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1.
ACS Macro Lett ; 11(5): 636-642, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35570814

RESUMO

Biodegradable and lipid-like highly branched poly(ß-amino ester)s, HPAESA, were developed to enhance the biological functions of adipose-derived stem cells by gene transfection. Biodegradability reduces the cytotoxicity of HPAESA and enables controlled DNA release. Lipid mimicry enhances cellular uptake and endosomal escape of HPAESA/DNA polyplexes. HPAESA are able to transfect rat adipose-derived stem cells (rADSs) and human ADSCs (hADSCs) with orders of magnitude higher efficiency than commercial gene transfection reagents, with cell viability exceeding 90%. Most importantly, HPAESA can effectively transfer the nerve growth factor (NGF)-encoding plasmid to rADSCs and induce high NGF secretion, which significantly promotes neurite outgrowth of PC12 cells.

2.
Sci Total Environ ; : 155947, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35577090

RESUMO

Agricultural sector is the basic industry providing food for human and supporting the development of national economy. The agricultural green total factor productivity (AGTFP) plays a significant role in coordinating agriculture sustainable development and pollution abatement. We employ a nonseparable undesirable output modified three-stage data envelopment analysis to evaluate the AGTFP of China's 30 provinces from 2000- 2018. We construct a more comprehensive AGTFP measurement indicator system, including seven separable inputs and three non-separable inputs and one separable good output and two non-separable bad outputs. The empirical results demonstrate that it is necessary to run a stochastic frontier analysis to eliminate the influence of random error and external environment. We get a more scientific and accurate results. The real AGTFP experiences an increase trend during the sample. From the spatial perspective, there is an obvious regional difference across the country. Efficiency decomposition indicates that the source of inefficiency is mainly from two undesirable outputs. Therefore, policy implications are put forward.

3.
Cell ; 185(10): 1777-1792.e21, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35512705

RESUMO

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.

4.
Nutr J ; 21(1): 29, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562805

RESUMO

BACKGROUND AND AIMS: Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. METHODS: Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. RESULTS: There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: ß = - 0.50, P <  0.001; CC: ß = - 0.14, P = 0.087; CT: ß = - 0.20, P = 0.011; TT: ß = - 1.19, P <  0.001). Moreover, the decline in trend in genotype TT participants was stronger than in genotype CC participants (P for difference <  0.001) and genotype CT participants (P for difference <  0.001), while there was no significant difference between genotype CC and genotype CT participants (P for difference = 0.757). CONCLUSIONS: Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

5.
J Healthc Eng ; 2022: 2580419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494513

RESUMO

Lung adenocarcinoma is the most common non-small-cell lung cancer. In this paper, we aim to investigate the expression of chemokine ligand 1 (cx3cl1) and chemokine ligand 28 (CCL28) in spinal metastases of lung adenocarcinoma and their correlation with clinical features and prognosis. We analyzed the clinical data of 40 patients with lung adenocarcinoma and spinal metastases who underwent surgery in our hospital from January 2018 to January 2021 retrospectively. The expression levels of cx3cl1 and CCL28 in bone metastases were detected by immunohistochemistry, and the staining results were sorted and classified. Combined with the follow-up results and clinicopathological data, we statistically analyzed the expression of cx3cl1 and CCL28 in spinal bone metastases and their correlation with prognosis. Among the 40 patients with spinal metastasis of lung adenocarcinoma, 7 cases were strongly positive for cx3cl1, 25 cases were moderately positive, and 8 cases were weakly positive and negative. CCL28 was strongly positive in 9 cases, moderately positive in 26 cases, weakly positive and negative in 5 cases. The expression of cx3cl1 was correlated with ECOG score (P = 0.005) and visceral organ metastasis (P = 0.004), but not with age, sex, and the number of bone metastases (P > 0.05). The expression of CCL28 was correlated with ECOG score (P = 0.022) and visceral organ metastasis (P = 0.003), but not with age, sex, and the number of bone metastases (P > 0.05). The OS of patients with strong cx3cl1 positive was significantly shorter than that of patients with medium positive and weak positive (P < 0.001). The survival time was 10, 7, and 4 months, respectively. The OS of patients with strong positive CCL28 was significantly shorter than that of patients with medium positive and weak positive CCL28 (P = 0.004). The survival time was 12, 8, and 4 months, respectively. Univariate analysis showed that ECOG score (P < 0.001), chemotherapy (P = 0.032), visceral organ metastasis (P = 0.002), cx3cl1 expression (P < 0.001), and CCL28 expression (P = 0.004) were the risk factors of OS. Cox regression analysis showed that the expression of cx3cl1 was an independent risk factor for OS in patients with spinal metastasis of lung adenocarcinoma (P = 0.044). Cx3cl1 and CCL28 were highly/strongly positive in spinal metastases of lung adenocarcinoma. The level of cx3cl1 can be used as an index to judge the clinical prognosis of patients with spinal metastasis of lung adenocarcinoma, which can better reflect the prognosis of patients than CCL28.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias da Coluna Vertebral , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiocina CX3CL1 , Quimiocinas CC/metabolismo , Humanos , Ligantes , Prognóstico , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário
6.
Sci Total Environ ; : 155694, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35523343

RESUMO

Source-specific risk apportionment for soil heavy metals (HMs) is crucial for pollution mitigation and risk control in coal-mining areas. The ecological and human health risks resulting from different sources were evaluated through an integrated method that combines risk assessments with positive matrix factorization (PMF) model. Thirty soil samples were collected from a typical coal-mining city in central China and analyzed for six HMs (Cu, Ni, Pb, Cd, As, and Hg). The results indicate that surface soil in the study area suffered from moderate HMs pollution, especially pollution by Cd and Hg. Four potential sources of soil HMs were identified and quantified in the study area, including natural source (27.7%), traffic emissions (33.4%), agricultural practices (16.2%), and industrial activities (22.7%). The ecological risk of the study area was at moderate level, and the leading contributions in urban and suburban areas were from industrial activities and agricultural practices, respectively. The non-carcinogenic risks for adults and children were lower than the risk threshold, while the carcinogenic risks ranged between 1E-06 and 1E-04, suggesting that carcinogenic risks and hazards to human health should not be neglected. Traffic emissions and natural sources mainly contributed to the non-carcinogenic and carcinogenic risks, due to the strong non-carcinogenicity and carcinogenicity of As and Ni. These findings highlight the ecological and health risks linked to potential sources of soil HMs contamination and provide valuable information on the reduction of corresponding risks for local environmental managers.

7.
Methods ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35526723

RESUMO

Brief therapy for insomnia (BTI) is a short-term cognitive behavioral therapy for insomnia. At present, there is no study combining BTI with digital technology. However, in the context of the outbreak of coronavirus disease 2019 (COVID-19), patients with acute insomnia may need an online treatment which can quickly improve insomnia symptoms. Our team built a digital BTI (dBTI) platform based on the WeChat mini program. This research provides a framework design and a course design of dBTI, and evaluates the system via recruiting participants suffering from acute insomnia in pandemic. What's more, it explores patients' adherence, the efficiency of the system and their relationship. As the result demonstrates, 68% of participants have completed more than half of the course with medium to high adherence. Gender, pre-sleep arousal scale (PSAS) somatic score and insomnia severity index (ISI) score have affected participants' adherence, and higher adherence has led to better improvement in the severity of insomnia and somatic pre-sleep arousal. It is proved that the platform we built is effective, which not only offers an entry point for the study of how to set up a dBTI platform, but also provides theoretical basis for its clinical application.

8.
J Biochem Mol Toxicol ; : e23091, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543488

RESUMO

Nuclear receptor subfamily 6 group A member 1 (NR6A1) is involved in promoting the apoptotic process of vascular smooth muscle cells (VSMCs) which is a critical process involved in atherosclerosis, but the action mechanism remains to be determined. Therefore, we studied the underlying mechanisms by which NR6A1 accelerated VSMC apoptosis in atherosclerosis. An atherosclerosis model has been established in apolipoprotein E-deficient rats with a high-fat diet for 12 weeks, which was characterized by pathological aortic plaques, increased lipid deposition and collagen content in aortic tissues, and high cholesterol and triglycerides levels in the serum. NR6A1 was experimentally shown to increase at protein level rather than messenger RNA level in atherosclerotic rats. Immunofluorescence exhibited the main location of NR6A1 in the cell nucleus of rat aortic tissues. By performing ectopic expression experiments, NR6A1 was demonstrated to suppress the viability and expedite the apoptosis of VSMCs, corresponding to augmented caspase-3, caspase-8, and caspase-9 activities. It was further unraveled that NR6A1 could activate receptor-interacting serine/threonine-protein kinase 3 (RIPK3) by inducing its phosphorylation. Conversely, RIPK3 inhibitor GSK872 undermined the proapoptotic effect of NR6A1 on VSMCs. The co-immunoprecipitation assay identified that linear ubiquitin chain assembly complex (LUBAC) can be pulled down by NR6A1. Furthermore. LUBAC inhibited the expression of NR6A1 by promoting its linear ubiquitination, thereby dephosphorylating RIPK3 and consequently inhibiting the VSMC apoptosis. Overall, LUBAC-induced linear ubiquitination of NR6A1 can potentially arrest the apoptosis of VSMCs in atherosclerosis by downregulating RIPK3 and attenuating caspase activity. This finding suggests promising athero-protective targets by limiting VSMC apoptosis.

9.
Front Neurol ; 13: 830705, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547375

RESUMO

Background: This study aimed to investigate the association between the hyperdense basilar artery sign (HBAS) on non-enhanced computed tomography (CT) and clinical outcomes in patients with acute basilar artery occlusion (BAO) who underwent endovascular treatment (EVT). Methods: Eligible patients who underwent EVT due to acute BAO between January 2014 and May 2019 were divided into two groups based on HBAS. HBAS was assessed by two neuroradiologists using five grades on nonenhanced CT. The primary outcome was a favorable functional outcome (defined as a modified Rankin Scale [mRS] of 0-3) at 90 days. Secondary outcomes included successful recanalization and mortality within 90 days. Results: Among 829 patients with BAO as assessed with CT angiography, magnetic resonance angiography, or digital subtraction angiography, 643 patients were treated with EVT. Of these, 51.32% (330/643) had HBAS. Patients with HBAS were older and had more severe neurological deficits and a higher frequency of atrial fibrillation than those without HBAS. There was no significant difference in favorable outcome (adjusted odds ratio [aOR]: 1.354, 95% confidence interval [CI]: 0.906-2.024; p = 0.14), successful recanalization (aOR: 0.926, 95% CI: 0.616--1.393; p = 0.71), and mortality (aOR: 1.193, 95% CI: 0.839-1.695; p = 0.33) between patients with or without HBAS. Subgroup analysis showed that the HBAS predicted a favorable outcome in patients aged <60 years (aOR: 2.574, 95% CI: 1.234-5.368; p = 0.01) and patients with vertebral artery-V4 segment occlusion (aOR: 3.738, 95% CI: 1.212-11.530; p = 0.02). In patients with HBAS, the baseline National Institutes of Health Stroke Scale (NIHSS) score, posterior circulation-Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS), and stent retriever were associated with successful recanalization. Conclusions: Our study did not find a significant association between HBAS and favorable outcomes and successful recanalization in patients with BAO who underwent EVT. Moreover, large prospective studies are warranted to further investigate this relationship.

10.
J Immunol Res ; 2022: 1786395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450395

RESUMO

Adoptive allogeneic natural killer (NK) cell therapy has shown promise in treating castration-resistant prostate cancer (CRPC), which is the terminal stage of prostate cancer (PCa) and incurable. Thus, we employed an efficient manufacturing method for the large-scale ex vivo expansion of high-quality NK cells from peripheral blood of healthy donors. In the present study, we evaluated the in vitro cytotoxicity of NK cells against human PCa cell lines and in vivo antitumor activity in a preclinical mouse model of CRPC. CCK-8 results demonstrated that the NK cells exerted potent cytotoxicity against all PCa cell lines in vitro. The NK cells were activated when cocultured with PCa C4-2 cells, evidenced by upregulation of the degranulation marker CD107a and secretion of cytokines (TNF-α and IFN-γ). In a xenograft mouse model of CRPC, the caliper, CT, and ultrasonography examination results showed that the size of tumors treated with NK cells was significantly smaller than that in the control group. Moreover, ultrasonography examination also indicated that the NK cell treatment evidently reduced the blood supply of the tumors and HE staining results demonstrated that the NK treatment increased the proportion of necrosis in the tumor specimen compared to PBS treatment. Meanwhile, the NK cell treatment did not cause significant serum IL-6 elevation. Therefore, our study suggested that the expanded NK cells exhibited significant cytotoxicity against PCa cell lines in vitro and excellent therapeutic efficacy against CRPC in a xenograft mouse model, which was of great value for the clinical treatment of CRPC.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias de Próstata Resistentes à Castração , Animais , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Humanos , Células Matadoras Naturais/metabolismo , Masculino , Camundongos , Neoplasias de Próstata Resistentes à Castração/terapia
11.
Mol Cancer ; 21(1): 106, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477569

RESUMO

BACKGROUND: Lung cancer is a kind of malignancy with high morbidity and mortality worldwide. Paclitaxel (PTX) is the main treatment for non-small cell lung cancer (NSCLC), and resistance to PTX seriously affects the survival of patients. However, the underlying mechanism and potential reversing strategy need to be further explored. METHODS: We identified ALDH2 as a PTX resistance-related gene using gene microarray analysis. Subsequently, a series of functional analysis in cell lines, patient samples and xenograft models were performed to explore the functional role, clinical significance and the aberrant regulation mechanism of ALDH2 in PTX resistance of NSCLC. Furthermore, the pharmacological agents targeting ALDH2 and epigenetic enzyme were used to investigate the diverse reversing strategy against PTX resistance. RESULTS: Upregulation of ALDH2 expression is highly associated with resistance to PTX using in vitro and in vivo analyses of NSCLC cells along with clinicopathological analyses of NSCLC patients. ALDH2-overexpressing NSCLC cells exhibited significantly reduced PTX sensitivity and increased biological characteristics of malignancy in vitro and tumor growth and metastasis in vivo. EHMT2 (euchromatic histone lysine methyltransferase 2) inhibition and NFYA (nuclear transcription factor Y subunit alpha) overexpression had a cooperative effect on the regulation of ALDH2. Mechanistically, ALDH2 overexpression activated the RAS/RAF oncogenic pathway. NSCLC/PTX cells re-acquired sensitivity to PTX in vivo and in vitro when ALDH2 was inhibited by pharmacological agents, including the ALDH2 inhibitors Daidzin (DZN)/Disulfiram (DSF) and JIB04, which reverses the effect of EHMT2. CONCLUSION: Our findings suggest that ALDH2 status can help predict patient response to PTX therapy and ALDH2 inhibition may be a promising strategy to overcome PTX resistance in the clinic.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Aldeído-Desidrogenase Mitocondrial , Fator de Ligação a CCAAT/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Antígenos de Histocompatibilidade , Histona-Lisina N-Metiltransferase , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fatores de Transcrição
12.
Front Plant Sci ; 13: 824585, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463421

RESUMO

Ceramide synthases (CSs) produce ceramides from long-chain bases (LCBs). However, how CSs regulate immunity and cell death in Arabidopsis thaliana remains unclear. Here, we decipher the roles of two classes of CS, CSI (LAG1 HOMOLOG 2, LOH2) and CSII (LOH1/3), in these processes. The loh1-2 and loh1-1 loh3-1 mutants were resistant to the bacterial pathogen Pseudomonas syringae pv maculicola (Psm) DG3 and exhibited programmed cell death (PCD), along with increased LCBs and ceramides, at later stages. In loh1-2, the Psm resistance, PCD, and sphingolipid accumulation were mostly suppressed by inactivation of the lipase-like proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) and PHYTOALEXIN DEFICIENT 4 (PAD4), and partly suppressed by loss of SALICYLIC ACID INDUCTION DEFICIENT 2 (SID2). The LOH1 inhibitor fumonisin B1 (FB1) triggered EDS1/PAD4-independent LCB accumulation, and EDS1/PAD4-dependent cell death, resistance to Psm, and C16 Cer accumulation. Loss of LOH2 enhances FB1-, and sphinganine-induced PCD, indicating that CSI negatively regulates the signaling triggered by CSII inhibition. Like Cer, LCBs mediate cell death and immunity signaling, partly through the EDS1/PAD4 pathway. Our results show that the two classes of ceramide synthases differentially regulate EDS1/PAD4-dependent PCD and immunity via subtle control of LCBs and Cers in Arabidopsis.

13.
Front Vet Sci ; 9: 841762, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464364

RESUMO

The beneficial function of fermented feed in livestock industry has been widely investigated. However, little is known about the effects of fermented feed on different weaned-day piglets. This study aimed to investigate the effects of fermented diet on the growth performance, intestinal function, and microbiota of piglets weaned at the age of 21 and 28 days. The results found that weaning on day 21 significantly increased (p < 0.05) average daily gain (ADG), and average daily feed intake (ADFI) (calculated based on wet weight and dry matter), while reduced (p < 0.05) feed to gain ratio (F:G), the activities of trypsin and lipase of jejunum and the villus height of ileum, compared with 28-days weaning. The protein levels of Occludin, Claudin-1, and ZO-1 of ileum in the groups weaning on day 21 were less (p < 0.05) than the groups weaning on day 28. Moreover, dietary supplementation with fermented diet upregulated (p < 0.05) the Occludin, Claudin-1, and ZO-1 proteins of ileum, compared with the groups treated with control diet both weaning on day 21 and 28. In addition, dietary supplementation with fermented diet decreased (p < 0.05) the relative abundance of Clostridia (class) and increased (p < 0.05) the Bacteroidia (class) level of cecal microbiota, compared with the groups treated with control diet both weaning on day 21 and 28. However, supplementation with fermented diet did not affect the concentrations of short-chain fatty acids in the cecum (p > 0.05). Therefore, our data suggest that the feed digestibility is improved in piglets weaned at 21 days, but intestinal barrier function is weaker than in piglets weaned at 28 days. However, compared with feeding control diet, supplementation with fermented diet both improved the feed conversion and intestinal barrier function of weaned piglets by modulating intestinal microbiota.

14.
Antioxidants (Basel) ; 11(4)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35453342

RESUMO

Mastitis (inflammation of the mammary gland) commonly occurs in dairy cattle during the periparturient period (transition period), in which dairy cattle experience physiological and hormonal changes and severe negative energy balance, followed by oxidative stress. To maintain successful lactation and combat negative energy balance (NEB), excessive fat mobilization occurs, leading to overproduction of reactive oxygen species (ROS). Excessive fat mobilization also increases the concentrations of nonesterified fatty acids (NEFA) and ß-hydroxybutyric acid (BHB) during the periparturient period. In addition, the excessive utilization of oxygen by cellular respiration in the mammary causes abnormal production of oxidative stress (OS). OS impairs the immunity and anti-inflammatory efficiency of periparturient dairy cattle, increasing their susceptibility to mastitis. To alleviate oxidative stress and subsequent mastitis, antioxidants are supplemented to dairy cattle from an external source. Extensive studies have been conducted on the supplementation of selenium (Se) and vitamins E and B9 to mitigate mastitis during the transition period in dairy cattle. Altogether, in the current review, we discuss the research development on bovine mastitis and its major causes, with special emphasis on oxidative stress during the transition period. Moreover, we discuss the antioxidant, immunoregulatory, and anti-inflammatory properties of Se and vitamins E and B9 and their role in the control of bovine mastitis in periparturient dairy cattle.

15.
Front Cardiovasc Med ; 9: 814873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433861

RESUMO

Objective: Jailed balloon technique (JBT) is an active side branch (SB) protection strategy and is considered to be superior to the jailed wire technique (JWT) in reducing SB occlusion. However, no randomized trials have proved that. We aim to investigate whether JBT could decrease the SB occlusion rate. Methods: Conventional versus Intentional straTegy in patients with high Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion (CIT-RESOLVE) (NCT02644434, registered on December 31, 2015) (https://clinicaltrials.gov) is a randomized trial that assessed the effects of different strategies on SB occlusion rate in patients with a high risk of SB occlusion. The present subgroup analysis enrolled bifurcation lesions (2 mm ≤ reference vessel diameter of SB < 2.5 mm) with Visual estimation for Risk prEdiction of Side branch OccLusion in coronary bifurcation intervention (V-RESOLVE) score ≥ 12 points. The primary endpoint is SB occlusion. One-year clinical events were compared. Results: A total of 284 subjects at 16 sites were randomly assigned to the JBT group (n = 143) or the JWT group (n = 141). The rate of SB occlusion (9.1 vs. 19.9%, p = 0.02) and periprocedural myocardial infarction (defined by WHO, 7 vs. 14.9%, p = 0.03) is significantly lower in the JBT group than in the JWT group. The JBT and JWT groups showed no significant differences in cardiac death (0.7 vs. 0.7%, p = 1), myocardial infarction (MI, 6.3 vs. 7.1%, p = 0.79), target lesion revascularization (TLR, 1.4 vs. 2.1%, p = 0.68), and major cardiac adverse events (MACE, a composite of all-cause death, MI, or TLR, 8.4 vs. 10.6%, p = 0.52) during a 1-year follow-up. Conclusion: In patients with a high risk of SB occlusion (V-RESOLVE score ≥ 12 points), JBT is superior to JWT in reducing SB occlusion. However, no significant differences were detected in 1-year MACE.

16.
17.
ACS Appl Mater Interfaces ; 14(16): 18353-18359, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35417137

RESUMO

Li-rich layer-structured oxides are considered promising cathode materials for their specific capacities above 250 mAh·g-1. However, the drawbacks such as poor rate performance, fast capacity fading, and the continuous transition metal (TM) migration into the Li layer hinder their commercial applications. To address these issues, surface doping of Ti and Zr was conducted to the Li- and Mn-rich layered oxide (LMR), Li1.2Mn0.54Ni0.13Co0.13O2. The drop of the average discharge potentials of the Ti- and Zr-doped LMR was reduced by 593 and 346 mV in 100 cycles, respectively. With aberration-corrected scanning transmission electron microscopy and electron energy loss spectroscopy, we clarified that Ti4+ and Zr4+ ions are located near the surface of the material, anchor the surface oxygen, and stabilize the LMR structure. The difference in the strengths of the Ti-O and Zr-O bonds and the doping-resultant electronic structures were determined with density functional theory (DFT) calculations and soft X-ray absorption spectroscopy (SXAS), responsible for the electrochemical performance of surface-doped materials. These findings verify our modification strategies to enhance the cycling performances of the promising LMR cathode materials.

18.
IEEE Trans Cybern ; PP2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35476563

RESUMO

In this article, we shall investigate the event-triggered communication control problem for strict-feedback nonlinear systems with measurement outputs. First, two event-triggered communication schemes are designed. Based on both event-triggered schemes, the measurement output and control input signals are only transmitted at triggering time instants, which saves communication costs from the sensor to the controller and from the controller to the actuator. Meanwhile, Zeno behavior can be excluded under the proposed triggering schemes. Second, since the full-state information is not available to the controller, by developing an observer, the system state is estimated and a controller based on estimated state information is designed. Due to the irregular sampling of information communication and state estimation error affects each other, the parameters of the state observer, the controller, and the event-triggering mechanism should be jointly designed. It is proved that the closed-loop system state converges to the origin. Finally, a simulation example verifies the validity of the obtained theoretical result.

19.
Sci Transl Med ; 14(639): eabh2557, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35385340

RESUMO

Diabetic neuropathic pain (DNP) is a common and devastating complication in patients with diabetes. The mechanisms mediating DNP are not completely elucidated, and effective treatments are lacking. A-fiber sensory neurons have been shown to mediate the development of mechanical allodynia in neuropathic pain, yet the molecular basis underlying the contribution of A-fiber neurons is still unclear. Here, we report that the orphan G protein-coupled receptor 177 (GPR177) in A-fiber neurons drives DNP via WNT5a-mediated activation of transient receptor potential vanilloid receptor-1 (TRPV1) ion channel. GPR177 is mainly expressed in large-diameter A-fiber dorsal root ganglion (DRG) neurons and required for the development of DNP in mice. Mechanistically, we found that GPR177 mediated the secretion of WNT5a from A-fiber DRG neurons into cerebrospinal fluid (CSF), which was necessary for the maintenance of DNP. Extracellular perfusion of WNT5a induced rapid currents in both TRPV1-expressing heterologous cells and nociceptive DRG neurons. Computer simulations revealed that WNT5a has the potential to bind the residues at the extracellular S5-S6 loop of TRPV1. Using a peptide able to disrupt the predicted WNT5a/TRPV1 interaction suppressed DNP- and WNT5a-induced neuropathic pain symptoms in rodents. We confirmed GPR177/WNT5A coexpression in human DRG neurons and WNT5A secretion in CSF from patients with DNP. Thus, our results reveal a role for WNT5a as an endogenous and potent TRPV1 agonist, and the GPR177-WNT5a-TRPV1 axis as a driver of DNP pathogenesis in rodents. Our findings identified a potential analgesic target that might relieve neuropathic pain in patients with diabetes.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Peptídeos e Proteínas de Sinalização Intracelular , Neuralgia , Receptores Acoplados a Proteínas G , Canais de Cátion TRPV , Proteína Wnt-5a , Animais , Diabetes Mellitus/metabolismo , Neuropatias Diabéticas/metabolismo , Gânglios Espinais/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Neuralgia/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPV/metabolismo , Proteína Wnt-5a/metabolismo
20.
Materials (Basel) ; 15(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35407831

RESUMO

An austenite-ferrite duplex low-density steel (Fe-12Mn-7Al-0.2C-0.6Si, wt%) was designed and fabricated by cold rolling and annealing at different temperatures. The tensile properties, microstructure evolution, deformation mechanism and stacking fault energy (SFE) of the steel were systemically investigated at ambient temperature. Results show two phases of fine equiaxed austenite and coarse band-like δ-ferrite in the microstructure of the steel. With increasing annealing temperature, the yield and tensile strengths decrease while the total elongation increases. At initial strains, the deformation is mainly concentrated in the fine austenite and grain boundaries of the coarse δ-ferrite, and the interior of the coarse δ-ferrite gradually deforms with further increase in the strain to 0.3. No twinning-induced plasticity (TWIP) or transformation-induced plasticity (TRIP) occurred during the tensile deformation. Considering element segregation and two-phase proportion, the chemical composition of austenite was measured more precisely. The SFE of the austenite is 39.7 mJ/m2, and the critical stress required to produce deformation twins is significantly higher than the maximum flow stress of the steel.

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