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1.
FEBS Open Bio ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166887

RESUMO

Elucidation of the mechanisms underlying multidrug resistance (MDR) is required to ensure the efficacy of chemotherapy against gastric cancer (GC). To investigate this issue, here we identified that microRNA-765 (miRNA-765) is upregulated both in MDR GC cell lines and in specimens from patients not responding to chemotherapy. In addition, downregulation of miRNA-765 increased the sensitivity of GC cells to anticancer drugs, while its over-expression had the opposite effect. Moreover, miRNA-765 suppressed drug-induced apoptosis and positively regulated the expression of MDR-related genes. Finally, we showed that the basic leucine zipper ATF-like transcription factor 2 (BATF2), a tumor suppressor gene, is the functional target of miRNA-765. In summary, these results suggest that miRNA-765 may promote MDR via BATF2 in GC cells.

2.
Comput Math Methods Med ; 2020: 5487168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104203

RESUMO

Multimodal medical images are useful for observing tissue structure clearly in clinical practice. To integrate multimodal information, multimodal registration is significant. The entropy-based registration applies a structure descriptor set to replace the original multimodal image and compute similarity to express the correlation of images. The accuracy and converging rate of the registration depend on this set. We propose a new method, logarithmic fuzzy entropy function, to compute the descriptor set. It is obvious that the proposed method can increase the upper bound value from log(r) to log(r) + ∆(r) so that a more representative structural descriptor set is formed. The experiment results show that our method has faster converging rate and wider quantified range in multimodal medical images registration.

3.
Water Res ; 173: 115540, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32018172

RESUMO

Microbial community dynamics were characterized following combined catalysis and biodegradation treatment trains for mixtures of 1,4-dioxane and chlorinated volatile organic compounds (CVOCs) in laboratory microcosms. Although a few specific bacterial taxa are capable of removing 1,4-dioxane and individual CVOCs, many microorganisms are inhibited when these contaminants are present in mixtures. Chemical catalysis by tungstated zirconia (WOx/ZrO2) and hydrogen peroxide (H2O2) as a non-selective treatment was designed to achieve nearly 20% 1,4-dioxane and over 60% trichloroethene and 50% dichloroethene removals. Post-catalysis, bioaugmentation with 1,4-dioxane metabolizing bacterial strain,Pseudonocardia dioxanivorans CB1190, removed the remaining 1,4-dioxane. The evolution of the microbial community under different conditions was time-dependent but relatively independent of the concentrations of contaminants. The compositions of microbiomes tended to be similar regardless of complex contaminant mixtures during the biodegradation phase, indicating a r-K strategy transition attributed to the shock experienced during catalysis and the subsequent incubation. The originally dominant genera Pseudomonas and Ralstonia were sensitive to catalytic oxidation, and were overwhelmed by Sphingomonas, Rhodococcus, and other catalyst-tolerant microbes, but microbes capable of biodegradation of organics thrived during the incubation. Methane metabolism, chloroalkane-, and chloroalkene degradation pathways appeared to be responsible for CVOC degradation, based on the identifications of haloacetate dehalogenases, 2-haloacid dehalogenases, and cytochrome P450 family. Network analysis highlighted the potential interspecies competition or commensalism, and dynamics of microbiomes during the biodegradation phase that were in line with shifting predominant genera, confirming the deterministic processes guiding the microbial assembly. Collectively, this study demonstrated that catalysis followed by bioaugmentation is an effective treatment for 1,4-dioxane in the presence of high CVOC concentrations, and it enhanced our understanding of microbial ecological impacts resulting from abiotic-biological treatment trains. These results will be valuable for predicting treatment synergies that lead to cost savings and improve remedial outcomes in short-term active remediation as well as long-term changes to the environmental microbial communities.

4.
Cell Death Dis ; 11(2): 102, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029721

RESUMO

Despite the fact that Otto H. Warburg discovered the Warburg effect almost one hundred years ago, why cancer cells waste most of the glucose carbon as lactate remains an enigma. Warburg proposed a connection between the Warburg effect and cell dedifferentiation. Hypoxia is a common tumor microenvironmental stress that induces the Warburg effect and blocks tumor cell differentiation. The underlying mechanism by which this occurs is poorly understood, and no effective therapeutic strategy has been developed to overcome this resistance to differentiation. Using a neuroblastoma differentiation model, we discovered that hypoxia repressed cell differentiation through reducing cellular acetyl-CoA levels, leading to reduction of global histone acetylation and chromatin accessibility. The metabolic switch triggering this global histone hypoacetylation was the induction of pyruvate dehydrogenase kinases (PDK1 and PDK3). Inhibition of PDKs using dichloroacetate (DCA) restored acetyl-CoA generation and histone acetylation under hypoxia. Knocking down PDK1 induced neuroblastoma cell differentiation, highlighting the critical role of PDK1 in cell fate control. Importantly, acetate or glycerol triacetate (GTA) supplementation restored differentiation markers expression and neuron differentiation under hypoxia. Moreover, ATAC-Seq analysis demonstrated that hypoxia treatment significantly reduced chromatin accessibility at RAR/RXR binding sites, which can be restored by acetate supplementation. In addition, hypoxia-induced histone hypermethylation by increasing 2-hydroxyglutarate (2HG) and reducing α-ketoglutarate (αKG). αKG supplementation reduced histone hypermethylation upon hypoxia, but did not restore histone acetylation or differentiation markers expression. Together, these findings suggest that diverting pyruvate flux away from acetyl-CoA generation to lactate production is the key mechanism that Warburg effect drives dedifferentiation and tumorigenesis. We propose that combining differentiation therapy with acetate/GTA supplementation might represent an effective therapy against neuroblastoma.

5.
Science ; 367(6473): 79-83, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896715

RESUMO

Particle accelerators represent an indispensable tool in science and industry. However, the size and cost of conventional radio-frequency accelerators limit the utility and reach of this technology. Dielectric laser accelerators (DLAs) provide a compact and cost-effective solution to this problem by driving accelerator nanostructures with visible or near-infrared pulsed lasers, resulting in a 104 reduction of scale. Current implementations of DLAs rely on free-space lasers directly incident on the accelerating structures, limiting the scalability and integrability of this technology. We present an experimental demonstration of a waveguide-integrated DLA that was designed using a photonic inverse-design approach. By comparing the measured electron energy spectra with particle-tracking simulations, we infer a maximum energy gain of 0.915 kilo-electron volts over 30 micrometers, corresponding to an acceleration gradient of 30.5 mega-electron volts per meter. On-chip acceleration provides the possibility for a completely integrated mega-electron volt-scale DLA.

6.
Chem Biol Interact ; 317: 108945, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31935363

RESUMO

Liver fibrosis is a common pathological consequence of liver injury, which increases liver failure-related morbidity and mortality. Hence, anti-fibrotic treatment is urgently needed. Oxidative stress plays a pivotal role in the progression of liver fibrosis. Thus, targeting ROS may be an effective strategy for liver fibrosis treatment. In this study, we investigated four benzoquinones derivatives, including 5-isopropyl-2-methyl-1,4-benzoquinone (TQ), 2-tert-butyl-1,4-benzoquinone (tBu-Q) 2,5-dimethyl-p-benzoquinone (Dime-Q) and p-benzoquinone (Ph-Q), as well as the evaluation of their antioxidant activity and anti-fibrotic effects on activated hepatic stellate cells and TAA-induced mice. Electrochemical analysis showed that all compounds possessed antioxidant property. The result was first confirmed by in vitro experiments, which revealed potential anti-fibrotic activity of all four compounds at the cellular level. Benzoquinone derivatives act as ROS-scavenging molecules, which modulated the TLR4-CD14 signaling pathway to inhibit the expression of procaspase-1 and IL-1ß in cells, induced apoptosis via a mitochondrial pathway by upregulating the ratio of Bax/Bcl-2 and by activating caspase-3, as well as inhibited the expression of the anti-apoptotic proteins FLIP and XIAP in activated LX-2 cells. In addition, a TAA (Thioacetamide)-induced mouse model was used to further validate the results. Treatment with benzoquinone derivatives significantly decreased the levels of liver injury markers and lipid peroxidation caused by excessive ROS, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). Moreover, treatment with benzoquinone derivatives significantly inhibited extracellular matrix (ECM) deposition and downregulated the mRNA and protein expression of liver fibrosis markers, such as collagen I, alpha-smooth muscle actin (α-SMA), and TIMP-1. In summary, these results indicate that benzoquinone derivatives may act as potential therapeutic drugs against liver fibrosis.


Assuntos
Antioxidantes/farmacologia , Benzoquinonas/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Tioacetamida/toxicidade , Actinas/genética , Actinas/metabolismo , Animais , Biomarcadores , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo
7.
Acta Pharmacol Sin ; 41(1): 47-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31607752

RESUMO

T cell metabolic activation plays a crucial role in inflammation of atherosclerosis. Shikonin (SKN), a natural naphthoquinone with anti-inflammatory activity, has shown to exert cardioprotective effects, but the effect of SKN on atherosclerosis is unclear. In addition, SKN was found to inhibit glycolysis via targeting pyruvate kinase muscle isozyme 2 (PKM2). In the present study, we investigated the effects of SKN on hyperhomocysteinemia (HHcy)-accelerated atherosclerosis and T cell inflammatory activation in ApoE-/- mice and the metabolic mechanisms in this process. Drinking water supplemented with Hcy (1.8 g/L) was administered to ApoE-/- mice for 2 weeks and the mice were injected with SKN (1.2 mg/kg, i.p.) or vehicle every 3 days. We showed that SKN treatment markedly attenuated HHcy-accelerated atherosclerosis in ApoE-/- mice and significantly decreased inflammatory activated CD4+ T cells and proinflammatory macrophages in plaques. In splenic CD4+ T cells isolated from HHcy-ApoE-/- mice, SKN treatment significantly inhibited HHcy-stimulated PKM2 activity, interferon-γ secretion and the capacity of these T cells to promote macrophage proinflammatory polarization. SKN treatment significantly inhibited HHcy-stimulated CD4+ T cell glycolysis and oxidative phosphorylation. Metabolic profiling analysis of CD4+ T cells revealed that Hcy administration significantly increased various glucose metabolites as well as lipids and acetyl-CoA carboxylase 1, which were reversed by SKN treatment. In conclusion, our results suggest that SKN is effective to ameliorate atherosclerosis in HHcy-ApoE-/- mice and this is at least partly associated with the inhibition of SKN on CD4+ T cell inflammatory activation via PKM2-dependent metabolic suppression.

8.
J Am Chem Soc ; 142(1): 512-519, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31829626

RESUMO

It is meaningful but challenging to develop a fluorescent probe for temperature sensing in living cells because it should possess the features of good cytocompatibility, easy read out, and high resolution. Herein, we successfully synthesized emissive star-like cage-based organic temperature-sensitive polymers that can assemble into nanoparticles in aqueous solution. The obtained nanoparticle can be easily tuned to full-color emission (including white light emission) with a temperature resolution of at least 0.5 °C by encapsulating different doses of guest dyes ((4-dimethylamino-2'-butoxychalcone (DMBC) and Nile Red (NR)) through a cascade Förster resonance energy transfer (FRET) effect. Moreover, the white light emission polymeric hybrid nanoparticles exhibit reversible stimuli response toward temperature and can be used as probes for temperature sensing in live cells through their fluorescent color variation between white and orange emission with good cytocompatibility.

9.
Food Funct ; 11(1): 200-210, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31845693

RESUMO

Selenium (Se) is an essential trace element for living organisms and plays diverse biological roles. Endometritis is a common reproductive disorder in dairy cows, causing huge economic losses. In this study, we explored the effects of Se on lipopolysaccharide (LPS)-induced endometritis in mice and expounded its underlying mechanism of action. We validated the anti-inflammatory effects of Se in vivo by establishing a mouse model of endometriosis induced by LPS. Se significantly reversed the LPS-induced uterine histopathological changes, MPO activity and inflammatory cytokine levels in vivo. Simultaneously, TLR4 and its downstream signaling pathways, lipid rafts and cholesterol levels in the tissues were also attenuated by Se under LPS stimulation. In addition, the molecular mechanism of the Se anti-inflammatory effect was clarified in mouse endometrial epithelial cells. Se inhibited TLR4-mediated NF-κB and IRF3 signal transduction pathways to reduce the production of inflammatory factors. We found that Se promoted the consumption of cholesterol to suppress the lipid rafts coming into being and inhibited the TLR4 positioning to the lipid raft to prevent the inflammatory response caused by LPS. Meanwhile, Se activated the LxRα-ABCA1 pathway to cause the outflow of cholesterol in cells. The anti-inflammatory effect of Se was disrupted by silencing LxRα. In conclusion, Se exerted anti-inflammatory effects most likely by the LxRα-ABCA1 pathway activation, which inhibited lipid rafts by depleting cholesterol and ultimately impeded the migration of TLR4 to lipid rafts.

10.
Dev Comp Immunol ; 105: 103582, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31874194

RESUMO

Laccases (Lacs) are copper-containing oxidase enzymes that are found in various plants, fungi, and microorganisms. For invertebrates, particularly insects and crustaceans, Lacs have been shown to be involved in immune responses. In shrimp, a Lac gene has been cloned and functionally characterized, which revealed that it is involved in shrimp anti-pathogen infection. In the present study, a novel Lac gene (LvLac2) was cloned from Litopenaeus vannamei. Real-time RT-PCR analysis showed that LvLac2 is induced by white spot syndrome virus (WSSV)- or Vibrio alginolyticus infection. In addition, the downregulated expression of LvLac2 decreased the cumulative mortality of WSSV- or V. alginolyticus infected shrimps. Moreover, LvLac2 is also induced by oxidative stress. Knocking down the expression of LvLac2 decreased the severity of hepatopancreatic injury caused by oxidative stress, as well as reduced the cumulative shrimp mortality during oxidative stress. Furthermore, gene reporter assays showed that the expression of LvLac2 is regulated by NF-E2-related factor 2, which is the key transcription factor of the oxidative stress response signaling pathway. Our study revealed that LvLac2 not only participates in immune responses against infections in L. vannamei but is also involved in oxidative stress responses.

11.
J Agric Food Chem ; 68(2): 652-659, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31869222

RESUMO

Casein phosphopeptides are known to enhance zinc absorption, but the underlying mechanism remains unclear. Here, a gastrointestinal casein hydrolysate (CH) was found to keep zinc in solution despite heavy precipitation of calcium and phosphate, the omnipresent mineral nutrients that could co-precipitate zinc out of solution instantly and almost completely under physiologically relevant conditions. Dynamic light scattering, transmission electron microscopy, and energy-dispersive X-ray analysis displayed the CH-mediated formation of zinc/calcium phosphate (Zn/CaP) nanocomplexes aggregated from rather small nanoclusters. The ex vivo mouse ileal loop experiments revealed enhanced intestinal zinc absorption by CH's prevention of zinc co-precipitation with CaP, and the treatments with specific inhibitors unveiled the involvement of macropinocytic internalization, lysosomal degradation, and transcytosis in the intestinal uptake of zinc from Zn/CaP nanocomplexes. A low calcium-to-phosphorus ratio adversely affected CH's efficiency to enhance zinc solubility and absorption. Overall, our study provides a new paradigm for casein phosphopeptides to improve zinc bioavailability.


Assuntos
Fosfatos de Cálcio/química , Caseínas/química , Intestino Delgado/metabolismo , Zinco/química , Zinco/metabolismo , Animais , Disponibilidade Biológica , Fosfatos de Cálcio/metabolismo , Caseínas/metabolismo , Absorção Intestinal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/metabolismo
12.
Cancer Res ; 79(22): 5758-5768, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31585940

RESUMO

Angiogenesis is a hallmark of cancer that promotes tumor progression and metastasis. However, antiangiogenic agents have limited efficacy in cancer therapy due to the development of resistance. In clear cell renal cell carcinoma (ccRCC), AXL expression is associated with antiangiogenic resistance and poor survival. Here, we establish a role for GAS6/AXL signaling in promoting the angiogenic potential of ccRCC cells through the regulation of the plasminogen receptor S100A10. Genetic and therapeutic inhibition of AXL signaling in ccRCC tumor xenografts reduced tumor vessel density and growth under the renal capsule. GAS6/AXL signaling activated the expression of S100A10 through SRC to promote plasmin production, endothelial cell invasion, and angiogenesis. Importantly, treatment with the small molecule AXL inhibitor cabozantinib or an ultra-high affinity soluble AXL Fc fusion decoy receptor (sAXL) reduced the growth of a pazopanib-resistant ccRCC patient-derived xenograft. Moreover, the combination of sAXL synergized with pazopanib and axitinib to reduce ccRCC patient-derived xenograft growth and vessel density. These findings highlight a role for AXL/S100A10 signaling in mediating the angiogenic potential of ccRCC cells and support the combination of AXL inhibitors with antiangiogenic agents for advanced ccRCC. SIGNIFICANCE: These findings show that angiogenesis in renal cell carcinoma (RCC) is regulated through AXL/S100A10 signaling and support the combination of AXL inhibitors with antiangiogenic agents for the treatment of RCC.

13.
Environ Res ; 179(Pt A): 108778, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629946

RESUMO

BACKGROUND: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. OBJECTIVE: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. METHOD: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. RESULTS: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF2α and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF2α suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10). CONCLUSIONS: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

14.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3022-3034, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602849

RESUMO

To characterize the chemical constituents of Huanbei Zhike Prescription by ultra-high performance liquid chromatography-time of flight mass spectrometry( UPLC-Q-TOF-MS/MS). A Thermo Syncronls C18 column( 2. 1 mm×100 mm,1. 7 µm) was used with methanol( A)-0. 1% formic acid solution( B) as the mobile phase for gradient elution. The injection volume was 2 µL; the column temperature was 40 ℃; the flow rate was 0. 3 m L·min-1; and electrospray ionization( ESI) source was used to collect data in positive and negative ion modes. The ion scanning range was m/z 50-1 200,with capillary voltage of 3 000 V,ion source temperature of100 ℃,atomization gas flow rate of 50 L·h-1,desolvent gas flow rate of 800 L·h-1,desolvent temperature of 400 ℃,cone hole voltage of 40 V,with argon as the collision gas and the collision energy was 20-35 V. The excimer ion peak information was analyzed by Waters UNIFI data processing software. The molecular formula with error within 1×10-5 was compared with the data in database to identify the compounds. The secondary fragment ion information of the target compound was selected,and then compared with the retention time and fragmentation patterns provided by the database and the existing literature to further confirm the compositions and structures of the compounds. A total of 68 main compounds in Huanbei Zhike Prescription were identified,including 38 flavonoids,10 organic acids,6 terpenoids and 10 nitrogen-containing compounds,of which 12 compounds were verified by the control substances. This method is rapid and accurate,which provides a new strategy for the qualitative analysis of the chemical constituents of Huanbei Zhike Prescription,and lays a foundation for the further study and quality control of the compound pharmacodynamic substance.


Assuntos
Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Espectrometria de Massas em Tandem , Terpenos/análise
15.
Environ Sci Technol ; 53(20): 12026-12034, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525872

RESUMO

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.


Assuntos
Citocromo P-450 CYP2E1 , Efeitos Tardios da Exposição Pré-Natal , Biomarcadores , Peso ao Nascer , Desinfecção , Feminino , Glutationa Transferase , Humanos , Exposição Materna , Polimorfismo Genético , Gravidez , Trialometanos
16.
Phys Chem Chem Phys ; 21(38): 21262-21266, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31538166

RESUMO

Binary skutterudite-type IrP3 possesses a unique structural configuration that exhibits unusual electronic, thermoelectric, and dynamical properties and can be applied in thermoelectric generators; IrP3 has unique square (P4) rings stacked with a relatively loose arrangement and thus has been expected to exhibit fascinating evolution in the bonding patterns and electronic properties under high pressure. Herein, we systematically investigated the global energetically stable structures of IrP3 under ambient- and high-pressure conditions using the swarm intelligence-based structure searching technique in combination with first-principles calculations. Our theoretical prediction shows that the skutterudite-type structure with the Im3[combining macron] symmetry is most stable under ambient conditions. An orthorhombic structure with the Pmma space group was predicted to be energetically superior to the Im3[combining macron] phase above 47.60 GPa. The abrupt volume collapse at the corresponding phase boundaries even reached 14.67%, stemming from the abrupt collapse of large voids in the Im3[combining macron] phase. To explore the possibility of the occurrence of pressure-induced metallization and superconducting states under compressive conditions, the electronic band structures were investigated. Our results showed that the Im3[combining macron] phase was a narrow-gap semiconductor with the band gap of 1.04 eV, whereas the high-pressure Pmma IrP3 was a metallic phase with the superconducting transition temperature of 2.40 K. The current results are beneficial for the further understanding of other skutterudite-type compounds under high pressure.

17.
J Med Genet ; 56(11): 758-764, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31413119

RESUMO

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a heterogenous neurodegenerative disorder named after its pathological features. It has long been considered a disease of genetic origin. Recently, the GGC repeated expansion in the 5'-untranslated region (5'UTR) of the NOTCH2NLC gene has been found in adult-onset NIID in Japanese individuals. This study was aimed to investigate the causative mutations of NIID in Chinese patients. METHODS: Fifteen patients with NIID were identified from five academic neurological centres. Biopsied skin samples were analysed by histological staining, immunostaining and electron microscopic observation. Whole-genome sequencing (WGS) and long-read sequencing (LRS) were initially performed in three patients with NIID. Repeat-primed PCR was conducted to confirm the genetic variations in the three patients and the other 12 cases. RESULTS: Our patients included 14 adult-onset patients and 1 juvenile-onset patient characterised by degeneration of multiple nervous systems. All patients were identified with intranuclear inclusions in the nuclei of fibroblasts, fat cells and ductal epithelial cells of sweat glands. The WGS failed to find any likely pathogenic variations for NIID. The LRS successfully identified that three patients with adult-onset NIID showed abnormalities of GGC expansion in 5'UTR of the NOTCH2NLC gene. The GGC repeated expansion was further confirmed by repeat-primed PCR in seven familial cases and eight sporadic cases. CONCLUSION: Our findings provided evidence that confirmed the GGC repeated expansion in the 5'UTR of the NOTCH2NLC gene is associated with the pathogenesis of NIID. Additionally, the GGC expansion was not only responsible for adult-onset patients, but also responsible for juvenile-onset patients.

18.
Sci Rep ; 9(1): 11055, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363137

RESUMO

Current brain spheroids or organoids derived from human induced pluripotent stem cells (hiPSCs) still lack a microglia component, the resident immune cells in the brain. The objective of this study is to engineer brain region-specific organoids from hiPSCs incorporated with isogenic microglia-like cells in order to enhance immune function. In this study, microglia-like cells were derived from hiPSCs using a simplified protocol with stage-wise growth factor induction, which expressed several phenotypic markers, including CD11b, IBA-1, CX3CR1, and P2RY12, and phagocytosed micron-size super-paramagnetic iron oxides. The derived cells were able to upregulate pro-inflammatory gene (TNF-α) and secrete anti-inflammatory cytokines (i.e., VEGF, TGF-ß1, and PGE2) when stimulated with amyloid ß42 oligomers, lipopolysaccharides, or dexamethasone. The derived isogenic dorsal cortical (higher expression of TBR1 and PAX6) and ventral (higher expression of NKX2.1 and PROX1) spheroids/organoids displayed action potentials and synaptic activities. Co-culturing the microglia-like cells (MG) with the dorsal (D) or ventral (V) organoids showed differential migration ability, intracellular Ca2+ signaling, and the response to pro-inflammatory stimuli (V-MG group had higher TNF-α and TREM2 expression). Transcriptome analysis exhibited 37 microglia-related genes that were differentially expressed in MG and D-MG groups. In addition, the hybrid D-MG spheroids exhibited higher levels of immunoreceptor genes in activating members, but the MG group contained higher levels for most of genes in inhibitory members (except SIGLEC5 and CD200). This study should advance our understanding of the microglia function in brain-like tissue and establish a transformative approach to modulate cellular microenvironment toward the goal of treating various neurological disorders.

19.
Bioresour Technol ; 293: 122020, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31470231

RESUMO

A lab-scale acidogenic sulfate-reducing reactor with N2 stripping was continuously operated to uncover its microbial mechanism treating highly sulfate-containing organic wastewaters. Results showed that sulfate reduction efficiency decreased with the influent COD/sulfate ratios. Microbial community analysis showed that VFA accumulation mainly caused by the predominance of fermentative bacteria including Streptococcus and Oceanotoga. Genus Desulfovibrio was the most predominant SRB and enriched at low influent COD/sulfate ratios. Although Bifidobacterium, Atopobium, Wohlfahrtiimonas, Dysgonomonas etc. had low average abundance, they were identified keystone genera by the co-occurrence network analysis. The functions of the microbial community were not insignificantly influenced by COD/sulfate ratios. All predicted functional genes involved in dissimilatory sulfate reduction reached their maximum abundances at influent COD/sulfate ratio of 1.5, while the assimilatory sulfate reduction was favored at the COD/sulfate ratio lower than 2.


Assuntos
Carbono , Desulfovibrio , Reatores Biológicos , Sulfatos , Águas Residuárias
20.
Water Res ; 165: 115008, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31461682

RESUMO

Stormwater biofilters have been increasingly used to mitigate the impact of climate change on the export of contaminants including nitrate to water bodies. Yet, their performance is rarely tested under high-intensity rainfall events, which are predicted to occur more frequently under climate change scenarios. We examined the potential of biochar to improve the resilience of woodchip biofilters under simulated high-intensity rainfall events and linked denitrification to biochar-mediated changes in hydrological (physical), chemical, and biological properties of woodchip biofilters. Results showed that nitrate removal capacity of woodchip biofilters decreased with increases in rainfall intensity or duration and decreases in antecedent drying time. However, adding biochar to woodchips significantly decreased the exhaustion rate of woodchips, only when the hydraulic residence time (HRT) was less than 5 h. At longer HRT (>5 h), the benefits of biochar became less apparent. We attributed the improved denitrification during high nitrate loading to biochar's ability to decrease dissolved oxygen in pore water and increase water holding capacity and retention of dissolved organic carbon and nitrate-all of which could increase nitrate utilization. Biochar increased the net microbial biomass but did not affect the relative abundance of denitrifying genes, which indicates that a shift in microbial biomass could not fully explain the observed increase in nitrate removal in biochar-augmented woodchip biofilters. Overall, the results showed that biochar could increase the resiliency of woodchip biofilters for denitrification in high-intensity rainfall events, a worst-case scenario, thereby mitigating the water quality degradation during climate change.


Assuntos
Reatores Biológicos , Desnitrificação , Carvão Vegetal , Nitratos
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