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Aspirin and its active metabolite salicylate have emerged as promising agents for the chemoprevention of colorectal cancer (CRC). Moreover, aspirin suppresses the progression of established CRCs. However, the underlying molecular mechanisms are not completely understood. Here we found that salicylate induces the expression of the miR-34a and miR-34b/c genes, which encode tumor suppressive microRNAs, in a p53-independent manner. Salicylate activated AMPK, thereby activating NRF2, which directly induced miR-34a/b/c expression via ARE motifs. In addition, salicylate suppressed c-MYC, a known repressor of NRF2-mediated transactivation, via activating AMPK. The suppression of c-MYC by salicylate was necessary for NRF2-mediated activation of miR-34a/b/c . Inactivation of miR-34a/b/c largely abrogated the inhibitory effects of salicylate on migration, invasion and metastasis formation by CRC cells. In the future, aspirin and its derivates may be used therapeutically to activate miR-34a and miR-34b/c in tumors that have lost p53.

This study aims to clarify the N6-methyladenosine (m6A) modification of LINC01006, which is involved in migration, invasion and proliferation of non-small cell lung cancer (NSCLC). LINC01006 and METTL3 expressions were analyzed in TCGA-LUAD cohort. Colony formation assay, wound-healing assay and transwell assay were performed to evaluate the ability of colony formation, migration and invasion. Q-PCR and western blot analysis determined gene expressions. M6A-RNA immunoprecipitation and m6A quantification assay were used to evaluate m6A modification. qChIP assay was used to validate transcriptional target. Luciferase assay validated the miRNA targets and transcriptional targets. In-situ xenograft model were included to evaluate tumor proliferation in vivo. LINC01006 and METTL3 expressions were elevated in NSCLC cells and tissues. LINC01006 promoted the migration and invasion of NSCLC via epithelial - mesenchymal transition (EMT). The expression of LINC01006 was positively correlated to the expression of METTL3. METTL3 promoted tumor formation and proliferation in the in-situ xenograft model of NSCLC. The expression of LINC01006 was increased by METTL3 via m6A modification. c-MYC directly induced METTL3. Both c-MYC and LINC01006 were commonly targeted by miR-34a/b/c and miR-2682, and thereby c-MYC/METTL3/LINC01006 formed a positive feedback loop through miRNA targets in NSCLC. LINC01006 is an oncogenic lncRNA, which induces migration, invasion and proliferation of NSCLC. METTL3 increases LINC01006 expression through stabilizing LINC01006 mRNA. c-MYC, as a transcription factor, activates METTL3, which results in an elevated level of LINC01006. c-MYC, METTL3 and LINC01006 form a positive feedback loop through multiple miRNA targets in NSCLC.

A large proportion of women experience depression during the postpartum period. Few studies have investigated the use of mobile technology to prevent postpartum depression in women. This study investigated the preliminary effectiveness of the CareMom program, a new app-based cognitive behavioral therapy program, on reducing the depressive symptoms of mothers during the very early postpartum period via a pilot randomized controlled study. The participants were recruited during birth hospitalization (within 3 days after giving birth) and randomized to the waiting-list control and CareMom groups. Over the four-week intervention period, the CareMom group was required to complete 28 daily challenges via CareMom. The depressive (via EPDS) and anxiety (via GAD-7) levels of participants were measured at baseline and every 7 days postbaseline for 4 weeks. A total of 112 eligible participants were randomly allocated to the two groups (CareMom: n = 57; control: n = 55). At week 4, the CareMom group achieved a significantly lower EPDS score than the control group at week 4 (p = 0.037). In addition, the EPDS (p < 0.001) scores of the CareMom group were significantly lower than the baseline values. However, the control group did not show any significant reduction in this measure. No significant reduction of GAD-7 scores was observed for CareMom and control groups at week 4. This study provides preliminary evidence of the effectiveness of CareMom in reducing depressive symptoms in the general postpartum population during the very early postpartum period.

The Underwater Internet of Things (UIoT) has emerged as one of the prominent technologies in the development of future ocean monitoring systems, where mobile edge elements (such as autonomous underwater vehicles (AUVs)) provide a promising method for the data collection from sensor nodes. However, as an important part of the UIoT, underwater wireless sensor networks (UWSNs) are severely affected by the underwater dynamic environment. For instance, node locations change continuously, which significantly increases the difficulty of data collection. To solve this problem, the concept of an inevitable communication space (ICS) is proposed. The ICS is calculated by analyzing the variation in the position of nodes and the communication range. Furthermore, an ICS-based dynamic data collection algorithm (ICS-DDCA) for UIoT is proposed to collect underwater data. This method utilizes the ICS instead of the initial location of the node for data collection to further improve the performance of the algorithm and shorten the data collection time. The simulation results demonstrate that compared with the energy-efficient data collection over AUV-assisted (EEDA) and data collection algorithms based on probabilistic neighborhood (PNCS-GHA), ICS-DDCA can effectively reduce the collection time, while ensuring the full completion of data collection.

Background: Patients with Parkinson's disease (PD) and sarcopenia often exhibit resilience, frailty, disability, and depression, highlighting the complex and interrelated nature of these conditions. Objective: Despite the presence of clinical manifestations of muscle atrophy in both PD and sarcopenia, accurately discerning the coexistence of sarcopenia in PD patients remains a challenging task with significant implications for treatment strategies and prognostic assessments. This study aims to elucidate the specific ultrasonic diagnostic parameters associated with PD accompanied by sarcopenia through a comparative analysis of muscle ultrasound parameters in patients with PD, thereby presenting a novel approach for rapid identification of this condition. Methods: A total of 110 participants were enrolled in this study, including patients with PD and control subjects. Demographic data, clinical characteristics, physical performance tests, appendicular skeletal muscle mass index (ASMI), bioelectrical impedance analysis and muscle ultrasound measurements were collected from all participants. The muscle ultrasound measurements encompassed assessments of muscle thickness, pennation angle and shear wave elastography at various anatomical sites. Results: PD patients exhibited decreased muscle strength and physical performance, and increased shear wave elastography value. In PD patients with sarcopenia, body circumference, including calf circumference, mid-arm circumference, Waist-to-Hip Ratio and body mass index (BMI) were all significantly decreased. Biceps brachii muscle thickness (MT) and gastrocnemius MT decreased in PD patients with sarcopenia and low ASMI. Binary logistic regression analysis revealed that male PD patients, BMI and gastrocnemius MT were predictive factors for ASMI in PD patients. Conclusion: Biceps brachii MT and gastrocnemius MT are important indicators for distinguishing whether PD patients have sarcopenia. Male patients, low BMI and gastrocnemius MT were identified as valid predictors of low ASMI in PD patients. The findings of this study provide important insights into the use of muscle ultrasound in the diagnosis of PD with sarcopenia.

Abstract Background: Parkinson’s disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data. Methods: Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes. Results: GBD 2021 estimated 508,378 (95% UI: 430,499–592,748) incident cases of PD, 92,035 (95% UI: 75,908–108,133) deaths, and 2,159,514 (95% UI: 1,826,196–2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004–2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. Conclusions: The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.

Sodium butyrate (NaB) is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R) injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg) was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO) mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt), and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1β, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.

Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) in Parkinson’s disease (PD) patients with mild cognitive impairment (MCI). Methods This was a randomized, double-blind, controlled study. We consecutively enrolled PD patients with MCI (PD-MCI) from the Second Affiliated Hospital of Soochow University from September 2021 to November 2022. The patients were randomly assigned to the active rTMS group ( n  = 15) and the sham rTMS group ( n  = 15), and received 10HZ rTMS over left DLPFC for 7 consecutive days. A battery of neuropsychological assessments was performed on participants pre-test and post-test, including attention, executive function, memory, language, and visuospatial function. A resting electroencephalograph (EEG) was recorded, and the absolute and relative power of delta, theta, low alpha, high alpha, and beta were compared between the two groups. Follow-up assessments were performed at baseline, 1 week, 4 weeks, and 3 months after rTMS treatment. Results Finally, 30 patients completed the follow-up. After 1 week of treatment, compared to baseline, the active group showed significant improvement on the Montreal Cognitive Assessment (MoCA) scale ( P  = 0.019), Auditory Verbal Fluency Test (AVLT) immediate recall ( P  = 0.001), AVLT long-delayed recall ( P  = 0.006), AVLT recognition ( P  = 0.015) and Boston naming ( P  = 0.012), while the time of Trail Making Test B ( P  = 0.022) was decreased. Compared to the sham group, a significant increase in the percentage change of the global relative high alpha power was shown in the active group ( P  = 0.012). The data showed an increase in the percentage change of the relative high alpha power in the left frontal region ( P  = 0.041). Moreover, the correlation analysis revealed that the MoCA score was positively correlated with the relative high alpha power ( P  = 0.004). There was no significant change in the sham group. Conclusion High-frequency rTMS over left DLPFC contributes to cognitive improvement in PD-MCI patients and increased relative high alpha power may be associated with cognitive improvement. Trial registration This study has been registered at Chinese Clinical Trial Registry (identifier: ChiCTR2000039557). Registered on 31 October 2020.

To describe the characteristics of severe and critically ill children with first-wave SARS-CoV-2 Omicron infection admitted to the pediatric intensive care unit (PICU) at the National Children's Regional Medical Center in Northeast China and to explore factors associated with poor outcomes. This observational cohort study was conducted in a PICU in northeastern China and included children under 18 years of age who were severely and critically ill due to SARS-CoV-2 Omicron infection between December 2022 and February 2023. Patients were categorized into two groups: the invasive mechanical ventilation (IMV) group and the non-IMV group. The primary outcome measured was the need for IMV, while secondary outcomes included death or prolonged PICU stay. Univariate and multivariate logistic regression analyses were performed to identify risk factors for poor outcomes. A total of 38 severe and critically ill children were included in the study. Of these, 25 (66%) were diagnosed with respiratory failure, and four (16%) developed acute respiratory distress syndrome. Additionally, 21 (55%) were diagnosed with COVID-19-associated neurological disorders, and 18 (47%) received IMV. Multivariate logistic regression analysis identified the chest computed tomography (CT) score, based on the COVID-19 Risk Assessment and Diagnosis System (CO-RADS), was statistically significant as an independent predictor for IMV in severe and critically ill children (odds ratio [OR]: 2.781 [95% confidence interval (CI): 1.021-7.571]). Furthermore, the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score and serum aspartate aminotransferase (AST) levels at admission were found to be independent predictors of death or prolonged PICU stay. Respiratory failure and COVID-19-associated neurological disorders were the most common complications among severe and critically ill children with first-wave SARS-CoV-2 Omicron infection. Chest CT score, PELOD-2 score, and serum AST levels may serve as important indicators of poor outcomes in this patient population.