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1.
Nat Commun ; 12(1): 339, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436626

RESUMO

Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity.

2.
Biosens Bioelectron ; 174: 112827, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33257182

RESUMO

The regulation of biocatalytic cascades in microenvironments for high performance and extended applications is still challenging. Herein, we develop a rolling circle amplification (RCA)-based one-pot method to prepare the micron-sized DNA flowers (DFs), which achieve the co-encapsulation and spatial regulation of bi-enzyme molecules, glucose oxidase (GOx) and horseradish peroxidase (HRP). In this system, GOx and HRP are integrated into the DFs simultaneously during RCA with the bridging of magnesium between enzyme residues and phosphate backbones on DFs. The cascade of GOx/HRP is regulated with the formation of highly ordered and hydrogen-bonded water environment in the cavity of DFs, resulting in an enhanced cascade catalytic efficiency compared with that in homogeneous solution. Moreover, the high density of DNA scaffold ensures the encapsulation of GOx/HRP with high efficiency. Accordingly, a glucose electrochemical biosensor with amplified signal response is fabricated using the as-prepared GOx/HRP DFs as biosensing interface, realizing sensitive detection of glucose. Further, through designing the complementary sequence of aptamer into the programmable circular template of RCA, the bi-enzyme co-encapsulated DFs are versatilely applied to sensitive and selective detection of cancerous exosomes and thrombin in "signal-on" and "signal-off" modes, respectively, which are further applied to the analysis of complex biological samples successfully. Overall, the encapsulation of multi-enzyme with DFs proposes a promising strategy to regulate the microenvironment of biocatalytic cascades, which hold great potential in biotechnology, bioanalysis and disease diagnosis.

3.
Biosens Bioelectron ; : 112898, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33358287

RESUMO

As a kind of promising nanomaterials, metal nanoclusters (MNCs) generally composed of several to hundreds of metal atoms have received increasing interest owing to their unique properties, such as ultrasmall size (<2 nm), fascinating physical and chemical properties, and so on. Recently, template-assisted synthesis of MNCs (e.g., Au, Ag, Cu, Pt and Cd) has attracted extensive attention in biological fields. Up to now, various templates (e.g., dendrimers, polymers, DNAs, proteins and peptides) with different configurations and spaces have been applied to prepare MNCs with the advantages of facile preparation, controllable size, good water-solubility and biocompatibility. Herein, we focus on the recent advances in the template-assisted synthesis of MNCs, including the templates used to synthesize MNCs, and their applications in biosensing, bioimaging, and disease theranostics. Finally, the challenges and future perspectives of template-assisted synthesized MNCs are highlighted. We believe that this review could not only arouse more interest in MNCs but also promote their further development and applications by presenting the recent advances in this area to researchers from various fields, such as chemistry, material science, physiology, biomedicine, and so on.

4.
Psychosom Med ; Publish Ahead of Print2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33337594

RESUMO

OBJECTIVE: In recent studies, the COVID-19 pandemic has been associated with increased risk of mental health problems across many subpopulations including pregnant and postnatal women. This study examined the prevalence and correlates of depressive symptoms (depression hereafter) in Chinese pregnant and postpartum women during the COVID-19 pandemic. METHODS: This is a multicentre, cross-sectional study comprising 1,309 pregnant and postpartum women across 12 provinces in China during the COVID-19 pandemic. Depression was assessed using the 9-item Patient Health Questionnaire (PHQ9). Univariate analysis and multivariate logistic regression analyses were conducted. RESULTS: The prevalence of depression in pregnant and postpartum women was 27.43% (95% CI=25.01%-29.85%). Women who were worried about themselves or their babies being infected with COVID-19 (OR=2.562, 95%CI=1.670-3.929), and those who had delayed regular medical check-ups (OR=2.434, 95%CI=1.580-3.750) were at higher risk of depression. Compared to those living in central and western parts of China, women living in northern (OR=0.513, 95%CI=0.326-0.807) and southeastern parts of China (OR=0.626, 95%CI=0.463-0.846) were less likely to have depression." CONCLUSION: The COVID-19 pandemic was associated with an increased likelihood of mental health problems among pregnant and postnatal women. Over a quarter of the pregnant and postpartum women in China suffered from depression during the COVID-19 pandemic. Considering the negative health impact of depression, preventive measures, regular mental health screening and medical check-ups are needed with the goal to reduce the risk of depression in this vulnerable population during a pandemic.

5.
Lab Med ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33135738

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO) has been considered to be an independent risk factor of heart failure (HF). OBJECTIVES: To further determine the plasma levels of TMAO in patients who have HF with preserved ejection fraction (HFpEF), and to analyze the relationship between TMAO and HFpEF risk. METHODS: A total of 57 control participants and 61 patients with HFpEF were recruited. We measured and analyzed plasma levels of TMAO and performed biochemical examination of all patients. RESULTS: The mean (SD) plasma levels of TMAO in patients with HFpEF (6.84 [1.12] µmol/L) were significantly higher than in controls (1.63 [0.08] µmol/L; P <.01). The area under the curve (AUC) of TMAO and N-terminal pro b-type natriuretic peptide (NT-proBNP) was 0.817 and 0.924, respectively, which were determined by receiver operating characteristic (ROC) analysis. TMAO was an independent risk factor in patients with HFpEF, as revealed by univariate and multivariate logistic regression analysis. The level of TMAO was correlated with blood urea nitrogen (BUN), creatinine, and NT-proBNP. CONCLUSIONS: TMAO level was highly associated with HFpEF risk.

6.
Quintessence Int ; 51(9): 753-762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32901236

RESUMO

OBJECTIVE: Conservative treatment modalities are recommended for managing masticatory myalgia in individuals with temporomandibular disorders. The aim of this study was to retrospectively review and compare the effectiveness of four conservative treatments: counseling and occlusal splint therapy, counseling and manipulation integrated with electrophysiotherapy, the combination of the two treatments, and counseling only. METHOD AND MATERIALS: One hundred and sixty-eight patients who had myalgia with limited jaw movement were retrospectively observed in this study. Between January 2015 and December 2017, 63 patients received counseling and stabilization occlusal splint therapy (Group 1), 35 patients received counseling and manipulation integrated with electrophysiotherapy (Group 2), 33 patients received the combination of counseling, splint therapy, and manipulation integrated with electrophysiotherapy (Group 3), and 37 patients received counseling only (Group 4). All subjects were followed up for 12 weeks. The intensity of spontaneous pain, palpation pain, chewing pain in the masticatory muscles, and range of pain-free maximal mouth opening were recorded in the clinical assessments. Intragroup and intergroup differences were examined by using analysis of variance (ANOVA) and the Kruskal-Wallis test. RESULTS: Spontaneous pain in the masticatory muscles was relieved significantly in all groups at the 6-week visit (P < .05), and no significant difference was found among the groups (P > .05). Palpation pain was relieved significantly at the 9-week visit in the counseling + occlusal splint therapy group, counseling + manipulation + electrophysiotherapy group, and counseling + occlusal splint + manipulation + electrophysiotherapy group (P < .05). In the treatment group with counseling alone, significant palpation pain relief occurred at 12 weeks. Chewing pain was relieved significantly at the 6-week visit in the counseling + occlusal splint therapy group, counseling + manipulation + electrophysiotherapy group, and counseling + occlusal splint + manipulation + electrophysiotherapy group (P < .05), yet no significant difference compared to the baseline was observed in the counseling-only group (P > .05). A significant increase in the maximal range of pain-free mouth opening was observed at the 9-week visit in the counseling + occlusal splint therapy group, and at the 3-week visit in the counseling + manipulation + electrophysiotherapy group and counseling + occlusal splint + manipulation + electrophysiotherapy group (P < .05). Nevertheless, no significant change in the range of mouth opening was found throughout the follow-up period in the counseling-only group (P > .05). CONCLUSION: Each of the included treatment modalities relieved spontaneous pain and tenderness to palpation of the masticatory muscles during the follow-up intervals. Counseling alone did not help patients with chewing pain and limited mouth opening in the short term. Treatment protocols including counseling, occlusal splint therapy, and manipulation, integrated with electrophysiotherapy showed the best short-term outcomes for symptomatic improvement.


Assuntos
Tratamento Conservador , Mialgia , Humanos , Mandíbula , Placas Oclusais , Estudos Retrospectivos
7.
Ann Palliat Med ; 9(5): 2862-2871, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921087

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO) has been identified as a new biomarker of cardiovascular disease. Our aim was to evaluate the plasma levels of TMAO in patients with or without heart failure (HF), and to indicate the correlation between plasma TMAO level and HF classification in northern Chinese patients. METHODS: A total of 112 control participants and 184 HF patients participated in this study. Plasma levels of TMAO and N-terminal probrain natriuretic peptide (NT-proBNP) in all participants were examined and analyzed. RESULTS: The plasma TMAO levels were remarkably higher in HF patients than that in control participants (7.0±0.6 vs. 1.5±0.1 µmol/L; P<0.01). In addition, the plasma TMAO levels of significantly increased from NYHA II to NYHA IV group (3.5±0.9, 6.0±0.8 and 8.1±1.0 µmol/L, respectively). The receiver operating characteristic analysis (ROC) showed that area under the curve (AUC) of TMAO was 0.881 (P<0.01). Furthermore, the AUC value for TMAO was 0.857 (95% CI: 0.674-1.000; P<0.01), 0.845 (95% CI: 0.778-0.911; P<0.01) and 0.914 (95% CI: 0.872-0.956; P<0.01) in NYHA II, NYHA III and NYHA IV groups, respectively. Univariate and multivariate logistic regression analysis indicated that TMAO was an independent risk factor for HF in patients. The level of TMAO was positively correlated with NT-proBNP. However, the diagnostic ability of TMAO was lower than that of NT-proBNP. CONCLUSIONS: TMAO was an independent predictor of HF, moreover, the TMAO levels were highly associated with HF classification in northern Chinese patients.

8.
Pestic Biochem Physiol ; 170: 104705, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980068

RESUMO

Magnolia officinalis, as a well-known herb worldwide, has been widely used to treat multiple diseases for a long time. In this study, the petroleum ether extract from M. officinalis showed effective antifungal activity against seven plant pathogens (particularly against R. solani with an inhibition rate of 100.00% at 250 µg/mL). Honokiol and magnolol, isolated by the bioassay-guided method, exhibited greater antifungal activity than tebuconazole (EC50 = 3.07 µg/mL, p ≤ 0.001) against R. solani, which EC50 values were 2.18 µg/mL and 3.48 µg/mL, respectively. We used transcriptomics to explore the mechanism of action of honokiol against R. solani. Results indicated that honokiol may exert antifungal effects by blocking the oxidative phosphorylation metabolic pathway. Further studies indicated that honokiol induced ROS overproduction, disrupted the mitochondrial function, affected respiration, and blocked the TCA cycle, which eventually inhibited ATP production. Besides, honokiol also damaged cell membranes and caused morphological changes. This study demonstrated that the lignans isolated from M. officinalis possess the potential to be developed as botanical fungicides.


Assuntos
Lignanas/farmacologia , Magnolia , Antifúngicos/farmacologia , Bioensaio , Compostos de Bifenilo
9.
Sleep Med ; 75: 282-286, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32919351

RESUMO

PURPOSE: To examine insomnia disorder and its association with sociodemographic factors and poor mental health in 2019 novel coronavirus (COVID-19) inpatients in Wuhan, China. DESIGN: and Methods: A total of 484 COVID-19 inpatients in Wuhan Tongji Hospital were selected and interviewed with standardized assessment tools. Insomnia disorder was measured by the Chinese version of the Insomnia Severity Index (ISI-7), a total score of 8 or more was accepted as the threshold for diagnosing insomnia disorder. RESULTS: The prevalence of insomnia disorder in the whole sample was 42.8%. Binary logistic regression analysis revealed that female gender, younger age, and higher fatigue and anxiety severity were more likely to experience insomnia disorder. CONCLUSION: Given the high rate of insomnia disorder status among COVID-19 inpatients in Wuhan, China, and its negative effects, follow-up assessments and appropriate psychological interventions for insomnia disorder are needed in this population.


Assuntos
/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , China , Estudos Transversais , Feminino , Hospitalização , Humanos , Comportamento de Busca de Informação , Pacientes Internados/psicologia , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/psicologia , Fatores Socioeconômicos
10.
Nat Prod Res ; : 1-9, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32787575

RESUMO

Seven new phenylpropanoids, including two pairs of enantiomers of 8-O-4'-type neolignans, named (±)-xanthiifructins A-B (1a/1b-2a/2b), a pair of simple phenylpropanoid derivatives (±)-xanthiifructins C (3a/3b), and a racemic phenylpropanoid derivative xanthiifructin D (4), together with four known analogues (5-8) were isolated from the fruits of Xanthium sibiricum. Racemic xanthiifructins A-C were separated on chiral HPLC columns. Their structures were elucidated by comprehensive spectroscopic data analysis and comparison with the literatures. The anti-inflammatory and cytotoxic activities were evaluated for all isolates. Among them, (-)-xanthiifructin C (3b) exhibited potent inhibitory effect against nitric oxide production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with an IC50 value of 9.94 ± 0.57 µM. All compounds obviously were inactive for three human tumor cell lines (MCF-7, HepG2, and A549) with IC50 values much more than 10 µM.

11.
World J Gastroenterol ; 26(25): 3586-3602, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32742128

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors. Identification of diagnostic and therapeutic biomarkers for PDAC is urgently needed. Transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) has been linked to the progression of various human cancers. Nevertheless, the function and role of TBL1XR1 in pancreatic cancers are unclear. AIM: To elucidate the function and potential mechanism of TBL1XR1 in the development of PDAC. METHODS: Ninety patients with histologically-confirmed PDAC were included in this study. PDAC tumor samples and cell lines were used to determine the expression of TBL1XR1. CCK-8 assays and colony formation assays were carried out to assess PDAC cell viability. Flow cytometry was performed to measure the changes in the cell cycle and cell apoptosis. Changes in related protein expression were measured by western blot analysis. Animal analysis was conducted to confirm the impact of TBL1XR1 in vivo. RESULTS: Patients with TBL1XR1-positive tumors had worse overall survival than those with TBL1XR1-negative tumors. Moreover, we found that TBL1XR1 strongly promoted PDAC cell proliferation and inhibited PDAC cell apoptosis. Moreover, knockdown of TBL1XR1 induced G0/G1 phase arrest. In vivo animal studies confirmed that TBL1XR1 accelerated tumor cell growth. The results of western blot analysis showed that TBL1XR1 might play a key role in regulating PDAC cell proliferation and apoptosis via the PI3K/AKT pathway. CONCLUSION: TBL1XR1 promoted PDAC cell progression and might be an effective diagnostic and therapeutic marker for pancreatic cancer.

12.
J Affect Disord ; 275: 145-148, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32658818

RESUMO

INTRODUCTION: High risk of mental health problems is associated with Coronavirus Disease 2019 (COVID-19). This study explored the prevalence of depressive symptoms (depression hereafter) and its relationship with quality of life (QOL) in clinically stable patients with COVID-19. METHODS: This was an online survey conducted in COVID-19 patients across five designated isolation hospitals for COVID-19 in Hubei province, China. Depression and QOL were assessed with standardized instruments. RESULTS: A total of 770 participants were included. The prevalence of depression was 43.1% (95%CI: 39.6%-46.6%). Binary logistic regression analysis found that having a family member infected with COVID-19 (OR=1.51, P = 0.01), suffering from severe COVID-19 infection (OR=1.67, P = 0.03), male gender (OR=0.53, P<0.01), and frequent social media use to obtain COVID-19 related information (OR=0.65, P<0.01) were independently associated with depression. Patients with depression had lower QOL than those without. CONCLUSION: Depression is highly prevalent in clinically stable patients with COVID-19. Regular screening and appropriate treatment of depression are urgently warranted for this population.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Qualidade de Vida/psicologia , Adulto , Ansiedade/epidemiologia , China/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Pandemias , Prevalência , Inquéritos e Questionários
13.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2907-2915, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627466

RESUMO

This study was carried out to investigate the chemical constituents from Xanthii Fructus(the fruits of Xanthium sibiricum). The compounds were separated and purified by silica gel column chromatography, Sephadex LH-20 and ODS chromatography and semi-preparative HPLC. Base on HR-ESI-MS, NMR and other spectral data, their structures were identified. The anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide(LPS)-induced macrophage RAW264.7 as a screening model. A total of twenty-one compounds were isolated from the EtOAc fraction of 95% ethanol extract and identified as uracil(1), thymine(2), uridine(3), indole-3-carbaldehyde(4), indole-3-carboxylic acid(5), 2'-O-methyluridine(6), guanosine(7), 2,4(1H,3H)-quinazolinedione(8), 3-hydroxy-3-(2-hydroxyethyl)indolin-2-one(9), nicotinamide(10), N-acetyl-L-phenylalaninol(11), heliolactam(12), terresoxazine(13), caudatin(14), qingyangshengenin(15), caudatin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(16), caudatin-3-O-ß-D-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(17), caudatin-3-O-α-L-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-α-L-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside(18), qinyangshengenin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside(19), qinyangshengenin-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-digitoxopyranoside(20), rostratamine-3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside(21). Compounds 5-21 are obtained from genus Xanthium for the first time. Compounds 12 and 13 indirectly exhibited anti-inflammatory activity by suppressing LPS-induced NO production in RAW264.7 cells with IC_(50) values of(15.45±0.56) and(20.14±0.78) µmol·L~(-1), respectively.


Assuntos
Frutas , Xanthium , Cromatografia Líquida de Alta Pressão , Glicosídeos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
14.
Theranostics ; 10(18): 8250-8263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724469

RESUMO

Chemo-gene therapy is an emerging synergetic modality for the treatment of cancers. Herein, we developed pH-responsive multifunctional DNA nanomicelles (DNMs) as delivery vehicles for controllable release of doxorubicin (Dox) and anaplastic lymphoma kinase (ALK)-specific siRNA for the chemo-gene synergetic therapy of anaplastic large cell lymphoma (ALCL). Methods: DNMs were synthesized by performing in situ rolling circle amplification (RCA) on the amphiphilic primer-polylactide (PLA) micelles, followed by functionalization of pH-responsive triplex DNA via complementary base pairing. The anticancer drug Dox and ALK-specific siRNA were co-loaded to construct Dox/siRNA/DNMs for chemo-gene synergetic cancer therapy. When exposed to the acidic microenvironment (pH below 5.0), C-G·C+ triplex structures were formed, leading to the release of Dox and siRNA for gene silencing to enhance the chemosensitivity in ALCL K299 cells. The chemo-gene synergetic anticancer effect of Dox/siRNA/DNMs on ALCL was evaluated in vitro and in vivo. Results: The pH-responsive DNMs exhibited good monodispersity at different pH values, good biocompatibility, high drug loading capacity, and excellent stability even in the human serum. With the simultaneous release of anticancer drug Dox and ALK-specific siRNA in response to pH in the tumor microenvironment, the Dox/siRNA/DNMs demonstrated significantly higher treatment efficacy for ALCL compared with chemotherapy alone, because the silencing of ALK gene expression mediated by siRNA increased the chemosensitivity of ALCL cells. From the pathological analysis of tumor tissue, the Dox/siRNA/DNMs exhibited the superiority in inhibiting tumor growth, low toxic side effects and good biosafety. Conclusion: DNMs co-loaded with Dox and ALK-specific siRNA exhibited significantly enhanced apoptosis of ALCL K299 cells in vitro and effectively inhibited tumor growth in vivo without obvious toxicity, providing a potential strategy in the development of nanomedicines for synergetic cancer therapy.

15.
Inorg Chem ; 59(16): 11554-11561, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32568526

RESUMO

Lone pair cation-based novel coordination compounds Sn[(pdc)(H2O)] (Sn-I) and (H2bpy)[Bi(pdc)2(Hpdc)]·5H2O (Bi-I) (pdc = pyridine-2,6-dicarboxylate; bpy = 4,4'-bipyridine) were synthesized through mild hydrothermal reactions. While Sn-I crystallizing in the polar space group, Pca21, exhibits a helical chain structure consisting of SnO3N distorted seesaws, 2,6-pdc linkers, and water molecules, Bi-I crystallizing in the centrosymmetric (CS) space group, P1̅, reveals a pseudo-3D network composed of BiO5N3 polyhedra, 2,6-pdc ligands, H2bpy2+ cations, and isolated H2O molecules. The lone cations Sn2+ and Bi3+ in the title compounds are in a highly deformed polyhedral environment. The single-crystal-to-single-crystal transformation from Sn-I to the anhydrous Sn[(pdc)] (Sn-II) with the polar noncentrosymmetric structure was successfully achieved upon heating crystals of Sn-I. UV-vis diffuse reflectance spectra indicate that the introduction of Sn2+ or Bi3+ red-shifts the adsorption edges upon coordination. Powder second-harmonic generation (SHG) measurements indicate that Sn-I and Sn-II are type-I phase-matchable and exhibit SHG intensity of ca. 15 and 35 times that of α-SiO2, respectively. Solid state photoluminescence (PL) measurements indicate that Bi-I is an excellent green emitting phosphor with the quantum efficiency up to 26% and outstanding decay lifetime of 1.82 ms at room temperature.

16.
Int Immunopharmacol ; 84: 106601, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32422528

RESUMO

BACKGROUND: Although colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs. METHODS: Based on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected. RESULTS: A total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event ofcolitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27-69 days) among all monotherapies. CONCLUSIONS: ICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.

19.
Arch Toxicol ; 94(4): 1203-1213, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32112223

RESUMO

Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). The occurrence of hyperleukocytosis with As2O3 treatment seriously affects the early survival rate of APL patients, but no definite explanation for such a complication has been clearly established. To clarify the causes of this situation, AS3MT polymorphisms 14215 (rs3740390), 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) and profiles of plasma arsenic metabolites were evaluated in a group of 54 newly diagnosed APL patients treated with single-agent As2O3. High-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) was used to determine the concentrations of plasma arsenic metabolites. Plasma arsenic methylation metabolism capacity was evaluated by the percentage of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). The results showed that APL patients who developed hyperleukocytosis had a higher plasma iAs%, but a lower MMA% and PMI than those who did not develop hyperleukocytosis during As2O3 treatment. In addition, patients with the AS3MT 14215 (rs3740390) CC genotype had significantly higher plasma iAs% and incidence of hyperleukocytosis, but lower PMI than patients with the CT + TT genotype. Conversely, we did not observe statistically significant associations between the occurrence of hyperleukocytosis and AS3MT 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) polymorphisms in our study subjects. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3.

20.
Liver Int ; 40(6): 1378-1394, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32145145

RESUMO

BACKGROUND: NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non-apoptotic form of cell death induced by iron-dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression. METHOD: Mice were fed on MCD-diet to mimic NASH progression and gene expression in liver was analysed by RNA-seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture. RESULTS: RNA-seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD-diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD-fed mice. Scavenging of ferroptosis-linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD-diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation. CONCLUSION: Our results demonstrate an important role of ferroptosis in the progression of MCD-diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment.

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