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1.
Int J Pharm ; 590: 119929, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010395

RESUMO

Immune checkpoint inhibitors (ICIs), like monoclonal antibodies of PD-1, CTLA-4, and their ligands, are effective only in some populations of patients with cancer, because the immunosuppressive state of the tumor microenvironment (TME) in some patients cannot be effectively reversed after ICI therapy. Sialic acid (SA) receptors in the Siglec family are highly expressed on the surface of tumor-associated macrophages (TAMs) and most have immunosuppressive effects. Therefore, targeting TAMs (the siglec axis) to reverse tumor immunosuppression may provide a new direction for the development of novel tumor immunotherapies. We designed a Zoledronic acid (ZA)-loaded liposome modified by a SA-octadecylamine conjugate (ZA-SL) to act as a novel nanomedicine delivery platform. This platform can efficiently deliver ZA to TAMs through the combination of SA and Siglec-1 and exerts specific cytotoxicity or phenotypic remodeling of M2-like TAMs depending on the drug concentration in TAMs. In vivo experiments showed that ZA-SL had good TAM targeting ability, and after treatment, the S180 tumors of mice were significantly inhibited, and the proportion of M1-like TAMs was significantly higher than that of M2-like TAMs with no significant adverse reactions in mice. Therefore, SA-modified ZA-loaded liposomes may provide a promising strategy for cancer immunotherapy.

2.
Plants (Basel) ; 9(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065969

RESUMO

Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes represent the most important disease resistance genes in plants. The genome sequence of kiwifruit (Actinidia chinensis) provides resources for the characterization of NBS-LRR genes and identification of new R-genes in kiwifruit. In the present study, we identified 100 NBS-LRR genes in the kiwifruit genome and they were grouped into six distinct classes based on their domain architecture. Of the 100 genes, 79 are truncated non-regular NBS-LRR genes. Except for 37 NBS-LRR genes with no location information, the remaining 63 genes are distributed unevenly across 18 kiwifruit chromosomes and 38.01% of them are present in clusters. Seventeen families of cis-acting elements were identified in the promoters of the NBS-LRR genes, including AP2, NAC, ERF and MYB. Pseudomonas syringae pv. actinidiae (pathogen of the kiwifruit bacterial canker) infection induced differential expressions of 16 detected NBS-LRR genes and three of them are involved in plant immunity responses. Our study provides insight of the NBS-LRR genes in kiwifruit and a resource for the identification of new R-genes in the fruit.

3.
Stem Cell Res ; 49: 101997, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-33002718

RESUMO

Long QT syndrome (LQTS), an inherited cardiac ion channelopathy, is associated with ventricular arrhythmias and risk of sudden death. LQTS sub-type 2 (LQT2) is caused by pathogenic variants in KCNH2 encoding the α-subunit of Kv11.1, thus affecting the rapid component of delayed rectifier K+ current (IKr) channel during the action potential. In this study, non-integrational Sendai reprogramming method was used to generate an induced-pluripotent-stem-cell (iPSC) line carrying the KCNH2 c.2464G>A (p.Val822Met) pathogenic variant from a LQT2 patient. This patient-specific iPSC line NUIGi003-A harbouring the c.2464G>A variant expressed pluripotency markers and demonstrated the differentiation potential to all three germ layers.

4.
Stem Cell Res ; 49: 101996, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-33002719

RESUMO

Two human induced pluripotent stem cell (hiPSC) lines (NUIGi038-A, NUIGi038-B) were generated from dermal fibroblasts of a healthy 47 year old female using non-integrational Sendai reprogramming method expressing OCT4, SOX2, KLF4 and C-MYC. Characterization of both hiPSC lines was confirmed by the expression of typical pluripotency markers and differentiation potential in vitro.

5.
Eur J Pharmacol ; : 173630, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33045197

RESUMO

Glucocorticoids are commonly used in clinic, but the immunosuppression seriously hinders their usage. Herein, immunomodulatory effect of artesunate (AS) on hydrocortisone (HC)-induced immunosuppression was investigated. HC-induced immunosuppression mice (HC mice) were established by intramuscular administration with HC (20 mg/kg) once a day for 5 consecutive days. The results showed HC mice challenged with Escherichia coli on the sixth day presented a lower ability to clear bacteria, decreased TNF-α in blood, decreased spleen index and thymus index. Significantly, AS (20 mg/kg) treatment not only enhanced the ability of HC mice to clear bacteria, but also increased spleen index, the levels of pro-inflammatory cytokines from 78.7 ±â€¯12.1 ng/ml (TNF-α) and 48.7 ±â€¯8.6 pg/ml (IL-6) to 174.0 ±â€¯90.5 ng/ml and 783.3 ±â€¯90.5 pg/ml, number of white blood cells in blood, and sIgA in colon. Subsequently, HC-induced immunosuppression peritoneal macrophages model (HC cells) was established via addition of HC (0.5 µg/ml) for 0.5 h, and then LPS (100 ng/ml) was added to clarify the functional status of the cells. The results showed HC inhibited TNF-α and IL-6 mRNA expressions and their release, but AS (2.5 µg/ml) could increase TNF-α and IL-6 mRNA expressions and their release. AS inhibited GILZ mRNA up-regulated by HC and increases TLR4/NF-κB p65 expressions down-regulated by HC. Our findings revealed that AS's effect is closely related to the improvement of the TLR4/NF-κB signal transduction pathway via inhibiting the up-regulation of GILZ mRNA, demonstrating AS does possess immunomodulatory effects and is worth further investigation in the future.

6.
Sci Rep ; 10(1): 16563, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024145

RESUMO

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

8.
Small ; : e2005217, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33035390

RESUMO

Optoelectronic-neuromorphic transistors are vital for next-generation nanoscale brain-like computational systems. However, the hardware implementation of optoelectronic-neuromorphic devices, which are based on conventional transistor architecture, faces serious challenges with respect to the synchronous processing of photoelectric information. This is because mono-semiconductor material cannot absorb adequate light to ensure efficient light-matter interactions. In this work, a novel neuromorphic-photoelectric device of vertical van der Waals heterojunction phototransistors based on a colloidal 0D-CsPbBr3 -quantum-dots/2D-MoS2 heterojunction channel is proposed using a polymer ion gel electrolyte as the gate dielectric. A highly efficient photocarrier transport interface is established by introducing colloidal perovskite quantum dots with excellent light absorption capabilities on the 2D-layered MoS2 semiconductor with strong carrier transport abilities. The device exhibits not only high photoresponsivity but also fundamental synaptic characteristics, such as excitatory postsynaptic current, paired-pulse facilitation, dynamic temporal filter, and light-tunable synaptic plasticity. More importantly, efficiency-adjustable photoelectronic Pavlovian conditioning and photoelectronic hybrid neuronal coding behaviors can be successfully implemented using the optical and electrical synergy approach. The results suggest that the proposed device has potential for applications associated with next-generation brain-like photoelectronic human-computer interactions and cognitive systems.

9.
BMC Genomics ; 21(1): 686, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008286

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs playing vital roles in regulating posttranscriptional gene expression. Elucidating the expression regulation of miRNAs underlying pig testis development will contribute to a better understanding of boar fertility and spermatogenesis. RESULTS: In this study, miRNA expression profile was investigated in testes of Duroc and Meishan boars at 20, 75, and 270 days of age by high-throughput sequencing. Forty-five differentially expressed miRNAs were identified from testes of Duroc and Meishan boars before and after puberty. Integrated analysis of miRNA and mRNA profiles predicted many miRNA-mRNA pairs. Gene ontology and biological pathway analyses revealed that predicted target genes of ssc-mir-423-5p, ssc-mir-34c, ssc-mir-107, ssc-mir-196b-5p, ssc-mir-92a, ssc-mir-320, ssc-mir-10a-5p, and ssc-mir-181b were involved in sexual reproduction, male gamete generation, and spermatogenesis, and GnRH, Wnt, and MAPK signaling pathway. Four significantly differentially expressed miRNAs and their predicted target genes were validated by quantitative real-time polymerase chain reaction, and phospholipase C beta 1 (PLCß1) gene was verified to be a target of ssc-mir-423-5p. CONCLUSIONS: This study provides an insight into the functional roles of miRNAs in testis development and spermatogenesis and offers useful resources for understanding differences in sexual function development caused by the change in miRNAs expression between Duroc and Meishan boars.

10.
Front Immunol ; 11: 580968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013934

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has been on a global rise. While animal models have rendered valuable insights to the pathogenesis of NAFLD, discrepancy with patient data still exists. Since non-alcoholic steatohepatitis (NASH) involves chronic inflammation, and CD4+ T cell infiltration of the liver is characteristic of NASH patients, we established and characterized a humanized mouse model to identify human-specific immune response(s) associated with NAFLD progression. Immunodeficient mice engrafted with human immune cells (HIL mice) were fed with high fat and high calorie (HFHC) or chow diet for 20 weeks. Liver histology and immune profile of HIL mice were analyzed and compared with patient data. HIL mice on HFHC diet developed steatosis, inflammation and fibrosis of the liver. Human CD4+ central and effector memory T cells increased within the liver and in the peripheral blood of our HIL mice, accompanied by marked up-regulation of pro-inflammatory cytokines (IL-17A and IFNγ). In vivo depletion of human CD4+ T cells in HIL mice reduced liver inflammation and fibrosis, but not steatosis. Our results highlight CD4+ memory T cell subsets as important drivers of NAFLD progression from steatosis to fibrosis and provides a humanized mouse model for pre-clinical evaluation of potential therapeutics.

11.
Aging (Albany NY) ; 122020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024057

RESUMO

In this study, we established a simple and practical tool for early identification of potentially high-risk individuals among elderly COVID-19 patients. Included were 2106 laboratory-confirmed COVID-19 patients aged 60 years and above in 30 provinces of mainland China. Using discrimination (the area under the receiver-operator characteristic curve [AUC]) and calibration (Hosmer-Lemeshow goodness-of-fit test and calibration plots), a nomogram for predicting critically ill cases was developed, and its performance was examined using an internal validation cohort (444 patients) and external cohort (770 patients). The proportion of critically ill patients was 11.8% (248/2106). The most common symptoms at the onset of illness were fever (66.6%), cough (34.1%), fatigue (23.3%), and expectoration (23.6%). Older age, history of chronic obstructive pulmonary disease, fever, fatigue, shortness of breath, and lymphocyte percentage lower than 20% at admission were associated with increased risk of becoming critically ill. The AUCs for the six-variable-based nomogram were 0.77 (95% CI: 0.73-0.82), 0.73 (95% CI: 0.67-0.79), and 0.77 (95% CI: 0.71-0.83) in the development, internal validation, and external validation cohorts, respectively. This six-variable-based nomogram could potentially serve as a practical and reliable tool for early identification of elderly COVID-19 patients at high risk of becoming critically ill.

12.
Liver Int ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025620

RESUMO

BACKGROUND/AIMS: Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis worldwide, but it is long-neglected. We aimed to understand global trends and regional differences in incidence of HEV infection, thereby making global tailored prevention strategies. METHODS: This study is a post-hoc analysis of the data from Global Burden of Disease Study 2017. Annual HEV incident cases and incidence rates from 1990 to 2017 were collected. Changes in incident cases and estimated annual percentage changes (EAPCs) of age-standardized incidence rates (ASRs) were calculated to quantify the temporal trends of HEV infection. RESULTS: Globally, HEV ASRs decreased by an average 0.16% (95%CI 0.14%-0.17%) per year from 279.79 per 100,000 in 1990 to 269.70 per 100,000 in 2017; however, the number of HEV incident cases increased by 17.63% from 16.53 million in 1990 to 19.44 million in 2017. Against the global trend of ASR falling, an increasing trend was reported in Oceania (EAPC=0.03 95%CI 0.03-0.04) and Western Europe (EAPC=0.02 95%CI 0.01-0.03). The number of HEV incident cases increased remarkably in low (63.07%) and low-middle (37.46%) SDI regions between 1990 and 2017. Additionally, the number of HEV incident cases increased by 4.63% in high SDI regions, mainly in 40 plus age group. Surprisingly, more than 40% of HEV incident cases in Western Europe in 2017 were over 40 years old. CONCLUSIONS: HEV is still pending in hyperendemic regions, and it is emerging in low endemic regions, suggesting more efforts should be done to make targeted prevention strategies.

13.
Oncol Rep ; 44(5): 1985-1996, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000253

RESUMO

Renal cell carcinoma (RCC) is the most common type of renal cancer. Long non­coding RNA (lncRNA) has been reported to play a vital role in the development and progression of various types of cancer type. However, the underlying molecular mechanisms of PLK1S1 in regulating RCC progression remain unclear. In the present study, PLK1S1 was upregulated in RCC tissues and cells, and PLK1S1 expression was also significantly elevated in stage IV RCC tissues. Kaplan­Meier analysis showed that patients with high PLK1S1 expression had a shorter overall survival time compared with those with low PLK1S1 expression. Moreover, bioinformatics analysis and luciferase reporter assay demonstrated that PLK1S1 inhibited microRNA (miR)­653 expression by direct interaction. Functional analyses demonstrated that a miR­653 inhibitor promoted short hairpin PLK1S1­attenuated cell proliferation, invasion and sorafenib resistance of RCC cells. In addition, C­X­C motif chemokine receptors 5 (CXCR5) was identified as an effector of PLK1S1/miR­653­mediated tumorigenesis and drug resistance in RCC cells. Lastly, xenograft experiments demonstrated that PLK1S1 knockdown inhibited tumor growth in vivo. Reverse transcription­quantitative PCR and western blot analysis revealed that PLK1S1 knockdown upregulated the expression level of miR­653, whilst downregulating the expression level of CXCR5. In conclusion, the present study revealed that PLK1S1 promoted tumor progression and sorafenib resistance in RCC through regulation of the miR­653/CXCR5 axis, which may offer a novel treatment strategy for patients with RCC.

14.
J Environ Manage ; 277: 111439, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035939

RESUMO

Overgrazing is the main driver of grassland degradation and productivity reduction in northern China. The restoration of degraded grasslands depends on optimal grazing regimes that modify the source-sink balance to promote best carbon (C) assimilation and allocation, thereby promoting rapid compensatory growth of the grazed plants. We used in situ13CO2 labeling and field regrowth studies of Stipa grandis P.A. Smirn.to examine the effects of different grazing intensities (light, medium, heavy, and grazing exclusion) on photosynthetic C assimilation and partitioning, on reallocation of non-structural carbohydrates during regrowth, and on the underlying regulatory mechanisms. Light grazing increased the sink demand of newly expanded leaves and significantly promoted 13C fixation by increasing the photosynthetic capacity of the leaves and accelerating fructose transfer from the stem. Although C assimilation decreased under medium and heavy grazing, S. grandis exhibited a tolerance strategy that preferentially allocated more starch and 13C to the roots for storage to balance sink competition between newly expanded leaves and the roots. Sucrose phosphate synthase (SPS), sucrose synthase (SS), and other plant hormones regulated source-sink imbalances during regrowth. Abscisic acid promoted accumulation of aboveground biomass by stimulating stem SPS activity, whereas jasmonate increased root starch synthesis, thereby increasing belowground biomass. Overall, S. grandis could optimize source-sink relationships and above- and belowground C allocation to support regrowth after grazing by the regulating activities of SPS, SS and other hormones. These results provide new insights into C budgets under grazing and guidance for sustainable grazing management in semi-arid grasslands.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33052017

RESUMO

Ubiquitin-specific protease 21 (USP21) has been implicated in several types of cancer. It promotes or suppresses tumor growth in a cell-context dependent manner. Cholangiocarcinoma is a malignant tumor with a high mortality rate. However, the role of USP21 in cholangiocarcinoma remains unknown. Here, we identify that the level of USP21 is upregulated in cholangiocarcinoma using bioinformatics analysis and confirm this elevation in RBE cell lines. Cell counting and 5-ethynyl-2'-deoxyuridine incorporation assays reveal that USP21 promotes the proliferation of cholangiocarcinoma. Wound healing and transwell assays demonstrate that USP21 accelerates RBE cell migration. In addition, rescue assays reveal that reintroduction of USP21 wildtype other than the deubiquitinase-deficient C221A mutant restores USP21 depletion-induced attenuation in cell proliferation and migration, indicative of the requirement of the deubiquitinase activity. Collectively, these data indicate that USP21 is critically involved in cholangiocarcinoma tumorigenesis and may be an effective target for the treatment of cholangiocarcinoma.

17.
Cancer Lett ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32931886

RESUMO

Hypoxia is a hallmark of cancer. To cope with hypoxic conditions, tumor cells alter their transcriptional profiles mainly through hypoxia-inducible factors (HIFs) and epigenetic reprogramming. Hypoxia, in part through HIF-dependent mechanisms, influences the expression or activity of epigenetic regulators to control epigenetic reprogramming, including DNA methylation and histone modifications, which regulate hypoxia-responsive gene expression in cells. Conversely, epigenetic regulators and chromatin architecture can modulate the expression, stability, or transcriptional activity of HIF. Understanding the complex networks between HIFs, epigenetic regulators, and chromatin reprogramming in response to hypoxia will provide insight into the fundamental mechanism of transcriptional adaptation to hypoxia, and may help identify novel targets for future therapies. In this review, we will discuss the comprehensive relationship between HIFs, epigenetic regulators, and chromatin reprogramming under hypoxic conditions.

18.
J Integr Plant Biol ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32965083

RESUMO

Cuticular wax is a natural barrier on terrestrial plant organs, which protects plants from damages caused by a variety of stresses. Here, we report the identification and functional characterization of a cuticular-wax-related gene, Zea mays L. SEMI-ROLLED LEAF 5 (ZmSRL5). The loss-of-function mutant srl5, which was created by a 3,745 bp insertion in the first intron that led to the premature transcript, exhibited abnormal wax crystal morphology and distribution, which, in turn, caused the pleiotropic phenotypes including increased chlorophyll leaching and water loss rate, decreased leaf temperature, sensitivity to drought, as well as semi-rolled mature leaves. However, total wax amounts showed no significant difference between wild type and semi-rolled leaf5 (srl5) mutant. The phenotype of srl5 was confirmed through the generation of two allelic mutants using CRISPR/Cas9. ZmSRL5 encodes a CASPARIAN-STRIP-MEMBRANE-DOMAIN-LIKE (CASPL) protein located in plasma membrane, and highly expressed in developing leaves. Further analysis showed that the expressions of the most wax related genes were not affected or slightly altered in srl5. This study, thus, primarily uncovers that ZmSRL5 is required for the structure formation of the cuticular wax and could increase the drought tolerance by maintaining the proper cuticular wax structure in maize.

19.
Ann Epidemiol ; 49: 13-19, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32951803

RESUMO

PURPOSE: China has the world's largest burden of hepatitis B virus (HBV) infection. However, there are few studies reported on the latest prevalence of hepatitis B surface antigen (HBsAg) among pregnant women in China. We aimed to assess the prevalence of HBV infection and its associated risk factors among pregnant women in Yunnan, which is a province with relatively high prevalence of blood-borne viruses. METHODS: We conducted a cross-sectional study of 15,641 pregnant women who underwent routine antenatal screening for HBsAg in Yunnan between 2013 and 2016. Logistic regression analyses were used to examine the associations between HBV infection and risk factors. RESULTS: Overall, 7.89% (95% confidence interval (CI), 7.47%-8.31%) of the 15,641 pregnant women tested positive for HBsAg. Multivariable logistic regression analysis showed that advanced age (≥35 years old; adjusted odds ratio [aOR], 2.43-2.59), Hani ethnicity (aOR, 1.97; 95% CI, 1.22-3.17), unemployed women (aOR, 1.88; 95% CI, 1.30-2.72), multigravidas (aOR, 1.21; 95% CI, 1.05-1.40), and multiparas (aOR, 1.28; 95% CI, 1.10-1.49) were more likely to be infected with HBV. HBV infection was associated with cesarean section and preterm birth, with aORs of 1.31 (1.17-1.48) and 1.23 (1.00-1.51), respectively. In the subgroup analysis, the association between Hani ethnicity and HBV infection was significantly higher in women aged 35 years or older (aOR = 5.15; 95% CI, 1.51-17.55) than in women younger than 35 years of age (aOR = 1.69; 95% CI, 1.00-2.86). CONCLUSIONS: HBV infection among 15,641 pregnant women was of high-intermediate endemicity in Yunnan, China. Advanced age, Hani ethnicity, unemployment, and multigravid and multiparous statuses were associated with an increased prevalence of HBV infection. High-risk pregnant women should be paid more attention during routine antenatal examination.

20.
Biomacromolecules ; 21(10): 3966-3983, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32960043

RESUMO

Wound dressings are widely used to promote wound healing. Traditional dressings need the help of tape to fix onto the wounds, which are not suitable in the human body. In addition, hemostasis of internal wounds is usually treated with direct sutures which will cause secondary trauma to the patient and increase the risk of infection. Therefore, development of new dressings with high tissue adhesion and biocompatibility is of great clinical significance. The highly adhesive wound dressings can firmly attach to external and internal wounds, and form a barrier to prevent bacterial invasion, accelerate healing, and avoid secondary damage caused by sutures. Hydrogels are soft materials that possess a 3D network structure with tunable physical and chemical properties, which provides ideal conditions to support the wound healing process. In this review, we summarize the recent advances in developing hydrogel-based wound dressings as well as their adhesion mechanism. Moreover, the prospects of these wound dressings over the coming years are also covered.

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