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1.
Cell Death Dis ; 12(4): 364, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824309

RESUMO

MLL3 is a histone H3K4 methyltransferase that is frequently mutated in cancer, but the underlying molecular mechanisms remain elusive. Here, we found that MLL3 depletion by CRISPR/sgRNA significantly enhanced cell migration, but did not elevate the proliferation rate of cancer cells. Through RNA-Seq and ChIP-Seq approaches, we identified TNS3 as the potential target gene for MLL3. MLL3 depletion caused downregulation of H3K4me1 and H3K27ac on an enhancer ~ 7 kb ahead of TNS3. 3C assay indicated the identified enhancer interacts with TNS3 promoter and repression of enhancer activity by dCas9-KRAB system impaired TNS3 expression. Exogenous expression of TNS3 in MLL3 deficient cells completely blocked the enhanced cell migration phenotype. Taken together, our study revealed a novel mechanism for MLL3 in suppressing cancer, which may provide novel targets for diagnosis or drug development.

2.
Molecules ; 26(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802596

RESUMO

Cross-strand lateral ion-pairing interactions are important for antiparallel ß-sheet stability. Statistical studies suggested that swapping the position of cross-strand lateral residues should not significantly affect the interaction. Herein, we swapped the position of ammonium- and carboxylate-containing residues with different side-chain lengths in a cross-strand lateral ion-pairing interaction in a ß-hairpin. The peptides were analyzed by 2D-NMR. The fraction folded population and folding free energy were derived from the chemical shift data. The ion-pairing interaction energy was derived using double mutant cycle analysis. The general trends for the fraction folded population and interaction energetics remained similar upon swapping the position of the interacting charged residues. The most stabilizing cross-strand interactions were between short residues, similar to the unswapped study. However, the fraction folded populations for most of the swapped peptides were higher compared to the corresponding unswapped peptides. Furthermore, subtle differences in the ion-pairing interaction energy upon swapping were observed, most likely due to the "unleveled" relative positioning of the interacting residues created by the inherent right-handed twist of the structure. These results should be useful for developing functional peptides that rely on lateral ion-pairing interactions across antiparallel ß-strands.

3.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33808007

RESUMO

Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis (MC) is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic syndrome remains unclear. This study was conducted to examine the prevention effect of Momordica cochinchinensis aril (MCA) on obesity, non-alcoholic fatty liver and insulin resistance in mice. MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver damage were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) signaling pathway in the human fatty liver HuS-E/2 cell model. Our data indicate that MCA altered the microbial contents of the gut and modulated microbial dysbiosis in the host, and consequently is involved in the prevention of HFD-induced adiposity, insulin resistance and non-alcoholic fatty liver disease.

4.
Int J Biol Macromol ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33838185

RESUMO

Peroxisome proliferator-activated receptor α (PPARα) play a key role in the regulation of metabolic homeostasis, inflammation, cellular growth, and differentiation. To further explore the potential role of PPARα in the energy homeostasis of fatty liver hemorrhagic syndrome (FLHS), we reported the prokaryotic expression and purification of chicken PPARα subunit protein, and successfully prepared a polyclonal antibody against PPARα recombinant protein. The 987 bp PPARα subunit genes were cloned into the pEASY-T3 clone vector. Then the plasmid PCR products encoding 329 amino acids were ligated to pEASY-Blunt E2 vector and transformed into BL21 to induce expression. The recombinant PPARα subunit protein, containing His-tag, was purified by affinity column chromatography using Ni-NTA affinity column. Rabbit antiserum was generated by using the concentration of recombinant PPARα subunit protein as the antigen. The results of western blotting showed that the antiserum can specifically recognize chicken endogenous PPARα protein. Immunohistochemistry and immunofluorescence showed that the PPARα mainly existed in the nucleus of hepatocytes, renal epithelial cells and hypothalamic endocrine nerve cells. More importantly, western blotting and real-time quantitative PCR indicated that FLHS significantly decreased the expression of PPARα.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33809956

RESUMO

The COVID-19 pandemic may cause a nursing shortage. Prelicensure nursing students who are exposed to high-stress COVID-19 events are related to defective career decision-making. This study validated the COVID-19 attitude scale and clarified how their attitudes about COVID-19 affected their behavioral intentions toward career decision-making. We conducted a cross-sectional study and recruited a convenience sample of 362 prelicensure nursing students from Northern and Central Taiwan. Two measurements were applied, including the Nursing Students Career Decision-making instrument and COVID-19 attitude scale. We used AMOS (version 22.0) to perform a confirmatory factor analysis. The Cronbach α of the COVID-19 attitude scale was 0.74 and consisted of four factors. The most positive attitude was the nursing belief factor, and the least positive factor was emotional burden. Prelicensure nursing students' COVID-19 attitudes were significantly positively associated with their career decision-making attitudes and perceived control (ß = 0.41 and ß = 0.40, respectively; p < 0.001). All the key latent variables explained significantly 23% of the variance in the career decision-making behavioral intentions module. In conclusion, the COVID-19 attitude scale is valid. Although the prelicensure nursing students' COVID-19 attitudes had no direct effect on career decision-making intentions, they had a direct effect on career decision-making attitudes and the perceived control.


Assuntos
Estudantes de Enfermagem , Atitude , Atitude do Pessoal de Saúde , Estudos Transversais , Humanos , Pandemias , Inquéritos e Questionários , Taiwan/epidemiologia
6.
J Clin Invest ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830945

RESUMO

One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell-mediated cytotoxicity, we identified atractylenolide I (ATT-I) that significantly promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non-ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced major histocompatibility class I (MHC-I)-mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient-derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation, empowers T-cell cytotoxicity, and thus elevates the tumor response to immunotherapy.

7.
Medicine (Baltimore) ; 100(14): e25304, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832100

RESUMO

BACKGROUND: Preoperative skin preparation is associated with surgical site infection (SSI). Traditional preoperative shaving fails to reduce the risk of SSI. The efficacy of 2% chlorhexidine for preoperative skin preparation in percutaneous coronary intervention (PCI) is sketchy. The aim of this trial was to evaluate whether preoperative skin preparation performed with chlorhexidine was not inferior to a conventional hair removal method. METHODS: Seventy-eight patients undergoing PCI were randomized into 2 groups of 39 patients, receiving either single sterilization with 2% chlorhexidine or hair shaving respectively between July 2016 and October 2016. The primary endpoints were wound infection rate and bacterial counts. Secondary endpoints were rate of SSI and adverse effects of 2% chlorhexidine. RESULTS: The results showed that 2% chlorhexidine significantly reduced the colonization of Staphylococcus aureus (P = .032), S epidermidis (P = .000), and miscellaneous bacteria (P = .244) in comparison with hair shaving, respectively. Redness in 24 hours after surgery was observed in 6 patients in the control group (15.4%) and 5 patients (12.8%) in 2% chlorhexidine group. There was no statistically significant difference in SSI rate between 2 skin preparations. CONCLUSION: In PCI, preoperative skin preparation with 2% chlorhexidine was not inferior to conventional hair shaving in terms of the wound infection rate and SSI rate.

8.
BMC Biol ; 19(1): 67, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832502

RESUMO

BACKGROUND: Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche. RESULTS: In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies. CONCLUSIONS: These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.

9.
J Appl Oral Sci ; 29: e20200734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33825762

RESUMO

OBJECTIVE: To compare tooth movement rate and histological responses with three different force magnitude designs under osteoperforation in rabbit models. METHODOLOGY: 48 rabbits were divided into three groups: Group A, Group B, and Group C, with traction force of 50 g, 100 g, 150 g, respectively. Osteoperforation was performed at the mesial of the right mandibular first premolar, the left side was not affected. One mini-screw was inserted into bones between two central incisors. Coil springs were fixed to the first premolars and the mini-screw. Tooth movement distance was calculated, and immunohistochemical staining of PCNA, OCN, VEGF, and TGF-ß1 was analyzed. RESULTS: The tooth movement distance on the surgical side was larger than the control side in all groups (P<0.01). No significant intergroup difference was observed for the surgical side in tooth movement distance among the three groups (P>0.05). For the control side, tooth movement distance in Group A was significantly smaller than Groups B and C (P<0.001); no significant difference in tooth movement distance between Group B and Group C was observed (P>0.05). On the tension area of the moving premolar, labeling of PCNA, OCN, VEGF and TGF-ß1 were confirmed in alveolar bone and periodontal ligament in all groups. PCNA, OCN, VEGF and TGF-ß1 on the surgical side was larger than the control side in all groups (P<0.001). CONCLUSION: Osteoperforation could accelerate orthodontic tooth movement rate in rabbits. Fast osteoperforation-assisted tooth movement in rabbits was achieve with light 50 g traction.


Assuntos
Ligamento Periodontal , Técnicas de Movimentação Dentária , Animais , Dente Pré-Molar , Coelhos
10.
Nutrients ; 13(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805289

RESUMO

Probiotics are reported to improve gastrointestinal (GI) function via regulating gut microbiota (GM). However, exactly how probiotics influence GM and GI function in elders is poorly characterized. Therefore, in this study, we assessed the effect of the probiotic Lacticaseibacillus paracasei PS23 (LPPS23) on the GM and GI function of aged mice. There were four groups of senescence-accelerated mouse prone-8 (SAMP8) mice (n = 4): a non-treated control group, a saline control group, a low dose LPPS23 group (1 × 108 colony-forming unit (CFU)/mouse/day), and a high dose LPPS23 group (1 × 109 CFU/mouse/day). Non-treated mice were euthanized at 16 weeks old, and others were euthanized at 28 weeks old. The next-generation sequencing results revealed that LPPS23 enriched Lactobacillus and Candidatus_Saccharimonas, while the abundance of Lachnospiraceae_UCG_001 decreased in aged mice given LPPS23. The abundance of Lactobacillus negatively correlated with the abundance of Erysipelotrichaceae. Moreover, LPPS23 improved the GI function of aged mice due to the longer intestine length, lower intestinal permeability, and higher phagocytosis in LPPS23-treated mice. The ELISA results showed that LPPS23 attenuated the alterations of pro-inflammatory factors and immunoglobulins. The abundance of LPPS23-enriched Lactobacillus was positively correlated with healthy GI function, while Lachnospiraceae_UCG_001, which was repressed by LPPS23, was negatively correlated with a healthy GI function in the aged mice according to Spearman's correlation analysis. Taken together, LPPS23 can effectively modulate GM composition and improve GI function in aged SAMP8 mice.

11.
EBioMedicine ; 66: 103301, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33813137

RESUMO

BACKGROUND: Sphingolipid metabolism is among the top dysregulated pathways in non-small cell lung carcinomas (NSCLC). However, the molecular control of sphingolipid metabolic reprogramming in cancer progression remains unclear. METHODS: We first determined the correlation between sphingolipid metabolic gene expression and patient prognosis. We then carried out sphingolipidomics analysis of health individual and NSCLC patient sera as well as B3GNT5 and GAL3ST1 genetically perturbed NSCLC cell lines. We used these cell lines to perform tumorigenesis study to determine the cellular role of B3GNT5 and GAL3ST1 in cancer growth and progression. FINDINGS: The expression of B3GNT5 and GAL3ST1 among sphingolipid metabolic enzymes is most significantly associated with patient prognosis, whilst sphingolipidomics analysis of healthy individual and NSCLC patient sera identifies their metabolites, lacto/neolacto-series glycosphingolipid and sulfatide species, as potential biomarkers that were more effective than current clinical biomarkers for staging patients. Further network analysis of the sphingolipidomes reveals a circular network of coregulated sphingolipids, indicating that the lacto/neolacto-series glycosphingolipid/sulfatide balance functions as a checkpoint to determine sphingolipid metabolic reprograming during patient progression. Sphingolipidomics analysis of B3GNT5/GAL3ST1 genetically perturbed NSCLC cell lines confirms their key regulatory role in sphingolipid metabolism, while B3GNT5 and GAL3ST1 expression has an opposite role on tumorigenesis. INTERPRETATION: Our results provide new insights whereby B3GNT5 and GAL3ST1 differentially regulate sphingolipid metabolism in lung cancer growth and progression. FUNDING: This work was supported by the Natural Science Foundation of China (81872142, 81920108028); Guangzhou Science and Technology Program (201904020008); Guangdong Science and Technology Department (2020A0505100029, 2019A1515011802, 2020A1515011280, 2020B1212060018, 2020B1212030004); China Postdoctoral Science Foundation (2019M650226, 2019M650227).

12.
Appl Opt ; 60(10): 2877-2885, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798167

RESUMO

We present a compact, monolithic optical reference for the frequency stabilized laser of future inter-satellite laser interferometer missions. A prototype based on the integration of a high-finesse cavity and associate optics has been designed to be space compatible while maintaining sufficient stability. The prototype has then been developed with a space-qualified bonding technique, and an in situ multi-degree-of-freedom alignment method. The performances of the optical reference have been studied by beat note analysis with another frequency stabilized laser, and the preliminary results are in agreement with the potential requirements of future space missions.

13.
Cancers (Basel) ; 13(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799802

RESUMO

Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.

14.
Pharmaceuticals (Basel) ; 14(3)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803943

RESUMO

Acute heart failure (AHF) commonly arises from decompensated chronic heart failure or sudden structural and functional breakdown causing a decrease in cardiac contractility and consequently fluid accumulation and systemic congestion. Current treatment for AHF aims at reducing fluid overload and improving hemodynamic which results in quick symptom relief but still poor prognostic outcome. This study utilizes a zebrafish AHF model induced by aristolochic acid (AA) to look for natural products that could attenuate the progression of AHF. The project started off by testing nearly seventy herbal crude extracts. Two of the positive extracts were from Chinese water chestnuts and are further studied in this report. After several rounds of chromatographical chemical fractionation and biological tests, a near pure fraction, named A2-4-2-4, with several hydrophilic compounds was found to attenuate the AA-induced AHF. A2-4-2-4 appeared to inhibit inflammation and cardiac hypertrophy by reducing MAPK signaling activity. Chemical analyses revealed that the major compound in A2-4-2-4 is actually lactate. Pure sodium lactate showed attenuation of the AA-induced AHF and inflammation and cardiac hypertrophy suppression as well, suggesting that the AHF attenuation ability in A2-4-2-4 is attributable to lactate. Our studies identify lactate as a cardiac protectant and a new therapeutic agent for AHF.

15.
J Contam Hydrol ; 239: 103793, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33714178

RESUMO

In this paper, a machine learning algorithm based on artificial neural network architecture investigates the correlation between drainage chemistries in seepage water and ambient weather conditions around waste rock piles. The proposed neural network consists of a long short-term memory unit and a fully connected neural network which uses sequenced input to consider current and previous weather impact on the drainage chemistries. A 20-year (1998-2017) monitoring database obtained from the full-scale waste rock pile of the Equity Silver mine in BC, Canada is used for validating the proposed approach. The neural network is trained based on total precipitation and mean temperature as input and the acidity as output. The results indicate that the calculated acidity from the trained neural network matches with that measured in the field well. In addition, the accuracy of calculated acidity can be further increased by adding a time tag of acidity measurement date into the input layer. This refined approach can capture the long-term evolution and dynamics of hydrogeochemical and biochemical properties inside the waste rock piles.

16.
Chem Res Toxicol ; 34(3): 833-838, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647205

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver and associates with obesity, hyperlipidemia, and insulin resistance. NAFLD could lead to nonalcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and even cancers. The development of therapy for NAFLD has been proven difficult. Emerging evidence suggests that liver X receptor (LXR) antagonist is a potential treatment for fatty liver disease. However, concerns about the cholesterol-increasing effects make it questionable for the development of LXR antagonists. Here, the overweight monkeys were fed with LXRß-selective antagonist sophoricoside or LXRα/ß dual-antagonist morin for 3 months. The morphology of punctured liver tissues was examined by H&E staining. The liver, heart, and kidney damage indices were analyzed using plasma. The blood index was assayed using complete blood samples. We show that LXRß-selective antagonist sophoricoside and LXRα/ß dual-antagonist morin alleviated lipid accumulation in the liver in overweight monkeys. The compounds resulted in higher plasma TC or LDL-c contents, increased white blood cell and lymphocyte count, and decreased neutrophile granulocyte count in the monkeys. The compounds did not alter plasma glucose, apolipoprotein A (ApoA), ApoB, ApoE, lipoprotein (a) (LPA), nonesterified fatty acid (NEFA), aspartate transaminases (AST), creatinine (CREA), urea nitrogen (UN), and creatine kinase (CK) levels. Our data suggest that LXRß-selective and LXRα/ß dual antagonism may lead to hypercholesterolemia in nonhuman primates, which calls into question the development of LXR antagonist as a therapy for NAFLD.

17.
J Formos Med Assoc ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33715926

RESUMO

BACKGROUND/PURPOSE: To investigate the clinical presentation and survival outcomes of patients with both a high prostate-specific antigen (PSA) value and non-metastatic prostate cancer (PC). METHODS: In total, 2053 PC patients were managed in our institute between January 2008 and December 2014. A total of 343 (16.7%) patients who presented with PSA values > 100 ng/mL were enrolled. Non-metastatic and metastatic PC were identified in 67 (group 1) and 276 (group 2) patients, respectively. Furthermore, 75 metastatic PC patients with PSA values < 20 ng/mL were included (group 3) for comparison. All demographics and survival outcomes were retrospectively reviewed by a questionnaire. RESULTS: Group 2 patients had a higher PSA level than did group 1 (median: 1095 vs. 283 ng/mL, p < 0.001), and a higher Gleason grade than did groups 1 and 3 (grade group 4 plus 5: 60%, 77%, and 56%, for groups 1, 2, and 3, respectively; p < 0.001). Other demographics were similar among groups. Group 1 patients survived significantly longer than group 2 and 3 in terms of overall and cancer-specific survival rates (5-year overall survival rates: 87.5%, 46.3%, and 66.9%; 5-year cancer-specific survival rates: 94.7%, 52.7%, and 68.7% for groups 1, 2, and 3, respectively). Group 1 patients receiving local definitive treatments, such as radiation therapy or cryoablation, received survival and metastasis-free benefits compared to those without local treatment. CONCLUSION: Patients with a high PSA value were not destined to have metastatic PC. Non-metastatic PC patients with a high PSA level obtained a survival benefit from local prostate-definitive treatments.

18.
Genesis ; : e23415, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33682352

RESUMO

VPS4B (vacuolar protein sorting 4B), a member of the ATPase associated with diverse cellular activities (AAA) protein family, is a component of the endosomal sorting complexes required for transport machinery which regulates the internalization and lysosomal degradation of membrane proteins. We previously reported that VPS4B is one of the pathogenic genes related to dentin dysplasia type I, although its function was largely unknown. To investigate the role of VPS4B in tooth development, we deleted the Vps4b gene in mice. We found that heterozygous knockout mice (Vps4b+/- ) developed normally and were fertile. However, homozygous deletion of the Vps4b gene resulted in early embryonic lethality of Vps4b-/- mice at approximately embryonic day 9.5 (E9.5). To investigate the underlying molecular mechanisms, we examined the molecular functions of VPS4B in vivo and in vitro. Cell experiments showed that VPS4B influenced the proliferation, apoptosis, and cell cycle of transfected human neuroblastoma cells (IMR-32 cells) with over-expression or knockdown of VPS4B. Moreover, qRT-PCR detection showed that the mRNA expression levels of apoptosis-, cell cycle-, and endocytosis-related genes was significantly down or up-regulated in RNA interference-mediated knockdown of VPS4B in IMR-32 cells and Vps4b+/- E12.5 embryos. We accordingly speculated that signal transduction disorders of cell endocytosis are a contributing factor to the prenatal lethality of Vps4b-/- mice.

19.
Talanta ; 228: 122261, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773715

RESUMO

Defect engineering in the photoelectrochemical (PEC) process of photoelectrodes has been extensively studied. But insufficient attention has been received about the impact of metal vacancies (VM) in PEC process. Herein, the influence of Cu vacancies (VCu) on PEC performance of copper oxide (CuO) derived from Cu-based metal-organic gel (Cu-MOG) precursor was reported. It can be found that the presence of more VCu can improve the PEC activity of CuO photocathode by facilitating the charge separation and transfer. Moreover, the as-prepared CuO was presented as a new PEC sensor to detect l-cysteine (L-Cys) on the basis of the excellent PEC performance, which showed high sensitivity and selectivity. Good linear response of L-Cys within the range of 0.1-6 µM was performed with a detection limit of 0.04 µM. This work not only provides insights into the role of VM in the PEC process of photocathodes, but also proved the high potential applicability of CuO as a PEC device for biomolecule detection.

20.
Talanta ; 228: 122270, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773718

RESUMO

Excess free copper in serum has been identified to induce neurodegenerative diseases such as Alzheimer's disease, thus it is very important to determine copper (II) ions (Cu2+) content for human health test. Herein we developed a point-of-care testing (POCT) platform through a luminescence "on-off" recognition mechanism of serum copper. Microsized europium coordination polymer particles (Eu-CPs), which was prepared with citric acid (CA) and europium nitrate hexahydrate through a hydrothermal route, were then successfully loaded with the mixture of 2,6-pyridinedicarboxylic acid (DPA) and poly(vinyl alcohol) (PVA) to form electrospun nanofibrous films (ENFFs). The as-prepared Eu-CPs/DPA/PVA ENFFs exhibited red emission at 618 nm when exciting at 280 nm, with the quantum yields of 22.2% owing to the antenna effect from DPA to Eu3+. Furthermore, the strong luminescence could be selectively quenched by Cu2+ through coordination with DPA to interrupt the antenna effect. With that, Cu2+ was successfully detected in the range of 2-45 µM with a detection of limit of 1.3 µM, well matching with the requirement of clinic test of excess free copper induced neurodegenerative diseases. As a proof of concept at last, this POCT platform was used to detect free copper in spiked serum samples with a recovery of 101.1%-105.2%, demonstrating that this platform provides significant potential for use in clinical test.

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