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1.
Neural Regen Res ; 18(3): 634-642, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018188

RESUMO

Chronic spinal cord compression (CSCC) is induced by disc herniation and other reasons, leading to movement and sensation dysfunction, with a serious impact on quality of life. Spontaneous disc herniation rarely occurs in rodents, and therefore establishing a chronic spinal cord compression (CSCC) animal model is of crucial importance to explore the pathogenesis and treatment of CSCC. The absence of secreted protein, acidic, and rich in cysteine (SPARC) leads to spontaneous intervertebral disc degeneration in mice, which resembles human disc degeneration. In this study, we evaluated whether SPARC-null mice may serve as an animal model for CSCC. We performed rod rotation test, pain threshold test, gait analysis, and Basso Mouse Scale score. Our results showed that the motor function of SPARC-null mice was weakened, and magnetic resonance images revealed compression at different spinal cord levels, particularly in the lumbar segments. Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes, activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype; it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway. Notably, these findings are characteristics of CSCC. Therefore, we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

2.
ESC Heart Fail ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125306

RESUMO

AIMS: Malnutrition is common in patients with heart failure (HF) and is associated with poorer quality of life and increased mortality; however, an effective screening tool for malnutrition and its impact on the readmission of patients with HF is uncertain. Our objectives were to study (i) the nutritional status of Chinese hospitalized patients with HF and its impact on readmission and (ii) the validity of seven malnutrition screening tools. METHODS AND RESULTS: In this study, univariate and multivariate analyses of Cox proportional hazards regression were used to determine important predictors of readmission. The endpoint was readmission due to HF or non-HF. A total of 402 patients were included (66.4% male, median age 62 years [range: 20-92 years], median NT-proBNP 5,229 ng/L). During a median follow-up of 159 days, 150 patients (37%) were readmitted to the hospital. After adjusting for confounders, only malnutrition assessed using the Controlling Nutritional Status (CONUT) nutrition score was independently associated with readmission (P = 0.0293). A base model for predicting readmission with a C-statistic of 0.680 and subsequent addition of various nutritional screening tools improved its performance over the base model. Patients with malnutrition had a twofold increased risk of readmission. CONCLUSIONS: We found that the prevalence of malnutrition among hospitalized patients with HF in China is very high and that malnutrition significantly increases the risk of readmission in these patients. CONUT is a validated screening tool for malnutrition and may provide valuable prognostic information.

3.
Stem Cell Res Ther ; 13(1): 441, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056386

RESUMO

OBJECTIVE: Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal transplantation strategy are still unclear. Therefore, exploring the optimal treatment strategy of UCMSCs in animal studies by systematic review can provide reference for the development of animal studies and clinical research in the future. METHODS: Databases of PubMed, Ovid-Embase, Web of Science, CNKI, WanFang, VIP, and CBM were searched for the literature in February 11, 2022. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction. RESULTS AND DISCUSSION: A total of 40 animal studies were included for combined analysis. In different subgroups, the results of traditional meta-analysis and network meta-analysis were consistent, that is, the therapeutic effect of high-dose (≥ 1 × 106) transplantation of UCMSCs was significantly better than that of low dose (< 1 × 106), the therapeutic effect of local transplantation of UCMSCs was significantly better than that of intravenous transplantation, and the therapeutic effect of subacute transplantation of UCMSCs was significantly better than that of acute and chronic transplantation. However, in view of the inherent risk of bias and limited internal and external validity of the current animal studies, more high-quality, direct comparison studies are needed to further explore the optimal transplantation strategy for UCMSCs in the future.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Animais , Transplante de Células-Tronco Mesenquimais/métodos , Metanálise em Rede , Traumatismos da Medula Espinal/terapia , Cordão Umbilical
4.
Int J Mol Sci ; 23(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36077538

RESUMO

Upland cotton (Gossypium hirsutum L.) is one of the important fiber crops. Cotton flowers usually appear white (or cream-colored) without colored spots at the petal base, and turn pink on the next day after flowering. In this study, using a mutant showing pink petals with crimson spots at their base, we conducted comparative metabolome and transcriptome analyses to investigate the molecular mechanism of coloration in cotton flowers. Metabolic profiling showed that cyanidin-3-O-glucoside and glycosidic derivatives of pelargonidins and peonidins are the main pigments responsible for the coloration of the pink petals of the mutant. A total of 2443 genes differentially expressed (DEGs) between the white and pink petals were identified by RNA-sequencing. Many DEGs are structural genes and regulatory genes of the anthocyanin biosynthesis pathway. Among them, MYB21, UGT88F3, GSTF12, and VPS32.3 showed significant association with the accumulation of cyanidin-3-O-glucoside in the pink petals. Taken together, our study preliminarily revealed the metabolites responsible for the pink petals and the key genes regulating the biosynthesis and accumulation of anthocyanins in the pink petals. The results provide new insights into the biochemical and molecular mechanism underlying anthocyanin biosynthesis in upland cotton.


Assuntos
Antocianinas , Gossypium , Antocianinas/metabolismo , Flores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Glucosídeos/metabolismo , Gossypium/genética , Gossypium/metabolismo , Metaboloma , Transcriptoma
5.
Front Cardiovasc Med ; 9: 924551, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966555

RESUMO

Foam cell formation is the hallmark of the development and progression of atherosclerosis. The aim of this study was to investigate the regulatory effects of three polymethoxyflavones (PMFs), namely, tangeretin (TAN), 5,6,7,3',4',5'-hexamethoxyflavone (HxMF), and 3,5,6,7,8,3',4'-heptamethoxyflavone (HpMF) on macrophage-derived foam cell formation and to further explore the molecular mechanisms. The RAW264.7 macrophage-derived foam cell model was successfully induced by oxidized low-density lipoprotein (ox-LDL) (80 µg/ml). It showed that TAN, HxMF, and HpMF alleviated ox-LDL-induced NO release while also inhibiting the expression of IL-1ß, IL-6, and TNF-α in RAW264.7 cells. Uptake of excess ox-LDL was inhibited by TAN, HxMF, and HpMF, resulting in the reduction of its foam cell formation. Moreover, TAN, HxMF, and HpMF promoted HDL-mediated cholesterol efflux. Western blot experiment showed that TAN, HxMF, and HpMF inhibited the expression of scavenger receptor class A type I (SRA1) and cluster of differentiation 36 (CD36), while upregulating peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα), phospholipid ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SRB1) expression. Together, our findings suggested that PMFs inhibited foam cell formation might inhibit lipid uptake via downregulating SRA1/CD36 expression and promote cholesterol efflux from foam cells via upregulating PPARγ/LXRα/ABCG1/SRB1 expression. This antiatherosclerotic activity is expected to provide new insights into the development of healthcare uses for PMFs.

6.
Phys Rev Lett ; 129(7): 070401, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36018690

RESUMO

The non-Hermitian skin effect (NHSE), the accumulation of eigen-wave functions at boundaries of open systems, underlies a variety of exotic properties that defy conventional wisdom. While the NHSE and its intriguing impact on band topology and dynamics have been observed in classical or photonic systems, their demonstration in a quantum gas system remains elusive. Here we report the experimental realization of a dissipative Aharonov-Bohm chain-non-Hermitian topological model with NHSE-in the momentum space of a two-component Bose-Einstein condensate. We identify signatures of the NHSE in the condensate dynamics, and perform Bragg spectroscopy to resolve topological edge states against a background of localized bulk states. Our Letter sets the stage for further investigation on the interplay of many-body statistics and interactions with the NHSE, and is a significant step forward in the quantum control and simulation of non-Hermitian physics.

7.
Front Microbiol ; 13: 962326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935244

RESUMO

Listeria monocytogenes (LM) induces efficient and specific T-cell immune responses in the host. Listeriolysin O (LLO) is the main virulence protein of LM. LLO helps LM escape from the lysosome. However, the pronounced pathogenicity of LM limits its practical application as a live bacterial vector. Listeria ivanovii (LI) also displays intracellular parasitic abilities, cell to cell transfer, and other LM properties, with an elevated biosafety relative to LM. We have confirmed that LI can be used as a viable bacterial vaccine vector. However, we have also observed in vivo that LI vector vaccine candidates survive in the immune organ (spleen) for a shorter time compared with the survival time of LM and elicit weaker immune responses compared with LM. Studies have confirmed that hemolysin correlates with some important biological properties of Listeria, including cell invasion, intracellular proliferation, and the ability to induce immune responses. We speculated that the weaker immunogenicity of LI compared to LM may be related to the function of ivanolysin O (ILO). Here, we established a hemolysin gene deletion strain, LIΔilo, and a modified strain, LIΔilo:hly, whose ilo was replaced by hly. The hemolysin-modified strain was attenuated; however, it led to significantly improved invasive and proliferative activities of antigen-presenting cells, including those of RAW 264.7 macrophages, compared with the effects of LI. Mice immunized twice with LIΔilo:hly showed higher cytokine levels and better challenge protection rates than LI-immunized mice. This is the first description in Listeria carrier vaccine research of the modification of LI hemolysin to obtain a better vaccine carrier than LI. The recombinant strain LIΔilo:hly showed good biosafety and immunogenicity, and thus appears to be a good vector strain for vaccine development.

8.
Placenta ; 127: 37-42, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35952596

RESUMO

INTRODUCTION: We aimed to systemically investigate the diagnostic capacity of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio in fetal growth restriction (FGR). METHODS: We systematically searched the PubMed, MEDLINE, Cochrane Library, and EMBASE databases for relevant studies from inception to 15 May 2022. All potentially relevant studies were assessed and then pooled. RESULTS: Eight studies with 339 patients and 5111 controls were included. A sFlt-1/PlGF ratio >33 was demonstrated a predictive value for FGR with a pooled sensitivity of [0.63, 95% confidence interval (CI) = 0.54-0.71], specificity of (0.84, 95% CI = 0.83-0.85), and area under the curve (AUC) of 0.8354. The pooled sensitivity, specificity, and AUC for the sFlt-1/PlGF ratio ≥85 group were 0.79 (95% CI = 0.66-0.89), 0.69 (95% CI = 0.65-0.74), and 0.8197, respectively. DISCUSSION: These findings revealed that the sFlt-1/PlGF ratio could be a potential indicator in predicting FGR and FGR + PE. More studies are needed to support the conclusion.


Assuntos
Retardo do Crescimento Fetal , Pré-Eclâmpsia , Biomarcadores , Feminino , Retardo do Crescimento Fetal/diagnóstico , Humanos , Fator de Crescimento Placentário , Pré-Eclâmpsia/diagnóstico , Valor Preditivo dos Testes , Receptor 1 de Fatores de Crescimento do Endotélio Vascular
9.
Biophys J ; 121(18): 3370-3380, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36016497

RESUMO

Complexin-1 is an essential protein for neuronal exocytosis that acts to depress spontaneous fusion events while enhancing evoked neurotransmitter release. In addition to binding soluble N-ethylmaleimide-sensitive factor attachment protein receptors, it is well established that complexin associates with membranes in a manner that depends upon membrane curvature. In the present work, we examine the membrane binding of complexin using electron paramagnetic resonance spectroscopy, fluorescence anisotropy, and total internal reflection fluorescence microscopy. The apparent membrane affinity of complexin is found to strongly depend upon the concentration of protein used in the binding assay, and this is a result of a limited number of binding sites for complexin on the membrane interface. Although both the N- and C-terminal regions of complexin associate with the membrane interface, membrane affinity is driven by its C-terminus. Complexin prefers to bind liquid-disordered membrane phases and shows an enhanced affinity toward membranes containing phosphatidylinositol 4-5-bisphosphate (PI(4,5)P2). In the presence of PI(4,5)P2, complexin is displaced from the membrane surface by proteins that bind to or sequester PI(4,5)P2. In particular, the neuronal calcium sensor synaptotagmin-1 displaces complexin from the membrane but only when PI(4,5)P2 is present. Complexin and synaptotagmin compete on the membrane interface in the presence of PI(4,5)P2, and this interaction may play a role in calcium-triggered exocytosis by displacing complexin from its fusion-inhibiting state.


Assuntos
Cálcio , Fosfatidilinositol 4,5-Difosfato , Proteínas Adaptadoras de Transporte Vesicular/química , Sítios de Ligação , Cálcio/metabolismo , Exocitose , Proteínas do Tecido Nervoso/química , Neurotransmissores , Proteínas SNARE/metabolismo , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/metabolismo , Sinaptotagmina I/química
10.
PLoS One ; 17(8): e0273112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35960730

RESUMO

BACKGROUND: Since the successful development of Coronavirus Disease (COVID-19) vaccine, COVID-19 vaccination has been actively advocated all over the world. As the key population for COVID-19 vaccination, the acceptance of Healthcare Workers (HCWs) is not only related to their risk of contracting COVID-19 infection at work, but also affects the decision of the general population on COVID-19 vaccination. Currently, a series of observational studies have been conducted on the acceptance of COVID-19 vaccines among HCWs in China, but there are presently no all-inclusive reviews. Therefore, this paper reviewed to identify a reliable estimate of acceptance rate of COVID-19 vaccine among HCWs in China. METHODS: We conducted a search on PubMed, EMbase, The Cochrane Library, Web of Science, CNKI (Chinese National Knowledge Infrastructure), Wanfang Database, CBM (Chinese Biomedical Literature Database) and VIP database (Chinese Scientific Journal Database) from January 2020 to June 2022. The quality of included articles was estimated using the Newcastle-Ottawa Quality Assessment tool suitable for cross-sectional studies and STATA 16 was used for analysis, A random-effects model was used to calculate acceptance rate for COVID-19 vaccine, as well as subgroup analysis and sensitivity analysis. RESULT: This review included 18 studies involving 45,760 subjects, all of which were of medium or high quality. Meta-analysis results represented that, the pooled estimated acceptance rate of COVID-19 vaccine among HCWs in China was 78% (95%CI: 73-83%), and the pooled acceptance rate in 2021 (82%, 95%CI: 78-86%) was significantly higher than that in 2020 (73%, 95%CI: 65%-81%). Subgroup analysis showed different acceptance rates for COVID-19 vaccine among HCWs with different characteristics. CONCLUSION: The result revealed that HCWs in China generally have a high acceptance rate of COVID-19 vaccines, but the acceptance rate varies with different characteristics of the population. Therefore, corresponding training should be carried out for HCWs with different characteristics, and they should play an exemplary and leading role in COVID-19 vaccination, so as to improve the vaccination rate of the whole population and form an immune barrier at an early date.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Estudos Transversais , Pessoal de Saúde , Humanos , Vacinação
11.
Ginekol Pol ; 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35997215

RESUMO

OBJECTIVES: An increase in homocysteine (Hcy) concentration is closely related to polycystic ovary syndrome (PCOS). This study aimed to further explore serum homocysteine concentration and its influencing factors in clinically young (≤ 35 years) patients with PCOS and hyperandrogenism. MATERIAL AND METHODS: An electrochemical immunoassay was used to investigate the changes in serum homocysteine and related indexes in clinically young patients with PCOS and hyperandrogenism, and the results were statistically analyzed. RESULTS: Serum homocysteine concentration in clinically young patients with PCOS and hyperandrogenism (n = 208) was found to be significantly higher than in the control group (n = 663) (15.21 ± 9.99 vs. 12.56 ± 7.20 µmol/L, p < 0.0001), and the total testosterone concentration (1.65 ± 0.68 ng/mL) was higher in the PCOS group than in the control group (1.52 ± 0.58 ng/mL), p = 0.007. The receiver operating characteristic curve showed that the area under the curve of homocysteine in predicting PCOS was 0.606, and the 95% confidence interval (CI) was 0.563-0.650 (p < 0.001). The homocysteine concentrations of the two groups were graded, and it was found that the percentage of patients with homocysteine levels > 15 µmol/L was 26.92% in the PCOS group and 19.15% in the control group; the difference between the two groups was statistically significant (p = 0.0143). The serum homocysteine levels of the two groups were higher in obese patients than in non-obese patients (normal weight vs. overweight), and the difference in the control group was statistically significant. CONCLUSIONS: Serum homocysteine concentration in clinically young patients with PCOS and hyperandrogenism is elevated, so hyperhomocysteinemia can be used as one of the potential indicators of PCOS. In the process of the diagnosis and treatment of patients with PCOS, serum homocysteine concentration and body weight should both be considered.

12.
J Med Virol ; 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36000452

RESUMO

Chronic hepatitis B virus (HBV) infection is an important public health problem. Polygonum perfoliatum L. is a traditional medicinal herb and has been reported to have pharmacological activities such as anti-inflammatory, antibacterial, and antiviral. In this study, the antiviral activities and mechanisms of Polygonum perfoliatum L. extract against HBV and the effective components were investigated. The results showed that the total extract of Polygonum perfoliatum L. reduced the levels of HBV e antigen (HBeAg) secretion and the viral covalently closed circular DNA (CCC DNA) formation, but had little or no negative effects on viral capsid assembly and pregenomic RNA packaging. Further fractionation showed that the water extract (WE) fraction exerted comparable anti-HBV activities with the total extract, especially in inhibiting the CCC DNA formation and HBeAg production, indicating that the effective antiviral components are mainly distributed in this fraction. Further study showed that the phenolic acids constituents, protocatechuic acid, and gallic acid, but not ethyl caffeate, which is reported enriched in the WE fraction, showed strong anti-HBV activities in inhibiting viral core DNA synthesis, CCC DNA formation, and HBeAg production. These results suggested that the Polygonum perfoliatum L. total extract and the related phenolic acids like protocatechuic acid and gallic acid could inhibit HBV replication and also indicated the potential utility of Polygonum perfoliatum L. and related constituents as sources of novel antivirals against HBV.

13.
Inorg Chem ; 61(27): 10598-10608, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35763666

RESUMO

Enhanced interfacial charge separation is of great importance to high-efficiency photocatalytic hydrogen production. Herein, we successfully fabricated novel ZIF-67/CdS hollow sphere (HS) and ZIF-8/CdS HS heterostructures through an in situ self-assembly process, in which ZIF-67 and ZIF-8 are closely coated on CdS HSs to form "double-shell"-like structures. This hierarchical heterostructure with porous outer layers on the surface of CdS HSs can expose accessible active sites and possess close contact. Upon visible-light illumination, the optimal proportion of ZIF-67/CdS HS displays a hydrogen generation rate of 1721 µmol g-1 h-1, which is 11.9 and 3.1 times higher than that of a pure CdS HS (145 µmol g-1 h-1) and ZIF-8/CdS HS (555 µmol g-1 h-1), respectively. The proposed photocatalytic mechanism is explored: ZIF-8/CdS HS follows the type-II mechanism, and ZIF-67/CdS HS follows the Z-scheme mechanism. The reason for the higher photocatalytic activity of ZIF-67/CdS HS is that ZIF-67 not merely with a porous structure facilitates the diffusion of H2 gas, but with a well-matched band structure promotes charge transfer and separation.

14.
Respir Res ; 23(1): 172, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761396

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a challenging clinical problem. Discovering the potential metabolic alterations underlying the ARDS is important to identify novel therapeutic target and improve the prognosis. Serum and urine metabolites can reflect systemic and local changes and could help understanding metabolic characterization of community-acquired pneumonia (CAP) with ARDS. METHODS: Clinical data of patients with suspected CAP at the First Affiliated Hospital of Wenzhou Medical University were collected from May 2020 to February 2021. Consecutive patients with CAP were enrolled and divided into two groups: CAP with and without ARDS groups. 1H nuclear magnetic resonance-based metabolomics analyses of serum and urine samples were performed before and after treatment in CAP with ARDS (n = 43) and CAP without ARDS (n = 45) groups. Differences metabolites were identifed in CAP with ARDS. Furthermore, the receiver operating characteristic (ROC) curve was utilized to identify panels of significant metabolites for evaluating therapeutic effects on CAP with ARDS. The correlation heatmap was analyzed to further display the relationship between metabolites and clinical characteristics. RESULTS: A total of 20 and 42 metabolites were identified in the serum and urine samples, respectively. Serum metabolic changes were mainly involved in energy, lipid, and amino acid metabolisms, while urine metabolic changes were mainly involved in energy metabolism. Elevated levels of serum 3-hydroxybutyrate, lactate, acetone, acetoacetate, and decreased levels of serum leucine, choline, and urine creatine and creatinine were detected in CAP with ARDS relative to CAP without ARDS. Serum metabolites 3-hydroxybutyrate, acetone, acetoacetate, citrate, choline and urine metabolite 1-methylnicotinamide were identified as a potential biomarkers for assessing therapeutic effects on CAP with ARDS, and with AUCs of 0.866 and 0.795, respectively. Moreover, the ROC curve analysis revealed that combined characteristic serum and urine metabolites exhibited a better classification system for assessing therapeutic effects on CAP with ARDS, with a AUC value of 0.952. In addition, differential metabolites strongly correlated with clinical parameters in patients with CAP with ARDS. CONCLUSIONS: Serum- and urine-based metabolomics analyses identified characteristic metabolic alterations in CAP with ARDS and might provide promising circulatory markers for evaluating therapeutic effects on CAP with ARDS.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Síndrome do Desconforto Respiratório , Ácido 3-Hidroxibutírico , Acetoacetatos , Acetona , Biomarcadores , Infecções Comunitárias Adquiridas/diagnóstico , Humanos , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Pneumonia/diagnóstico por imagem , Curva ROC , Síndrome do Desconforto Respiratório/diagnóstico por imagem
15.
PLoS One ; 17(6): e0270038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35709074

RESUMO

BACKGROUND: Since the outbreak of the respiratory infectious disease caused by the novel coronavirus in 2019, the COVID-19 epidemic has posed a serious threat to the life and safety of the public, and has also seriously affected the normal study and life of college students in China. Although a series of studies have been conducted on college students' knowledge, attitudes and practices of COVID-19, the results vary widely. This study aimed to evaluate the pooled estimated level of knowledge, attitudes, and practices (KAP) about COVID-19 among college students in China. METHODS: We conducted a comprehensive search on Scopus, ProQuest, PubMed, EMbase, Web of Science, the Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP Database and Wanfang Database up to 13 February 2022. We then assessed the quality of included studies using a checklist developed by the Joanna Briggs Institute (JBI) for cross-sectional studies and analyzed using STATA.15 after two researchers independently extracted relevant data and entered them into Microsoft Excel. Funnel plots and Egger's regression tests were used to check for publication bias, and sensitivity analysis was performed to assess the robustness of the results. A random-effects model was used for the meta-analysis, on the basis of which subgroup analyses were performed by time of investigation (study period) and by gender and major of the subjects. RESULT: A total of 42 studies including 174,440 subjects were included in this review, and the quality of the included studies was mainly intermediate and advanced. The findings of the meta-analysis showed that the overall levels of Chinese college students' knowledge, positive and negative attitudes, and practice of preventive measures towards COVID-19 were 74% (95%CI: 69%-79%), 84% (95%CI: 80%-88%), 31% (95%CI: 23%-38%) and 82% (95%CI: 77%-86%), respectively. The results of subgroup analysis showed that female and medical college students had higher levels of knowledge and practice on COVID-19. CONCLUSION: The study findings showed that the overall KAP level of college students in China included in the study was relatively optimistic. Influenced by gender, major and time, there were differences in the KAP level of college students. In order to promote the effective prophylaxis and control of pandemic, we recommend implementing targeted measures to improve the awareness rate of COVID-19-related knowledge among this group and the implementation rate of COVID-19 preventive measures among male and non-medical college students.


Assuntos
COVID-19 , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Estudantes
16.
J Clin Med ; 11(10)2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35628836

RESUMO

BACKGROUND: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplantation. METHODS: Brain extracts of TBI mice were used in vitro to simulate the different phase TBI influences on the differentiation of human NSCs. Protein profiles of brain extracts were analyzed. Neuronal differentiation and the activation of autophagy and the WNT/CTNNB pathway were detected after brain extract treatment. RESULTS: Under subacute TBI brain extract conditions, the neuronal differentiation of hNSCs was significantly higher than that under acute brain extract conditions. The autophagy flux and WNT/CTNNB pathway were activated more highly within the subacute brain extract than in the acute brain extract. Autophagy activation by rapamycin could rescue the neuronal differentiation of hNSCs within acute TBI brain extract. CONCLUSIONS: The subacute phase around 7 days after TBI in mice could be a candidate timepoint to encourage more neuronal differentiation after transplantation. The autophagy flux played a critical role in regulating neuronal differentiation of hNSCs and could serve as a potential target to improve the efficacy of transplantation in the early phase.

17.
Front Genet ; 13: 876689, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571050

RESUMO

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy with poor prognosis. We explored the RNA sequence data and clinical information of AML patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database to search for the core molecule for prognosis. The DC-STAMP expression was significantly higher in AML patients, which was linked to old age, unfavorable cytogenetic risk, and death (all p < 0.05). Furthermore, it was revealed that high DC-STAMP expression was an independent unfavorable factor for overall survival (OS) by univariate analysis [hazard ratio (HR): 2.683; 95% confidence interval (CI): 1.723-4.178; p < 0.001] and multivariate analysis (HR: 1.733; 95% CI: 1.079-2.781; p = 0.023). The concordance index (C-index 0.734, 95% CI: 0.706-0.762), calibration curves, and decision curve analysis showed the certain predictive accuracy of a nomogram model based on multivariate analysis for OS. In addition, we found that the differentially expressed gene (DEG) enrichment pathways of high- and low-DC-STAMP expression group enrichment pathways were focused on channel activity and platelet alpha granule by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), while gene set enrichment analysis (GSEA) pathways were mainly involved in mTORC1 signaling and TNF-α signaling via the NF-kB pathway. Moreover, a protein-protein interaction (PPI) network demonstrated that DC-STAMP interacted with two hub genes (PPBP and PF4), which were highly regulated and associated with poor survival. Finally, high DC-STAMP expression showed a significantly positive correlation with four immune cell [NK CD56 (dim) cells, macrophages, cytotoxic cells, and CD8 (+) T cells] infiltration and high level of immune checkpoint genes (PDCD1, CD274, CTLA-4, and TIGIT). Therefore, our results suggest that high expression of DC-STAMP predicts adverse outcomes for AML patients.

18.
J Biol Chem ; 298(6): 102016, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35525273

RESUMO

Ubiquitin-fold modifier 1 (UFM1) is a recently identified ubiquitin-like posttranslational modification with important biological functions. However, the regulatory mechanisms governing UFM1 modification of target proteins (UFMylation) and the cellular processes controlled by UFMylation remain largely unknown. It has been previously shown that a UFM1-specific protease (UFSP2) mediates the maturation of the UFM1 precursor and drives the de-UFMylation reaction. Furthermore, it has long been thought that UFSP1, an ortholog of UFSP2, is inactive in many organisms, including human, because it lacks an apparent protease domain when translated from the canonical start codon (445AUG). Here, we demonstrate using the combination of site-directed mutagenesis, CRISPR/Cas9-mediated genome editing, and mass spectrometry approaches that translation of human UFSP1 initiates from an upstream near-cognate codon, 217CUG, via eukaryotic translation initiation factor eIF2A-mediated translational initiation rather than from the annotated 445AUG, revealing the presence of a catalytic protease domain containing a Cys active site. Moreover, we show that both UFSP1 and UFSP2 mediate maturation of UFM1 and de-UFMylation of target proteins. This study demonstrates that human UFSP1 functions as an active UFM1-specific protease, thus contributing to our understanding of the UFMylation/de-UFMylation process.


Assuntos
Cisteína Endopeptidases , Peptídeo Hidrolases , Proteínas , Códon de Iniciação/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Endopeptidases/metabolismo , Humanos , Peptídeo Hidrolases/metabolismo , Biossíntese de Proteínas , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Ubiquitina/metabolismo
19.
Mol Neurobiol ; 59(6): 3665-3677, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35362812

RESUMO

Direct current electric field (DCEF) steers the migration of various neural cells. Microglia, as macrophage of the central nervous system (CNS), however, have not been reported to engage in electrotaxis. Here, we applied electric fields to an in vitro environment and found directional migration of BV2 microglia toward the cathode, in a DCEF strength-dependent manner. Transcriptome analysis then revealed significant changes in the mitogen-activated protein kinase cascades. In terms of mechanism, DCEF coordinated microglia movement by regulating the ERK/GSK3ß/cofilin signaling pathway, and PMA (protein kinase C activator) reversed cell migration through intervention of the ERK/GSK3ß/cofilin axis. Meanwhile, LiCl (GSK3ß inhibitor) showed similar functions to PMA in the electrotaxis of microglia. Furthermore, pharmacological and genetic suppression of GSK3ß or cofilin also modulated microglia directional migration under DCEF. Collectively, we discovered the electrotaxis of BV2 microglia and the essential role of the ERK/GSK3ß/cofilin axis in regulating cell migration via modulation of F-actin redistribution. This research highlights new insight toward mediating BV2 directional migration and provides potential direction for novel therapeutic strategies of CNS diseases.


Assuntos
Fatores de Despolimerização de Actina , Microglia , Movimento Celular/fisiologia , Glicogênio Sintase Quinase 3 beta , Transdução de Sinais
20.
Hum Mutat ; 43(7): 928-939, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35391506

RESUMO

There is growing evidence that synonymous codon variants (SCVs) can cause disease through the disruption of different processes of protein production. The aim of the study is to investigate whether the 14 SCVs reported in the F9 variant database were the pathogenic causes of hemophilia B. The impacts of SCVs on splicing and protein expression were detected using a combination of in silico prediction, in vitro minigene splicing assay and cell expression detection. The splicing transcripts were identified and quantified by co-amplification fluorescent PCR. The mechanism of splicing was verified by a modified pU1snRNA and pU7snRNA approach. Aberrant splicing patterns were found in eight SCVs. Five of the 8 SCVs produced almost all aberrant splicing isoforms, which were expected to truncate protein, three of them presented a partial defect on both splicing and protein secretion, the overall effects were consistent with the residual Factor IX activity of the affected cases. Neither the pre-messenger RNA (mRNA) splicing process nor the protein function was impaired in the rest six SCVs. In conclusion, our study firstly revealed the pathogenic mechanism of the 14 F9 SCVs and highlighted the importance of performing mRNA splicing analysis and protein expression studies of SCVs in inherited disorders.


Assuntos
Fator IX/genética , Hemofilia B , Splicing de RNA , Mutação Silenciosa , Códon , Hemofilia B/genética , Humanos , Splicing de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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