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1.
J Interpers Violence ; : 886260520971613, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33140674

RESUMO

Adolescent dating violence (ADV) is a serious concern with various negative impacts on adolescent development. Research on ADV has predominantly been conducted in urban areas and has generally focused on physical and sexual forms of violence. The purpose of this study was to assess prevalence rates of various forms of ADV by gender in the rural context. A convenience sample of rural adolescents responded to an online survey. In total, 131 responses were used for this study. Participants reported perpetration and victimization experiences of physical abuse, sexual abuse, threatening behavior, relational aggression, verbal abuse, and cyber dating abuse. Descriptive statistics and chi-square analyses were used to determine gender differences in proportion and frequency of ADV. Results reveal that various forms of ADV are occurring in the rural context, with many of both males and females reporting perpetration and victimization. Overall, verbal and cyber ADV are the most common. Gender analysis reveals that males were significantly more likely to be victimized by physical abuse victimization, whereas females were significantly more likely to be victimized by sexual abuse. Though the proportion of adolescents reporting ADV were high in this study, most participants reported lower frequencies of ADV. Results support the urgent need in rural areas for education and prevention that target physical, sexual, and psychological components of healthy relationships. Rural dating violence prevention efforts must emphasize the importance of mutual respect across gender, rather than solely presenting this lesson to males in a traditional gendered manner. Results also suggest the need for rural areas to adopt comprehensive sex education that details sexual relationships that are consensual and healthy.

2.
Stem Cell Res Ther ; 11(1): 480, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176873

RESUMO

BACKGROUND: Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. METHODS: To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes. RESULTS: The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. CONCLUSIONS: This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.

3.
Jpn J Infect Dis ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33132302

RESUMO

This study aimed to develop and validate a bedside risk analysis system for predicting the clinical severity and prognosis of patients with COVID-19. A total of 444 COVID-19 patients were included and were randomly assigned into two groups at a ratio of 2:1 as derivation and validation groups. The new scoring system comprised of eight variables, which included history of having malignant diseases, history of having diabetes mellitus, dyspnea, respiratory rate of >24 bpm, C-reactive protein (CRP) of >14 mg/L, white blood cell count of >8×109/L, platelets count of <180×1012/L, and lymphocyte count of <1×109/L. The sensitivity analysis revealed that this new score performed better than the sequential organ failure assessment (SOFA) score at the first day of admission. The receiver characteristic curve analysis revealed that this score predicted severe cases of COVID-19 infection at 0.831 (95% confidence interval: 0.783-0.879) and 0.798 (95% confidence interval: 0.727-0.869) of the area under the curve in the derivation and validation group. The proposed risk score system is a fairly reliable and robust tool for evaluating the severity and prognosis of patients with COVID-19. This may help to early identify severe patients with poor prognosis, who may require more intense interventions.

4.
Neurochem Res ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211272

RESUMO

Currently, there is no cure for spinal cord injury (SCI), a heavy burden on patients physiology and psychology. We found that microRNA-139-5p (miR-139-5p) expression was significantly downregulated in damaged spinal cords in mice. So, we aimed to test the effect of treatment with miR-139-5p on functional recovery and neuropathic pain in mice with SCI and investigate the underlying mechanism. The luciferase reporter assay revealed that miR-139-5p directly targeted mammalian sterile 20-like kinase 1 (Mst1), and miR-139-5p treatment suppressed Mst1 protein expression in damaged spinal cords of mice. Wild-type mice and Mst1(-/-) mice were exposed to SCI and treated with miR-139-5p agomir via intrathecal infusion. Treatment of SCI mice with miR-139-5p accelerated locomotor functional recovery, reduced hypersensitivities to mechanical and thermal stimulations, and promoted neuronal survival in damaged spinal cords. Treatment with miR-139-5p enhanced phosphorylation of adenosine monophosphate-activated protein kinase alpha (AMPKα), improved mitochondrial function, and suppressed NF-κB-related inflammation in damaged spinal cords. Deficiency of Mst1 had similar benefits in mice with SCI. Furthermore, miR-139-5p treatment did not provide further protection in Mst1(-/-) mice against SCI. In conclusion, miR-139-5p treatment enhanced functional recovery and reduced pain hypersensitivity in mice with SCI, possibly through targeting Mst1.

5.
Chem Commun (Camb) ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043913

RESUMO

A bifunctional thiourea-catalyzed asymmetric tandem α-functionalization/1,3-proton shift reaction of benzylidene succinimides with ß-trifluoromethyl enones has been developed. A series of F3C-containing chiral Rauhut-Currier type products were obtained in moderate to high yields (up to 98%) with excellent enantioselectivities (up to >99% ee). This represents the first example of benzylidene succinimides undergoing tandem α-functionalization/1,3-proton shift in catalytic enantioselective transformation.

6.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1109-1113, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059809

RESUMO

OBJECTIVE: To study the role of blood purification in the treatment of severe adenovirus pneumonia. METHODS: A total of 57 children with severe adenovirus pneumonia who underwent mechanical ventilation from February to June, 2019, were enrolled. According to whether blood purification was performed, they were divided into a purification group with 22 children and a conventional group with 35 children. Related clinical indices were collected, including duration of fever, duration of mechanical ventilation, length of stay in the intensive care unit (ICU), and mortality rate. The purification group was analyzed in terms of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before blood purification and at 48 hours after blood purification, as well as stroke volume variation (SVV), thoracic fluid content (TFC), arterial partial pressure of oxygen/fraction of inhaled oxygen (P/F) value, and partial pressure of carbon dioxide (PCO2) before blood purification and at 6, 12, 24, and 48 hours after blood purification. RESULTS: Compared with the conventional group, the purification group had significantly shorter duration of fever, duration of mechanical ventilation, and length of stay in the ICU (P<0.05), and there was no significant difference in the mortality rate between the two groups (P>0.05). The purification group had significant reductions in IL-6 and TNF-α after blood purification, (P<0.05) and significant reductions in SVV and TFC at 12, 24, and 48 hours after blood purification (P<0.01), as well as a significant increase in P/F value and a significant reduction in PCO2 at 6, 12, 24, and 48 hours after blood purification (P<0.01). CONCLUSIONS: Blood purification as an auxiliary therapy can effectively improve the clinical symptoms of children with severe adenovirus pneumonia, and is thus an option for the treatment of severe adenovirus pneumonia in children.

7.
J Orthop Surg Res ; 15(1): 453, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008473

RESUMO

PURPOSE: Olecranon fracture is a common upper limb fracture, and several surgical approaches have been advocated for its fixation. To overcome the complications associated with common techniques, we present a novel shape-memory alloy concentrator, an alternative for tension band compression, to fix olecranon fracture. METHODS: Fifty-seven patients (26 men and 31 women) with olecranon fracture, with a mean age of 45 years, were included in this study. Each patient had undergone open reduction and internal fixation using the Nitinol (Ni-Ti) arched shape-memory connector (ASC). The clinical assessments were performed using the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Mayo Elbow Performance (MEP) score, which were both recorded at the final follow-up visit. RESULTS: The patients were followed up for 44 months on average (range, 31 to 56 months). No patients were lost to follow-up, and all of the olecranon fractures healed in an average of 15 weeks (range, 10 to 34 weeks). The mean DASH score was 8.6 (range, 0 to 32.4), and the mean MEP score was 92.5 (range, 74 to 100). Nine patients showed postoperative complications: prominent hardware (2), infection (1), loss of the range of functional motion (5), and heterotopic ossification (1). CONCLUSION: The ASC may serve as a favorable device for multi-fragmented and comminuted fractures with rare hardware irritation and may also provide continuous concentrative compression to accelerate osseous healing, thereby aiding the restoration and permitting an early rehabilitation with a low incidence of postoperative complications.

8.
IEEE Trans Med Imaging ; PP2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064649

RESUMO

Spectral computed tomography is able to provide quantitative information on the scanned object and enables material decomposition. Traditional projection-based material decomposition methods suffer from the nonlinearity of the imaging system, which limits the decomposition accuracy. Inspired by the generative adversarial network, we proposed a novel parallel multi-stream generative adversarial network (PMS-GAN) to perform projection-based multi-material decomposition in spectral computed tomography. By designing the differential map and incorporating the adversarial network into loss function, the decomposition accuracy was significantly improved with robust performance. The proposed network was quantitatively evaluated by both simulation and experimental study. The results show that PMS-GAN outperformed the reference methods with certain robustness. Compared with Pix2pix-GAN, PMS-GAN increased the structural similarity index by 172% on the contrast agent Ultravist370, 11% on bones, and 71% on bone marrow, respectively, in a simulated test scenario. In an experimental test scenario, 9% and 38% improvements of the structural similarity index on the biopsy needle and on a torso phantom were observed, respectively. The proposed network demonstrates its capability of multi-material decomposition and has certain potential toward clinical applications.

9.
J Phys Chem Lett ; 11(21): 9493-9500, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33108729

RESUMO

Site-specific labeling of proteins with a paramagnetic tag is an efficient way to provide atomic-resolution information about the dynamics, interactions, and structures of the proteins and protein-ligand complexes. The paramagnetic effects manifested in NMR spectroscopy generally contain paramagnetic relaxation enhancement, pseudocontact shifts (PCSs), and residual dipolar coupling (RDC), and these effects correlate closely with the flexibility of protein-tag conjugates. The rigidity of the paramagnetic tag is greatly important in decoding the structural details of macromolecular complexes, because paramagnetic averaging reduces the PCSs and RDCs. Here we show that the dynamic exchange of the metal chelating moiety is a key factor in determining the rigidity of the paramagnetic tag in the protein conjugates. Decreasing the conformational exchange rates in the metal chelating moiety greatly minimizes the paramagnetic averaging and thus increases PCSs and RDCs. This effect has been demonstrated in an open-chain tag, Py-l-Cys-DTPA, which generates large PCSs and RDCs that are comparable to those of the reported cyclic DOTA-like tags. The proposed route offers a unique way to design suitable paramagnetic tags for applications in biological systems.

10.
PLoS One ; 15(10): e0239382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031442

RESUMO

Floral initiation plays a critical role for reproductive success in plants, especially fruit trees. However, little information is known on the mechanism of the initiation in loquat (Eriobotrya japonica Lindl.). Here, we used transcriptomic, expression and functional analysis to investigate the candidate genes in floral initiation in loquat. Comparative transcriptome analysis showed differentially expressed genes (DEGs) were mainly enriched in the metabolic pathways of plant hormone signal transduction. The DEGs were mainly involved in the gibberellin, auxin, cytokinin, abscisic acid, salicylic acid and ethylene signaling pathways. Meanwhile, some transcription factors, including MADS-box (MCM1, AGAMOUS, DEFICIENS and SRF), MYB (Myeloblastosis), TCP (TEOSINTE BRANCHED 1, CYCLOIDEA and PCF1), WOX (WUSCHEL-related homeobox) and WRKY (WRKY DNA-binding protein), were significantly differentially expressed. Among these key DEGs, we confirmed that an AGL17 ortholog EjAGL17 was significantly upregulated at the flower bud transition stage. Phylogenetic tree analysis revealed that EjAGL17 was grouped into an AGL17 clade of MADS-box transcription factors. Protein sequence alignment showed that EjAGL17 included a distinctive C-terminal domain. Subcellular localization of EjAGL17 was found only in the nucleus. Expression levels of EjAGL17 reached the highest at the development stage of flower bud transition. Moreover, ectopic expression of EjAGL17 in Arabidopsis significantly exhibited early flowering. Our study provides abundant resources of candidate genes for studying the mechanisms underlying the floral initiation in loquat and other Rosaceae species.

11.
Med Image Anal ; 67: 101812, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33129140

RESUMO

Accurate ventricular volume measurements are the primary indicators of normal/abnor- mal cardiac function and are dependent on the Cardiac Magnetic Resonance (CMR) volumes being complete. However, missing or unusable slices owing to the presence of image artefacts such as respiratory or motion ghosting, aliasing, ringing and signal loss in CMR sequences, significantly hinder accuracy of anatomical and functional cardiac quantification, and recovering from those is insufficiently addressed in population imaging. In this work, we propose a new robust approach, coined Image Imputation Generative Adversarial Network (I2-GAN), to learn key features of cardiac short axis (SAX) slices near missing information, and use them as conditional variables to infer missing slices in the query volumes. In I2-GAN, the slices are first mapped to latent vectors with position features through a regression net. The latent vector corresponding to the desired position is then projected onto the slice manifold, conditioned on intensity features through a generator net. The generator comprises residual blocks with normalisation layers that are modulated with auxiliary slice information, enabling propagation of fine details through the network. In addition, a multi-scale discriminator was implemented, along with a discriminator-based feature matching loss, to further enhance performance and encourage the synthesis of visually realistic slices. Experimental results show that our method achieves significant improvements over the state-of-the-art, in missing slice imputation for CMR, with an average SSIM of 0.872. Linear regression analysis yields good agreement between reference and imputed CMR images for all cardiac measurements, with correlation coefficients of 0.991 for left ventricular volume, 0.977 for left ventricular mass and 0.961 for right ventricular volume.

12.
Mol Psychiatry ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929213

RESUMO

Schizophrenia (SCZ) is a neuropsychiatric disorder with aberrant expression of multiple genes. However, identifying its exact causal genes remains a considerable challenge. The brain-specific transcription factor POU3F2 (POU domain, class 3, transcription factor 2) has been recognized as a risk factor for SCZ, but our understanding of its target genes and pathogenic mechanisms are still limited. Here we report that POU3F2 regulates 42 SCZ-related genes in knockdown and RNA-sequencing experiments of human neural progenitor cells (NPCs). Among those SCZ-related genes, TRIM8 (Tripartite motif containing 8) is located in SCZ-associated genetic locus and is aberrantly expressed in patients with SCZ. Luciferase reporter and electrophoretic mobility shift assays (EMSA) showed that POU3F2 induces TRIM8 expression by binding to the SCZ-associated SNP (single nucleotide polymorphism) rs5011218, which affects POU3F2-binding efficiency at the promoter region of TRIM8. We investigated the cellular functions of POU3F2 and TRIM8 as they co-regulate several pathways related to neural development and synaptic function. Knocking down either POU3F2 or TRIM8 promoted the proliferation of NPCs, inhibited their neuronal differentiation, and impaired the excitatory synaptic transmission of NPC-derived neurons. These results indicate that POU3F2 regulates TRIM8 expression through the SCZ-associated SNP rs5011218, and both genes may be involved in the etiology of SCZ by regulating neural development and synaptic function.

13.
Ecotoxicol Environ Saf ; 205: 111333, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979802

RESUMO

Plant growth-promoting rhizobacteria (PGPR) are a specific category of microbes that improve plant growth and promote greater tolerance to metal stress through their interactions with plant roots. We evaluated the effects of phytoremediation combining the cadmium accumulator Solanum nigrum L. and two Cd- and Pb-resistant bacteria isolates. To understand the interaction between PGPR and their host plant, we conducted greenhouse experiments with inoculation treatments at Nanjing Agricultural University (Jiangsu Province, China), in June 2018. Two Cd- and Pb-resistant PGPR with various growth-promoting properties were isolated from heavy metal-contaminated soil. 16S rRNA analyses indicated that the two isolates were Bacillus genus, and they were named QX8 and QX13. Pot experiments demonstrated that inoculation may improve the rhizosphere soil environment and promote absorption of Fe and P by plants. Inoculation with QX8 and QX13 also enhanced the dry weight of shoots (1.36- and 1.7-fold, respectively) and roots (1.42- and 1.96-fold) of plants growing in Cd- and Pb-contaminated soil, and significantly increased total Cd (1.28-1.81 fold) and Pb (1.08-1.55 fold) content in aerial organs, compared to non-inoculated controls. We also detected increases of 23% and 22% in the acid phosphatase activity of rhizosphere soils inoculated with QX8 and QX13, respectively. However, we did not detect significant differences between inoculated and non-inoculated treatments in Cd and Pb concentrations in plants and available Cd and Pb content in rhizosphere soils. We demonstrated that PGPR-assisted phytoremediation is a promising technique for remediating heavy metal-contaminated soils, with the potential to enhance phytoremediation efficiency and improve soil quality.


Assuntos
Cádmio/análise , Chumbo/análise , Rhizobiaceae/metabolismo , Microbiologia do Solo , Poluentes do Solo/análise , Solanum nigrum/efeitos dos fármacos , Biodegradação Ambiental , Cádmio/metabolismo , China , Chumbo/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , RNA Ribossômico 16S , Rizosfera , Solo/química , Poluentes do Solo/metabolismo , Solanum nigrum/crescimento & desenvolvimento , Solanum nigrum/metabolismo
14.
J Am Chem Soc ; 142(34): 14619-14626, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32786795

RESUMO

Pursuing polymers that can transform from a nonconjugated to a conjugated state under mechanical stress to significantly change their properties, we developed a new generation of ladder-type mechanophore monomers, bicyclo[2.2.0]hex-5-ene-peri-naphthalene (BCH-Naph), that can be directly and efficiently polymerized by ring-opening metathesis polymerization (ROMP). BCH-Naphs can be synthesized in multigram quantities and functionalized with a wide range of electron-rich and electron-poor substituents, allowing tuning of the optoelectronic and physical properties of mechanically generated conjugated polymers. Efficient ROMP of BCH-Naphs yielded ultrahigh molecular weight polymechanophores with controlled MWs and low dispersity. The resulting poly(BCH-Naph)s can be mechanically activated into conjugated polymers using ultrasonication, grinding, and even simple stirring of the dilute solutions, leading to changes in absorption and fluorescence. Poly(BCH-Naph)s represent an attractive polymechanophore system to explore multifaceted mechanical response in solution and solid states, owing to the synthetic scalability, functional diversity, efficient polymerization, and facile mechanoactivation.

15.
Oncol Lett ; 20(4): 51, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32788938

RESUMO

The application of additive manufacturing (AM) technology has been widely used in various medical fields, including craniomaxillofacial surgery. The aim of the present study was to examine the surgical efficiency and post-operative outcomes of patient-specific titanium mandibular reconstruction using AM. Major steps in directly designing and manufacturing 3D customized titanium implants are discussed. Furthermore, pre-operative preparations, surgical procedures and post-operative treatment outcomes were compared among patients who received mandibular reconstruction using a customized 3D titanium implant, titanium reconstruction plates or vascularized autologous fibular grafting. Use of a customized titanium implant significantly improved surgical efficiency and precision. When compared with mandibular reconstruction using the two conventional approaches, patients who received the customized implant were significantly more satisfied with their facial appearance, and exhibited minimal post-operative complications in the 12-month follow-up period. Patients who underwent mandibular reconstruction using a customized titanium implant displayed improved mandibular contour symmetry, restored occlusal function, normal range of mouth opening and no temporomandibular joint related pain; all complications frequently experienced by patients who undergo conventional approaches of mandibular reconstruction.

16.
Environ Chem Lett ; : 1-11, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32837481

RESUMO

The outbreak of coronavirus named COVID-19, initially identified in Wuhan, China in December 2019, has spread rapidly at the global scale. Most countries have rapidly stopped almost all activities including industry, services and transportation of goods and people, thus decreasing air pollution in an unprecedented way, and providing a unique opportunity to study air pollutants. While satellite data have provided visual evidence for the global reduction in air pollution such as nitrogen dioxide (NO2) worldwide, precise and quantitative information is missing at the local scale. Here we studied changes in particulate matter (PM2.5, PM10), carbon monoxide (CO), NO2, sulfur dioxide (SO2) and ozone (O3) at 10 urban sites in Hangzhou, a city of 7.03 million inhabitants, and at 1 rural site, before city lockdown, January 1-23, during city lockdown, January 24-February 15, and during resumption, February 16-28, in 2020. Results show that city lockdown induced a sharp decrease in PM2.5, PM10, CO, and NO2 concentrations at both urban and rural sites. The NO2 decrease is explained by reduction in traffic emissions in the urban areas, and by lower regional transport in rural areas during lockdown, as expected. SO2 concentrations decreased from 6.3 to 5.3 µg m-3 in the city, but increased surprisingly from 4.7 to 5.8 µg m-3 at the rural site: this increase is attributed both to higher coal consumption for heating and emissions from traditional fireworks of the Spring Eve and Lantern Festivals during lockdown. Unexpectedly, O3 concentrations increased by 145% from 24.6 to 60.6 µg m-3 in the urban area, and from 42.0 to 62.9 µg m-3 in the rural area during the lockdown. This finding is explained by the weakening of chemical titration of O3 by NO due to reductions of NOx fresh emissions during the non-photochemical reaction period from 20:00 PM to 9:00 AM (local time). During the lockdown, compared to the same period in 2019, the daily average concentrations in the city decreased by 42.7% for PM2.5, 47.9% for PM10, 28.6% for SO2, 22.3% for CO and 58.4% for NO2, which is obviously explained by the absence of city activities. Overall, we observed not only the expected reduction in some atmospheric pollutants (PM, SO2, CO, NO2), but also unexpected increases in SO2 in the rural areas and of ozone (O3) in both urban and rural areas, the latter being paradoxically due to the reduction in nitrogen oxide levels. In other words, the city lockdown has improved air quality by reducing PM2.5, PM10, CO, and NO2, but has also decreased air quality by augmenting O3 and SO2.

17.
Cancer Lett ; 492: 185-196, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758616

RESUMO

Breast cancer is the most common cancer among women worldwide, with 70% being estrogen receptor-positive (ER+). Although ER-targeted treatment is effective in treating ER + breast cancer, chemoresistance and metastasis still prevail. Outcome-predictable biomarkers can help improve patient prognosis. Through the analysis of the Array Express database, The Cancer Genome Atlas-Breast Cancer datasets, and breast tumor tissue array results, we found that cytochrome c oxidase subunit 5a (COX5A) was related to poor prognosis of ER + breast cancer. Further studies revealed that COX5A was positively associated with metastasis and chemoresistance in ER + breast cancer. In vitro experiments showed that knockdown of COX5A was accompanied by a decrease in ERα expression, cell cycle arrest, and epithelial-mesenchymal transition blockade, resulting in an inhibition of proliferation and invasion. Knockdown of COX5A enhanced the chemosensitivity of breast cancer cells by decreasing adenosine triphosphate and increasing reactive oxygen species levels. We report that miR-204 can target and inhibit the expression of COX5A, thus, reversing the functions of COX5A in ER + breast cancer cells. We found that COX5A may serve as a prognostic biomarker in ER + breast cancer.

18.
Proc Natl Acad Sci U S A ; 117(34): 20566-20575, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32788347

RESUMO

The complexity of the cellular medium can affect proteins' properties, and, therefore, in-cell characterization of proteins is essential. We explored the stability and conformation of the first baculoviral IAP repeat (BIR) domain of X chromosome-linked inhibitor of apoptosis (XIAP), BIR1, as a model for a homodimer protein in human HeLa cells. We employed double electron-electron resonance (DEER) spectroscopy and labeling with redox stable and rigid Gd3+ spin labels at three representative protein residues, C12 (flexible region), E22C, and N28C (part of helical residues 26 to 31) in the N-terminal region. In contrast to predictions by excluded-volume crowding theory, the dimer-monomer dissociation constant K D was markedly higher in cells than in solution and dilute cell lysate. As expected, this increase was partially recapitulated under conditions of high salt concentrations, given that conserved salt bridges at the dimer interface are critically required for association. Unexpectedly, however, also the addition of the crowding agent Ficoll destabilized the dimer while the addition of bovine serum albumin (BSA) and lysozyme, often used to represent interaction with charged macromolecules, had no effect. Our results highlight the potential of DEER for in-cell study of proteins as well as the complexities of the effects of the cellular milieu on protein structures and stability.


Assuntos
Multimerização Proteica , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/química , Dimerização , Espectroscopia de Ressonância de Spin Eletrônica , Células HeLa , Humanos , Conformação Proteica
19.
Mol Psychiatry ; 25(11): 2672-2684, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32826963

RESUMO

Genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms (SNPs) associated with bipolar disorder (BD), but what the causal variants are and how they contribute to BD is largely unknown. In this study, we used FUMA, a GWAS annotation tool, to pinpoint potential causal variants and genes from the latest BD GWAS findings, and performed integrative analyses, including brain expression quantitative trait loci (eQTL), gene coexpression network, differential gene expression, protein-protein interaction, and brain intermediate phenotype association analysis to identify the functions of a prioritized gene and its connection to BD. Convergent lines of evidence prioritized protein-coding gene G Protein Nucleolar 3 (GNL3) as a BD risk gene, with integrative analyses revealing GNL3's roles in cell proliferation, neuronal functions, and brain phenotypes. We experimentally revealed that BD-related eQTL SNPs rs10865973, rs12635140, and rs4687644 regulate GNL3 expression using dual luciferase reporter assay and CRISPR interference experiment in human neural progenitor cells. We further identified that GNL3 knockdown and overexpression led to aberrant neuronal proliferation and differentiation, using two-dimensional human neural cell cultures and three-dimensional forebrain organoid model. This study gathers evidence that BD-related genetic variants regulate GNL3 expression which subsequently affects neuronal proliferation and differentiation.

20.
Environ Res ; 190: 109931, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32781323

RESUMO

Removal of toxic aniline from wastewater is of great importance in industrial manufacture. Traditional electrochemical methods encounter obstacles such as high energy consumption in mineralization and severe electrode passivation in electro-polymerization. In this paper, we report a practical electro-polymerization method by using Ti/Sb-SnO2/PbO2 anode to treat high concentration aniline wastewater. The cyclic voltammetric experiment was conducted and the problem of electrode passivation was solved by increasing the electrode potential. In the experiments of treating aniline wastewater, the produced solid polymer can separate from water rather than sticking to electrode surface. Elemental analysis shows that oxygen is incorporated in the polymer. Experiments were conducted under different conditions, including current density, pH and initial concentration of aniline and Na2SO4. The electro-polymerization route accounts for nearly 50% contribution in the removal of chemical oxygen demand (COD). Our electro-polymerization method gives an apparent current efficiency (ACE) of 232.15% and an energy consumption (Ep) of 0.008658 kWh g-1COD-1 when half of COD is removed at a current density of 15 mA cm-2, pH of 7.0, initial aniline concentration of 1.2 g L-1 and Na2SO4 concentration of 4 g L.-1.

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