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1.
Ann Palliat Med ; 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32389007

RESUMO

BACKGROUND: Clinical manifestations and histological lesions of IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are different, but related, and are also correlated with the renal outcomes. This study aimed to compare the features of immunoglobulin A nephropathy (IgAN) and HSPN in adult patients with diffuse endocapillary proliferation (DEP) lesions aiming to clarify the differences and relationships in the clinicopathological findings and outcome. METHODS: Twelve patients with DEP-IgAN and 10 patients with DEP-HSPN were enrolled. Twenty four patients with IgAN (NDEP-IgAN) and matched 20 patients with HSPN (NDEP-HSPN) were enrolled at the same ratio (1:2). The clinicopathological features, clinical efficacy, and renal outcomes were analyzed in the four groups. RESULTS: DEP patients with IgAN or HSPN had worse clinical manifestations (more severe proteinuria, lower serum ALB, higher incidence of gross hematuria). The proteinuria in the DEP-HSPN group was more severe than in the DEP-IgAN group. There was no significant difference in the serum creatinine among four groups. The incidence of endothelial swelling was significantly higher in the DEP-HSPN group than in the NDEP-HSPN group and DEP-IgAN group. The S1 score of Oxford classification was more common in the DEP-IgAN group than in the DEP-HSPN. None in the DEP-IgAN group reached endpoint events during the follow-up period, while the renal outcomes were significantly poorer in the DEP-HSPN group than in the DEP-IgAN and NDEP-HSPN groups. No significant difference was observed in the cumulative renal survival among four groups (χ 2 =7.264, P=0.064), but patients in the DEP-HSPN group had markedly lower renal cumulative survival rate as compared to the NDEP-HSPN group (χ 2 =4.875, P=0.027). CONCLUSIONS: The DEP is significantly associated with more severe proteinuria and hematuria regardless the IgAN and HSPN. Among DEP patients, patients with HSPN have poor therapeutic efficacy and renal outcomes, even under active immunosuppressive therapy, as compared to those with IgAN.

2.
BMC Nephrol ; 21(1): 182, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410665

RESUMO

BACKGROUND: Thalassemia is a group of hereditary diseases characterized by a common recessive monogenic hematological disorder, presenting a significant public health concern in the developing countries. Recent studies have identified the renal effects of thalassemia syndrome. Chronic hypoxia, long-term anemia, iron overload, and iron chelators are the major causes of renal tubular dysfunction and glomerular filtration abnormalities, while glomerulonephritis is not considered a major cause of abnormal urinalysis. CASE PRESENTATION: We report a case of a 38-year-old female patient with immunoglobulin A (IgA) nephropathy accompanied by anemia who was misdiagnosed initially, but was diagnosed with alpha-thalassemia after gene tests. We administered a combination of oral prednisolone, leflunomide, and angiotensin receptor blockers as well as folic acid and mecobalamin. During the follow-up, her proteinuria was significantly reduced, and her anemia was improved. CONCLUSIONS: The possibility of occurrence of thalassemia should be considered in IgA nephropathy complicated with refractory anemia, especially in high-incidence areas of the disease.

3.
Ticks Tick Borne Dis ; : 101427, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32370927

RESUMO

The three-host tick Haemaphysalis longicornis is an obligate blood-sucking ectoparasite. In life-stage transitions, microRNAs (miRNAs) show a variety of expression changes. To investigate these changes, deep sequencing technology was applied to identify the conserved and potentially novel miRNAs expressed during the different life stages of H. longicornis. Total RNA from eggs, unfed larvae, unfed nymphs and unfed adults was extracted for deep sequence analysis. Deep sequencing on a Hiseq 4000 generated a total of 111,192,069 reads, grouped into four small RNA (sRNA) libraries, one for each of the four developmental stages of H. longicornis. Among these sequences, 78 conserved and 55 potentially novel miRNAs were identified, including stage-specific and differentially expressed miRNAs. Gene ontology (GO) analysis indicated significantly enriched GO terms related to cell proliferation and differentiation, including specific terms for the processes of development, growth, metabolism, regulation of biological functions, reproduction, and membrane enzyme regular activity. Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis revealed a significant enrichment of the insulin, notch, Hippo, and Wnt signaling pathways for growth and development. Our data highlight the abundance of miRNA changes (conserved and potentially novel) in the different life stages of H. longicornis. In particular, stage-specific miRNAs, as observed, are essential regulators for the development of H. longicornis.

5.
Neurology ; 94(17): e1811-e1819, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32241954

RESUMO

OBJECTIVE: To investigate the association of carotid atherosclerosis, dilation, and stiffness with imaging markers of cerebral small vessel disease (CSVD) in a community-based sample. METHODS: The study comprised 1,051 participants (age 57.5 ± 9.2 years). Carotid plaques, intima-media thickness (IMT), diastolic diameter, pulse wave velocity, and stiffness index (ß) were measured by ultrasound. Imaging markers of CSVD, including lacunes, cerebral microbleeds, dilated PVS, and white matter hyperintensities (WMH) volume, were assessed. RESULTS: Carotid plaque was associated with the presence of lacunes (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.78-4.33; p < 0.001) and larger WMH volume (natural log transformed, ß ± SE, 0.32 ± 0.10; p = 0.002). The increased carotid diameter was associated with the presence of lacunes (OR 1.82, 95% CI 1.22-2.72; p = 0.003), larger WMH volume (ß ± SE, 0.37 ± 0.10; p < 0.001), and PVS in the basal ganglia (OR 1.59, 95% CI 1.20-2.11; p = 0.001). Associations of carotid dilation and CSVD were independent of carotid IMT and plaque. Most parenchymal lesions were located in the basal ganglia and deep white matter. Carotid IMT and stiffness were not associated with CSVD. CONCLUSIONS: Carotid atherosclerosis and dilation are associated with imaging markers of CSVD. The noninvasive carotid assessment would seem to be a rational approach to risk stratification of CSVD.

6.
Thorac Cancer ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32239681

RESUMO

Immune checkpoint inhibitors, the new standard in cancer therapy, present durable responses in numerous solid tumors and hematologic malignancies, as well as resulting in an increased incidence of immune-related adverse events (irAEs). Diarrhea is a common irAE, with an incidence rate of approximately 10% to 13%. It is important to distinguish between diarrhea symptomatic of an infection, which is the main differential diagnosis, and immune-related diarrhea. Here, we report a case of an advanced lung cancer patient who presented with diarrhea as a result of treatment with tislelizumab, a novel PD-1 inhibitor. Although the patient initially responded to corticosteroid treatment, diarrhea recurred upon dosage tapering, and eventually improved on treatment with ganciclovir and vancomycin. Therefore, clinicians must remain highly vigilant against infection and carefully distinguish symptoms of infection from irAEs by performing repeated blood or fecal examinations for pathogens, colonoscopy, and biopsy.

7.
Chem Commun (Camb) ; 56(38): 5174-5177, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32267259

RESUMO

Boron-doped carbon nanodot materials, comprising evenly distributed BC3-nanodots in a layered carbon matrix, are prepared through a pre-assembly assisted carbonization synthetic strategy. The prepared materials are endowed with high electron affinity and distortion resistance, which provides a stable framework while generating affinity to substrates.

8.
Nat Neurosci ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341541

RESUMO

Individuals immersed in groups sometimes lose their individuality, take risks they would normally avoid and approach outsiders with unprovoked hostility. In this study, we identified within-group neural synchronization in the right dorsolateral prefrontal cortex (rDLPFC) and the right temporoparietal junction (rTPJ) as a candidate mechanism underlying intergroup hostility. We organized 546 individuals into 91 three-versus-three-person intergroup competitions, induced in-group bonding or no-bonding control manipulation and measured neural activity and within-group synchronization using functional near-infrared spectroscopy. After in-group bonding (versus control), individuals gave more money to in-group members than to out-group members and contributed more money to outcompete their rivals. In-group bonding decreased rDLPFC activity and increased functional connectivity between the rDLPFC and the rTPJ. Especially during the out-group attack, in-group bonding also increased within-group synchronization in both the rDLPFC and the rTPJ, and within-group rDLPFC synchronization positively correlated with intergroup hostility. Within-group synchronized reduction in prefrontal activity might explain how in-group bonding leads to impulsive and collective hostility toward outsiders.

9.
EBioMedicine ; 53: 102696, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32143183

RESUMO

BACKGROUND: Tumor cells display metabolic changes that correlate with malignancy, including an elevated hydrolysis of monoacylglycerol (MAG) in various cancer types. However, evidence is absent for the relationship between MAG lipolysis and NSCLC. METHODS: MAG hydrolase activity assay, migration, invasion, proliferation, lipids quantification, and transactivation assays were performed in vitro. Tumor xenograft studies and lung metastasis assays were examined in vivo. The correlations of MAGL/ABHD6 expression in cancerous tissues with the clinicopathological characteristics and survival of NSCLC patients were validated. FINDINGS: ABHD6 functions as the primary MAG lipase and an oncogene in NSCLC. MAG hydrolase activities were more than 11-fold higher in cancerous lung tissues than in paired non-cancerous tissues derived from NSCLC patients. ABHD6, instead of MAGL, was significantly associated with advanced tumor node metastasis (TNM) stage (HR, 1.382; P = 0.004) and had a negative impact on the overall survival of NSCLC patients (P = 0.001). ABHD6 silencing reduced migration and invasion of NSCLC cells in vitro as well as metastatic seeding and tumor growth in vivo. Conversely, ectopic overexpression of ABHD6 provoked the pathogenic potential. ABHD6 blockade significantly induced intracellular MAG accumulation which activated PPARα/γ signaling and inhibited cancer pathophysiology. INTERPRETATION: The present study provide evidence for a previously uncovered pro-oncogenic function of ABHD6 in NSCLC, with the outlined metabolic mechanisms shedding light on new potential strategies for anticancer therapy. FUND: This work was supported by the Project for Major New Drug Innovation and Development (2015ZX09501010 and 2018ZX09711001-002-003).

10.
Technol Cancer Res Treat ; 19: 1533033820905825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32216582

RESUMO

MicroRNAs are known to be important in a variety of cancer types. The specific expression and roles of miR-338-3p in the context of gastric cancer, however, remains largely unknown. In this study, we found that miR-338-3p was expressed significantly lower in established/primary human gastric cancer cells than that in human gastric epithelial cells; miR-338-3p is also decreased in human gastric cancer tissues and was positively associated with the worse prognosis of patients with gastric cancer. Enforced expression of miR-338-3p could inhibit cell growth, survival, and proliferation, while inducing cell apoptosis. In addition, miR-338-3p negatively regulated SOX5 expression through directly binding to the 3'-untranslated region of SOX5, and an inverse correlation was found between miR-338-3p and SOX5 messenger RNA expression in gastric cancer tissues. Furthermore, miR-338-3p-induced inactivation of Wnt/ß-catenin signaling was greatly abrogated by SOX5 upregulation. Finally, we found that hypoxic conditions were linked with reduced miR-338-3p expression in the context of gastric cancer. In conclusion, miR-338-3p acts as a tumor suppressor in gastric cancer, possibly by directly targeting SOX5 and blocking Wnt/ß-catenin signaling. These findings might provide novel therapeutic targets for gastric cancer.

12.
Nat Commun ; 11(1): 653, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005833

RESUMO

The industrial synthesis of ammonia (NH3) using iron-based Haber-Bosch catalyst requires harsh reaction conditions. Developing advanced catalysts that perform well at mild conditions (<400 °C, <2 MPa) for industrial application is a long-term goal. Here we report a Co-N-C catalyst with high NH3 synthesis rate that simultaneously exhibits dynamic and steady-state active sites. Our studies demonstrate that the atomically dispersed cobalt weakly coordinated with pyridine N reacts with surface H2 to produce NH3 via a chemical looping pathway. Pyrrolic N serves as an anchor to stabilize the single cobalt atom in the form of Co1-N3.5 that facilitates N2 adsorption and step-by-step hydrogenation of N2 to *HNNH, *NH-NH3 and *NH2-NH4. Finally, NH3 is facilely generated via the breaking of the *NH2-NH4 bond. With the co-existence of dynamic and steady-state single atom active sites, the Co-N-C catalyst circumvents the bottleneck of N2 dissociation, making the synthesis of NH3 at mild conditions possible.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32069396

RESUMO

Multiemissive sensors are being actively pursued, because of their ratiometric luminescent detection capabilities, which demonstrates better sensitivity and selectivity than conventional single-emission sensors. Herein, we present a trichromatic white-light-emitting metal-organic framework (MOF) composite (Z3) by simultaneously incorporating red/green-emitting Pt/Ru complex cations into porous blue-emitting bio-MOF-1 through post-synthetic modification. With the help of a three-dimensional (3-D) dual-ratiometric luminescence recognition method, and unique turn-on responses of the red emission toward amine compounds (ACs), including NH3 and aliphatic amines, via confinement-induced luminescence enhancement effect, Z3 can work as a dual-ratiometric luminescent sensor for discrimination of 7 out of 11 AC vapors. This work not only provides a new AC sensing mechanism (confinement effect) that can induce a "turn-on" response but also proves that the accuracy and selectivity of composite sensor can be greatly improved through the combination of 3-D recognition method and the confinement effect. Thus, it open up fresh opportunities to develop composite sensors with excellent sensing and differentiating ability.

15.
Nature ; 578(7796): 577-581, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32076270

RESUMO

Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and cellular processes. However, whether sensors for H2O2 also exist on the cell surface remains unknown. In plant cells, H2O2 triggers an influx of Ca2+ ions, which is thought to be involved in H2O2 sensing and signalling. Here, by using forward genetic screens based on Ca2+ imaging, we isolated hydrogen-peroxide-induced Ca2+ increases (hpca) mutants in Arabidopsis, and identified HPCA1 as a leucine-rich-repeat receptor kinase belonging to a previously uncharacterized subfamily that features two extra pairs of cysteine residues in the extracellular domain. HPCA1 is localized to the plasma membrane and is activated by H2O2 via covalent modification of extracellular cysteine residues, which leads to autophosphorylation of HPCA1. HPCA1 mediates H2O2-induced activation of Ca2+ channels in guard cells and is required for stomatal closure. Our findings help to identify how the perception of extracellular H2O2 is integrated with responses to various external stresses and internal cues in plants, and have implications for the design of crops with enhanced fitness.


Assuntos
Arabidopsis/enzimologia , Arabidopsis/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas Quinases/metabolismo , Arabidopsis/genética , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Cisteína/química , Cisteína/metabolismo , Ativação Enzimática , Mutação , Oxirredução , Células Vegetais/metabolismo , Domínios Proteicos , Proteínas Quinases/química
16.
Sci Total Environ ; 712: 136486, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931222

RESUMO

Landfill cover should ideally have a medium with high water retention ability and low hydraulic conductivity to prevent rainfall infiltrating into the hazardous waste layer. Even though biochar amended soil (BAS) is advocated as cover medium, the interactions between biochar and plant, as well as the effects of biochar aging and plant growth on soil hydraulic properties are still not clear. This study aims to investigate the effects of grass (Cynodon dactylon) growth in BAS on soil water retention and saturated hydraulic conductivity (ks) over a two-year period. Four ground conditions were tested, namely bare silty sand with and without biochar, vegetated silty sand with and without biochar. The biochar content was kept at 10% (v/v). During the first 6 months, soil water content corresponding to field capacity (FC) and permanent wilting point (PWP) in grassed soil increased by 17% and 27%, respectively. With biochar inclusion, 43% and 57% additional increases in FC and PWP respectively were observed. Moreover, ks in biochar-amended grassed soil decreased by 50%. Furthermore, grass growth from 6 to 24 months reduced FC by 32%, PWP by 40% but caused 20 times increase in ks of grassed soil. With the presence of biochar, FC and PWP decreased by only 6% and 8%, respectively, and ks increased by 200% due to the enhanced plant growth (specifically root growth) by biochar. After two years, ks of grassed soil with biochar was 16 times smaller than that without biochar. This study demonstrated the effectiveness of biochar in maintaining the enhanced soil water retention ability and reduced ks in vegetated soil over a two-year study period.


Assuntos
Solo , Carvão Vegetal , Instalações de Eliminação de Resíduos , Água
17.
Thorac Cancer ; 11(3): 498-504, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31970923

RESUMO

Immune checkpoint inhibitors represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Management of irAEs is based on clinical experience because it is not easy to conduct prospective trials to evaluate the best treatment strategy. Using a combination of search terms in the PubMed and Embase databases, we reviewed all cases in the English language citing toxicities associated with either pembrolizumab, nivolumab, ipilimumab, atezolizumab, tremelimumab, durvalumab, avelumab or any combination of these agents published before 20 May 2019. A total of 128 reports with 239 cases were included in the study. Here, we summarize the spectrum of toxicities, safety in special patients, rechallenging after irAEs and agents used for treatment of irAEs in those reports.

18.
Chem Commun (Camb) ; 56(7): 1141-1144, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31895360

RESUMO

The spatial arrangements of Ti species would affect the electronic metal-support interactions and the proportion of Ce3+ sites for ceria-supported Ru catalysts. Ti-Surface-loaded CeO2 supported Ru catalysts exhibited excellent ammonia synthesis activity, which is attributed to a larger proportion of Ru metal, more electrons of Ru species and better adsorption ability of hydrogen and nitrogen.

19.
Brain Imaging Behav ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898093

RESUMO

Cerebral microbleeds (CMBs) in dialysis patients have recently attracted much attention, and the different locations of CMBs indicate different pathological processes. Previous studies on the relationship between CMBs and cognitive impairment (CI) in the general population and in dialysis patients have reported controversial results. A total of 180 chronic dialysis patients were enrolled in our study. Based on brain magnetic resonance imaging (MRI) analysis of CMBs, the patients were divided into 4 groups (without-CMBs group, strictly lobar group, strictly deep group, and mixed group). A wide range of cognitive tests was administered to evaluate cognitive function. The risk factors for CMBs were explored, and the correlation between CMB distribution and CI was investigated by regression analysis. The prevalence of CMBs was 32.8% in the total study population, 36.1% in the haemodialysis (HD) subgroup and 26.2% in the peritoneal dialysis (PD) PD subgroup. Sixteen subjects (8.9%) were classified as the lobar group, 12 subjects (6.7%) as the mixed group, and 31 subjects (17.2%) as the deep group. A significant association was shown between deep CMBs and impaired cognitive function, involving overall cognitive function, memory, language ability and executive function. Deep CMBs were significantly associated with dialysis vintage, mean arterial pressure (MAP) and lacunar infarcts number, while deep CMBs showed no correlation with dialysis modality and current heparin medication. Deep CMBs are closely associated with global and specific CI in dialysis patients. Blood pressure control may prevent deep CMBs and their associated CI.

20.
Nanotoxicology ; 14(2): 162-180, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31703536

RESUMO

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.

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