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Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss of function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending on the specific functionalized EVs and the appropriate engineering strategy. In this study, we demonstrated the design of a drug delivery system of peptide CAQK-modified, siRNA-loaded EVs (C-EVs-siRNA) for SCI-targeted therapy. The peptide CAQK was anchored through a chemical modification to the membranes of EVs isolated from induced neural stem cells (iNSCs). CCL2-siRNA was then loaded into the EVs through electroporation. The modified EVs still maintained the basic properties of EVs and showed favorable targeting and therapeutic effects

The article examines the films of Chinese cinema of the 20th — early 21st centuries, which reflect the main ethical principles of Confucianism. It is noted that in contrast to the processes of commercialization of cinematography, when, first of all, emphasis is placed on the vivid visualization of the film, many outstanding Chinese directors pay attention to ethical principles in the life of society and an individual, relying on the teachings of Confucius, which continue to play an important role in spiritual life of China. The films "Goddess" (1934), "Spring Waters Flow to the East" (1947), "Hero" (2002), "The Horn is calling" (2007) were selected for analysis, which allow us to explore the ethics of Confucianism presented in them in historical discourse. The behavior models of the main characters, which were formed under the influence of Confucianism and are characteristic of Chinese society, reproduced in the films are considered and analyzed. It is noted that although the commercialization of films is taking place in Chinese cinema under the influence of globalization processes, there is a tendency to preserve the ethical principles of Confucianism and embody them in artistic works of cinema.

Catalytic conversion of biomass derivative glucose to high-purity HMF over modified MCM-41 with multiple acid sites in biphasic system.

The idiopathic inflammatory myopathies (IIMs) are a group of connective tissue diseases that afect multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the most common and heterogeneous complication of IIMs, with its degree ranging from mild to fatal. Thus, it is critical to identify clinical features and validated biomarkers for predicting disease progression and prognosis, which could be beneficial for therapy adjustment. In this review, we discuss predictors for rapid progression of IIM-ILD and propose guidance for disease monitoring and implications of therapy. Systematic screening of myositis-specific antibodies, measuring serum biomarker levels, pulmonary function tests, and chest high-resolution computer tomography will be beneficial for the evaluation of disease progression and prognosis.

The rapid development of big data technology has attracted a variety of sectors, including tertiary education. The purpose of this paper is to construct a precision teaching mode based on big data technology in order to improve teaching quality and further promote education and teaching reform. The proposed mode, based on the theory of precision teaching in colleges and universities as well as the intrinsic properties of big data teaching activities, describes five procedures for analyzing learning situations, determining teaching goals, preparing teachers, and evaluating teachers. When the big data-based precision teaching mode is applied to the “Python Language Programming” course, the results show that students are more satisfied with the design of the teaching and more efficient in learning. It is believed that this mode will significantly improve students' academic performance and their ability to work independently and collaboratively as a result of more frequently online and offline interactions between teachers and students.

The B-cell lymphoma 2 (BCL-2) protein family plays a pivotal role in regulating the apoptosis process. BCL-2, as an antiapoptotic protein in this family, mediates apoptosis resistance and is an ideal target for cell death strategies in cancer therapy. Traditional treatment modalities target BCL-2 by occupying the hydrophobic pocket formed by BCL-2 homology (BH) domains 1-3, while in recent years, the BH4 domain of BCL-2 has also been considered an attractive novel target. Herein, we describe the discovery and identification of DC-B01, a novel BCL-2 inhibitor targeting the BH4 domain, through virtual screening combined with biophysical and biochemical methods. Our results from surface plasmon resonance and cellular thermal shift assay confirmed that the BH4 domain is responsible for the interaction between BCL-2 and DC-B01. As evidenced by further cell-based experiments, DC-B01 induced cell killing in a BCL-2-dependent manner and triggered apoptosis via the mitochondria-mediated pathway. DC-B01 disrupted the BCL-2/c-Myc interaction and consequently suppressed the transcriptional activity of c-Myc. Moreover, DC-B01 inhibited tumor growth in vivo in a BCL‑2‑dependent manner. Collectively, these results indicate that DC-B01 is a promising BCL-2 BH4 domain inhibitor with the potential for further development.

The low carbon-to-nitrogen (C/N) ratio in wastewater will inhibit pollutant removal, and more seriously, it will cause an increment of nitrous oxide (N2O) emissions of constructed wetlands (CWs). Raising the C/N ratio of wastewater is an effective way to solve this problem, while it may cause secondary pollution and is costly. Assembling plant diversity promotes N removal, while the effects of plant diversity and increasing C/N ratio on global warming potential (GWP) combined by N2O and methane (CH4) is lack of comparison. In this study, 108 CW microcosms were established to explore the effects of increasing the C/N ratio from 1 to 5 and assembling plant diversity on N removal and GHG emissions. Results showed that when the C/N ratio was 1, (1) increasing species richness reduced N2O and CH4 emissions then reduced the GWP by 70%; (2) the presence of Arundo donax in microcosms reduced GWP by 72%; (3) an A. donax × Tradescantia fluminensis × Reineckia carnea mixture resulted in a high N removal and decreased the GWP per g N removal by 92% with a cost increment of 0.05 USD per m3 wastewater treated; and (4) as the C/N ratio increasing to 5, the GWP per g N removal of monocultures was reduced by 96%, but the cost increased by at least 0.29 USD per m3 wastewater treated. In summary, configuring plant diversity in CWs is an efficient, clean and cost-effective measure to treat wastewater with a low C/N ratio.

Eight cadavers were included in this anatomical study.This study aimed to confirm the anatomical feasibility of extradural transfer of the contralateral T11 ventral root (VR) to the ipsilateral L2 level and the contralateral L1 VR to the ipsilateral L3 level to restore lower limb function in cases of paraplegia.Motor dysfunction due to hemiplegia significantly affects the daily life of patients. To date, unlike in cases of upper limb dysfunction, there are few studies on the surgical management of lower limb movement dysfunction.Eight cadavers were included in this study to confirm the feasibility of the nerve transfer. After separating the VR and dorsal root at each level, the VRs at the T11 and L1 levels were anastomosed with the VRs of L2 and L3, respectively. The length of the VRs of donor roots and the distance between the donor and recipient nerves were measured. HE staining was performed to verify the number of axons and the cross-sectional area of the VRs. Lumbar x-rays of 60 healthy adults were used to measure the distance between the donor and recipient nerves.After exposing the bilateral extradural each root, the VRs could be easily isolated from the whole root. The distance between the VRs of T11 and L2, L1, and L3 was significantly longer than the length of the donor nerve. Therefore, the sural nerve was used for grafting. The measurements performed on the lumbar x-rays of the 60 healthy adults confirmed the results. The number of axons and cross-sectional area of the VRs were measured.Our study confirmed the anatomical feasibility of transferring the VRs of T11 to L2 and that of L1 to L3 to restore lower limb function in cases of hemiplegia.5.

Background: Acute myeloid leukaemia (AML) with t (8;21) or inv (16), called core binding factor (CBF) AML, has a favourable prognosis. However, some CBF-AML patients have persistent measurable residual disease (MRD) and are more likely to relapse after standard chemotherapy treatment. The CAG regimen, composed of cytarabine, aclarubicin and granulocyte colony-stimulating factor, has been proven to be effective and safe in treating refractory AML patients. Method: We performed a retrospective study to evaluate the efficacy of the CAG regimen to eliminate MRD detected by RUNX1::RUNX1T1 and CBFβ::MYH11 transcript levels by quantitative polymerase chain reaction (Q-PCR) among 23 patients. Molecular response was defined as the ratio of fusion transcript after treatment to that before treatment greater than or equal to 0.5. Result: The molecular response rate and median decrease ratio of fusion transcripts at themolecular level of the CAG regimen were 52.5% and 0.53, respectively. Among the 15 patients who had a poor molecular response to the high/intermediate-dose cytarabine regimen, the median decrease ratios of transcripts at the molecular level of high/intermediate-dose cytarabine and CAG were 1.55 and 0.53 (P=0.028), respectively, and 6 of 15 patients achieved amolecular response to CAG (40%). The median disease-free survival was 18 months, and the overall survival rate at three years among all patients was 72.7%±10.7%. The common treatment-related adverse events were nausea (100%), thrombocytopenia (39%) and neutropenia (37.5%). Conclusion: The CAG regimen may have activity in CBF-AML patients and could provide a new option for patients who have a poor molecular response to high/intermediate-dose cytarabine.

Background There are few studies that focus on the impact of online physical education teaching on college students during the coronavirus disease 2019 (COVID-19) pandemic. This research focuses on the impact of online physical education among medical school students in China by comparing physical fitness test results for three consecutive years from 2019 to 2021. Method This study is a longitudinal survey. The subjects of the experiments were students enrolled in a medical school who completed a physical fitness test for three consecutive years from 2019 to 2021. The student subjects were divided into two groups, namely, male and female. The test indices included body mass index (BMI), vital capacity (VC), 50-metre run, sit-and-reach, standing long jump, pull-up (male), 1000-metre run (male), sit-ups (female) and 800-metre run (female). Repeated measures ANOVA method was used in physical fitness test indices at three consecutive time points ranging from 2019 to 2021. The Greenhouse-Geisser correction was applied when Mauchly’s hypothesis test did not meet the assumption of sphericity, and the Bonferroni method was used for pairwise comparisons. Results A total of 3360 students (1490 males and 1870 females) completed physical fitness tests in three consecutive years from 2019 to 2021. The proportion of overweight and obesity in male students was significantly higher than that in female students (28.0% vs. 12.7%). For all subjects, in 2020, the BMI and VC indexes improved, while the 800-/1000-metre running indexes declined. In 2021, all indexes except sit-and-reach increased. Conclusion The pairwise comparisons of physical fitness test results from 2019 to 2021 show that online physical education is effective in improving all items except long-distance running. Future research needs to involve a larger and geographically more dispersed sample to further analyse the effectiveness of online physical education.

Purpose We aimed to investigate the predictive validity of monocyte to high-density lipoprotein cholesterol ratio (MHR) for coronary artery lesions (CALs) and intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Methods MHR values of a total of 207 KD patients were calculated and analyzed with regard to their clinical characteristics and outcomes. We compared the differences in clinical data and laboratory parameters between CAL + group and CAL- group as well as between IVIG-resistant group and IVIG-responsive group. Spearman correlation analysis was applied to evaluate the correlation between C-reactive protein (CRP) and MHR. Multivariate logistic regression was used to identify risk factors of CALs and IVIG resistance. Receiver operating characteristic (ROC) curve analysis was chosen to determine the optimal cutoff value of MHR and its validity in predicting CALs and IVIG resistance. Results The MHR level was significantly higher in CAL + group, with cut-off value of 1.30 g/L, yielding sensitivity of 0.753 and specificity of 0.805, as well as in IVIG-resistant group, with cut-off value of 1.03 g/L, yielding sensitivity of 0.97 and specificity of 0.485. Multivariate logistic regression showed that MHR was an independent risk factor for CALs but not for IVIG resistance. According to the Spearman correlation analysis, CRP was positively correlated with the MHR. Conclusions As a practical, cost-effective inflammatory biomarker, MHR has a significantly predictive value in KD children complicated with CALs and IVIG-resistance. Paying more attention to the changes of MHR in KD children may contribute to better understanding of KD development and prognosis in clinical practice.

Background The world faces severe challenges from migraine and tension-type headache (TTH), which cause grave disability to patients and place a heavy burden on their caregivers. However, headaches in specific individual regions have rarely been investigated. Therefore, we aimed to fully analyse and describe the current status and changing trends in migraine and TTH in non-high-income East and Southeast Asia to provide more detailed real-world information for policy-making. Methods The migraine and TTH data used for analysis were all extracted from the Global Burden of Disease (GBD) database. We adopted three major indicators of disease burden, including prevalence, incidence, and years lived with disability (YLD), and two major metrics, including the absolute number and the age-standardized rate, in our present study for further evaluation by age and sex. The results are presented in the form of mean values and 95% uncertainty intervals (UIs). In addition, the differences between non-high-income East and Southeast Asia and other regions, as well as the potential associations between headache burden and socioeconomic background, were explored. Results In 2019, approximately 195,702,169 migraine patients and 291,924,564 TTH patients lived in non-high-income East Asia, and 113,401,792 migraine patients and 179,938,449 TTH patients lived in non-high-income Southeast Asia. In terms of specific countries and regions, the highest age-standardized YLD rate (ASYR) of migraine was in Thailand [645 (95% UI: 64 to 1,554)]. The highest ASYR of TTH was in Indonesia [54 (95% UI: 15 to 197)]. Furthermore, people between the ages of 40 and 44, especially females, were identified as the main population that suffered from migraine and TTH. Unfortunately, we did not observe a significant association between headache burden and socioeconomic background. Conclusions To date, the threats from migraine and TTH in non-high-income East and Southeast Asia are still serious and ongoing, leading to prominently negative impacts on the daily life and work of local residents. Therefore, full attention and sound guidelines are urgently needed to obtain greater advantages in fighting against the burden of headache disorders in the future.

In order to make the drug specifically aggregate at the tumor site, we had developed a targeted drug delivery system based on pH responsive mesoporous silica nanoparticles. Mesoporous silica nanoparticles (MSN-COOH) were prepared and doxorubicin (DOX) was loaded into the pores of MSN-COOH, and then polyethyleneimine (PEI) and anisamide (AA) were modified on the surface of mesoporous silica, named DOX@MSN-PEI-AA(DMPA). DMPA specifically entered tumor cells through AA-mediated receptor endocytosis; PEI dissociated from the surface of the MSN in the acidic environment of cellular lysosomes/endosomes due to protonation of PEI, resulting in steady release of the encapsulated DOX from the pores of MSN in the cytoplasm of the target cells.

Background: There are few studies on the impact of online physical education that have been conducted with college students during the coronavirus disease 2019 (COVID-19) pandemic. This research focuses on the impact of online physical education among medical school students in China by comparing physical fitness test results for three consecutive years from 2019 to 2021. Method: The subjects of the experiments were students enrolled in a medical school who completed a physical fitness test for three consecutive years from 2019 to 2021. The test items included body mass index (BMI), vital capacity (VC), 50-metre run, sit and reach, standing long jump, pull-ups (male), 1000-metre run (male), sit-ups (female) and 800-metre run (female). Noting that students participated in online physical education in 2020, this paper discusses the impact of online physical education on the physical fitness of college students based on a comparative analysis of physical fitness test results from 2019, 2020 and 2021. Results: The weight index of male students shows a downwards trend from 2019 to 2021. The proportion of overweight and obesity in male students was significantly higher than that in female students (27.1% vs. 11.7%). For all subjects, in 2020, the BMI and VC indexes improved, while the 800/1000-metre running indexes declined. In 2021, all indexes except sit-and-reach increased. Conclusion: The pairwise comparisons of physical fitness test results from 2019 to 2021 show that online physical education is effective in improving all items except long-distance running. Future research needs to involve a larger and geographically more dispersed sample to further analyse the effectiveness of online physical education.

Surface-enhanced Raman scattering (SERS) has been a useful sensing technique, in which inelastic light scattering can be significantly enhanced by absorbing molecules onto rough metal surfaces or nanoparticles. Although many methods have been developed to prepare SERS substrates, it is still highly desirable and challenging to design SERS substrates, especially with highly ordered and controlled three-dimensional (3D) structures. In this work, we develop novel SERS substrates with regular volcano-shaped polymer structures using the versatile solvent on-film annealing method. Polystyrene (PS) nanospheres are first synthesized by surfactant-free emulsion polymerization and assembled on poly(methyl methacrylate) (PMMA) films. After annealing in acetic acid vapors, PMMA chains are selectively swollen and wet the surfaces of the PS nanospheres. By selectively removing the PS nanospheres using cyclohexane, volcano-shaped PMMA films can be obtained. Compared with flat PMMA films with water contact angles of ∼74°, volcano-shaped PMMA films exhibit higher water contact angles of ∼110° due to the sharp features and rough surfaces. The volcano-shaped PMMA films are then coated with gold nanoparticles (AuNPs) as SERS substrates. Using rhodamine 6G as the probe molecules, the SERS results show that the Raman signals of the volcano-shaped PMMA/AuNP hybrid substrates are much higher than those of the pristine PMMA films and PMMA films with AuNPs. For the volcano-shaped PMMA/AuNP hybrid substrates using 400 nm PS nanospheres, a high enhancement factor (EF) value of ∼1.12 × 10

A green and inexpensive natural deep eutectic solvent (NADES) was screened and integrated with an ultrasonic technique for extracting chlorogenic acid (CGA) from artemisiae scopariae herba. Response surface methodology was employed to investigate significant factors and optimize their influence. Proline–malic acid exhibited an excellent extraction capacity with a yield of 28.23 mg/g under the optimal conditions of water content of 15% (wt), solid–liquid ratio of 1.0/10 (g/mL), ultrasonic power of 300 W, and extraction time of 25 min. Simultaneously, the stability and antioxidant activity analysis exhibited a better performance of CGA in NADES than that in water and ethanol. The hydrogen-bonding interaction between CGA and natural deep eutectic molecules enhanced the stability and meanwhile protected the antioxidant activity of CGA.

Background Overweight and obesity rates have increased rapidly in Chinese school-age children, and previous studies have indicated that poor dietary literacy can lead to unhealthy eating behaviours. However, few studies have investigated the association between the dietary literacy of daily diet providers and the eating behaviours and nutritional status of school-age children raised by the providers. Thus, we aimed to explore this association. Methods We collected data on the eating behaviours and nutritional status of children in two primary schools in Anhui Province, as well as the dietary literacy of their daily diet providers. T-tests, one-way ANOVA, chi-square tests, and multiple linear regression were used to analyse the association. Results We found significant differences in the scores on the Questionnaire of Children's Daily Diet Providers' Dietary Literacy (QCDDPDL) by region, relationship with the child, age, and educational level of the daily diet provider (all p p p = .006). Conclusions Our study showed that the dietary literacy of diet providers may influence children's health and eating behaviours. Improving the dietary literacy of diet providers may promote the health status and eating behaviours of school-age children.

Fast and high selective dehydrogenation of formic acid (FA) is regarded as one of the most promising pathways to obtain the clean energy carrier: hydrogen. In this work, a nitrogen and Cr2O3 co-doped hierarchical carbon material has been successfully synthesized by in-situ pyrolysis of NH2-MIL-101(Cr) in one step, followed by boiling in hot NaOH solution for surface etching. The activated carbon material is used to anchor the ultrafine Pd nanoparticles (2.18 nm) for formic acid dehydrogenation (FAD). As a result, the 5 wt% Pd@Cr2O3-NPCB-850 exhibits an excellent catalytic activity towards FAD: the turnover frequency (TOF) value is as high as 11 241 h−1 at 333 K, and the selectivity of H2 is up to 100%. The excellent catalytic performance is mainly attributed to the existence of N species and Cr2O3, which plays an important role of electron transfer and anti-aggregation. Our studies open a new methodology for convenient and fast syntheses of nitrogen and metal oxide co-doped activated carbon material, which also provides potential access for producing more highly effective catalysts for other catalytic reactions.

Plant species diversity affects plant nutrient pools, however, previous studies have not considered plant nutrient concentrations and biomass simultaneously. In this study, we conducted an experimental system with 90 microcosms simulating constructed wetlands (CWs). Four species were selected to set up a plant species richness gradient (1, 2, 3, 4 species) and fifteen species compositions. The plant biomass, plant N, phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) concentrations and pools were analyzed. Results showed that, (1) plant species richness increased plant biomass, and the presence of Oenanthe javanicae increased while the presence of Reineckia carnea decreased plant biomass; (2) plant species richness only increased plant K and Mg concentrations of the communities and plant Mg concentration of the species, and the presence of O. Javanica increased while the presence of R. Japonicus decreased plant N and P concentrations of the communities; (3) plant species richness increased plant N, P, K, Ca, and Mg pools, and the presence of O. Javanica increased while the presence of R. Carnea decreased plant N, P, K, Ca and Mg pools; (4) the four-species mixture produced more biomass and nutrient pools than the corresponding highest specific species monocultures. In case the plant uptake can remove nutrients from CWs through harvesting, the results suggest that both nutrient concentrations and biomass must be considered when evaluating the accumulation of nutrients. Assembling plant communities with high species richness (four species) or certain species (such as O. Javanica) is recommended to remove more nutrients from CWs through harvesting.

Background The global pandemic of COVID-19 has brought huge changes to people's lifestyles, college students have also been affected seriously. Evidence about these significant changes indicated that college students were more prone to feel anxious and depressed. To derive a precise assessment of the prevalence of anxiety symptom and depressive symptom among college students worldwide, we conducted this meta-analysis. Methods Based on the guidance of PRISMA, literature was searched in Pubmed, Web of Science, Embase, and PsycArticles (last search November 6, 2020). These articles after the screening were analyzed by a random-effects model to estimate the pooled prevalence of anxiety symptom and depressive symptom. Also, subgroup analysis, sensitivity analysis, and publication bias were performed in this meta-analysis. Results The results showed that the pooled anxiety symptom prevalence was 31% (95% CI: 23-39%), pooled depressive symptom prevalence was 34% (95% CI: 27-41%). Subgroup analysis showed that the prevalence of anxiety symptom and depressive symptom among different countries’ college students were different, and the pooled depressive symptom prevalence of females was higher compared with males. Limitations The prevalence of anxiety symptom and depressive symptom in worldwide college students could be better assessed by a standard and reliable questionnaire. Conclusions The results suggest that the prevalence of anxiety symptom and depressive symptom during the COVID-19 pandemic is relatively high. Except for interventions that should be taken to control the pandemic urgently, mental health services are also needed to decrease the risk of anxiety and depression among college students.

BackgroundSelf-harm (SH) increases significantly in early adolescence with great variability, and childhood maltreatment (CM) contributes to this increase. Understanding the developmental pathway from CM to SH could provide clues for SH prevention. This study used latent class analysis (LCA) to detect the phenotype of SH and explored the role of psychological resilience in the pathway from the CM to SH phenotype.MethodsA cross-sectional study was conducted with 5724 early adolescents from three middle schools in Anhui Province, China. We categorized SH into five subtypes based on their severity and further explored SH phenotypes by LCA to detect the heterogeneity of SH. Moreover, a path model was performed to test the mediation of resilience in the CM-SH association.ResultsThe prevalence rates of highly lethal SH, less lethal SH with visible tissue damage, SH without visible tissue damage, self-harmful behaviours with latency damage and psychological SH were 10.2%, 25.8%, 35.5%, 20.8% and 28.2%, respectively. Three interpretable phenotypes of SH were identified: low SH (57.8%), medium SH (29.0%), and high SH (13.2%). Furthermore, CM was positively associated with the SH phenotype, psychological resilience mediated the association between CM and the SH phenotype (all ps < 0.01), and a larger mediating effect was observed in the medium SH (22.41%).ConclusionsOur findings offer new perspectives that improving psychological resilience can be used as an efficient intervention to reduce the risk of SH among early adolescents who have experienced CM.

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin β3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.

Background: Our previous study revealed the chemokine CCL22 and its receptor CCR4 are elevated in cervical cancer (CC) tissues. The present study aimed to investigate the potential role of EZH2-induced epigenetic activation of CCL22/CCR4 and caused EMT remodeling in CC. Methods: We evaluated whether CCL22-CCR4 expression levels could be regulated by EZH2 and subsequently evaluated the mechanism of EZH2 on the CCL22-CCR4. The animal model supported the experimental findings. Results: CCL22 and CCR4 were significant up-regulated in CC samples compared with normal cervix tissues, and obvious induction of promoter DNA methylation levels of CCL22and CCR4 was shown in CC tissues. Demethylation reactivated the transcription of CCL22 and CCR4. DNMT3A was found to directly bind to the CCL22and CCR4 promoter regions in vitro. Downregulation of the expression of EZH2 in CC cell lines altered DNMT3A expression, induced CCL22and CCR4 promoters’ methylation level as well, and decreased CCL22and CCR4 mRNA expression. An in vivo assay showed that, EZH2 regulated the expression of CCL22/CCR4 components through DNMT3A, consistent with the in vitro results. In EZH2-silenced CC cells, migration was reduced, levels of EMT related markers, including vimentin, slug, snail and β-catenin, were all reduced, and ZO-1 increased. In DNMT3A-silenced CC cells, migration was induced and vimentin, slug, snail and β-catenin were all induced, ZO-1 reduced. Inhibition of CCL22 protein significantly decreased migration of CC cells and vimentin, slug, snail and β-catenin, increased ZO-1. Conclusions: Overall, EZH2 thus appears to regulate CCL22/CCR4 expression via epigenetic activation, causing EMT process remodeling in CC progression.

Purpose This meta-analysis aimed to clarify the clinical effects and safety of Sacubitril/Valsartan (Sac/Val) administration in patients with ST-segment elevation myocardial infarction (STEMI). Methods This analysis was registered with PROSPERO (CRD42022364008). Researchers performed a systematic search of English and Chinese databases to identify available randomized controlled trials from inception to September 30, 2022. The experimental group was given Sac/Val, while the control group was given conventional angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). Study screening and data extraction were conducted by two independent researchers. Cochrane Handbook 6.3 was used for quality evaluation and bias assessment. Risk ratio (RR) and 95% confidential interval (95% CI) were adopted for enumeration data. Mean difference (MD) and 95% CI were adopted for measurement data. Results A total of 7 studies with 964 patients were included in the meta-analysis. The outcomes of clinical effects, including rehospitalization for heart failure (HF), left ventricular ejection fraction (LVEF), major adverse cardiac events (MACEs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration at 24 weeks, were respectively RR = 0.45 (95% CI: 0.35 to 0.66), MD = 3.44 (95% CI: 2.66 to 4.22), RR = 0.50 (95% CI: 0.40 to 0.62), and MD=-155.55 (95% CI: -226.35 to -84.75). Meanwhile, the outcomes of adverse side effects, including hypotension, hyperkalemia, cough, and worsening renal function, were respectively RR = 1.81 (95% CI: 1.09 to 3.02), RR = 0.58 (95% CI: 0.17 to 1.93), RR = 0.84 (95% CI: 0.26 to 2.72), and RR = 0.55 (95% CI: 0.23 to 1.33). Conclusions Compared with conventional ACEI/ARB, Sac/Val was found to improve cardiac function, decrease the risk of HF, and reduce MACEs incidence in patients after STEMI. However, in terms of adverse side effects, Sac/Val did not show a significant advantage over ACEI/ARB.

BackgroundVascular dementia (VaD) and carotid atherosclerotic plaques are common in the elderly population, conferring a heavy burden on families and society. Accumulating evidence indicates carotid atherosclerotic plaques to be a risk factor for VaD. However, the underlying mechanisms for this association are mainly unknown.Materials and methodsWe analyzed temporal cortex gene expression data of the GSE122063 dataset and gene expression data of the GSE163154 dataset to identify commonly differentially expressed genes (DEGs). Then we performed functional enrichment analysis, immune cell infiltration and evaluation, correlation analysis between differentially expressed immune-related genes (DEIRGs) and immune cells, receiver operating characteristic (ROC) analysis, and drug-gene analysis.ResultsWe identified 41 overlapped DEGs between the VaD and carotid atherosclerosis plaque datasets. Functional enrichment analyses revealed that these overlapped DEGs were mainly enriched in inflammatory and immune-related processes. Immunocyte infiltration and evaluation results showed that M0 macrophages, M2 macrophages, and T cells gamma delta had a dominant abundance in carotid atherosclerosis plaque samples, and M0 macrophages showed a significantly different infiltration percentage between the early and advanced stage plaques group. Resting CD4 memory T cells, M2 macrophages, and naive B cells were the top three highest infiltrating fractions in VaD. Furthermore, B cells and NK cells showed a different infiltration percentage between VaD and matched controls. We identified 12 DEIRGs, and the result of correlation analysis revealed that these DEIRGs were closely related to differentially expressed immune cells. We identified five key DEIRGs based on ROC analysis. The drug-gene interaction analysis showed that four drugs (avacopan, CCX354, BMS-817399, and ASK-8007) could be potential drugs for VaD and carotid atherosclerotic plaques treatment.ConclusionCollectively, these findings indicated that inflammatory and immune-related processes be a crucial common pathophysiological mechanism shared by VaD and carotid plaques. This study might provide new insights into common molecular mechanisms between VaD and carotid plaques and potential targets for the treatment.