transcriptome data from female and male individuals show more male- than female-biased genes in catkin and leaf tissues, and indicate enrichment for male-biased genes in the pseudo-autosomal regions. Our study provides valuable genomic resources for further studies of sex -determining regions in the Salicaceae family, and sex chromosome evolution.

3.
Ann Hematol ; 100(3): 675-689, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33523290

RESUMO

2019 coronavirus disease (COVID-19) presents as a newly recognized pneumonia that has brought about a global pandemic and is increasingly considered as a systemic illness. We investigated the clinical and laboratory features of recovered COVID-19 patients without pre-existing hematologic diseases at Wuhan No. 1 Hospital. Fifty-nine male and 68 female Chinese patients were included with the median age at 64 years in the present study. Eosinopenia (37.80%), monocytosis (51.97%), lymphocytopenia (25.20%), and anemia (51.97%) were the most common hematologic findings in our cohort, particularly in severe or critically ill COVID-19. The levels of changes in leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelets, hemoglobin levels, mean corpuscular volume (MCV), and mean cell hemoglobin concentration (MCHC) are overall associated with lung involvement, oxygen demand, and disease activity. However, changes of eosinophils (end hospitalization-baseline) (coefficients = 10.32; 95% CI = 1.03-19.60, P = 0.03) and basophils (Max - Min) (coefficients = 71.43; 95% CI = 8.55-134.31, P = 0.03) were independent predictors of delayed recovery in the hospital by the multivariate analysis in this recovered population. A variety of hematologic changes are associated with the severity and clinical outcome of recovered COVID-19 patients, which warrants further exploration of their underlying mechanisms.

4.
World J Pediatr ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625696

RESUMO

BACKGROUND: Hereditary renal tubular disease can cause hypercalciuria, acid-base imbalance, hypokalemia, hypomagnesemia, rickets, kidney stones, etc. If these diseases are not diagnosed or treated in time, they can cause kidney damage and electrolyte disturbances, which can be detrimental to the maturation and development of the child. Glomerular involvement in renal tubular disease patients has only been considered recently. METHODS: We screened 71 papers (including experimental research, clinical research, etc.) about Dent's disease, Gitelman syndrome, and cystinosis from PubMed, and made reference. RESULTS: Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage. Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage, morphological changes, and glomerular lesions. CONCLUSIONS: This article focuses on the progress of changes in glomerular podocyte function in Dent disease, Gitelman syndrome, and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.

5.
Oncogene ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627782

RESUMO

Genomic instability induced by DNA damage and improper DNA damage repair is one of the main causes of malignant transformation and tumorigenesis. DNA double strand breaks (DSBs) are the most detrimental form of DNA damage, and nonhomologous end-joining (NHEJ) mechanisms play dominant and priority roles in initiating DSB repair. A well-studied oncogene, the ubiquitin ligase Cullin 4A (CUL4A), is reported to be recruited to DSB sites in genomic DNA, but whether it regulates NHEJ mechanisms of DSB repair is unclear. Here, we discovered that the CUL4A-DTL ligase complex targeted the DNA-PKcs protein in the NHEJ repair pathway for nuclear degradation. Overexpression of either CUL4A or DTL reduced NHEJ repair efficiency and subsequently increased the accumulation of DSBs. Moreover, we demonstrated that overexpression of either CUL4A or DTL in normal cells led to genomic instability and malignant proliferation. Consistent with the in vitro findings, in human precancerous lesions, CUL4A expression gradually increased with increasing malignant tendency and was negatively correlated with DNA-PKcs and positively correlated with γ-H2AX expression. Collectively, this study provided strong evidence that the CUL4A-DTL axis increases genomic instability and enhances the subsequent malignant transformation of normal cells by inhibiting NHEJ repair. These results also suggested that CUL4A may be a prognostic marker of precancerous lesions and a potential therapeutic target in cancer.

6.
Tree Physiol ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33416074

RESUMO

During their lifetimes, plants are exposed to different abiotic stress factors eliciting various physiological responses and triggering important defense processes. For UV-B radiation responses in forest trees, the genetics and molecular regulation remain to be elucidated. Here, we exposed Pinus tabuliformis Carr., a major conifer from Northern China, to short-term high-intensity UV-B and employed a systems biology approach to characterize the early physiological processes and the hierarchical gene regulation, which revealed a temporal transition from primary to secondary metabolism, the buildup of enhanced antioxidant capacity, and stress-signaling activation. Our findings showed that photosynthesis and biosynthesis of photosynthetic pigments were inhibited, while flavonoids and their related derivates biosynthesis as well as glutathione and glutathione S-transferase mediated antioxidant processes were enhanced. Likewise, stress related phytohormones (jasmonic acid, salicylic acid, and ethylene), kinase, and ROS signal transduction pathways were activated. Biological processes regulated by auxin and karrikin were, for the first time, found to be involved in plant defense against UV-B by promoting the biosynthesis of flavonoids and the improvement of antioxidant capacity in our research system. Our work evaluated the physiological and transcriptome perturbations in a conifer's response to UV-B, and generally, highlighted the necessity of a systems biology approach in addressing plant stress biology.

7.
J Hazard Mater ; 408: 124930, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33387723

RESUMO

As a widely used ampholytic surfactant, cocoamidopropyl betaine (CAPB) has been improved to enhance waste activated sludge (WAS) reduction in the short-time aerobic digestion (STAD) system, but how system pH value affects the synergetic combined process has not been discussed. This research evaluated how alkalinity affects soluble microbial products (SMP) dynamics and WAS reduction in the synergetic system. After adding CAPB, the biodegradation rate constant of VSS (kVSS), TCOD (kTCOD) and CAPB (kCAPB) were much higher than that of without adding CAPB; pH value at 7.0-8.0 showed the maximum specific oxygen uptake rate (SOUR) of WAS, leading to the highest WAS reduction efficiency. Further study indicated that CAPB can significantly improve the release of extracellular polymeric substances (EPS), leading to the increased SMP concentrations and low molecular weight fractions (MWF) proportions in SMP; more SMP with low MWF fraction led to the increased SOUR, thus further accelerate the WAS reduction; increasing pH could improve the foaminess and solubility of CAPB, thus further improve the organics release and SMP accumulation, which could be quickly removed in the system. This findings lay the foundation of the practical application of the synergetic combination system in WAS reduction.

8.
Arch Toxicol ; 95(3): 949-958, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33458792

RESUMO

Azoxymethane (AOM) is a widely used carcinogen to study chemical-induced colorectal carcinogenesis and is an agent for studying fulminant hepatic failure. The inter-strain susceptibility to acute toxicity by AOM has been reported, but its association with host genetics or gut microbiota remains largely unexplored. Here a cohort of genetically diverse Collaborative Cross (CC) mice was used to assess the contribution of host genetics and the gut microbiome to AOM-induced acute toxicity. We observed variation in AOM-induced acute liver failure across CC strains. Quantitative trait loci (QTL) analysis revealed three chromosome regions significantly associated with AOM toxicity. Genes located within these QTL, including peroxisome proliferator-activated receptor alpha (Ppara), were enriched for enzyme activator and nucleoside-triphosphatase regulator activity. We further demonstrated that the protein level of PPARα in liver tissues from sensitive strains was remarkably lower compared to levels in resistant strains, consistent with protective role of PPAR family in liver injury. We discovered that the abundance levels of gut microbial families Anaeroplasmataceae, Ruminococcaceae, Lactobacillaceae, Akkermansiaceae and Clostridiaceae were significantly higher in the sensitive strains compared to the resistant strains. Using a random forest classifier method, we determined that the relative abundance levels of these microbial families predicted AOM toxicity with the area under the receiver-operating curve (AUC) of 0.75. Combining the three genetic loci and five microbial families increased the predictive accuracy of AOM toxicity (AUC of 0.99). Moreover, we found that Ruminococcaceae and Lactobacillaceae acted as mediators between host genetics and AOM toxicity. In conclusion, this study shows that host genetics and specific microbiome members play a critical role in AOM-induced acute toxicity, which provides a framework for analysis of the health effects from environmental toxicants.

9.
Food Chem ; 339: 128159, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152898

RESUMO

During production in Chinese baijiu fermentation process, huge amounts of the by-product vinasse are generated and generally utilized as low-value animal feed. We applied alkaline extraction in combination with ultrasonication to recover vinasse proteins, which were then hydrolyzed by complex protease Corolase PP for 8 h to obtain peptide fractions (VPH-1, -2, -3) displaying high DPPH radical scavenging activity. VPH-3 (<3 kDa) separated by ultrafiltration had EC50 values lower than those of VPH-1 and -2 for reactive oxygen species (ROS) and reactive nitrogen species (RNS) radicals, and significantly inhibited production of NO and pro-inflammatory cytokines in LPS-stimulated RAW264.7 macrophage cells. Active peptides and their amino acid sequences were identified by LC-MS/MS analysis, and five synthesized peptides (particularly KLPDHPKLPK and VDVPVKVPYS) displayed strong anti-inflammatory activity at concentration 0.25 mg/mL. These findings will be useful in future commercial development of baijiu vinasse, including application as a new source of bioactive peptides.


Assuntos
Bebidas Alcoólicas , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Peptídeos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Antioxidantes/química , Cromatografia Líquida , Avaliação Pré-Clínica de Medicamentos , Hidrólise , Camundongos , Peptídeos/análise , Peptídeos/química , Proteínas de Plantas/análise , Proteínas de Plantas/farmacologia , Hidrolisados de Proteína/análise , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Células RAW 264.7 , Espécies Reativas de Oxigênio , Espectrometria de Massas em Tandem
10.
Genome Biol ; 21(1): 291, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267872

RESUMO

BACKGROUND: Tetracentron sinense is an endemic and endangered deciduous tree. It belongs to the Trochodendrales, one of four early diverging lineages of eudicots known for having vesselless secondary wood. Sequencing and resequencing of the T. sinense genome will help us understand eudicot evolution, the genetic basis of tracheary element development, and the genetic diversity of this relict species. RESULTS: Here, we report a chromosome-scale assembly of the T. sinense genome. We assemble the 1.07 Gb genome sequence into 24 chromosomes and annotate 32,690 protein-coding genes. Phylogenomic analyses verify that the Trochodendrales and core eudicots are sister lineages and showed that two whole-genome duplications occurred in the Trochodendrales approximately 82 and 59 million years ago. Synteny analyses suggest that the γ event, resulting in paleohexaploidy, may have only happened in core eudicots. Interestingly, we find that vessel elements are present in T. sinense, which has two orthologs of AtVND7, the master regulator of vessel formation. T. sinense also has several key genes regulated by or regulating TsVND7.2 and their regulatory relationship resembles that in Arabidopsis thaliana. Resequencing and population genomics reveals high levels of genetic diversity of T. sinense and identifies four refugia in China. CONCLUSIONS: The T. sinense genome provides a unique reference for inferring the early evolution of eudicots and the mechanisms underlying vessel element formation. Population genomics analysis of T. sinense reveals its genetic diversity and geographic structure with implications for conservation.

11.
Scand J Immunol ; : e12989, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33113222

RESUMO

2019 coronavirus disease (COVID-19) presents as a newly recognized pneumonia and could rapidly progress into acute respiratory distress syndrome which has brought about a global pandemic. Until now, no curative therapy has been strongly recommended for COVID-19 except for personalized supportive care. T cells and virus-specific T cells are essential to protect against virus infection, including COVID-19. Delayed immune reconstitution (IR) and cytokine storm (CS) remain serious obstacles for the cure of COVID-19. Most COVID-19 patients, especially among elderly patients, had marked lymphopenia and increased neutrophils, but T cell counts in severe COVID-19 patients surviving the disease gradually restored later. Elevated pro-inflammatory cytokines, particularly IL-6, IL-10, IL-2 and IL-17, and exhausted T cells are found in peripheral blood and the lungs. It suggests that Thymosin α1 and adoptive COVID-19-specific T cells could improve IR, while convalescent plasma, IL-6 blockade, mesenchymal stem cells and corticosteroids could suppress CS. More clinical studies in this field worldwide are urgently warranted to pave the way for therapy of COVID-19 in the future.

12.
EBioMedicine ; 61: 103023, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33069062

RESUMO

BACKGROUND: We previously established a 53-gene prognostic signature for overall survival (OS) of gastric cancer patients. This retrospective multi-center study aimed to develop a clinically applicable gene expression detection assay and to investigate the prognostic value of this signature. METHODS: A TCGA gastric adenocarcinoma cohort (TCGA-STAD) was used for comparing 53-gene signature with other gene signatures. A high-throughput mRNA hybridization gene expression assay was developed to quantify the expression of 53-genes in formalin-fixed paraffin-embedded tissues of 540 patients enrolled from three hospitals. 180 patents were randomly selected from two hospitals to build a prognostic prediction model based on the 53-gene signature using leave-p-out (one-third out) cross-validation method together with Cox regression and Kaplan-Meier analysis, and the model was assessed on three validation cohorts. FINDINGS: In the evaluation phase, studies based on TCGA-STAD showed that the 53-gene signature was significantly superior to other three prognostic signatures and was independent of TCGA molecular subtypes and clinical factors. For clinical validation and utility, the prognostic scores were generated using the newly developed assay, which was reliable and sensitive, in 100 sampling training sets and were significantly associated with OS in 100 sampling validation sets. The scores were significantly associated with OS in three independent and combined validation cohorts, and in patients with stages II and III/IV. The multivariate Cox regression demonstrated that the prognostic power of the score was independent of clinical factors, consistent with those findings in the TCGA dataset. Finally, patients with good prognostic scores exhibited significantly a better 5-year OS rate from adjuvant FOLFOX chemotherapy after surgery than from other chemotherapies. INTERPRETATION: The 53-gene prognostic score system is clinically applicable for predicting the OS of patients independent of clinical factors in gastric cancers, which could also be a promising predictive biomarker for FOLFOX regimen. FUNDING: Chinese National Science and Technology, National Natural Science Foundation and Natural Science Foundation of Jiangsu Province.

13.
Nat Commun ; 11(1): 5269, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077749

RESUMO

Azaleas (Ericaceae) comprise one of the most diverse ornamental plants, renowned for their cultural and economic importance. We present a chromosome-scale genome assembly for Rhododendron simsii, the primary ancestor of azalea cultivars. Genome analyses unveil the remnants of an ancient whole-genome duplication preceding the radiation of most Ericaceae, likely contributing to the genomic architecture of flowering time. Small-scale gene duplications contribute to the expansion of gene families involved in azalea pigment biosynthesis. We reconstruct entire metabolic pathways for anthocyanins and carotenoids and their potential regulatory networks by detailed analysis of time-ordered gene co-expression networks. MYB, bHLH, and WD40 transcription factors may collectively regulate anthocyanin accumulation in R. simsii, particularly at the initial stages of flower coloration, and with WRKY transcription factors controlling progressive flower coloring at later stages. This work provides a cornerstone for understanding the underlying genetics governing flower timing and coloration and could accelerate selective breeding in azalea.


Assuntos
Cromossomos de Plantas/genética , Genoma de Planta , Proteínas de Plantas/genética , Rhododendron/genética , Antocianinas/biossíntese , Vias Biossintéticas , Carotenoides/metabolismo , Cromossomos de Plantas/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas/metabolismo , Rhododendron/crescimento & desenvolvimento , Rhododendron/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
Front Pharmacol ; 11: 1249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973502

RESUMO

Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.

15.
Life (Basel) ; 10(9)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927618

RESUMO

During space travel, humans are continuously exposed to two major environmental stresses, microgravity (µG) and space radiation. One of the fundamental questions is whether the two stressors are interactive. For over half a century, many studies were carried out in space, as well as using devices that simulated µG on the ground to investigate gravity effects on cells and organisms, and we have gained insights into how living organisms respond to µG. However, our knowledge on how to assess and manage human health risks in long-term mission to the Moon or Mars is drastically limited. For example, little information is available on how cells respond to simultaneous exposure to space radiation and µG. In this study, we analyzed the frequencies of chromosome aberrations (CA) in cultured human lymphoblastic TK6 cells exposed to X-ray or carbon ion under the simulated µG conditions. A higher frequency of both simple and complex types of CA were observed in cells exposed to radiation and µG simultaneously compared to CA frequency in cells exposed to radiation only. Our study shows that the dose response data on space radiation obtained at the 1G condition could lead to the underestimation of astronauts' potential risk for health deterioration, including cancer. This study also emphasizes the importance of obtaining data on the molecular and cellular responses to irradiation under µG conditions.

16.
J Biomater Appl ; : 885328220957902, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915665

RESUMO

In this paper, a complex porous dental implant with biodegradable magnesium alloy was designed based on selective laser melting (SLM). Finite element analysis (FEA) was used to simulate the stress distribution of dental implant and alveolar bone in two models of preliminary and later stages of implant. The stress concentration area of dental implants was found not in the porous structure, and the weak part of mechanical properties accords with the work requirements. The porous structure of dental implants can promote the function of cancellous bone in the process of conducting the stress of the dental implant, thus improving the bearing capacity of dental implants. In vitro fatigue experiments were carried out on the experimental samples produced by 3D printing. Through the cell contrast experiment, it was proved that the decomposed Mg2+ could reach the titanium surface smoothly through the porous structure and complete the proliferation of osteoblasts.

17.
J Integr Med ; 18(6): 478-491, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32907784

RESUMO

BACKGROUND: Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce the patient's steroid dose and maintain low disease activity in systemic lupus erythematosus (SLE). OBJECTIVE: This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE. SEARCH STRATEGY: A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included "systemic lupus erythematosus," "Chinese medicine" and "clinical trial," and their synonyms. Subject headings matching the above terms were also used. INCLUSION CRITERIA: This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids. DATA EXTRACTION AND ANALYSIS: Two authors independently conducted database search, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI). RESULTS: In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58-5.01; P < 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects. CONCLUSION: The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH's relevant bioactive constituents.

18.
Radiat Res ; 194(5): 485-499, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-32991727

RESUMO

We present a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe). Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 mice strains. We previously reported strong evidence for clustering of nearby DSB into single repair units as opposed to the classic "contact-first" model where DSB are considered immobile. Here we apply this clustering model to evaluate the number of remaining RIF over time. We also show that the newly introduced kinetic metrics can be used as surrogate biomarkers for in vivo radiation toxicity, with potential applications in radiotherapy and human space exploration. In particular, we observed an association between the characteristic time constant of RIF repair measured in vitro and survival levels of immune cells collected from irradiated mice. Moreover, the speed of DNA damage repair correlated not only with radiation-induced cellular survival in vivo, but also with spontaneous cancer incidence data collected from the Mouse Tumor Biology database, suggesting a relationship between the efficiency of DSB repair after irradiation and cancer risk.

19.
Nanoscale ; 12(38): 19814-19823, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32966495

RESUMO

Black phosphorus (BP) has emerged as a promising two-dimensional (2D) semiconductor for applications in electronics, optoelectronics, and energy storage. As is the case for many 2D materials, the fabrication of large-area BP thin films remains a considerable challenge. Here, we report the assembly of BP nanosheets into compact thin films using the Langmuir-Blodgett (LB) technique. The overlapping stacking between BP nanosheets is suppressed when the nanosheets are surrounded by fullerene C60 molecules due to physisorption. This allows for the fabrication of large-area BP films (20 mm × 18 mm) with a homogenous nanosheet distribution and negligible oxidation. The fabricated films show measurable absorption up to 2.3 µm. We use these films as active layers to demonstrate mm-sized BP heterojunction photodetectors with mA W-1 scale responsivities from the visible to the near-infrared. Photodetector internal quantum efficiencies at 660 nm and 808 nm are 5% and 1%, respectively.

20.
Food Res Int ; 136: 109434, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32846543

RESUMO

Zhenjiang aromatic vinegar (ZAV) is one of the most famous traditional Chinese cereal vinegars. The key aroma compounds in aged ZAV were characterized by gas chromatography-olfactometry-mass spectrometry (GC-O-MS), odor activity values (OAVs), aroma recombination and omission experiments. Sensory analysis revealed that higher odor intensity of caramel-like, buttery and overall complexity were observed for aged ZAV compared with fresh ZAV. A total of 68 compounds were quantitated, including 27 odorants with OAVs >1.0 in the aged ZAV. Sotolon was detected for the first time in Chinese cereal vinegars. Furthermore, the levels of 2,3-butanedione, 2-methylpropanal, sotolon, dimethyl trisulfide, 3-hydroxy-2-butanone, 2,4,5-trimethyloxazole and tetramethylpyrazine changed significantly during the aging process. Aroma recombination revealed that the aroma profile of the aged vinegar could be closely simulated. Omission experiments demonstrated the important contributions of seven aroma compounds to the aged ZAV aroma, including 2,3-butanedione, acetic acid, 2-methylpropanal, sotolon, 2,4,5-trimethyloxazole, 3-methylbutanoic acid and tetramethylpyrazine. This study indicates that the aging process substantially contribute to the overall aroma of ZAV.

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