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1.
J Colloid Interface Sci ; 598: 511-518, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33934016

RESUMO

Capacitive deionization (CDI) is considered as a promising desalination technology due to its low energy consumption and no two-second pollution. But the development of traditional CDI is limited by its two drawbacks, which are low deionization capacity and unavoidable parasitic reactions. Hybrid capacitive deionization (HCDI), which is composed of a faradic electrode and an electrical-double-layer electrode, effectively solves the above problem. Herein, we report a typical NASICON material Na3(VO)2(PO4)2F and modify it with rGO, then apply it in HCDI firstly and receive a superior desalination performance. Five samples are prepared by adding different contents GO solution and we choose the best one (NVOPF-4) with the lowest resistance for the desalination tests according to electrochemical performance. The result of desalination shows a high desalination capacity of 175.94 mg·g-1, low energy consumption of 0.35 kWh·kg-NaCl-1, and the energy recovery is 20% at a current density of 25 mg·g-1. NVOPF@rGO displays a promising ability for desalination in capacitive deionization, further confirming NASICON be a suitable material type for HCDI electrode materials.

2.
J Med Chem ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929200

RESUMO

Hexameric structure formation through packing of three C-terminal helices and an N-terminal trimeric coiled-coil core has been proposed as a general mechanism of class I enveloped virus entry. In this process, the C-terminal helical repeat (HR2) region of viral membrane fusion proteins becomes transiently exposed and accessible to N-terminal helical repeat (HR1) trimer-based fusion inhibitors. Herein, we describe a mimetic of the HIV-1 gp41 HR1 trimer, N3G, as a promising therapeutic against HIV-1 infection. Surprisingly, we found that in addition to protection against HIV-1 infection, N3G was also highly effective in inhibiting infection of human ß-coronaviruses, including MERS-CoV, HCoV-OC43, and SARS-CoV-2, possibly by binding the HR2 region in the spike protein of ß-coronaviruses to block their hexameric structure formation. These studies demonstrate the potential utility of anti-HIV-1 HR1 peptides in inhibiting human ß-coronavirus infection. Moreover, this strategy could be extended to the design of broad-spectrum antivirals based on the supercoiling structure of peptides.

3.
J Immunother Cancer ; 9(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33883257

RESUMO

BACKGROUND: In the tumor microenvironment, tumor cells are able to suppress antitumor immunity by competing for essential nutrients, including amino acids. However, whether amino acid depletion modulates the activity of CD8+ tumor-infiltrating lymphocytes (TILs) is unclear. METHOD: In this study, we evaluated the roles of amino acids and the Rag complex in regulating mammalian target of rapamycin complex 1 (mTORC1) signaling in CD8+ TILs. RESULTS: We discovered that the Rag complex, particularly RagD, was crucial for CD8+ T-cell antitumor immunity. RagD expression was positively correlated with the antitumor response of CD8+ TILs in both murine syngeneic tumor xenografts and clinical human colon cancer samples. On RagD deficiency, CD8+ T cells were rendered more dysfunctional, as demonstrated by attenuation of mTORC1 signaling and reductions in proliferation and cytokine secretion. Amino acids maintained RagD-mediated mTORC1 translocation to the lysosome, thereby achieving maximal mTORC1 activity in CD8+ T cells. Moreover, the limited T-cell access to leucine (LEU), overshadowed by tumor cell amino acid consumption, led to impaired RagD-dependent mTORC1 activity. Finally, combined with antiprogrammed cell death protein 1 antibody, LEU supplementation improved T-cell immunity in MC38 tumor-bearing mice in vivo. CONCLUSION: Our results revealed that robust signaling of amino acids by RagD and downstream mTORC1 signaling were crucial for T-cell receptor-initiated antitumor immunity. The characterization the role of RagD and LEU in nutrient mTORC1 signaling in TILs might suggest potential therapeutic strategies based on the manipulation of RagD and its upstream pathway.

4.
Org Lett ; 23(8): 3184-3189, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33792337

RESUMO

The vicinal diamine motif plays a significant role in natural products, drug design, and organic synthesis, and development of synthetic methods for the synthesis of diamines is a long-standing interest. Herein, we report a regioselective intermolecular three-component vicinal diamination of styrenes with acetonitrile and azodicarboxylates. The diamination products can be produced in moderate to excellent yields via the Ritter reaction. Synthetic applications and theoretical studies of this reaction have been conducted.

5.
PLoS One ; 16(4): e0250091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33872342

RESUMO

PURPOSE: Numerous studies have demonstrated that a variety of systemic inflammatory markers were associated with the survival of different tumors. However, the association between elevated postoperative neutrophil-lymphocyte ratio (postNLR) and long-term outcomes, including overall survival (OS), disease-free survival (DFS), in patients with solid tumors remains controversial. A systematic review was conducted to explore the association between the postNLR and long-term outcomes in solid tumors. MATERIALS AND METHODS: Relevant literature was identified using PubMed, Embase, Web of Science, and the Cochrane Library from the initiation of the databases to October 2020. Data were extracted from included studies reporting hazard ratio (HR) and 95% confidence intervals (CI), and were pooled using generic inverse-variance and random-effects modeling. 25 studies reporting on7539 patients were included in the analysis. RESULTS: Elevated postNLR was associated with poor OS (HR 1.87, 95% CI = 1.53-2.28; P < 0.00001), and worse DFS (HR 1.69, 95% CI = 1.28-2.22; P = 0.0002). Subgroup analyses showed that the trend of the pooled HR for most of the subgroups was not changed, and the heterogeneity of the same tumor type was not obvious. However, there was no correlation between high postNLR obtained within 7days and poor DFS (n = 3, HR 1.25, 95CI% = 0.54-2.88; P = 0.60). CONCLUSIONS: Elevated postNLR might be a readily available and inexpensive biomarker for long-term outcomes in solid tumors. Multicenter and prospective studies are needed to explore the impact of the postNLR on the prognosis of solid tumors.

6.
Biomed Environ Sci ; 34(4): 272-281, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33894806

RESUMO

Objective: This study aimed to use an air-liquid interface (ALI) exposure system to simulate the inhalation exposure of motorcycle exhaust particulates (MEPs) and then investigate the benchmark dose (BMD) of MEPs by evaluating cell relative viability (CRV) in lung epithelial BEAS-2B cells. Methods: The MEPs dose was characterized by measuring the number concentration (NC), surface area concentration (SAC), and mass concentration (MC). BEAS-2B cells were exposed to MEPs at different concentrations via ALI and CRV was determined using Cell Counting Kit (CCK-8) assay. BMD software was applied to calculate BMD and the lower limit of benchmark dose (BMDL) according to Akaike Information Coefficient (AIC), with P-value based on Hill, Linear, Polynomial, and Power model. Results: Our results reveal that BMD of NC and SAC were estimated by the best-fitting Hill model, while MC was estimated by Polynomial model. The BMDL for CRV following ALI exposure to MEPs were as follows: 364.2#/cm 3 for NC; 0.662 × 10 7 nm 2/cm 3 for SAC; and 0.278 µg/m 3 for MC. Conclusion: These results indicate that MEPs exposure via ALI system induces a dose-dependent decrease of CRV and provides the potential exposure threshold of MEPs in a lung cell model.

7.
Enzyme Microb Technol ; 146: 109781, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33812562

RESUMO

L-amino acid ligases (Lals) are promising biocatalysts for the synthesis of dipeptides with special biological properties. However, their poor (or broad) substrate specificity limits their industrial applications. To address this problem, a molecular engineering method for Lals was developed to enhance their catalytic performance. Based on substrate channeling, entrances to the active site for different substrates were identified, and the "gate" located around the active site pocket, which plays an essential role in substrate recognition, was then engineered to facilitate acceptance of L-Gln. Two mutants (L110Y and N108F/L110Y) were discovered to display significantly increased catalytic activity toward L-Ala and L-Gln in the biosynthesis of Ala-Gln. The catalytic efficiency (kcat/ Km) of the L110Y and N108F/L110Y mutants was improved by 2.64-fold and 4.06-fold, respectively, compared with that of the wild type. N108F/L110Y was then further applied for batch production of Ala-Gln, which showed that the released Pi yield was 694.47 µM, which was an increase of approximately 21.4 %, and the yield of Ala-Gln was approximately 2.59 mM-1 L-1 mg-1. Collectively, these findings suggest the potential practical application of this method in the rational design of Lals for increased catalytic performance.

8.
Infect Dis Poverty ; 10(1): 27, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33795011

RESUMO

BACKGROUND: Sexual transmission among men who have sex with men (MSM) is the dominant route of HIV transmission in China. Extensive use of geosocial networking (GSN) smartphone application (app) has dramatically changed the pattern of sexual behaviors and HIV risk among MSM, but data on HIV incidence and the changing risk behaviors of GSN app-using MSM are limited. We aims to assess the HIV incidence and its correlates among gay GSN app-using MSM in China. METHODS: We constructed an open cohort which was initiated and maintained using a GSN app to assess the HIV incidence among app-using MSM, recruited from June 2017 to December 2018. MSM completed an online questionnaire on their sociodemographic characteristics, sexual behaviors, recreational drug use and sexually transmitted infections status. Then each man had an HIV test, and those tested negatives were enrolled into the cohort. Participants completed follow-ups with additional HIV tests though the app during the study period, and were censored at HIV seroconversion or study end date. HIV incidence was calculated by dividing the sum of observed HIV seroconversions by the observed person-time. Univariate (Chi-square test and Fisher's exact test) and multivariate (proportional hazards regression) analyses were used to examine correlates of HIV incidence. RESULTS: A total of 6957 HIV negative MSM were enrolled in the open cohort, 37 seroconversions occurred among 1937 men contributing 1065 observed person-years: HIV incidence was 3.47 per 100 person-years [95% confidence interval (CI): 2.37-4.57]. More than five sexual partners [hazard ratio (HR) = 2.65, 95% CI: 1.04-6.67], and sex with HIV positive partners (HR = 3.82, 95% CI: 1.16-12.64) in the preceding six months were positively associated with HIV seroconversion. Consistent condom use for anal sex (HR = 0.27, 95% CI: 0.07-0.96), and reporting insertive anal sex only (HR = 0.23, 95% CI: 0.08-0.62) in the preceding six months were protective factors for HIV seroconversion. CONCLUSIONS: Tailored interventions targeting app-using MSM are urgently needed given their high risk of HIV. As a new tool for accessing MSM at higher HIV risk, GSN smartphone app could play an important role in HIV research among MSM.

9.
Phytomedicine ; 85: 153522, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33799223

RESUMO

BACKGROUND: Thousands of years of clinical application of Wutou decoction (WTD) support its reliable efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying molecular mechanism remains unclear, and the synergistic involvement of assistant herbs in WTD in enhancing the sovereign herb in treating RA is unknown. PURPOSE: This study aimed to investigate the efficacy-oriented compatibility of five herbs in WTD and the underlying mechanisms. METHODS: The anti-arthritic effects of WTD and the compatibilities of the five herbs in WTD were studied in vivo with adjuvant-induced arthritis (AIA) rat model and in vitro with LPS-induced RAW264.7 macrophage. Network pharmacology analysis was conducted to identify the dominant pathways involved in the anti-arthritis mechanisms of WTD and how the five herbs work synergistically. The results were further verified by in vivo and in vitro experiments. RESULTS: Our data revealed that the five herbs in WTD exert synergistic anti-arthritic effects on RA. Moreover, Radix Aconite (AC) is the principal anti-inflammatory component in WTD according to the extent of therapeutic effects exerted on the AIA rats. In vivo and in vitro experiments demonstrated that WTD inhibited NF-κB phosphorylation and simultaneously increased the expression of Nrf2, which were the major pathways identified by the network pharmacology analysis. The major assistant component, Herba Ephedrae (EP), evidently inhibited NF-κB mediated inflammatory response. The other assistant component, Radix Astragali (AS), considerably enhanced the expression of Nrf2 when used alone or in combination with AC. These combinations improved the anti-arthritis effects on the AIA rats better than that of AC alone. Nevertheless, WTD always achieved the best effects than any combinations both in vivo and in vitro. CONCLUSION: The ministerial herbs EP and AS intensify the anti-arthritic effects of AC by regulating the NF-κB-mediated inflammatory pathway and the Nrf2-mediated anti-oxidation pathway which are the major pathways of WTD for alleviating the symptoms of RA.

10.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(2): 188-194, 2021 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-33834674

RESUMO

OBJECTIVES: To evaluate the effects of antimicrobial peptide GH12 designed de novo on the structure, morphology, and composition of a cariogenic three-species biofilm. METHODS: The cariogenic three-species biofilm consis-ted of the cariogenic Streptococcus mutans (S. mutans) and commensal bacteria Streptococcus sanguinis (S. sanguinis) and Streptococcus gordonii (S. gordonii). The biofilm was treated using GH12 (2, 4, and 8 mg·L-1), and untreated biofilm was used as the control. Changes in the morphology and structure of the three-species biofilm were evaluated through crystal violet staining, scanning electron microscopy (SEM), and fluorescent in situ hybridization (FISH). Moreover, S. mutans in the biofilm was selectively cultured, and its colony-forming units were counted. RESULTS: The biomass and density of the cariogenic three-species biofilm treated with GH12 decreased compared with those of the control. The number of S. mutans decreased gradually and eventually became undetectable, whereas the number of S. gordonii and S. sanguinis increased and became predominant in the biofilm. CONCLUSIONS: GH12 can reduce the number of S. mutans within the cariogenic three-species biofilm, destroys its integrity, and consequently makes the biofilm easy to remove.


Assuntos
Cárie Dentária , Biofilmes , Humanos , Hibridização in Situ Fluorescente , Proteínas Citotóxicas Formadoras de Poros , Streptococcus mutans
11.
Int J Biol Sci ; 17(4): 1010-1025, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867825

RESUMO

The majority of cellular DNAs in eukaryotes are organized into linear chromosomes. In addition to chromosome DNAs, genes also reside on extrachromosomal elements. The extrachromosomal DNAs are commonly found to be circular, and they are referred to as extrachromosomal circular DNAs (eccDNAs). Recent technological advances have enriched our knowledge of eccDNA biology. There is currently increasing concern about the connection between eccDNA and cancer. Gene amplification on eccDNAs is prevalent in cancer. Moreover, eccDNAs commonly harbor oncogenes or drug resistance genes, hence providing a growth or survival advantage to cancer cells. eccDNAs play an important role in tumor heterogeneity and evolution, facilitating tumor adaptation to challenging circumstances. In addition, eccDNAs have recently been identified as cell-free DNAs in circulating system. The altered level of eccDNAs is observed in cancer patients relative to healthy controls. Particularly, eccDNAs are associated with cancer progression and poor outcomes. Thus, eccDNAs could be useful as novel biomarkers for the diagnosis and prognosis of cancer. In this review, we summarize current knowledge regarding the formation, characteristics and biological importance of eccDNAs, with a focus on the molecular mechanisms associated with their roles in cancer progression. We also discuss their potential applications in the detection and treatment of cancer. A better understanding of the functional role of eccDNAs in cancer would facilitate the comprehensive analysis of molecular mechanisms involved in cancer pathogenesis.

12.
J Zhejiang Univ Sci B ; 22(4): 330-340, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33835767

RESUMO

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Anticorpos Antivirais/sangue , Hipertensão/tratamento farmacológico , Carga Viral , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Biomarcadores , China , Feminino , Humanos , Hipertensão/complicações , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transcriptoma
13.
J Proteomics ; 241: 104224, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33845180

RESUMO

"Iron prawn" is a condition of severe growth retardation that fishers call. The giant river prawn (Macrobrachium rosenbergii) is a commercially important species contains high protein content and functional nutrients. However, no proteomic information is available for this species. We performed the shotgun 2DLC-MS/MS proteomic analysis of the total protein from "iron prawn". Total 19,758 peptides corresponding to 2613 high-confidence proteins were identified. These proteins range in size from 40 to 70 kDa. KEGG analysis revealed that the largest group consisting total 102 KEGG pathway proteins comparing the "iron prawn" with the normal prawn. Additionally, 7, 11, 1, 6, and 5 commercially important enzymes were found in the eyestalk, liver, muscle, ovary, and testis, respectively. The functions of these differently expressed enzymes include immune system action against pathogens, muscle contraction, digestive system metabolism, cell differentiation, migration, and apoptosis in the severe growth retardation of "iron prawn". Our work provides insight into the understanding of the formation mechanism of "iron prawn".

14.
Cell Signal ; 84: 110025, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33915247

RESUMO

Recent studies have emphasized microRNAs (miRs) as crucial regulators in the occurrence and development of pancreatic cancer that continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-873 and its associated mechanism to unravel the biological characteristics of pancreatic cancer stem cells in tumor growth. The expression patterns of pleckstrin-2 (PLEK2) and miR-873 were detected in the pancreatic cancer tissues. Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis. Finally, the tumor formation in nude mice was measured to verify the preceding results in vivo. Pancreatic cancer tissues exhibited a decline of miR-873 expression and an enhancement of PLEK2 expression. miR-873 targeted PLEK2 and downregulated its expression, leading to inhibition of PI3K/AKT pathway. Overexpressed miR-873 or silenced PLEK2 inhibited the self-renewal and proliferation while promoting the apoptosis of pancreatic cancer stem cells. Tumor formation was inhibited by overexpressed miR-873 or silenced PLEK2 in nude mice. Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.

15.
J Cardiothorac Surg ; 16(1): 61, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781323

RESUMO

BACKGROUND: To evaluate the role of multi-slice spiral computed tomography (MSCT) angiography in the diagnosis of spontaneous isolated visceral artery dissection (SIVAD). METHODS: Twenty-seven patients with abdominal SIVAD were included in the study. The MSCT scans of the patients were subjected to various post-processing techniques to visualize the visceral artery wall. Clinical features including arterial dissection, thrombosis, dissection length, true/false lumen, and complications were recorded. RESULTS: Type I, IIa, and IIb SIVADs were observed in 11, 6, and 10 patients, respectively. Superior mesenteric artery (SMA) dissection was the most common (n = 16), followed by abdominal aortic dissection (n = 6), splenic artery dissection (n = 2), renal artery dissection (n = 2), and splenic artery dissection (n = 1). One patient with SMA dissection suffered small intestine ischemia, 1 with splenic artery dissection had splenic infarction, and 1 patient with left renal artery dissection experienced renal infarction. The false lumen was bigger than the true lumen in 20 patients, with 9 patients having thrombus. The true lumen was bigger than the false lumen in 7 patients. CONCLUSIONS: MSCT angiography is a valuable technique in the diagnosis and treatment of patients with SIVAD. Patients with abdominal pain suspected due to SIVAD should be examined with MSCT angiography for early detection of SIVAD.

16.
J Control Release ; 333: 139-150, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33774121

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a growing medical problem associated with extensive metastasis and high mortality. Intraperitoneal (IP) administration of therapeutics promises to help the treatment of cancers originated from organs in the peritoneal cavity. In this study, we evaluated how physicochemical properties of self-assembled polycation/siRNA nanoparticles affect their IP delivery efficacy in an orthotopic PDAC model. We have examined the effect of covalent polycation modification with lipophobic and hydrophobic tetrafluoro-p-toluic acid (TFTA), hydrophobic cholesterol, and hydrophilic poly(ethylene glycol) respectively. The surface charge of the three different nanoparticles was also modulated by coating the surface with serum albumin. We found that positively charged fluorine-containing particles with lipophobic properties based on a mixture of positively charged polymeric AMD3100 CXCR4 antagonist (PAMD) and PAMD modified with TFTA (mPAMD-TFTA)/siRNA displayed the best cell uptake and transfection efficacy in vitro. Biodistribution evaluation of the nanoparticles in a syngeneic orthotopic PDAC model revealed that the fluorine-containing formulation also achieved the highest PDAC tumor accumulation after IP administration. With a combination of CXCR4 inhibition by PAMD and PLK1 downregulation by siRNA, the treatment with mPAMD-TFTA/siPLK1 showed significant inhibition of both primary and metastatic PDAC tumors. Overall, our study provides insights into and guides the design of the nanoparticles for improved IP delivery of siRNA in PDAC.

17.
Dalton Trans ; 50(12): 4408-4414, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33704289

RESUMO

Two complexes, namely [Zn(bpeb)(sda)] (1) and [Zn(poly-bpeb)(sda)] (2), were synthesized by an organic ligand with an extensively conjugated system, bpeb = 1,4-bis[2-(3-pyridyl) vinyl]-benzene, H2sda = sulfonyldibenzoic acid and d10 metal centers Zn2+. Structural analysis revealed that compound 1 was nonporous and possessed 7-fold interpenetrated three-dimensional (3D) frameworks constructed from one-dimensional (1D) Zn-bpeb and Zn-sda chains. Interestingly, due to the short distance between the vinyl groups from two neighboring bpeb ligands, compound 1 could undergo a photochemical [2 + 2] polymerization reaction to generate 2 in a single-crystal to single-crystal (SCSC) manner under the irritation of UV. Moreover, the organic polymer in 2 could be depolymerized by heating to realize the reversible transformation from 2 to 1. Furthermore, both compounds 1 and 2 could be used as fluorescent sensors for 2,4,6-trinitrophenol (TNP) with high selectivity and sensitivity.

18.
Neurochem Res ; 46(5): 1239-1251, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33646533

RESUMO

As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson's disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.

19.
J Int Med Res ; 49(2): 300060521993315, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33641489

RESUMO

OBJECTIVE: Myocardial ischemia/reperfusion (I/R) injury causes various severe heart diseases, including myocardial infarction. This study aimed to determine the therapeutic effect of atractylenolide I (ATR-I), which is an active ingredient isolated from Atractylodes macrocephala, on myocardial I/R injury. METHODS: Male Sprague-Dawley rats were randomly allocated to the five following groups (nine rats/group): control, I/R, and I/R + ATR-I preconditioning (10, 50, and 250 µg). The effects of ATR-I on rats with I/R injury were verified in cardiomyocytes with hypoxia/reoxygenation. Production of reactive oxygen species was determined. The proliferative ability of cardiomyocytes was detected using the bromodeoxyuridine assay. Mitochondrial membrane potential was measured using flow cytometry. Cellular apoptosis was assessed by flow cytometry and the terminal dUTP-digoxigenin nick end labeling assay. RESULTS: I/R and hypoxia/reoxygenation injury increased mitochondrial dysfunction and activated caspase-3 and Bax/B cell lymphoma 2 expression in vitro and in vivo. ATR-I pretreatment dose-dependently significantly attenuated myocardial apoptosis and suppressed oxidative stress as reflected by increased mitochondrial DNA copy number and superoxide dismutase activity, and decreased reactive oxygen species and Ca2+ content. CONCLUSION: ATR-I protects against I/R injury by protecting mitochondrial function and inhibiting activation of caspase-3.

20.
Ophthalmol Glaucoma ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33774215

RESUMO

PURPOSE: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) neuroretinal rim measurements. DESIGN: Prospective longitudinal cohort study PARTICIPANTS: One hundred and twenty-four eyes of 124 open angle glaucoma patients METHODS: Over a 5-year period, 124 open angle glaucoma patients had yearly DP, VFs, SD-OCT RNFL thickness scans, and optic nerve volume scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Progression by DP and VF occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if there was change greater than test-retest variability. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa coefficients were used to measure agreement of progressing eyes among modalities. MAIN OUTCOME MEASURES: Time to glaucoma progression among all 4 modalities RESULTS: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared to DP (16.1%, P<0.001), and global RNFL thickness (15.3%, P<0.001) respectively. Global MDB thickness detected glaucoma progression earlier than either DP (23 versus 44 months; P<0.001) or global RNFL thickness (23 versus 33 months; P<0.001). Among MDB progressing eyes, 46.2% were simultaneously or later confirmed by other conventional modalities. Agreement of glaucoma progressing eyes for all 4 modalities in paired fashion were slight to fair (k=0.095-0.300). CONCLUSION: High-density 3D SD-OCT neuroretinal rim measurements detected glaucoma progression approximately 1-2 years earlier compared to current clinically available structural tests (i.e. disc photos and 2D RNFL thickness measurements).

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