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1.
Front Immunol ; 12: 697751, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381450

RESUMO

Renal ischemia-reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3ß at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis.

2.
Int J Biol Macromol ; 185: 1022-1035, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34197859

RESUMO

Biochemical modification can endow the surface of implants with superior biological activity. Herein, silk fibroin (SF) protein and its anionic derivative peptides (Cs) were covalently immobilized onto a titanium implant surface via a polydopamine layer. The successful conjugation of SF and Cs was revealed by X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), and contact angle measurements. The addition of Cs prevented the conformational transition of silk fibroin to silk II. The deposition of apatite on its surface was significantly accelerated, and the bioactive composite coating was observed to enhance protein adsorption and cell proliferation. More importantly, it also promoted the osteogenic differentiation of bone marrow stem cells (BMSCs) for the quantitative and qualitative detection of alkaline phosphatase (ALP) and alizarin red (ARS). Overall, the stable performance and enhanced osteogenic property of the composite coating promote an extensive application for clinical titanium-based implants.


Assuntos
Fibroínas/farmacologia , Indóis/química , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Polímeros/química , Titânio/química , Adsorção , Animais , Apatitas/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fibroínas/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Microscopia de Força Atômica , Oxirredução , Peptídeos/química , Peptídeos/farmacologia , Espectroscopia Fotoeletrônica
3.
Circulation ; 144(7): 539-555, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34111939

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a common complication in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe congenital disorder associated with mutations in the FOXF1 gene. Although the loss of alveolar microvasculature causes PH in patients with ACDMPV, it is unknown whether increasing neonatal lung angiogenesis could prevent PH and right ventricular (RV) hypertrophy. METHODS: We used echocardiography, RV catheterization, immunostaining, and biochemical methods to examine lung and heart remodeling and RV output in Foxf1WT/S52F mice carrying the S52F Foxf1 mutation (identified in patients with ACDMPV). The ability of Foxf1WT/S52F mutant embryonic stem cells to differentiate into respiratory cell lineages in vivo was examined using blastocyst complementation. Intravascular delivery of nanoparticles with a nonintegrating Stat3 expression vector was used to improve neonatal pulmonary angiogenesis in Foxf1WT/S52F mice and determine its effects on PH and RV hypertrophy. RESULTS: Foxf1WT/S52F mice developed PH and RV hypertrophy after birth. The severity of PH in Foxf1WT/S52F mice directly correlated with mortality, low body weight, pulmonary artery muscularization, and increased collagen deposition in the lung tissue. Increased fibrotic remodeling was found in human ACDMPV lungs. Mouse embryonic stem cells carrying the S52F Foxf1 mutation were used to produce chimeras through blastocyst complementation and to demonstrate that Foxf1WT/S52F embryonic stem cells have a propensity to differentiate into pulmonary myofibroblasts. Intravascular delivery of nanoparticles carrying Stat3 cDNA protected Foxf1WT/S52F mice from RV hypertrophy and PH, improved survival, and decreased fibrotic lung remodeling. CONCLUSIONS: Nanoparticle therapies increasing neonatal pulmonary angiogenesis may be considered to prevent PH in ACDMPV.

4.
Biomed Mater ; 16(4)2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34098538

RESUMO

In this study, the silk fibroin/nano-hydroxyapatite/hyaluronic acid (SF/nHAp/HA) composite scaffolds with different HA contents were developed by blending, cross-linking and freeze-drying, and their physicochemical properties and cell biocompatibilityin vitrowere subsequently studied. It was observed that the molecular conformation of the composite scaffolds was mainly composed of silk I and a small amount of theß-sheets structure. On enhancing the HA content, the pore size of the scaffold decreased, while the porosity, water absorption, swelling ratio and mechanical properties were observed to increase. In particular, the SF/nHAp/HA scaffold with a 5.0 wt% ratio exhibited the highest water absorption and mechanical properties among the developed materials. In addition, thein vitrocytocompatibility analysis showed that the bone marrow mesenchymal stem cells exhibited excellent cell proliferation and osteogenic differentiation ability on the SF/nHAp/5.0 wt%HA scaffolds, as compared with the other scaffolds. It can be concluded that the developed composite scaffolds represent a promising class of materials for the bone tissue repair and regeneration.

5.
Nano Today ; : 101139, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33758593

RESUMO

Effective vaccines are vital to the fight against the COVID-19 global pandemic. As a critical component of a subunit vaccine, the adjuvant is responsible for strengthening the antigen-induced immune responses. Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses. Notably, even at a 5-fold lower antigen dose and with fewer injections, mice immunized with the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) in vitro than that of Alum-adsorbed RBD vaccine (Alu-RBD). Furthermore, we found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DC cells, CD4+ and CD8+ T lymphocytes. Our findings highlight the importance of MnARK adjuvant in the design of novel coronavirus vaccines and provide a rationale strategy to design protective vaccines through promoting cellular internalization and the activation of immune-related pathways.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33670002

RESUMO

The natural mountain forests in northwest China are recognized as a substantial carbon pool and play an important role in local fragile ecosystems. This study used inventory data and detailed field measurements covering different forest age groups (young, middle-aged, near-mature, mature, old-growth forest), structure of forest (tree, herb, litter and soil layer) and trees (leaves, branches, trunks and root) to estimate biomass, carbon content ratio, carbon density and carbon storage in Altai forest ecosystems. The results showed that the average biomass of the Altai Mountains forest ecosystems was 126.67 t·hm-2, and the descending order of the value was tree layer (120.84 t·hm-2) > herb layer (4.22 t·hm-2) > litter layer (1.61 t·hm-2). Among the tree parts, trunks, roots, leaves and branches accounted for 50%, 22%, 16% and 12% of the total tree biomass, respectively. The average carbon content ratio was 0.49 (range: 0.41-0.52). The average carbon density of forest ecosystems was 205.72 t·hm-2, and the carbon storage of the forest ecosystems was 131.35 Tg (standard deviation: 31.01) inside study area. Soil had the highest carbon storage (65.98%), followed by tree (32.81%), herb (0.78%) and litter (0.43%) layers. Forest age has significant effect on biomass, carbon content ratio, carbon density and carbon storage. The carbon density of forest ecosystems in study area was spatially distributed higher in the south and lower in north, which is influenced by climate, topography, soil types and dominant tree species.


Assuntos
Carbono , Ecossistema , Biomassa , Carbono/análise , Sequestro de Carbono , China , Florestas , Solo , Árvores
7.
Sci Total Environ ; 779: 146497, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-33752013

RESUMO

The transition to a healthier diet recommended by national dietary guidelines in China may not achieve sufficient environmental benefits. This study assesses China's potential of transforming into a sustainable diet and the trade-offs among reducing food-related environmental impacts, improving nutritional quality and respecting eating habits. We used multi-objective optimization to build optimized scenarios, with the lowest environmental footprint and greatest acceptability (i.e., with the minimum departure from the currently observed diet) as optimization goals, and adequate macro- and micronutrient intake levels as constraints. In doing so, we assessed the actual benefits and synergies of reducing carbon footprint (CF), water footprint (WF), and ecological footprint (EF) and improving health and respecting dietary acceptance under the corresponding scenarios. The results show that CF, WF and EF can be reduced by up to 19%, 15% and 30% respectively, while satisfying nutritional constraints and achieving the minimum deviation from the current food combination. The greatest synergistic benefits for CF, WF and EF are achieved when the minimum CF is the optimization goal; the maximum synergistic benefits for the environment, health and acceptability are achieved when the CF is reduced by 10%. Our findings identify the trade-offs and synergies dietary changes considering nutritional benefits, environmental sustainability and acceptability, and reveal the challenges and opportunities for achieving such synergies.


Assuntos
Pegada de Carbono , Dieta , China , Comportamento Alimentar , Valor Nutritivo
8.
Am J Respir Crit Care Med ; 204(3): 326-338, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33705684

RESUMO

Rationale: Although pulmonary endothelial progenitor cells (EPCs) hold promise for cell-based therapies for neonatal pulmonary disorders, whether EPCs can be derived from pluripotent embryonic stem cells (ESCs) or induced pluripotent stem cells remains unknown.Objectives: To investigate the heterogeneity of pulmonary EPCs and derive functional EPCs from pluripotent ESCs.Methods: Single-cell RNA sequencing of neonatal human and mouse lung was used to identify the heterogeneity of pulmonary EPCs. CRISPR/Cas9 gene editing was used to genetically label and purify mouse pulmonary EPCs. Functional properties of the EPCs were assessed after cell transplantation into neonatal mice with S52F Foxf1 mutation, a mouse model of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). Interspecies mouse-rat chimeras were produced through blastocyst complementation to generate EPCs from pluripotent ESCs for cell therapy in ACDMPV mice.Measurements and Main Results: We identified a unique population of EPCs, FOXF1+cKIT+ EPCs, as a subset of recently described general capillary cells (gCAPs) expressing SMAD7, ZBTB20, NFIA, and DLL4 but lacking mature arterial, venous, and lymphatic markers. FOXF1+cKIT+ gCAPs are reduced in ACDMPV, and their transcriptomic signature is conserved in mouse and human lungs. After cell transplantation into the neonatal circulation of ACDMPV mice, FOXF1+cKIT+ gCAPs engraft into the pulmonary vasculature, stimulate angiogenesis, improve oxygenation, and prevent alveolar simplification. FOXF1+cKIT+ gCAPs, produced from ESCs in interspecies chimeras, are fully competent to stimulate neonatal lung angiogenesis and alveolarization in ACDMPV mice.Conclusions: Cell-based therapy using donor or ESC/induced pluripotent stem cell-derived FOXF1+cKIT+ endothelial progenitors may be considered for treatment of human ACDMPV.


Assuntos
Células-Tronco Embrionárias/citologia , Células Progenitoras Endoteliais/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Síndrome da Persistência do Padrão de Circulação Fetal/terapia , Transplante de Células-Tronco , Animais , Animais Recém-Nascidos , Sistemas CRISPR-Cas , Quimera , Modelos Animais de Doenças , Células-Tronco Embrionárias/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/transplante , Fatores de Transcrição Forkhead/genética , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Recém-Nascido , Camundongos , Síndrome da Persistência do Padrão de Circulação Fetal/metabolismo , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Células-Tronco Pluripotentes , RNA-Seq , Ratos , Análise de Célula Única
9.
Artigo em Inglês | MEDLINE | ID: mdl-33435212

RESUMO

Creating a vital and lively urban environment is an inherent requirement of urban sustainable development, and understanding urban vibrancy is helpful for urban development policy making. The urban vibrancy theory needs more empirical supplementation and more evidence for the effect of the built environment on urban vibrancy. We use multisource urban spatial information data, including real-time population distribution (RPD) data and small catering business (SCB) data; quantitatively measure urban vibrancy; and build a comparative framework to explore the effect of the built environment on the urban vibrancy of a northwestern emerging city in China. The results demonstrate that the two urban vibrancy metrics present a spatial distribution pattern that is high in the south and low in the north areas of the city with significant spatial aggregation. Land-use intensity and diversity have strong positive effects on urban vibrancy but present a different pattern of effects on the two vibrancy measures. The influences on urban vibrancy of distance to the district center and distance to the nearest commercial complex are spatially complementary in the study area, and the effect of accessibility factors is weak. Our findings suggest that a somewhat cautious approach is required in the application of these classical planning theories to Urumqi.


Assuntos
Ambiente Construído , Planejamento de Cidades , China , Cidades , Reforma Urbana
10.
Brief Bioinform ; 22(1): 451-462, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31885041

RESUMO

Drug-target interactions (DTIs) play a crucial role in target-based drug discovery and development. Computational prediction of DTIs can effectively complement experimental wet-lab techniques for the identification of DTIs, which are typically time- and resource-consuming. However, the performances of the current DTI prediction approaches suffer from a problem of low precision and high false-positive rate. In this study, we aim to develop a novel DTI prediction method for improving the prediction performance based on a cascade deep forest (CDF) model, named DTI-CDF, with multiple similarity-based features between drugs and the similarity-based features between target proteins extracted from the heterogeneous graph, which contains known DTIs. In the experiments, we built five replicates of 10-fold cross-validation under three different experimental settings of data sets, namely, corresponding DTI values of certain drugs (SD), targets (ST), or drug-target pairs (SP) in the training sets are missed but existed in the test sets. The experimental results demonstrate that our proposed approach DTI-CDF achieves a significantly higher performance than that of the traditional ensemble learning-based methods such as random forest and XGBoost, deep neural network, and the state-of-the-art methods such as DDR. Furthermore, there are 1352 newly predicted DTIs which are proved to be correct by KEGG and DrugBank databases. The data sets and source code are freely available at https://github.com//a96123155/DTI-CDF.

11.
J Med Chem ; 64(2): 941-957, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33185430

RESUMO

GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as an HD target. In addition, we discovered a highly potent and specific GPR52 antagonist Comp-43 with an IC50 value of 0.63 µM by a structure-activity relationship (SAR) study. Further studies showed that Comp-43 reduces mHTT levels by targeting GPR52 and promotes survival of mouse primary striatal neurons. Moreover, in vivo study showed that Comp-43 not only reduces mHTT levels but also rescues HD-related phenotypes in HdhQ140 mice. Taken together, our study confirms that inhibition of GPR52 is a promising strategy for HD therapy, and the GPR52 antagonist Comp-43 might serve as a lead compound for further investigation.


Assuntos
Proteína Huntingtina/biossíntese , Doença de Huntington/tratamento farmacológico , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Animais , Comportamento Animal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Desenho de Fármacos , Humanos , Doença de Huntington/fisiopatologia , Doença de Huntington/psicologia , Camundongos , Modelos Moleculares , Neurônios/efeitos dos fármacos , Relação Estrutura-Atividade
13.
Front Bioeng Biotechnol ; 8: 573938, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33163480

RESUMO

Aims: To investigate the impact of subchondral bone cysts (SBCs) in stress-induced osseous and articular variations in cystic and non-cystic knee models using finite element analysis. Materials and Methods: 3D knee joint models were reconstructed from computed tomography (CT) and magnetic resonance imaging (MRI). Duplicate 3D models were also created with a 3D sphere mimicking SBCs in medial tibia. Models were divided into three groups. In group A, a non-cystic knee model was used, whereas in groups B and C, SBCs of 4 and 12 mm size were simulated, respectively. Cyst groups were further divided into three sub-groups. Each of sub-group 1 was composed of a solitary SBC in the anterior half of tibia adjacent to joint line. In sub-group 2, a solitary cyst was modeled at a lower-joint location, and in sub-group 3, two SBCs were used. All models were vertically loaded with weights representing double- and single-leg stances. Results: During single-leg stance, increase in subchondral bone stress in sub-groups B-1 and B-3 were significant (p = 0.044, p = 0.026). However, in sub-group B-2, a slight increase was observed than non-cystic knee model (9.93 ± 1.94 vs. 9.35 ± 1.85; p = 0.254). All the sub-groups in group C showed significantly increased articular stress (p < 0.001). Conversely, a prominent increase in peri-cystic cancellous bone stress was produced by SBCs in groups B and C (p < 0.001). Mean cartilage shear stress in sub-groups B-1 and B-2 (0.66 ± 0.56, 0.58 ± 0.54) was non-significant (p = 0.374, p = 0.590) as compared to non-cystic model (0.47 ± 0.67). But paired cysts of the same size (B-3) produced a mean stress of 0.98 ± 0.49 in affected cartilage (p = 0.011). Models containing 12 mm SBCs experienced a significant increase in cartilage stress (p = 0.001, p = 0.006, p < 0.001) in sub-groups C-1, C-2, and C-3 (1.25 ± 0.69, 1.01 ± 0.54, and 1.26 ± 0.59), respectively. Conclusion: The presence of large-sized SBCs produced an increased focal stress effect in articular cartilage. Multiple cysts further deteriorate the condition by increased osseous stress effect and high tendency of peripheral cyst expansion in simulated cystic knee models than non-cystic knee models.

14.
Medicine (Baltimore) ; 99(43): e22736, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120773

RESUMO

BACKGROUND: Gastrointestinal manifestations are common in patients with COVID-19, but the association between specific digestive symptoms and COVID-19 prognosis remains unclear. This study aims to assess whether digestive symptoms are associated with COVID-19 severity and mortality. METHODS: We will search PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials up to September, 2020, to identify studies that compared the prevalence of at least one specific digestive symptom between severe and non-severe COVID-19 patients or between non-survivors and survivors. Two independent reviewers will assess the risk of bias of the included cohort studies using the modified Newcastle-Ottawa Scale. Meta-analyses will be conducted to estimate the pooled prevalence of individual symptoms using the inverse variance method with the random-effects model. We will conduct subgroup analyses, sensitivity analyses, and meta-regression analyses to explore the sources of heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to assess the quality of the evidence. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: Our meta-analysis will comprehensively evaluate the association between different digestive symptoms and the severity and mortality of patients infected with COVID-19. This study will provide evidence to help determine whether special protective measures and treatment options are needed for patients with digestive system comorbidities during the COVID-19 pandemic. INPLASY REGISTRATION NUMBER: INPLASY202090055.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Doenças do Sistema Digestório/virologia , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , COVID-19 , Protocolos Clínicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Doenças do Sistema Digestório/diagnóstico , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Prognóstico , SARS-CoV-2
15.
Acta Biochim Biophys Sin (Shanghai) ; 52(10): 1120-1130, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33085763

RESUMO

Spontaneous abortion (SA) is the spontaneous loss of a pregnancy before 20 gestational weeks. The causes of SA are still largely unknown. Long noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) plays an important role in cellular progress. However, there is no report focusing on the role of UCA1 in SA. Here, we revealed that, compared with that in clinical samples from elective induced abortion, UCA1 expression was decreased in samples from SA patients as shown by qPCR method. The results demonstrated that UCA1 might be involved in the progress of SA. Then, we found that knockdown of UCA1 reduced cell viability and inhibited cell proliferation and migration of HTR-8/SVneo trophoblast cells as shown by CCK8, EdU, and Transwell methods. Furthermore, we demonstrated that UCA1 could act as a molecular sponge for miR-455 in HTR-8/SVneo cells as shown by luciferase reporter system method. In addition, miR-455 inhibited cell viability, cell proliferation and migration via regulating RUNX2 in HTR-8/SVneo cells. Ultimately, we illustrated that UCA1 plays its role via absorbing miR-455, thus promoting RUNX2 expression in HTR-8/SVneo cells. Collectively, this study first revealed the role and mechanism of UCA1 in the growth and migration of HTR-8/SVneo cells, indicating its potential as a diagnostic biomarker and therapeutic target for SA.


Assuntos
Aborto Espontâneo/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Trofoblastos/metabolismo , Biomarcadores , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação para Baixo , Feminino , Inativação Gênica , Humanos , MicroRNAs/genética , Gravidez , Transdução de Sinais/genética , Trofoblastos/citologia , Trofoblastos/ultraestrutura , Regulação para Cima
16.
Artigo em Inglês | MEDLINE | ID: mdl-32903545

RESUMO

Aims: In this study we have considered the three dimensional corrective forces for correction of scoliosis by using a patient specific finite element model. Materials and Methods: An objective function of corrective forces in three-dimensional space was defined. Computed tomography images were used to reconstruct three dimensional model of scoliotic trunk. Computer aided engineering software Abaqus was used to establish finite element model of deformed spine and its biomechanical characteristics were analyzed. By adjusting magnitude and position of corrective forces, objective function was minimized to achieve best orthopedic effect. The proposed corrective conditions were divided into three groups: (1) thoracic deformity; (2) lumbar deformity; (3) both thoracic and lumbar deformities were considered. Results: In all three cases, the objective function was reduced by 58, 52, and 63%, respectively. The best correction forces point was located on convex side of maximum displacement of vertebral body. Conclusion: Using minimum objective function method, spinal deformity in three-dimensional space can be sufficiently reduced. This study provides scientific basis for design of a new corrective brace for treatment of scoliosis.

17.
Epidemiol Psychiatr Sci ; 29: e152, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32772993

RESUMO

AIMS: The factors associated with suicidal ideation among adolescents have been extensively characterised, but the mechanisms underlying the complexities of the relationship between experiences of childhood trauma and suicidal ideation have been less studied. This study examined the direct effect of childhood trauma on suicidal ideation on the one hand and whether school bullying victimisation and Internet addiction mediate the association between childhood trauma and suicidal ideation on the other hand. METHODS: This school-based mental health survey was carried out in Qinghai Province in Northwest China in December 2019. We employed standardised questionnaires to collect sociodemographic and target mental health outcomes. Hierarchical multiple logistic regression and structural equation modelling were performed for the data analyses. RESULTS: This study included 5864 university students. The prevalence of lifetime suicidal ideation and Internet addiction were 34.7% and 21.4%, respectively. Overall, 16.4% and 11.4% of participants reported experiences of childhood trauma and school bullying victimisation, respectively. There were direct effects of childhood trauma, school bullying victimisation and Internet addiction on suicidal ideation. The total effect of childhood trauma on suicidal ideation was 0.201 (p < 0.001). School bullying victimisation and Internet addiction mediated the relationship between childhood trauma and suicidal ideation. Internet addiction played a mediating role between school bullying and suicidal ideation. CONCLUSIONS: Childhood trauma had both direct and indirect effects on suicidal ideation; these effects were mediated by school bullying victimisation and Internet addiction in Chinese university students. Elucidating these relationships will therefore be useful in developing and implementing more targeted interventions and strategies to improve the mental well-being of Chinese university students.


Assuntos
Comportamento Aditivo/psicologia , Bullying/estatística & dados numéricos , Vítimas de Crime/estatística & dados numéricos , Depressão/psicologia , Internet/estatística & dados numéricos , Estudantes/psicologia , Ideação Suicida , Adolescente , Comportamento Aditivo/epidemiologia , Criança , China/epidemiologia , Depressão/epidemiologia , Feminino , Humanos , Masculino , Saúde Mental , Prevalência , Inquéritos e Questionários
18.
J Pharmacol Exp Ther ; 375(1): 92-103, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32759272

RESUMO

Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation (CASP3siRNA), on ischemia/reperfusion (IR)-induced AKI. Utilizing a mouse model with 30-minute renal bilateral ischemia and 48-hour reperfusion, the renoprotection of CHBP or CASP3siRNA was demonstrated in renal function and structure, active caspase-3 and HMGB1 expression. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure and reduced active caspase-3 and HMGB1. Furthermore, differentially expressed genes (DEGs) were identified with fold change >1.414 and P < 0.05. In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (upregulated signal transducer and activator of transcription 5B and solute carrier family 22 member 7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without negative control small-interfering RNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (upregulated BCL6, SLPI, and SERPINA3M) as well as immunity, injury, and microvascular homeostasis (upregulated complement factor H and GREM1 and downregulated ANGPTL2). This proof-of-effect study indicated the potent renoprotection of CASP3siRNA upon CHBP at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1, and ANGPTL2, might be potential new biomarkers for clinical applications. SIGNIFICANCE STATEMENT: It is imperative to explore new strategies of cause-specific treatment and timely diagnosis for acute kidney injury (AKI). CHBP and CASP3siRNA synergistically protected kidney structure after 48-hour ischemia/reperfusion-induced AKI with reduced injury mediators CASP3 and high mobility group box 1. CHBP upregulated cell division-, function-, and metabolism-related genes, whereas CASP3siRNA further regulated immune response- and tissue homeostasis-associated genes. Combined CHBP and CASP3siRNA might be a potent and specific treatment for AKI, and certain dysregulated genes secretory leukocyte peptidase inhibitor and SERPINA3M could facilitate timely diagnosis.


Assuntos
Caspase 3/genética , Eritropoetina/uso terapêutico , Rim/efeitos dos fármacos , Fragmentos de Peptídeos/uso terapêutico , RNA Interferente Pequeno/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Transcriptoma/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Creatinina/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Proteína HMGB1/genética , Injeções Intraperitoneais , Injeções Intravenosas , Rim/irrigação sanguínea , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
19.
Ying Yong Sheng Tai Xue Bao ; 31(7): 2352-2362, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32715701

RESUMO

It is of great significance for the sustainable development of regional agriculture to understand the changes of agricultural climate resources during the growth period of local main crops. Based on data from 15 meteorological stations in tobacco planting area of Panxi region, Sichuan, from 1961 to 2017, the average temperature, diurnal temperature range, water deficit, and radiation were used to analyze the temporal and spatial distribution of agricultural climate resources such as light, temperature, and water in the whole growth period and each growth stages respectively. From 1961 to 2017, the average temperature of tobacco during the whole growth period gradually decreased from south to north in Panxi, while temperature showed an increasing trend in most areas. The area with significantly increased temperature accounted for 54.5% of the total planting area. The diurnal temperature range in most area of the eastern Panxi and some of the central Panxi showed an upward trend, and these areas accounted for 76.4% of the whole Panxi region. Water deficit gradually decreased from south to north, with an increasing trend in the whole region. The radiation during the growth stage of tobacco was high in the southwest and low in the northeast, and the climatic tendency was positive values in the southwest. During the study period, average temperature was the highest in the period from vigorous growth to the beginning of maturity, with an overall upward trend. The diurnal temperature rage and water deficit were the highest in transplanting squatting seedling stage. Radiation was the highest at the beginning of maturity, which increased slightly at the beginning of seedling growth.


Assuntos
Mudança Climática , Tabaco , Agricultura , China , Produtos Agrícolas , Temperatura
20.
ACS Omega ; 5(22): 13454-13461, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32548534

RESUMO

A silver-catalyzed dimerization of ethyl isocyanoacetates could trigger the tandem reaction of 3-(1-alkynyl) chromones under the basic condition in a one-pot reaction to afford xanthone skeletons with 2-imidazolyl substitution in an efficient manner. With the control experiment in hand, a mechanism including dimerization of isocyanoacetate/deprotonation/Michael addition/ring-opening/cyclization 1,2-elimination was deduced. Further investigation for the base was carried out, resulting in NaH as an optimal base to avoid the dimerization of 3-(1-alkynyl) chromones. The scope of this methodology was extended on the different substituents of 3-(1-alkynyl)-chromones and the potential of other N-heterocycle glycine ester anions to give the novel functional 2-nitrogen-derived xanthones.

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