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1.
Cell Prolif ; : e13000, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666296

RESUMO

OBJECTIVES: Mammalian spermatogenesis is a biological process of male gamete formation. Gonocytes are the only precursors of spermatogonial stem cells (SSCs) which develop into mature spermatozoa. DDX5 is one of DEAD-box RNA helicases and expresses in male germ cells, suggesting that Ddx5 plays important functions during spermatogenesis. Here, we explore the functions of Ddx5 in regulating the specification of gonocytes. MATERIALS AND METHODS: Germ cell-specific Ddx5 knockout (Ddx5-/- ) mice were generated. The morphology of testes and epididymides and fertility in both wild-type and Ddx5-/- mice were analysed. Single-cell RNA sequencing (scRNA-seq) was used to profile the transcriptome in testes from wild-type and Ddx5-/- mice at postnatal day (P) 2. Dysregulated genes were validated by single-cell qRT-PCR and immunofluorescent staining. RESULTS: In male mice, Ddx5 was expressed in germ cells at different stages of development. Germ cell-specific Ddx5 knockout adult male mice were sterile due to completely devoid of germ cells. Male germ cells gradually disappeared in Ddx5-/- mice from E18.5 to P6. Single-cell transcriptome analysis showed that genes involved in cell cycle and glial cell line-derived neurotrophic factor (GDNF) pathway were significantly decreased in Ddx5-deficient gonocytes. Notably, Ddx5 ablation impeded the proliferation of gonocytes. CONCLUSIONS: Our study reveals the critical roles of Ddx5 in fate determination of gonocytes, offering a novel insight into the pathogenesis of male sterility.

2.
Emerg Microbes Infect ; 10(1): 424-438, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33622191

RESUMO

Human adenovirus (HAdV) species B can cause severe acute respiratory diseases. However, the researches to combat this infection have been hampered by the lack of an animal model permissive to the virus. Here, we report in vitro and in vivo HAdV species B infections of tree shrews, the closest relative of primates. HAdV-3, -7, -14, and -55 efficiently replicated in primary cell cultures. After intranasal inoculation of tree shrews with HAdV-55, the viral replication in the oropharyngeal region remained high until day 5 post-infection and was still detected until day 12. HAdV-55 in the lung or turbinate bone tissues reached the highest levels between days 3 and 5 post-infection, which indicated viral replication in the upper and lower respiratory tracts. HAdV-55 infection caused severe interstitial pneumonia in the animal. IL-8, IL-10, IL-17A, and IFN-γ expression in the peripheral blood mononuclear cells from infected animals was up-regulated. The pre-vaccination with HAdV-55 cleared the virus faster in the respiratory tract, mitigated lung pathological changes. Finally, HAdV-55 infection was propagated among tree shrews. Our study demonstrated that the tree shrew is a permissive animal model for HAdV species B infection and may serve as a valuable platform for testing multiple anti-viral treatments.

3.
Ecotoxicol Environ Saf ; 208: 111687, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396019

RESUMO

Manganese (Mn) is demonstrated to be essential for plants. Ion homeostasis is maintained in plant cells by specialized transporters. PbMTP8.1, which encodes a putative Mn-CDF transporter in Pyrus bretschneideri Rehd, was expressed mainly in leaves and complemented the Mn hypersensitivity of the Mn-sensitive yeast mutant △pmr1 in previous research conducted by our laboratory. In the present study, we report that the expression of PbMTP8.1 can enhance Mn tolerance and accumulation in Saccharomyces cerevisiae. Subcellular localization analysis of the PbMTP8.1-GFP fusion protein indicated that PbMTP8.1 was targeted to the pre-vacuolar compartment (PVC). In addition, the overexpression of PbMTP8.1 in Arabidopsis thaliana conferred increased resistance to plants under toxic Mn levels, as indicated by increased fresh and dry weights of shoots and roots. Mn accumulation in vacuoles of PbMTP8.1-overexpressing plants was significantly increased when compared with that in wild-type plants under Mn stress. This suggests that a considerable proportion of Mn enters into the vacuoles through a PbMTP8.1-dependent mechanism. Taken together, these results indicate PbMTP8.1 is a Mn-specific transporter that is localized to the PVC, and confers Mn tolerance by sequestering Mn into the vacuole.


Assuntos
Arabidopsis/metabolismo , Proteínas de Transporte de Cátions/genética , Poluentes Ambientais/toxicidade , Manganês/toxicidade , Pyrus/metabolismo , Saccharomyces cerevisiae/metabolismo , Adaptação Biológica/genética , Arabidopsis/genética , Poluentes Ambientais/metabolismo , Manganês/metabolismo , Células Vegetais/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Pyrus/genética , Saccharomyces cerevisiae/genética , Vacúolos/metabolismo
4.
FEBS Open Bio ; 11(3): 932-943, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33470057

RESUMO

TWIST1 is an important basic helix-loop-helix protein linked to multiple physiological and pathological processes. Although TWIST1 is believed to be involved in vascular pathogenesis, its effects on homeostasis of smooth muscle cells (SMCs) remain poorly understood. Here, we show that TWIST1 protein levels were significantly elevated during SMC phenotypic switching in vivo and in vitro. TWIST1 overexpression promoted phenotypic switching of SMCs, while siRNA targeting of TWIST1 prevented cell transition. Mechanistically, TWIST1 decreased the level of microRNA-143/145, which governs smooth muscle marker gene transcription. In addition, TWIST1 repressed p68 mRNA and protein expression, a crucial modulator of SMC behavior and microRNA biogenesis. Our co-immunoprecipitation assay demonstrated a previously unrecognized molecular interaction between TWIST1 and p68 protein. Finally, we found that TWIST1 triggered SMC phenotypic switching and suppressed microRNA-143/145 expression by promoting the proteasomal degradation of p68. These data suggest a novel role of TWIST1 in the regulation of SMC homeostasis by modulating p68/microRNA-143/145 axis.

5.
Biomed Pharmacother ; 135: 111188, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33418304

RESUMO

OBJECTIVE: Oxidative stress and apoptosis play critical roles in the pathogenesis of heart failure (HF).Nuanxin capsule (NX) is a Chinese medicine that has outstanding protective effects on HF. The present study aimed to elucidate whether NX could protect HF against oxidative stress-induced apoptosis through intrinsic mitochondrial pathway. METHODS: In vivo, HF was induced by transverse aortic constriction. NX and Compound C (Comp C) were administered to C57BL/6 J mice for over a 4-week period. Cardiac function was assessed with echocardiography. In vitro, H9c2 cells were exposed to H2O2 in the presence or absence of NX and Compound C. Cell viability, cytotoxicity, reactive oxygen species (ROS) production, apoptosis, mitochondrial membrane potential (ΔΨm) and mitochondrial function by oxygen consumption rate (OCR) were detected. The expressions of cytochrome c, BAX, Bcl-2, cleaved caspase-3, AMPK and JNK were evaluated by western blotting. RESULTS: The results indicated that NX significantly improved cardiac function and enhanced the cell viability, ΔΨm and mitochondrial respiration. Also NX treatment reduced cell cytotoxicity and ROS production. Moreover, NX inhibited mitochondrial-mediated apoptosis by upregulating AMPK and downregulating JNK both in vivo and in vitro. The protective effects of NX on cardiac function by reducing oxidative stress-induced mitochondrial dependent apoptosis were reversed by Compound C treatment. CONCLUSIONS: These findings demonstrated that NX effectively improved cardiac function in TAC mice by reducing oxidative stress-induced mitochondrial dependent apoptosis by activating AMPK/JNK signaling pathway.

6.
ACS Nano ; 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33370531

RESUMO

Flexible and high-performance batteries are urgently required for powering flexible/wearable electronics. Lithium-sulfur batteries with a very high energy density are a promising candidate for high-energy-density flexible power source. Here, we report flexible lithium-sulfur full cells consisting of ultrastable lithium cloth anodes, polysulfone-functionalized separators, and free-standing sulfur/graphene/boron nitride nanosheet cathodes. The carbon cloth decorated with lithiophilic three-dimensional MnO2 nanosheets not only provides the lithium anodes with an excellent flexibility but also limits the growth of the lithium dendrites during cycling, as revealed by theoretical calculations. Commercial separators are functionalized with polysulfone (PSU) via a phase inversion strategy, resulting in an improved thermal stability and smaller pore size. Due to the synergistic effect of the PSU-functionalized separators and boron nitride-graphene interlayers, the shuttle of the polysulfides is significantly inhibited. Because of successful control of the shuttle effect and dendrite formation, the flexible lithium-sulfur full cells exhibit excellent mechanical flexibility and outstanding electrochemical performance, which shows a superlong lifetime of 800 cycles in the folded state and a high areal capacity of 5.13 mAh cm-2. We envision that the flexible strategy presented herein holds promise as a versatile and scalable platform for large-scale development of high-performance flexible batteries.

7.
Cancer Sci ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164305

RESUMO

High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in hepatocellular carcinoma (HCC) cells remains largely unclear. Here, we demonstrated that the expression HMGA2 was upregulated in HCC, and the elevated HMGA2 could promote tumor metastasis. Incubation HCC cells with Epidermal Growth Factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, while a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.

8.
Virol Sin ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165772

RESUMO

Human adenoviruses (HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3, -7, -4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population. Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAb) against HAdV-3, -4, -7, -14, -55, and -11 in total 278 healthy populations between 0 months and 49 years of age (228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at 12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1-2, 3-5, and 6-17 years, respectively. The seroprevalence was very low (0% ~ 8.1%) for all other four types. In adults aged between 18 and 49 years, HAdV-3, -4, and -7 (> 50.00%) were the most common types, followed by HAdV-14 (38.00%), -55 (34.00%), and -11 (24.00%). Adults tended to have high NAb titers against HAdV-4 and -55. HAdV-55-seropositive donors tended to be HAdV-11- and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14, -55, -11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.

9.
Sci Signal ; 13(657)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172955

RESUMO

The protein Dickkopf-1 (DKK1) is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC) and promotes metastatic progression through the induction of ß-catenin, a Wnt signaling effector. We investigated how DKK1 expression is induced in HCC and found that activation of the epidermal growth factor receptor (EGFR) promoted parallel MEK-ERK and PI3K-Akt pathway signaling that converged to epigenetically stimulate DKK1 transcription. In HCC cell lines stimulated with EGF, EGFR-activated ERK phosphorylated the kinase PKM2 at Ser37, which promoted its nuclear translocation. Also in these cells, EGFR-activated Akt phosphorylated the acetyltransferase p300 at Ser1834 Subsequently, PKM2 and p300 mediated the phosphorylation and acetylation, respectively, of histone H3 at the DKK1 promoter, which synergistically enhanced DKK1 transcription. The mechanism was supported with mutational analyses in cells and in a chemically induced HCC model in rats. The findings suggest that dual inhibition of the MEK and PI3K pathways might suppress the expression of DKK1 and, consequently, tumor metastasis in patients with HCC.

10.
Nanoscale ; 12(43): 22234-22244, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33141137

RESUMO

We find that the use of Au substrate allows fast, self-limited WS2 monolayer growth using a simple sequential exposure pattern of low cost, low toxicity precursors, namely tungsten hexacarbonyl and dimethylsulfide (DMS). We use this model reaction system to fingerprint the technologically important metal organic chemical vapour deposition process by operando X-ray photoelectron spectroscopy (XPS) to address the current lack of understanding of the underlying fundamental growth mechanisms for WS2 and related transition metal dichalcogenides. Au effectively promotes the sulfidation of W with simple organosulfides, enabling WS2 growth with low DMS pressure (<1 mbar) and a suppression of carbon contamination of as-grown WS2, which to date has been a major challenge with this precursor chemistry. Full WS2 coverage can be achieved by one exposure cycle of 10 minutes at 700 °C. We discuss our findings in the wider context of previous literature on heterogeneous catalysis, 2D crystal growth, and overlapping process technologies such as atomic layer deposition (ALD) and direct metal conversion, linking to future integrated manufacturing processes for transition metal dichalcogenide layers.

11.
Theor Appl Genet ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068118

RESUMO

KEY MESSAGE: A minor QTL for grain weight in rice, qTGW1.2b, was fine-mapped. Its casual gene OsVQ4 was confirmed through CRISPR/Cas9-targeted mutagenesis, exhibiting an effect that was larger than the original QTL effect. The CRISPR/Cas system exhibits a great potential for rice improvement, but the application was severely hindered due to insufficient target genes, especial the lack of validated genes underlying quantitative trait loci having small effects. In this study, a minor QTL for grain weight, qTGW1.2b, was fine-mapped into a 44.0 kb region using seven sets of near isogenic lines (NILs) developed from the indica rice cross (Zhenshan 97)3/Milyang 46, followed by validation of the causal gene using CRISPR/Cas9-targeted mutagenesis. In the NIL populations, 1000-grain weight of the Zhenshan 97 homozygous lines decreased by 0.9-2.0% compared with the Milyang 46 homozygous lines. A gene encoding VQ-motif protein, OsVQ4, was identified as the candidate gene based on parental sequence differences. The effect of OsVQ4 was confirmed by creating CRISPR/Cas9 knockout lines, whose 1000-grain weight decreased by 2.8-9.8% compared with the wild-type transgenic line and the recipient. These results indicate that applying genome editing system could create novel alleles with large phenotypic variation at minor QTLs, which is an effective way to validate causal genes of minor QTLs. Our study establishes a strategy for cloning minor QTLs, which could also be used to identify a large number of potential target genes for the application of CRISPR/Cas system.

12.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120315052, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33028095

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction and vascular remodeling. Despite significant advancement in our understanding of the pathogenesis of PAH in recent years, treatment options for PAH are limited and their prognosis remains poor. PAH is now seen as a severe pulmonary arterial vasculopathy with structural changes driven by excessive vascular proliferation and inflammation. Perturbations of a number of cellular and molecular mechanisms have been described, including pathways involving growth factors, cytokines, metabolic signaling, elastases, and proteases, underscoring the complexity of the disease pathogenesis. Interestingly, emerging evidence suggest that stem/progenitor cells may have an impact on disease development and therapy. In preclinical studies, stem/progenitor cells displayed an ability to promote endothelial repair of dysfunctional arteries and induce neovascularization. The stem cell-based therapy for PAH are now under active investigation. This review article will briefly summarize the updates in the research field, with a special focus on the contribution of stem/progenitor cells to lesion formation via influencing vascular cell functions and highlight the potential clinical application of stem/progenitor cell therapy to PAH.

13.
ACS Nano ; 14(11): 15293-15305, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33104341

RESUMO

We present multiplexer methodology and hardware for nanoelectronic device characterization. This high-throughput and scalable approach to testing large arrays of nanodevices operates from room temperature to milli-Kelvin temperatures and is universally compatible with different materials and integration techniques. We demonstrate the applicability of our approach on two archetypal nanomaterials-graphene and semiconductor nanowires-integrated with a GaAs-based multiplexer using wet or dry transfer methods. A graphene film grown by chemical vapor deposition is transferred and patterned into an array of individual devices, achieving 94% yield. Device performance is evaluated using data fitting methods to obtain electrical transport metrics, showing mobilities comparable to nonmultiplexed devices fabricated on oxide substrates using wet transfer techniques. Separate arrays of indium-arsenide nanowires and micromechanically exfoliated monolayer graphene flakes are transferred using pick-and-place techniques. For the nanowire array mean values for mobility µFE = 880/3180 cm2 V-1 s-1 (lower/upper bound), subthreshold swing 430 mV dec-1, and on/off ratio 3.1 decades are extracted, similar to nonmultiplexed devices. In another array, eight mechanically exfoliated graphene flakes are transferred using techniques compatible with fabrication of two-dimensional superlattices, with 75% yield. Our results are a proof-of-concept demonstration of a versatile platform for scalable fabrication and cryogenic characterization of nanomaterial device arrays, which is compatible with a broad range of nanomaterials, transfer techniques, and device integration strategies from the forefront of quantum technology research.

14.
Medicine (Baltimore) ; 99(36): e22077, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899078

RESUMO

RATIONALE: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver with malignant potential. It can be of solitary type, multifocal type, or diffuse type. Although there are some characteristic features on radiologic imaging, the definitive diagnosis of HEH is based on histopathology. The surgical treatment of HEH includes liver resection and transplant. PATIENT CONCERNS: A middle-aged woman presented with easy fatiguability and anorexia for 1 month was found to have multifocal lesions on radiological imaging. DIAGNOSIS: HEH was diagnosed by needle biopsy. It can be seen from imaging that this case is a multifocal form. The largest lesion increased from 3 to 3.3 cm within 2 months, with an increase of 9.45%; no other relevant literatures have been reported. INTERVENTIONS: The possibility of liver transplantation was suggested to the patient. However, the patient refused transplantation and was successfully treated by radical right hepatectomy and resection of the left lobe lesion. OUTCOMES: She remained disease-free throughout a year follow-up period. CONCLUSION: HEH is a rare disease with characteristic radiological and pathological features. Although liver transplantation is the preferred treatment for multifocal HEH, surgical excision represents one alternative when the lesions can be guaranteed to be completely excised.


Assuntos
Hemangioendotelioma Epitelioide/patologia , Neoplasias Hepáticas/patologia , Feminino , Hemangioendotelioma Epitelioide/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade
15.
Adv Mater ; 32(43): e2004798, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969108

RESUMO

Poor cyclability and safety concerns caused by the uncontrollable dendrite growth and large interfacial resistance severely restrict the practical applications of metal batteries. Herein, a facile, universal strategy to fabricate ceramic and glass phase compatible, and self-healing metal anodes is proposed. Various amalgam-metal anodes (Li, Na, Zn, Al, and Mg) show a long cycle life in symmetric cells. It has been found that liquid Li amalgam shows a complete wetting with the surface of lanthanum lithium titanate electrolyte and a glass-phase solid-state electrolyte. The interfacial compatibility between the lithium metal anode and solid-state electrolyte is dramatically improved by using an in situ regenerated amalgam interface with high electron/ion dual-conductivity, obviously decreasing the anode/electrolyte interfacial impedance. The lithium-amalgam interface between the metal anode and electrolyte undergoes a reversible isothermal phase transition between solid and liquid during the cycling process at room temperature, resulting in a self-healing surface of metal anodes.

16.
Biol Trace Elem Res ; 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32602052

RESUMO

Fluoride exposure may cause changes in blood pressure, but this conclusion is controversial. Therefore, this meta-analysis aims to investigate the potential relationship between fluoride exposure and blood pressure or hypertension. PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG MED ONLINE, and Chinese Scientific Journals Full-Text Databases (VIP) were searched; in addition, two related studies were added manually. In total, 7 observational studies were identified, the pooled odds ratios (ORs) for hypertension between high and reference fluoride exposure groups were calculated, and the pooled standardized weighted mean difference (SMD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was estimated using an inverse-variance weighted random-effects model; next, sensitivity analysis and subgroup analysis were used to assess potential sources of heterogeneity; furthermore, publication bias was assessed using the Begg and Egger test. In brief, there were no statistical differences between exposure groups and control groups in terms of blood pressure or hypertension when all included studies considered. However, subgroup analysis indicated that blood pressure will rise with the increase of fluoride exposure concentrations in endemic fluorosis areas. The corresponding pooled SMD estimates were 0.31 (95% CI 0.11, 0.51) and 0.27 (95% CI 0.11, 0.43) for SBP and DBP. Funnel plots suggested no asymmetry. Our findings support the possibility of a positive correlation between fluoride exposure and blood pressure in endemic fluorosis areas. Additional evidence is needed to assess the dose-response relationship between fluoride exposure and blood pressure.

17.
Am J Respir Crit Care Med ; 202(9): 1283-1296, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32692930

RESUMO

Rationale: The bHLH (basic helix-loop-helix) transcription factor TWIST1 (Twist-related protein 1) controls cell proliferation and differentiation in tissue development and disease processes. Recently, endothelial TWIST1 has been linked to pulmonary hypertension (PH) and endothelial-to-mesenchymal transition, yet the role of TWIST1 in smooth muscle cells (SMCs) remains so far unclear.Objectives: To define the role of TWIST1 in SMCs in the pathogenesis of PH.Methods: SMC-specific TWIST1-deficient mice, SMC-specific TWIST1 silencing in rats, mass spectrometry, immunoprecipitation, and chromatin immunoprecipitation were used to delineate the role of SMC TWIST1 in PH.Measurements and Main Results: In pulmonary vessels from patients with PH and rodent PH models, TWIST1 expression was markedly increased and predominantly localized to SMCs. SMC-specific TWIST1 deficiency or silencing attenuated the development of PH and distal vessel muscularization in chronically hypoxic mice and in monocrotaline-treated rats. In vitro, TWIST1 inhibition or silencing prevented pulmonary artery SMC proliferation and migration. Mechanistically, the observed effects were mediated, at least in part, by TWIST1-dependent degradation of GATA-6 (GATA-binding protein 6). BMPR2 (bone morphogenetic protein receptor-2) was identified as a novel downstream target of GATA-6, which directly binds to its promoter. Inhibition of TWIST1 promoted the recruitment of GATA-6 to the BMPR2 promoter and restored BMPR2 functional expression.Conclusions: Our findings identify a key role for SMC TWIST1 in the pathogenesis of lung vascular remodeling and in PH that is partially mediated via reduced GATA-6-dependent BMPR2 expression. Inhibition of SMC TWIST1 may constitute a new therapeutic strategy for the treatment of PH.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fator de Transcrição GATA6/efeitos dos fármacos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/fisiopatologia , Músculo Liso Vascular/efeitos dos fármacos , Proteína 1 Relacionada a Twist/efeitos dos fármacos , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Proliferação de Células/genética , Células Cultivadas/efeitos dos fármacos , Fator de Transcrição GATA6/genética , Humanos , Modelos Animais , Ratos Sprague-Dawley , Proteína 1 Relacionada a Twist/genética
18.
Hepatology ; 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32594528

RESUMO

The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor-associated macrophages (TAMs) are deemed as a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mechanism underlying the pro-metastatic effect of TAMs on HCC remains undefined. The present study manifested that TAMs were enriched in HCC. TAMs were characterized by an M2-polarized phenotype and accelerated migratory potential of HCC cells in vitro and in vivo. Furthermore, we found that M2-derived exosomes induced TAM-mediated pro-migratory activity. With the use of mass spectrometry, we identified that integrin, αM ß2 (CD11b/CD18), was notably specific and efficient in M2 macrophage-derived exosomes (M2 exos). Blocking either CD11b and/or CD18 elicited a significant decrease in M2 exos-mediated HCC cell metastasis. Mechanistically, M2 exos mediated an intercellular transfer of the CD11b/CD18, activating the MMP-9 signaling pathway in recipient HCC cells to support tumor migration. Collectively, the exosome-mediated transfer of functional CD11b/CD18 protein from TAMs to tumor cells may have the potency to boost the migratory potential of HCC cells, thus providing new insights into the mechanism of tumor metastasis.

19.
PeerJ ; 8: e8679, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32181056

RESUMO

Background: Grain weight is a grain yield component, which is an integrated index of grain length, width and thickness. They are controlled by a large number of quantitative trait loci (QTLs). Besides major QTLs, minor QTLs play an essential role. In our previous studies, QTL analysis for grain length and width was performed using a recombinant inbred line population derived from rice cross TQ/IRBB lines. Two major QTLs were detected, which were located in proximity to GS3 and GW5 that have been cloned. In the present study, QTLs for grain weight and shape were identified using rice populations that were homozygous at GS3 and GW5. Method: Nine populations derived from the indica rice cross TQ/IRBB52 were used. An F10:11population named W1, consisting of 250 families and covering 16 segregating regions, was developed from one residual heterozygote (RH) in the F7generation of Teqing/IRBB52. Three near isogenic line (NIL)-F2 populations, ZH1, ZH2 and ZH3 that comprised 205, 239 and 234 plants, respectively, were derived from three RHs in F10:11. They segregated the target QTL region in an isogenic background. Two NIL populations, HY2 and HY3, were respectively produced from homozygous progeny of the ZH2 and ZH3 populations. Three other NIL-F2 populations, Z1, Z2 and Z3, were established using three RHs having smaller heterozygous segments. QTL analysis for 1000-grain weight (TGW), grain length (GL), grain width (GW), and length/width ratio (LWR) was conducted using QTL IciMapping and SAS procedure with GLM model. Result: A total of 27 QTLs distributed on 12 chromosomes were identified. One QTL cluster, qTGW2/qGL2/qGW2 located in the terminal region of chromosome 2, were selected for further analysis. Two linked QTLs were separated in region Tw31911-RM266. qGL2 was located in Tw31911-Tw32437 and mainly controlled GL and GW. The effects were larger on GL than on GW and the allelic directions were opposite. qTGW2 was located in Tw35293-RM266 and affected TGW, GL and GW with the same allelic direction. Finally, qTGW2 was delimited within a 103-kb region flanked by Tw35293 and Tw35395. Conclusion: qTGW2 with significant effects on TGW, GL and GW was validated and fine-mapped using NIL and NIL-F2 populations. These results provide a basis for map-based cloning of qTGW2 and utilization of qTGW2 in the breeding of high-yielding rice varieties.

20.
Langmuir ; 36(13): 3514-3521, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32172567

RESUMO

An easy, effective, and reversible strategy for tuning the Krafft temperature (KT) of selenium-containing ionic surfactants, with head groups ranging in nature from anionic to amphoteric, has been achieved for the first time via the redox chemistry of selenium. After oxidation with H2O2, the selenide group was converted to a more hydrophilic selenoxide group. This made the oxidized forms of the surfactants more water-soluble, which results in a marked reduction in the KT. In contrast, the hydrophilic selenoxide was restored to its reduced form of selenide via reduction reaction, which allowed the KT value to return to its initial value. By alternating the oxidization and reduction treatments, the KT of the selenium-containing surfactants in this work could be reversibly switched over 5-10 cycles without causing obvious adverse distortions.

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