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Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.
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BACKGROUND: The incidence of colorectal cancer (CRC) in China is steadily rising, with a high proportion of advanced-stage diagnoses. This highlights the significance of early detection and prevention measures to enhance survival rates. Fecal immunochemical testing (FIT) is a globally recommended CRC screening method; however, limited research has been conducted on its application in Hainan. AIM: To assess the efficacy and adherence of FIT screening among average-risk individuals in Hainan, while also examining the risk factors associated with positive FIT results. METHODS: This population-based cross-sectional study implemented FIT screening for CRC in 2000 asymptomatic participants aged 40-75 years from five cities and 21 community health centers in Hainan Province. The study was conducted from August 2022 to April 2023, employing a stratified sampling method to select participants. Individuals with positive FIT results subsequently underwent colonoscopy. Positive predictive values for confirmed CRC and advanced adenoma were calculated, and the relationship between relevant variables and positive FIT results was analyzed using χ 2 tests and multivariate logistic regression. RESULTS: A total of 1788 participants completed the FIT screening, with a median age of 57 years (interquartile range: 40-75). Among them, 503 (28.1%) were males, and 1285 (71.9%) were females, resulting in an 89.4% compliance rate for FIT screening. The overall positivity rate of FIT was 4.4% [79 out of 1788; 95% confidence interval (CI): 3%-5%]. The specific positivity rates for Haikou, Sanya, Orient City, Qionghai City, and Wuzhishan City were 9.6% (45 of 468; 95%CI: 8%-11%), 1.3% (6 of 445; 95%CI: 0.1%-3.1%), 2.7% (8 of 293; 95%CI: 1.2%-4.3%), 3.3% (9 of 276; 95%CI: 1.0%-6.3%), and 4.2% (11 of 406; 95%CI: 1.2%-7.3%), respectively. Significant associations were found between age, dietary habits, and positive FIT results. Out of the 79 participants with positive FIT results, 55 underwent colonoscopy, demonstrating an 82.2% compliance rate. Among them, 10 had a clean gastrointestinal tract, 43 had polyps or adenomas, and 2 were confirmed to have CRC, yielding a positive predictive value of 3.6% (95%CI: 0.9%-4.2%). Among the 43 participants with polyps or adenomas, 8 were diagnosed with advanced adenomas, resulting in an advanced adenoma rate of 14.5% (95%CI: 10.1%-17.7%). CONCLUSION: In the Hainan region, FIT screening for CRC among asymptomatic individuals at average risk is feasible and well-received.
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Nitric oxide (NO) / ß-Lapachone (Lap) combined therapy by causing oxidative stress is an effective tumor therapy strategy. Herein, a dual-responsive lipid nanoparticles (LNPs) LSNO for NO / Lap co-delivery were constructed from the zinc-coordinated lipid (DSNO(Zn)) and the hydrophobic drug Lap in the presence of helper lipids (DOPE and DSPE-PEG2000). The zinc-coordinated structure in LSNO might elevate the Zn2+ content in tumor cells, contributing to antioxidant imbalance. The fluorescent assays proved the light-triggered NO release and fluorescent self-reporting abilities of LSNO. In addition, the LNPs had good drug release behavior under high concentration of GSH, indicating the NO / drug co-delivery capacity. In vitro antitumor assays showed that the NO / Lap combination treatment group could induce more significant tumor cell growth inhibition and cell apoptosis than individual NO or Lap treatment. The following mechanism studies revealed that NO / Lap combination treatment led to distinct oxidative stress by producing reactive oxygen species (ROS) and peroxynitrite anion (ONOO-). On the other hand, the intracellular redox balance could be further disrupted by Lap-induced NADPH consumption and Zn2+ / NO-induced reductase activities downregulation, thus promoting the degree of cell damage. Besides, it was also found that NO and Lap could directly damage nuclear DNA and induce mitochondrial dysfunction, thereby leading to caspase-3 activation and tumor cell death. These results proved that LSNO could serve as a promising multifunctional tumor therapy platform.
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Nanopartículas , Naftoquinonas , Óxido Nítrico , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio , Naftoquinonas/administração & dosagem , Naftoquinonas/farmacologia , Naftoquinonas/química , Óxido Nítrico/metabolismo , Óxido Nítrico/administração & dosagem , Humanos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Zinco/química , Zinco/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Lipídeos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologiaRESUMO
The nonviral delivery systems that combine genes with photosensitizers for multimodal tumor gene/photodynamic therapy (PDT) have attracted much attention. In this study, a series of ROS-sensitive cationic bola-lipids were applied for the gene/photosensitizer codelivery. Zn-DPA was introduced as a cationic headgroup to enhance DNA binding, while the hydrophobic linking chains may facilitate the formation of lipid nanoparticles (LNP) and the encapsulation of photosensitizer Ce6. The length of the hydrophobic chain played an important role in the gene transfection process, and 14-TDZn containing the longest chains showed better DNA condensation, gene transfection, and cellular uptake. 14-TDZn LNPs could well load photosensitizer Ce6 to form 14-TDC without a loss of gene delivery efficiency. 14-TDC was used for codelivery of p53 and Ce6 to achieve enhanced therapeutic effects on the tumor cell proliferation inhibition and apoptosis. Results showed that the codelivery system was more effective in the inhibition of tumor cell proliferation than individual p53 or Ce6 monotherapy. Mechanism studies showed that the production of ROS after Ce6 irradiation could increase the accumulation of p53 protein in tumor cells, thereby promoting caspase-3 activation and inducing apoptosis, indicating some synergistic effect. These results demonstrated that 14-TDC may serve as a promising nanocarrier for gene/PDT combination therapy.
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Lipossomos , Nanopartículas , Fotoquimioterapia , Porfirinas , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Linhagem Celular Tumoral , Nanopartículas/química , DNA , Porfirinas/químicaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) has a poor long-term prognosis. The competition of circular RNAs (circRNAs) with endogenous RNA is a novel tool for predicting HCC prognosis. Based on the alterations of circRNA regulatory networks, the analysis of gene modules related to HCC is feasible. METHODS: Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC. Gene function, pathway, and protein interaction analyses were performed for the differentially expressed genes (DEGs) in this regulatory network. In the protein-protein interaction network, hub genes were identified and subjected to regression analysis, producing an optimized four-gene signature for prognostic risk stratification in HCC patients. Anti-HCC drugs were excavated by assessing the DEGs between the low- and high-risk groups. A circRNA-microRNA-hub gene subnetwork was constructed, in which three hallmark genes, KIF4A, CCNA2, and PBK, were subjected to functional enrichment analysis. RESULTS: A four-gene signature (KIF4A, CCNA2, PBK, and ZWINT) that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort was developed. CDK inhibitors, PI3K inhibitors, HDAC inhibitors, and EGFR inhibitors were predicted as four potential mechanisms of drug action (MOA) in high-risk HCC patients. Subsequent analysis has revealed that PBK, CCNA2, and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion, regulating microsatellite instability (MSI), and exerting an impact on HCC progression. CONCLUSIONS: The present study highlights the role of the circRNA-related regulatory network, identifies a four-gene prognostic signature and biomarkers, and further identifies novel therapy for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , RNA Circular/genética , Prognóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , RNA Endógeno Competitivo , Fosfatidilinositol 3-Quinases , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , MicroRNAs/genética , Microambiente Tumoral , CinesinasRESUMO
BACKGROUND: Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. RESULTS: Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3'UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3'UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. CONCLUSIONS: This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis.
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Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Humanos , Zika virus/genética , Infecção por Zika virus/genética , RNA Viral/genética , Regiões 3' não Traduzidas , Vírus da Dengue/genética , Vírus da Dengue/metabolismo , Replicação Viral , Dengue/genética , Antivirais , Dineínas/genética , Dineínas/metabolismoRESUMO
Gap junction (GJ) is a special cell membrane structure composed of connexin. Connexin is widely distributed and expressed in all tissues except differentiated skeletal muscle, red blood cells, and mature sperm cells, which is related to the occurrence of many genetic diseases due to its mutation. Its function of regulating immune response, cell proliferation, migration, apoptosis, and carcinogenesis makes it a therapeutic target for a variety of diseases. In this paper, the possible mechanism of its action in nervous system-related diseases and treatment are reviewed.
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Conexina 43 , Conexinas , Masculino , Humanos , Conexinas/genética , Conexinas/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Sêmen/metabolismo , Junções Comunicantes/metabolismo , Sistema Nervoso/metabolismoRESUMO
Wood-rotting basidiomycetes have been investigated in the Chinese forest ecosystem for the past 30 years. Two hundred and five pathogenic wood-decayers belonging to 9 orders, 30 families, and 74 genera have been found in Chinese native forests, plantations, and gardens. Seventy-two species (accounting for 35% of the total pathogenic species) are reported as pathogenic fungi in China for the first time. Among these pathogens, 184 species are polypores, nine are corticioid fungi, eight are agarics and five are hydnoid basidiomycetes. One hundred and seventy-seven species (accounting for 86%) cause white rot, while 28 species (accounting for 14%) result in brown rot; 157 species grow on angiosperm trees (accounting for 76.5%) and 44 species occur on gymnosperm trees (accounting for 21.5%), only four species inhabit both angiosperms and gymnosperms (accounting for 2%); 95 species are distributed in boreal to temperate forests and 110 in subtropical to tropical forests. In addition, 17 species, including Fomitopsis pinicola, Heterobasidion parviporum, and Phellinidium weirii etc. which were previously treated as pathogenic species in China, do not occur in China according to recent studies. In this paper, the host(s), type of forest, rot type, and distribution of each pathogenic species in China are given.
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OBJECTIVES: Ferroptosis is a newly discovered cell death mode that has been confirmed to occur in the intestinal epithelial cells in ulcerative colitis (UC). In this study we aimed to elucidate the mechanism of ferroptosis and its association with adenosine monophosphate-activated protein kinase (AMPK) in UC. METHODS: Gene expression profiles of colonic mucosa (GSE87473) were downloaded. Both human colonic samples and dextran sodium sulfate (DSS)-induced colitis murine model were used. The molecular markers of ferroptosis were detected using western blot and immunohistochemistry. Symptoms, iron abundance, and lipid peroxidation level of the mouse model were measured to evaluate the role of AMPK activation in ferroptosis. RESULTS: Both gene and protein expressions of GPX4 and FTH1 were decreased in UC patients compared with the healthy controls. An increased iron abundance and lipid peroxidation level in colon tissues and damaged mitochondria were found in DSS-induced colitis. AMPK expression was decreased in UC patients and correlated with FTH1 and GPX4. Activation of AMPK with metformin inhibited ferroptosis in the colon, improved symptoms, and prolonged the lifespan in DSS-induced colitis mice. CONCLUSIONS: Ferroptosis can be observed in colonic tissues in UC. AMPK activation inhibits ferroptosis in murine colitis model, which may act as a potential target for the treatment of colitis.
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Colite Ulcerativa , Colite , Ferroptose , Humanos , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/metabolismo , Modelos Animais de Doenças , Ferro/efeitos adversos , Ferro/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Endometrial decidualization refers to a series of morphological changes and functional remodeling of the uterine endometrium to accept the embryo under the effect of estrogen and progesterone secreted by ovaries after ovulation. During decidualization, endometrial stromal cells (ESCs) proliferate and differentiate into decidual stromal cells, undergoing cytoskeletal rearrangement-mediated morphological changes and expressing decidualization markers, such as insulin-like growth factor-binding protein-1 and prolactin. Ras homology (Rho) proteins, a family of small G proteins, are well known as regulators of cellular morphology and involved in multiple other cellular processes. In this study, we found ras homolog family member B (RHOB) was the most significantly upregulated gene in the Rho protein family after the in vitro decidualization of human primary ESCs. RhoB expression was induced mainly by 3',5'-cyclic adenosine 5'-monophosphate (cAMP) / protein kinase A (PKA) / cyclic adenosine monophosphate-response element binding protein signaling and partly by progesterone signaling. Knockdown of RhoB in ESCs greatly inhibited actin cytoskeletal rearrangement, cell morphological transformation, and upregulation of insulin-like growth factor-binding protein-1, suggesting an indispensable role of RhoB in decidualization. Mechanistically, the downstream target of RhoB was semaphorin3A (Sema3A), which mediated its signaling via interacting with the receptor, plexinA4. More importantly, decreased expression of RhoB, Sema3A, and plexinA4 were detected in deciduas from patients with unexplained spontaneous miscarriage. Collectively, our results indicate that RhoB/Sema3A/plexinA4 signaling plays a positive role in endometrial decidualization and relates to unexplained spontaneous miscarriage, which is worthy of further exploration so as to provide new insights into therapeutic strategies for pregnancy diseases associated with poor decidualization.
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Proteínas Monoméricas de Ligação ao GTP , Receptores de Superfície Celular , Semaforina-3A , Células Estromais , Proteína rhoB de Ligação ao GTP , Aborto Espontâneo/metabolismo , Actinas/metabolismo , Monofosfato de Adenosina/metabolismo , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Decídua/metabolismo , Endométrio/metabolismo , Estrogênios/farmacologia , Feminino , Humanos , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Gravidez , Progesterona/metabolismo , Prolactina/metabolismo , Receptores de Superfície Celular/metabolismo , Semaforina-3A/metabolismo , Células Estromais/metabolismo , Proteína rhoB de Ligação ao GTP/metabolismoRESUMO
When seeds fallen from the mother trees, their initial contact physical environment was litter or soil. The dispersal positions of seeds (seeds positioned on top of the litter, the soil surface and beneath the litter) determine the process of their natural regeneration. We simulated three different dispersal positions of Castanopsis kawakamii, including seeds positioned on top of the litter (2 and 4 cm litter was placed below the seed layer), soil surface (without litter), and seeds beneath the litter (2, 4, 6 and 8 cm litter covers in the upper layer of seeds). We examined the effects of seed dispersal position on the chlorophyll fluorescence characteristics, non-structural carbohydrate, specific leaf area, leaf dry matter content and nutrient content of seedlings. The results showed that leaf nitrogen content per area of seedlings had significantly positive correlation with soluble sugar content, non-structural carbohydrate content, and negative correlation with specific leaf area across different dispersal positions. Seedlings of the moderate litter cover (2 and 4 cm) adopted resource acquisitive strategies by increasing relative chlorophyll content, soluble sugar content, non-structural carbohydrate content, leaf dry matter content, leaf nitrogen content and phosphorus contents per area, and decreasing specific leaf area to achieve their demands for rapid growth. Seedlings grew on soil surface and beneath the deep litter (6 and 8 cm) adopted the resource conservative strategies with higher leaf nitrogen content per mass and specific leaf area, lower leaf dry matter content, and non-structural carbohydrate content to intercept more effective light resources to compensate for the shady environment brought by deep litter. This would further decrease the probability of seedling mortality due to 'carbon starvation'. Seedlings under litter layer stored starch in leaf, and reduced the energy consumption of photosynthetic tissues (low PSâ ¡ maximum photochemical efficiency) to maintain seedling growth. Comprehensive analysis of entropy method indicated that low amount of litter cover (2 cm) significantly promoted seedling growth of C. kawakamii. In the future, we could regulate the thickness of litter layer to promote the growth and regeneration of C. kawakamii seedlings in natural forest.
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Fagaceae , Dispersão de Sementes , Carboidratos , Clorofila , Fluorescência , Nitrogênio/farmacologia , Plântula , Sementes , Solo , Açúcares/farmacologiaRESUMO
A novel three-dimensional CdII coordination polymer, namely, poly[[(µ3-benzene-1,4-diacetato)(µ2-benzene-1,4-diacetato)bis{µ2-bis[4-(2-methylimidazol-1-yl)phenyl]methanone}dicadmium(II)] tetartohydrate], {[Cd(C10H8O4)(C21H18N4O)]·0.25H2O}n or {[Cd(PBEA)(MIPMO)]·0.25H2O}n, (I), was synthesized by the hydrothermal method using benzene-1,4-diacetic acid (H2PBEA), bis[4-(2-methylimidazol-1-yl)phenyl]methanone (MIPMO) and Cd(NO3)2·6H2O. The title compound was structurally characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy and thermogravimetric analysis, and exhibits a three-dimensional pillar-layer framework based on CdII-PBEA layers and MIPMO pillars, which can be simplified into a pcu topological network. The title compound displays a highly selective and sensitive sensing for Fe3+ ions in aqueous solution. In addition, it displays a high photocatalytic activity for the degradation of methylene blue (MB) in water under UV light irradiation.
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The wood-inhabiting fungi play an integral role in wood degradation and the cycle of matter in the ecological system. They are considered as the "key player" in wood decomposition, because of their ability to produce all kinds of enzymes that break down woody lignin, cellulose and hemicellulose. In the present study, three new wood-inhabiting fungal species, Steccherinum fissurutum, S. punctatum and S. subtropicum spp. nov., collected from southern China, are proposed based on a combination of morphological features and molecular evidence. Steccherinum fissurutum is characterized by the resupinate, subceraceous basidiomata with cracked hymenophore, a monomitic hyphal system with clamped generative hyphae and cylindrical basidiospores; S. punctatum is characterized by the annual, punctate basidiomata with leathery hymenophore, cylindrical, strongly encrusted cystidia and ellipsoid basidiospores (3.6-4.5 ×2.6-3.4 µm); S. subtropicum is characterized by its effuse-reflexed basidiomata, a odontioid hymenophore with pink to lilac hymenial surface and ellipsoid basidiospores measuring as (2.8-3.4 × 2.0-2.7 µm). Sequences of ITS and nLSU rRNA markers of the studied samples were generated, and phylogenetic analyses were performed with maximum likelihood, maximum parsimony, and Bayesian inference methods. The ITS+nLSU analysis of the family Steccherinaceae indicated that the three new species clustered into the genus Steccherinum. Based on further analysis of ITS+nLSU dataset, the phylogenetic analysis confirmed that S. subtropicum was sister to S. enuispinum; S. fissurutum formed a monophyletic lineage; S. punctatum grouped with a clade comprised S. straminellum and S. ciliolatum.
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Basidiomycota , Polyporales , Polyporales/genética , Filogenia , Teorema de Bayes , ChinaRESUMO
Natural killer (NK) cells preferentially accumulate at maternal-foetal interface and are believed to play vital immune-modulatory roles during early pregnancy and related immunological dysfunction may result in pregnant failure such as recurrent miscarriage (RM). However, the mechanisms underlying the establishment of maternal-foetal immunotolerance are complex but clarifying the roles of decidual NK (dNK) cells offers the potential to design immunotherapeutic strategies to assist RM patients. In this report, we analysed RNA sequencing on peripheral NK (pNK) and decidual NK cells during early pregnancy; we identified an immunomodulatory dNK subset CXCR4+ CD56bright dNK and investigated its origin and phenotypic and functional characteristics. CXCR4+ CD56bright dNK displayed a less activated and cytotoxic phenotype but an enhanced immunomodulatory potential relative to the CXCR4 negative subset. CXCR4+ CD56bright dNK promote Th2 shift in an IL-4-dependent manner and can be recruited from peripheral blood and reprogramed by trophoblasts, as an active participant in the establishment of immune-tolerance during early pregnancy. Diminished CXCR4+ dNK cells and their impaired ability to induce Th2 differentiation were found in RM patients and mouse models of spontaneous abortion. Moreover, adoptive transfer of CXCR4+ dNK cells to NK-deficient (Nfil3-/-) mice showed great therapeutic potential of CXCR4+ dNK via recovering the Th2/Th1 bias and reducing embryo resorption rates. The identification of this new dNK cell subset may lay the foundation for understanding NK cell mechanisms in early pregnancy and provide potential prognostic factors for the diagnosis and therapy of RM.
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Aborto Habitual/prevenção & controle , Tolerância Imunológica/imunologia , Células Matadoras Naturais/imunologia , Receptores CXCR4/genética , Receptores CXCR4/imunologia , Aborto Habitual/sangue , Aborto Habitual/imunologia , Animais , Decídua/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Moléculas de Adesão de Célula Nervosa/sangue , Moléculas de Adesão de Célula Nervosa/genética , Moléculas de Adesão de Célula Nervosa/imunologia , Gravidez , Primeiro Trimestre da Gravidez , Receptores CXCR4/sangueRESUMO
PURPOSE: Cancer stem cells (CSCs) have been considered involving in tumorigenesis, local recurrence, and therapeutic drug resistance of hepatocellular carcinoma (HCC). To investigate novel and effective methods for targeting hepatic CSCs is crucial for a permanent cure of liver cancer. METHODS: The expression level of SIRT1 was detected in CSCs of HCC tissues and cancer cell lines. Expression of CSC markers, the self-renewal and tumorigenic ability of liver CSCs were analyzed with SIRT1 inhibition. Cellular senescence-related markers were used to detect CSCs senescence after inhibition of SIRT1. RESULTS: SIRT1 was highly expressed in CSCs of HCC cell lines and human HCC tissues. In vitro study revealed that decreasing of SIRT1 level significantly downregulated the stemness-associated genes of liver CSCs and reduced the CSC stemness properties. Also, downregulated SIRT1 suppressed liver CSCs proliferation by decreasing their self-renewal abilities. Furthermore, CSCs with decreased SIRT1 expression showed limited tumorigenicity and formed smaller HCC tumor in vivo. And SIRT1 decreased CSCs became more susceptible to chemotherapeutic drugs. Mechanistically, SIRT1 decreased CSCs became senescence through the activation of p53-p21 and p16 pathway. The data further indicated that the tumor formed from SIRT1-knockdown CSCs exhibited higher senescence-associated ß-galactosidase (SA-ß-Gal) activity but lower proliferative capacity. CONCLUSION: Taken together, these findings pointed that induction of senescence in liver CSCs is an effective tumor suppression method for HCC, and SIRT1 may be served as a promising target for HCC treatment.
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Small cell lung cancer (SCLC), an aggressive and devastating malignancy, is characterized by rapid growth and early metastasis. Although most patients respond to first-line chemotherapy, the majority of patients rapidly relapse and have a relatively poor prognosis. Fortunately, immunotherapy, mainly including antibodies that target the cytotoxic T lymphocyte antigen-4 (CTLA-4), checkpoints programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) to block immune regulatory checkpoints on tumor cells, immune cells, fibroblasts cells and endothelial cells, has achieved the milestone in several solid tumors, such as melanoma and non-small-cell lung carcinomas (NSCLC). In recent years, immunotherapy has made progress in the treatment of patients with SCLC, while its response rate is relatively low to monotherapy. Interestingly, the combination of immunotherapy with other therapy, such as chemotherapy, radiotherapy, and targeted therapy, preliminarily achieve greater therapeutic effects for treating SCLC. Combining different immunotherapy drugs may act synergistically because of the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of chemoradiotherapy in immunotherapy may augment antitumor immune responses because chemoradiotherapy can enhance tumor cell immunogenicity by rapidly inducing tumor lysis and releasing tumor antigens. In addition, since immunotherapy drugs and the molecular targets drugs act on different targets and cells, the combination of these drugs may achieve greater therapeutic effects in the treatment of SCLC. In this review, we focused on the completed and ongoing trials of the combination therapy for immunotherapy of SCLC to find out the rational combination strategies which may improve the outcomes for SCLC.
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With the changing lifestyle and the acceleration of aging in the Chinese population, the incidence and mortality of colorectal cancer (CRC) have risen in the last decades. On the contrary, the incidence and mortality of CRC have continued to decline in the USA since the 1980s, which is mainly attributed to early screening and standardized diagnosis and treatment. Rectal cancer accounts for the largest proportion of CRC in China, and its treatment regimens are complex. At present, surgical treatment is still the most important treatment for rectal cancer. Since the first Chinese guideline for diagnosis and treatment of CRC was issued in 2010, the fourth version has been revised in 2020. These guidelines have greatly promoted the standardization and internationalization of CRC diagnosis and treatment in China. And with the development of comprehensive treatment methods such as neoadjuvant chemoradiotherapy, targeted therapy, and immunotherapy, the post-operative quality of life and prognosis of patients with rectal cancer have improved. We believe that the inflection point of the rising incidence and mortality of rectal cancer will appear in the near future in China. This article reviewed the current status and research progress on surgical therapy of rectal cancer in China.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , China/epidemiologia , Humanos , Qualidade de Vida , Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgiaRESUMO
Heterobasidion species are amongst the most intensively studied polypores because several species are aggressive white rot pathogens of managed coniferous forests mainly in Europe and North America. In the present study, both morphological and multilocus phylogenetic analyses were carried out on Heterobasidion samples from Asia, Oceania, Europe and North America. Three new taxa were found, i.e., H. armandii, H. subinsulare, and H. subparviporum are from Asia and are described as new species. H. ecrustosum is treated as a synonym of H. insulare. So far, six taxa in the H. annosum species complex are recognized. Heterobasidion abietinum, H. annosum, and H. parviporum occur in Europe, H. irregulare, and H. occidentale in North America, and H. subparviporum in East Asia. The North American H. irregulare was introduced to Italy during the Second World War. Species in the H. annosum complex are pathogens of coniferous trees, except H. subparviporum that seems to be a saprotroph. Ten species are found in the H. insulare species complex, all of them are saprotrophs. The pathogenic species are distributed in Europe and North America; the Asian countries should consider the European and North American species as entry plant quarantine fungi. Parallelly, European countries should consider the American H. occidentale and H. irregulare as entry plant quarantine fungi although the latter species is already in Italy, while North America should treat H. abietinum, H. annosum s.s., and H. parviporum as entry plant quarantine fungi. Eight Heterobasidion species found in the Himalayas suggest that the ancestral Heterobasidion species may have occurred in Asia.
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BACKGROUND: Acute liver failure (ALF) is a significant and complex hepatic insult that may rapidly progress to life-threatening conditions. Recently, menstrual blood stem cells (MenSCs) have been identified as a group of easily accessible mesenchymal stem cells with the advantages of non-invasive acquisition, low immunogenicity, a greater capacity of self-renewal and multi-lineage differentiation, making them promising candidates for stem cell-based therapy to revolutionize the treatment strategies for liver failure. AIM: To investigate the therapeutic potential of MenSCs for treating ALF in pigs and to dynamically trace the biodistribution of transplanted cells. METHODS: MenSCs were labeled in vitro with PKH26, a lipophilic fluorescent dye. The treatment group received immediate transplantation of PKH26-labelled MenSCs (2.5 × 106/kg) via the portal vein after D-galactosamine injection, and the control group underwent sham operation. The survival time, liver function, and hepatic pathological changes were compared between the two groups. Three major organs (liver, lungs and spleen) were extracted from animals and imaged directly with the In vivo Imaging System (IVIS) at the predetermined time points. The regions of interest were drawn to quantify the cell uptake in different organs. RESULTS: The labelling procedure did not affect the morphology, viability or multipotential differentiation of MenSCs. Biochemical analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and prothrombin time (PT) measured at selected time points 24 h after transplantation were significantly decreased in the treatment group (P < 0.05). The survival time of ALF animals was prolonged in the treatment group compared with the control group (75.75 ± 5.11 h vs 53.75 ± 2.37 h, log rank, P < 0.001). The liver pathological tissue in the MenSC treatment group showed obviously increased numbers of remaining hepatocytes and a comparatively slight necrotic degree and area. In addition, the IVIS imaging revealed that PKH26-positive MenSCs were clearly retained in the liver initially and then diffused through the systemic circulation. Interestingly, the signal intensity in the liver increased obviously at 36 h, which corresponded to the biochemical result that liver function deteriorated most rapidly at 24 - 36 h. CONCLUSION: Our study demonstrates the therapeutic efficacy and homing ability of transplanted MenSCs in a large animal model of ALF and suggests that MenSC transplantation could be a promising strategy for treating ALF.