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1.
Front Cardiovasc Med ; 9: 890607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498004

RESUMO

Aortic dissection (AD) is a fatal cardiovascular disease. It is caused by a rupture of the aortic intima or bleeding of the aortic wall that leads to the separation of different aortic wall layers. Patients with untreated AD have a mortality rate of 1-2% per hour after symptom onset. Therefore, effective biomarkers and therapeutic targets are needed to reduce AD-associated mortality. With the development of molecular technology, researchers have begun to explore the pathogenesis of AD at gene and protein levels, and have made some progress, but the pathogenesis of AD remains unclear. Non-coding RNAs, such as microRNAs, lncRNAs, and circRNAs, have been identified as basic regulators of gene expression and are found to play a key role in the pathogenesis of AD. Thus, providing a theoretical basis for developing these non-coding RNAs as clinical biomarkers and new therapeutic targets for AD in the future. Previous studies on the pathogenesis of AD focused on miRNAs, but recently, there have been an increasing number of studies that explore the role of lncRNAs, and circRNAs in AD. This review summarizes the existing knowledge on the roles of various non-coding RNAs in the pathogenesis of AD, discusses their potential role as clinical biomarkers and therapeutic targets, states the limitations of existing evidence, and recommends future avenues of research on the pathogenesis of AD.

2.
Front Physiol ; 13: 861446, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492614

RESUMO

Background: The conventional FFRct numerical calculation method uses a model with a multi-scale geometry based upon CFD, and rigid walls. Therefore, important interactions between the elastic vessel wall and blood flow are not routinely considered. Changes in the resistance of coronary microcirculation during hyperaemia are likewise not typically incorporated using a fluid-structure interaction (FSI) algorithm. It is likely that both have resulted in FFRct calculation errors. Objective: In this study we incorporated both the influence of vascular elasticity and coronary microcirculatory structure on FFR, to improve the accuracy of FFRct calculation. Thus, in this study, a physics-driven 3D-0D coupled model including fluid-structure interaction was established to calculate accurate FFRct values. Methods: Based upon a novel geometric multi-scale modeling technology, a FSI simulation approach was used. A lumped parameter model (0D) was used as the outlet boundary condition for the 3D FSI coronary artery model to incorporate physiological microcirculation, with bidirectional coupling between the two models. Results: The accuracy, sensitivity, specificity, and both positive and negative predictive values of FFRDC calculated based upon the coupled 3D-0D model were 86.7, 66.7, 84.6, 66.7, and 91.7%, respectively. Compared to the calculated value using the basic CFD model (MSE = 5.9%, accuracy rate = 80%), the FFRCFD calculated based on the coupled 3D-0D model has a smaller MSE of 1.9%. Conclusion: The physics-driven coupled 3D-0D model that incorporates fluid-structure interactions not only consider the influence of the elastic vessel wall on blood flow, but also provides reliable microvascular resistance boundary conditions for the 3D FSI model. This allows for a calculation that is based upon conditions that are closer to the physiological environment, and thus improves the accuracy of FFRct calculation. It is likely that more accurate information will provide an enhanced recommendation regarding percutaneous coronary intervention (PCI) in the clinic.

3.
Front Physiol ; 13: 881826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492621

RESUMO

Background: The underuse of invasive fraction flow reserve (FFR) in clinical practice has motivated research towards its non-invasive prediction. The early attempts relied on solving the incompressible three-dimensional Navier-Stokes equations in segmented coronary arteries. However, transient boundary condition has a high resource intensity in terms of computational time. Herein, a method for calculating FFR based on steady-state geometric multiscale (FFRSS) is proposed. Methods: A total of 154 moderately stenotic vessels (40-80% diameter stenosis) from 136 patients with stable angina were included in this study to validate the clinical diagnostic performance of FFRSS. The method was based on the coronary artery model segmented from the patient's coronary CTA image. The average pressure was used as the boundary condition for the inlet, and the microcirculation resistance calculated by the coronary flow was used as the boundary condition for the outlet to calculate the patient-specific coronary hyperemia. Then, the flow velocity and pressure distribution and the FFRss of each coronary artery branch were calculated to evaluate the degree of myocardial ischemia caused by coronary stenosis. Also, the FFRSS and FFRCT of all patients were calculated, and the clinically measured FFR was used as the "gold standard" to verify the diagnostic performance of FFRSS and to compare the correlation between FFRSS and FFRCT. Results: According to the FFRSS calculation results of all patients, FFRSS and FFR have a good correlation (r = 0.68, p < 0.001). Similarly, the correlation of FFRSS and FFRCT demonstrated an r of 0.75 (95%CI: 0.67-0.72) (p < 0.001). On receiver-operating characteristic analysis, the optimal FFRSS cut point for FFR≤0.80 was 0.80 (AUC:0.85 [95% confidence interval: 0.79 to 0.90]; overall accuracy:88.3%). The overall sensitivity, specificity, PPV, and NPV for FFRSS ≤0.80 versus FFR ≤0.80 was 68.18% (95% CI: 52.4-81.4), 93.64% (95% CI: 87.3-97.4), 82.9%, and 91.1%, respectively. Conclusion: FFRSS is a reliable diagnostic index for myocardial ischemia. This method was similar to the closed-loop geometric multiscale calculation of FFR accuracy but improved the calculation efficiency. It also improved the clinical applicability of the non-invasive computational FFR model, helped the clinicians diagnose myocardial ischemia, and guided percutaneous coronary intervention.

4.
Front Mol Neurosci ; 15: 854000, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493329

RESUMO

Background: Diabetic peripheral neuropathic pain (DPNP) is a usual complication of diabetes with a high incidence and mortality. Many diabetes-related studies have been published in various journals. However, bibliometrics and visual analyses in the domain of DPNP research are still lacking. The study aimed to offer a visual method to observe the systematic overview of global research in this field from 2011 to 2021. Methods: The publications from the Science Citation Index Expanded in Web of Science (WOS) in the past 11 years (from 2011 to 2021) were collected and sorted out, and those related to DPNP were extracted and analyzed. The article language was limited in English. Then, CiteSpace V was used for the bibliometric analysis of the extracted literature. Results: A total of 1,422 articles met the inclusion criteria. A continuous but unstable growth in the amounts of papers published on DPNP was observed over the last 11 years. The subject sort of the 1,422 papers mainly concentrates on Endocrinology Metabolism, Clinical neurology and Neurosciences from the WOS. According to the research contribution in the field of DPNP, the United States occupies a leading position, with the highest amounts of publications, citations, open access, and the H- index. Conclusion: This study provides a visual analysis method for the trend of DPNP, and offers some hidden serviceable information that may define new directions for future research.

5.
Front Neurol ; 13: 844606, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493813

RESUMO

Objectives: To reveal the effects of repetitive transcranial magnetic stimulation (rTMS) on the improvement of cognitive function in patients with stress-related depression, and to enrich the neural mechanism(s) underlying rTMS so as to improve cognitive function in patients with stress-related depression. Methods: We conducted a randomized, double-blind, placebo-controlled study of rTMS in patients with stress-related depression who were 18-40 years of age. Patients were randomly allocated to either a sham or experimental group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Clinical assessments (HAMD, HAMA, DASS, MoCA), neuropsychologic (Stroop, WCST), and resting state fMRI and 1H-MRS assessments were executed at two time points-baseline and after the 10th rTMS session. Results: rTMS relieved the mental symptoms of patients in both groups. The MoCA score of patients in the experimental group increased; the number of correct answers increased significantly in Stroop testing, and the number of errors and omissions decreased significantly; the number of persistent errors decreased significantly; and the time used to complete the test decreased to an even greater extent in the WCST experimental group. The ReHo value in the lingual gyrus of the right hemisphere and the cuneus of the left and right hemispheres in the experimental group decreased after treatment. The DC value in the left and right hemispheric cuneus and postcentral gyrus of the left hemisphere in the experimental group diminished after treatment. The functional connections of these brain regions also changed as the Cho and NAA/Cr of the left DLPFC changed, with alterations related to the improvement in cognitive function. The level of choline (Cho) in the left DLPFC of the experimental group was significantly lower than that of the control group, and the level of N-acetylaspartate/creatine (NAA/Cr) in the left DLPFC of the control group was significantly higher than that of the experimental group. These changes were related to the overall improvement in cognitive function. Conclusions: Ten-Hz rTMS over the left DLPFC improved the cognitive function of patients with stress-related depression. The governing mechanism for this phenomenon may be via rTMS effects on multiple visual-related brain regions and their functional connections, and on the somatosensory cortex and its functional connection with visual and auditory cortex, reducing the level of Cho and stabilizing the level of NAA/Cr in the left DLPFC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35513247

RESUMO

OBJECTIVE: This study aimed to explore the effect and mechanism of chondrocyte apoptosis on the chemotaxis of osteoclast precursors (OCPs) during bone destruction. DESIGN: The relationship between cartilage and bone destruction was verified with a rat temporomandibular joint osteoarthritis (TMJOA) model. The pan-caspase inhibitor Z-VAD-FMK (ZVAD) was applied to confirm the chemotactic effect of chondrocyte apoptosis on OCPs. Synthesis and release of the key chemokine CX3CL1 in apoptotic and non-apoptotic chondrocytes was assessed with IHC, IF, WB, and ELISA. The function of CX3CL1-CX3CR1 axis in the chemotaxis of OCPs was examined by CX3XR1 inhibitor AZD8797 (AZD) and si-CX3CL1. The regulatory effect of p38 MAPK on CX3CL1 release was verified by p38 inhibitor PH-797804. RESULTS: A temporal and spatial association between cartilage degradation and bone resorption was found in the TMJOA model. The caspase-dependent chondrocyte apoptosis promoted chemotaxis of OCPs, which can be restrained by ZVAD. CX3CL1 was significantly upregulated when chondrocytes underwent apoptosis, and it plays a critical role in the recruitment of OCPs, blockage of CX3CL1-CX3CR1 axis result in less bone resorption in TMJOA. P38 MAPK was activated in apoptotic chondrocytes, and had a regulatory effect on the synthesis and release of CX3CL1. After inhibition of p38 by PH-797804, the chemotactic effect of apoptotic chondrocytes on OCPs was limited. CONCLUSIONS: This study indicates that apoptosis of chondrocytes in TMJOA enhances chemotaxis of OCPs toward osteoclast precursors through upregulation of the p38-CX3CL1 axis, thereby promoting the activation of local osteoclasts.

7.
J Clin Lab Anal ; : e24475, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35535385

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most severe cancers worldwide, particularly in China. Circular RNA (circRNA) plays an essential role in GC. Hsa_circ_0000285 regulates the progression of several cancers. However, its role in GC has not been reported. This study elucidated the molecular mechanism and role of hsa_circ_0000285 in GC progression. METHODS: GC cells were transfected with silencers of hsa_circ_0000285 and fibronectin 1 (FN1), an inhibitor of miR-1278, and their negative controls (NC). Mice were injected with short hairpin (sh) RNAs targeting hsa_circ_0000285 or NC. The expression levels of hsa_circ_0000285, miR-1278, and FN1 were assessed using western blotting and reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). Several assays were used to evaluate cell proliferation, invasion, and apoptosis. Tumor burden was also analyzed. The interactions between miR-1278, hsa_circ_0000285, and FN1 were ascertained using dual-luciferase reporter assays. An RNA immunoprecipitation (RIP) assay was used to assess the enrichment of hsa_circ_0000285 and miR-1278 in GC. RESULTS: Hsa_circ_0000285 was significantly overexpressed in the GC tissues. Silencing hsa_circ_0000285 inhibited cell proliferation and invasion, promoted apoptosis, and inhibited tumor development. Hsa_circ_0000285 sponged miR-1278. Inhibition of miR-1278 in vitro reversed the effects of hsa_circ_0000285 silencing on GC progression. MiR-1278 targeted FN1, and silencing FN1 neutralized the effects of miR-1278 inhibitors on GC progression. CONCLUSIONS: The hsa_circ_0000285/miR-1278/FN1 axis regulated GC progression. In addition, it may serve as a potential therapeutic biomarker for GC.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35518349

RESUMO

OBJECTIVE: To develop a putative microRNA (miRNA) and messenger RNA (mRNA) regulatory network of Danggui Buxue decoction's (DGBXD) amelioration of idiopathic pulmonary fibrosis (IPF). METHODS: The Gene Expression Omnibus (GEO) database was used to identify differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs). Using miRNet, the predicted target genes of identified DE-miRNAs were estimated, and then the target genes of DE-miRNAs in IPF were comprehensively examined. The Enrichr database was used to conduct functional enrichment and pathway enrichment. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was employed to obtain the target genes of DGBXD as well as active compounds. A putative miRNA-mRNA regulatory network of DGBXD acting on IPF was developed by intersecting the target genes of DGBXD with the DE-miRNA target genes in IPF. A bleomycin-induced mouse model was established and used to perform histopathology as well as real-time quantitative polymerase chain reaction (qRT-PCR) analyses of some miRNA-mRNA pairs. RESULTS: Fourteen upmodulated DE-miRNAs and six downmodulated DE-miRNAs were screened. The downstream target genes of upmodulated and downmodulated DE-miRNAs were predicted. Subsequently, 1160 upmodulated DE-mRNAs and 1427 downmodulated DE-mRNAs were identified. Then, target genes of DE-miRNAs comprising 49 downmodulated and 53 upmodulated target genes were further screened to perform functional enrichment and pathway enrichment analyses. Subsequently, 196 target genes of DGBXD were obtained from TCMSP, with six downregulated target genes and six upregulated target genes of DGBXD acting on IPF being identified. A promising miRNA-mRNA regulatory network of DGBXD acting on IPF was developed in this study. Moreover, mir-493 together with its target gene Olr1 and mir-338 together with Hif1a were further validated by qRT-PCR. CONCLUSION: This study proposed detailed possible processes of miRNA-mRNA modulatory axis in IPF and constructed a prospective IPF-related miRNA-mRNA modulatory network with the aim of alleviating IPF with DGBXD.

9.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35556385

RESUMO

Vertebrates evolved mechanisms for sodium conservation and gas exchange in conjunction with migration from aquatic to terrestrial habitats. Epithelial Na+ channel (ENaC) function is critical to systems responsible for extracellular fluid homeostasis and gas exchange. ENaC is activated by cleavage at multiple specific extracellular polybasic sites, releasing inhibitory tracts from the channel's α and γ subunits. Here we investigated the evolution of ENaC regulatory mechanisms to determine which features coevolved with the marine-terrestrial transition. We consistently found both activating cleavage sites in the ENaC α and γ subunits of terrestrial vertebrates, while they appeared only sporadically in fishes. We confirmed that cleavage occurred at sites found in the γ subunit from Australian lungfish, leading to channel activation. Phylogenetic analysis and likelihood ratio tests showed that proximal and distal polybasic tracts in ENaC subunits coevolved, consistent with the dual cleavage requirement for activation. They also showed a coevolutionary dependence of tandem polybasic tracts with terrestrial status and with lungs, coincident with the ENaC activator aldosterone. Amplification of transcripts by RT-PCR in ray-finned Polypteriformes and previously in lobe-finned lungfish suggest that transcripts for ENaC subunits with cleavage sites are readily detected at important sites of ion exchange (gills and kidney), but are difficult to detect in lungs. Analysis of ancestral reconstructions strongly suggests that the polybasic tracts appeared independently in the α and γ subunits of ENaC. Similar analyses of the PY motif, required for Nedd4-2 dependent regulation, showed no coevolutionary pattern and that the PY motif first arose in an ancient ancestral ENaC subunit. Our data suggest that changes associated with adaptation to terrestrial life provided selective pressure for the development of ENaC activation by proteolytic cleavage.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35561290

RESUMO

ABSTRACT: As a critical regulatory molecule, receptor-interacting protein kinase 3 (RIPK3) can mediate the signaling pathway of programmed necrosis. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been proved as a new substrate for RIPK3-induced necroptosis. In the present study, we aimed to investigate the regulatory mechanism of RIPK3 on phenylephrine (PE)-induced cardiomyocyte hypertrophy. Cardiomyocyte hypertrophy was induced by exposure to PE (100 µM) for 48 h. Primary cardiomyocytes were pretreated with RIPK3 inhibitor GSK'872 (10 µM), and RIPK3 siRNA was used to deplete the intracellular expression of RIPK3. The indexes related to myocardial hypertrophy, cell injury, necroptosis, CaMKII activation, gene expression, oxidative stress, and mitochondrial membrane potential were measured. We found that after cardiomyocytes were stimulated by PE, the expressions of hypertrophy markers, atrial and brain natriuretic peptides (ANP and BNP), were increased, the release of lactate dehydrogenase (LDH) was increased, the level of adenosine triphosphate (ATP)was decreased, the oxidation and phosphorylation levels of CaMKII were increased, and CaMKIIδ alternative splicing was disturbed. However, both GSK'872 and depletion of RIPK3 could reduce myocardial dysfunction, inhibit CaMKII activation and necroptosis, and finally alleviate myocardial hypertrophy. In addition, the pretreatment of RIPK3 could also lessen the accumulation of reactive oxygen species (ROS) induced by PE and stabilize the membrane potential of mitochondria. These results indicated that targeted inhibition of RIPK3 could suppress the activation of CaMKII and reduce necroptosis and oxidative stress, leading to alleviated myocardial hypertrophy. Collectively, our findings provided valuable insights into the clinical treatment of hypertrophic cardiomyopathy.

11.
China CDC Wkly ; 4(17): 358-363, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35547637

RESUMO

What is already known about this topic?: In the 1980s. benzene-induced leukemia (BIL) mainly occurred in shoemaking and painting industries. Now the industry distribution of benzene-induced leukemia may have changed over time. What is added by this report?: BlL cases mainly occurred in the manufacturing industry from 2005-2019, especially in private enterprises and small/medium-sized enterprises. The industry with the largest number of new cases of BIL was the general and special equipment manufacturing. The number of leukemia cases in emerging industries such as computer/electronic product manufacturing was found to be increasing. What are the implications for public health practice?: Strengthening supervision and regulation of manufacturing, especially of small/medium-sized enterprises and emerging manufacturing industry, may be effective in reducing BIL.

12.
Front Cardiovasc Med ; 9: 847362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571197

RESUMO

Some studies have reported that the activation of Ca2+/calmodulin dependent protein kinase (CaMKII) plays a vital role in the pathogenesis of cardiovascular disease. Moreover, receptor interacting protein kinase 3 (RIPK3)-mediated necroptosis is also involved in the pathological process of various heart diseases. In the present study, we aimed to investigate the effect of RIPK3-regulated CaMKII on necroptosis in heart failure (HF) and its underlying mechanism. Wild type (WT) and RIPK3-depleted (RIPK3-/-) mice were treated with transverse arch constriction (TAC). After 6 weeks, echocardiography, myocardial injury, CaMKII activity, necroptosis, RIPK3 expression, mixed lineage kinase domain-like protein (MLKL) phosphorylation, and mitochondrial ultrastructure were measured. The results showed that TAC aggravated cardiac dysfunction, CaMKII activation, and necroptosis in WT mice. However, depletion of RIPK3 alleviated cardiac insufficiency, CaMKII activation, and necroptosis in TAC-treated mice. To verify the experimental results, WT mice were transfected with AAV-vector and AAV-RIPK3 shRNA, followed by TAC operation. The findings were consistent with the expected results. Collectively, our current data indicated that the activation of CaMKII, MLKL and necroptosis in HF mice were increased in a RIPK3-dependent manner, providing valuable insights into the pathogenesis and treatment strategy of HF.

13.
Transl Cancer Res ; 11(4): 835-847, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571636

RESUMO

Background: To investigate the function of MAPT antisense RNA 1 (MAPT-AS1) in breast cancer (BC), evaluating its potential diagnostic value for BC patients. Methods: This study involved 498 patients with BC, 222 patients with benign breast diseases, including 74 cases each of of breast fibroadenoma, breast intraductal papilloma, and ductal hyperplasia and 429 healthy controls. We collected 20 cases of BC tissues and adjacent normal tissues and blood was taken from each participant. The expression levels of MAPT-AS1 were detected using reverse transcription polymerase chain reaction (RT-PCR). According to the median serum level of MAPT-AS1, patients were divided into a high expression group and a low expression group. We established MAPT-AS1 overexpression and knockdown in human BC cell line ZR-75-1 and MDA-MB-231 to study the function on cell proliferation [using cell counting kit-8 (CCK-8) assay], migration, and invasion (using Transwell assay). Results: The expression of MAPT-AS1 was significantly up-regulated in tissues and serum of BC patients compared with controls (P<0.0001 for both). Receiver operating characteristic (ROC) curve analysis showed that MAPT-AS1 had a large area under the curve (AUC) of 0.893. The expression of MAPT-AS1 in serum was closely related to the large tumor size, grade, tumor-node-metastasis (TNM) stages, and human epidermal growth factor receptor 2 (HER-2) expression status of BC patients. Overexpression of MAPT-AS1 activated the Wnt/ß-catenin signaling pathway, promoting proliferation, migration, and invasion. Conclusions: Overexpression of MAPT-AS1 in tissues and serum is a reliable diagnostic marker for BC, and MAPT-AS1 regulates the proliferation and metastasis of BC cells by activating the Wnt/ß-catenin signaling pathway.

14.
Front Psychol ; 13: 874820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572311

RESUMO

This paper studies the impact of a recent increase in the ratio of automated machines to ordinary capital (RAMOC) on the bias of technical change in the manufacturing industry and the mechanism influencing this. Using panel data of A-share listed manufacturing companies on the Shanghai and Shenzhen stock exchanges from 2012 to 2019, combined with the Xtfrontier model and trans-log production function, we measure the index of the bias of technical change of the manufacturing industry in China. Furthermore, we adopt a fixed effects model to test the impact of an increase of investment in automated machines on the bias of technical change. We also use an intermediary effect model to examine the intermediate mechanism from the perspectives of capital and skill matching. The results show that technical change in the manufacturing industry is biased toward automated machine capital. An incremental increase in RAMOC leads to technical change in the manufacturing industry becoming biased toward automated machine capital, wherein the intermediary mechanism is the labor structure effect. Based on industrial linkage, the investment in automated machines in the upstream (downstream) manufacturing industry increases, the technical change of the downstream (upstream) manufacturing industry is biased toward automated machine capital, and the forward linkage effect is greater than the backward linkage effect. This research enhances understanding of (1) the direction and characteristics of technical change in China, (2) how to improve the output efficiency of automated machines, (3) differences in factor revenue distribution, and (4) how new growth points in the economy can be cultivated. They show that we should encourage and support investment in automated machines, vigorously promote technical change to bias toward automated machine capital, improve the skill level of the labor force, and strengthen the match between automated machines and labor.

15.
Front Immunol ; 13: 814548, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572513

RESUMO

Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory multiple myeloma (R/R MM), the severity of cytokine release syndrome (CRS) can affect patient survival and the risk factors for CRS remain an intractable issue. We enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-B-cell maturation antigen (BCMA) CAR-T cells. The results showed the overall response rate was 94% (51/54) after CAR-T cell infusion, with a 100% incidence of CRS, including 47 patients with grade 1-2 (mild) CRS and 7 patients with grade 3-5 (severe) CRS. In the mild CRS group, the median progression-free survival (PFS) was 18.2 months (95% CI, 6.5 to 30.1) and the median overall survival (OS) was not reached yet. In the severe CRS group, median PFS and median OS were 1.9 months (95% CI, 0.2 to 3.8). Further analysis demonstrated that severe CRS had a shorter median PFS and OS than mild CRS (p=0.029, p=0.020). Bone marrow tumor burden was found to be independently associated with CRS. The grade of CRS was positively correlated with six serum cytokines levels including G-CSF, IL-6, IL-8, IP-10, MIP-1a and RANTES. In conclusion, early detection and management of CRS are imperative for the prevention of life-threatening complications and improvement in the survival of patients of CAR-T cell therapy. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR-OIC-17011272.

16.
Oxid Med Cell Longev ; 2022: 4526022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557984

RESUMO

The purpose of this research was to explore the underlying biological processes causing coronavirus disease 2019- (COVID-19-) related stroke. The Gene Expression Omnibus (GEO) database was utilized to obtain four COVID-19 datasets and two stroke datasets. Thereafter, we identified key modules via weighted gene co-expression network analysis, following which COVID-19- and stroke-related crucial modules were crossed to identify the common genes of COVID-19-related stroke. The common genes were intersected with the stroke-related hub genes screened via Cytoscape software to discover the critical genes associated with COVID-19-related stroke. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common genes associated with COVID-19-related stroke, and the Reactome database was used to annotate and visualize the pathways involved in the key genes. Two COVID-19-related crucial modules and one stroke-related crucial module were identified. Subsequently, the top five genes were screened as hub genes after visualizing the genes of stroke-related critical module using Cytoscape. By intersecting the COVID-19- and stroke-related crucial modules, 28 common genes for COVID-19-related stroke were identified. ITGA2B and ITGB3 have been further identified as crucial genes of COVID-19-related stroke. Functional enrichment analysis indicated that both ITGA2B and ITGB3 were involved in integrin signaling and the response to elevated platelet cytosolic Ca2+, thus regulating platelet activation, extracellular matrix- (ECM-) receptor interaction, the PI3K-Akt signaling pathway, and hematopoietic cell lineage. Therefore, platelet activation, ECM-receptor interaction, PI3K-Akt signaling pathway, and hematopoietic cell lineage may represent the potential biological processes associated with COVID-19-related stroke, and ITGA2B and ITGB3 may be potential intervention targets for COVID-19-related stroke.

17.
Foods ; 11(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35563949

RESUMO

Asarinin, an isomer of sesamin, has attracted attention because it has stronger biological properties than sesamin. The research on the conversion of sesamin into asarinin is limited. In this study, solid acid catalysts were screened and applied to promote the conversion of sesamin into asarinin in sesame oil. The results showed that citric acid loaded on zeolite beta (CTAH) was the optimal catalyst for asarinin production among the prepared catalysts. Characterization showed that CTAH had the greatest pore volume, largest surface area and strongest acid content. Response surface methodology (RSM) was applied to optimize the reaction conditions for asarinin yield using CTAH. The optimal reaction conditions were as follows: temperature, 85 °C; time, 2.7 h; catalyst amount, 1.6%. The predicted and experimental values of asarinin yield were 50.79 and 51.80 mg/100 g, respectively. The peroxide value and color in sesame oil samples treated with CTAH were clearly improved. In short, CTAH is a solid acid catalyst with potential application in the industrial conversion of sesamin into asarinin and in the improvement of sesame oil.

18.
Nanomicro Lett ; 14(1): 124, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543758

RESUMO

Triboelectric nanogenerators (TENGs) have shown promising potential for large-scale blue energy harvesting. However, the lack of reasonable designs has largely hindered TENG from harvesting energy from both rough and tranquil seas. Herein, a fully symmetrical triboelectric nanogenerator based on an elliptical cylindrical structure (EC-TENG) is proposed for all-weather blue energy harvesting. The novel elliptical cylindrical shell provides a unique self-stability, high sensitivity to wave triggering, and most importantly, an anti-overturning capability for the EC-TENG. Moreover, benefiting from its internal symmetrical design, the EC-TENG can produce energy normally, even if it was overturned under a rude oscillation in the rough seas, which distinguishes this work from previous reported TENGs. The working mechanism and output performance are systematically studied. The as-fabricated EC-TENG is capable of lighting 400 light-emitting diodes and driving small electronics. More than that, an automatic monitoring system powered by the EC-TENG can also monitor the water level in real-time and provide an alarm if necessary. This work presents an innovative and reliable approach toward all-weather wave energy harvesting in actual marine environments.

19.
Environ Res ; 212(Pt C): 113371, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35504339

RESUMO

Involuntary smoking was a major public health problem for women in China. Previous studies mainly focused on secondhand smoke (SHS), which referred to direct exposure to smoke from burning cigarettes. Little evidence existed about the relationship between thirdhand smoke (THS), the residual tobacco smoke remaining in the environment after tobacco had been smoked, and cervical cancer. The China Kadoorie Biobank (CKB) study recruited 0.3 million female participants from 10 areas across China during 2004-2008. After an 11.2-year median follow-up, we documented 1094 cervical cancer cases. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SHS and THS with cervical cancer incidence, respectively and jointly. Overall, 60.3% reported weekly SHS exposure, and 83.2% had been exposed to THS. Daily SHS exposure and THS exposure at the enrollment were associated with elevated risks of cervical cancer incidence, with adjusted HRs (95% CI) of 1.22 (1.06,1.42) and 1.24 (1.03,1.49), respectively. The longer the exposure duration, the higher the risks (P for trend = 0.006, 0.035, respectively). Compared with those who were neither exposed to SHS nor THS, those exposed to both SHS and THS had the highest risk, with adjusted HRs (95% CI) of 1.29 (1.05,1.58). Area of residence, breastfeeding duration and heating fuel types are potential effect modifiers. Among Chinese females, both SHS and THS were associated with higher risks of cervical cancer incidence, and a dose-response relationship was found between the exposure duration and cervical cancer risk. Our findings reinforce the need for proactive strategies for tobacco control, to protect women health.

20.
Prog Neurobiol ; 214: 102284, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35533809

RESUMO

Neurons in the central nervous system (CNS) are terminally differentiated cells that gradually lose their ability to support regeneration during maturation due to changes in transcriptomic and chromatin landscape. Similar transcriptomic changes also occur during development when stem cells differentiate into different types of somatic cells. Importantly, differentiated cells can be reprogrammed back to induced pluripotent stems cells (iPSCs) via global epigenetic remodeling by combined overexpression of pluripotent reprogramming factors, including Oct4, Sox2, Klf4, c-Myc, Nanog, and/or Lin28. Moreover, recent findings showed that many proneural transcription factors were able to convert non-neural somatic cells into neurons bypassing the pluripotent stage via direct reprogramming. Interestingly, many of these factors have recently been identified as key regulators of CNS neural regeneration. Recent studies indicated that these factors could rejuvenate mature CNS neurons back to a younger state through cellular state reprogramming, thus favoring regeneration. Here we will review some recent findings regarding the roles of genetic cellular state reprogramming in regulation of neural regeneration and explore the potential underlying molecular mechanisms. Moreover, by using newly emerging techniques, such as multiomics sequencing with big data analysis and Crispr-based gene editing, we will discuss future research directions focusing on better revealing cellular state reprogramming-induced remodeling of chromatin landscape and potential translational application.

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