Methods established for the detection of mineral levels in whole blood by the dried blood spot technique.

Mineral are intimately related to human health and disease, and detection of mineral content in the body is of great significance for the diagnosis and prevention of diseases. In this study, we validated the method developed to detect magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) levels in dried blood spots (DBS). In accordance with the requirements of the guidelines for the Bioanalytical Method Validation Guidance for Industry, we evaluate the linearity, sensitivity, precision, accuracy and selectivity of the developed methods. In addition, Mg, Cu, Fe, Zn and Se were quantified in 195 older adults using DBS technique, and its accuracy was assessed by comparing the results to those detected by inductively coupled plasma-mass spectrometry (ICP-MS). The method has excellent sensitivity and linear range to cover the concentration range of mineral elements in the general population with the required precision, accuracy and selectivity. The correlation coefficients of Mg, Cu, Fe, Zn and Se levels in blood detected by the DBS technique and ICP-MS were 0.638, 0.823, 0.463, 0.728 and 0.751, respectively (all P < 0.05), which indicated that there was a strong correlation between the detection results of the two methods. More than 95 % of the sample results in the Bland-Altman consistency test were within the acceptable limits of agreement (LOA) range, indicating that they had good consistency. DBS technique has good accuracy and reliability in detecting blood mineral levels in the elderly, suggesting potential in the quantification of mineral level in blood.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging reveals the protective effect of docosahexaenoic acid on glucose metabolism by reducing brain 27-hydroxycholesterol.

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

Effects of a food supplement containing phosphatidylserine on cognitive function in Chinese older adults with mild cognitive impairment: A randomized double-blind, placebo-controlled trial.

BACKGROUND: Phosphatidylserine (PS) and α-Linolenic acid (ALA), are positively associated with cognitive function, but their combination effects and possible mechanisms remain unclear. We aimed to explore the effects on cognition and potential mechanism of the supplements. METHODS: This randomized, double-blind, placebo-controlled trial recruited 190 MCI patients in Tianjin, China, and randomly assigned in intervention group and placebo group. Each group consumed two capsules every day for 12 months. Each capsule for intervention group contains 144 mg ALA, 31.5 mg PS and 3.6 mg Ginkgo total flavonoids as main functional components, with 0.48 mg Vitamin B1 (as thiamine hydrochloride), 0.48 mg Vitamin B6 (as pyridoxine hydrochloride) and 90 µg folic acid as supplement. Capsules for placebo group were identical but contain no active ingredients. Cognitive function, serum n-3 polyunsaturated fatty acids (PUFAs) and neurotransmitters were assessed at baseline and 12 months. Linear mixed effects model and causal mediation analysis were conducted to explore the effects and potential mechanism of the intervention. RESULTS: A total of 190 participants (mean [SD] age, 67.95 [5.62] years; 70 (36.8 %) male and 120 (63.2 %) female) were randomized to the placebo group (n = 95) and intervention group (n = 95). Compared with placebo group, the intervention group had statistically significant improvements in arithmetic testing (ß, 0.688; 95 % CI, 0.103-1.274), the similarity test (ß, 1.070; 95 % CI, 0.472-1.667) and short-term memory (ß, 0.600; 95 % CI, 0.399-0.800). Besides, the intervention group had statistically significant increases in serum ALA (ß, 1.620; 95 % CI, 0.967-2.265), DHA (ß, 2.797; 95 % CI, 1.075-4.532), EPA (ß, 1.472; 95 % CI, 0.296-2.643), acetylcholine (ß, 0.441; 95 % CI, 0.415-0.468), GABA (ß, 0.009; 95 % CI, 0.001-0.016) and 5-HT (ß, 0.160; 95 % CI, 0.081-0.238) compared to the placebo group. And the intervention may improve short-term memory by increasing serum ALA levels (average causal mediation effect = 0.132, 95 % CI, 0.053-0.225) with 19.7 % mediation proportion. CONCLUSIONS: This food supplement containing phosphatidylserine could improve different cognitive functions of MCI patients, especially short-term memory, and increase serum n-3 PUFAs and neurotransmitters levels. Serum ALA level might play a mediation role.

ß-hydroxybutyrate and mitochondria mediate the association between medium-chain fatty acids, DHA and mild cognitive impairment: a nested case-control study.

BACKGROUND: Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). ß-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms. METHODS: This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship. RESULTS: Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk. CONCLUSION: Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly.

Mental health difficulties and related factors in Chinese children and adolescents during the COVID-19 pandemic: a cross-sectional study

Abstract Objective: To examine the mental health status and related factors in children and adolescents, and to assess age groups and sexes differences in factors influencing mental health. Methods: This cross-sectional study was performed on Chinese children aged 6-18 years from November 2021 to January 2022. Mental health difficulties were accessed by the Strengths and Difficulties Questionnaire. Multivariate logistic regression was used to analyze factors associated with mental health status. Multiple linear regression was used to evaluate factors associated with the scores of the Strengths and Difficulties Questionnaire. Results: The prevalence of mental health difficulties was 12.98% (n =1348). Age (OR, 0.909, [95%CI, 0.830-0.996]), sex (OR, 1.424, [95%CI, 1.033-1.963]) and screen time on weekdays ("≥2" h/d vs "< 1" h/d: OR, 2.001, [95%CI, 1.300-3.080]) were related factors for mental health difficulties. For children (year ≤ 12), the strongest related factor for mental health difficulties was screen time on weekdays ("≥ 2" h/d vs "< 1" h/d: OR, 1.821 [95%CI, 1.203-2.755]). The risk of mental health difficulties in females with ≥ 2 h/d screen time on weekends was 3.420 times higher than those with < 1 h/d (OR, 3.420, [95%CI, 1.923-6.081]). Conclusion: The prevalence of mental health difficulties among children and adolescents was relatively high. The lower age, female sex and excessive screen time were associated with a higher risk of mental health difficulties. The factors influencing mental health varied by different age groups and sexes. Thus, specific measures for different age groups and sexes should be adopted to mitigate the impact.

LncRNA ZFPM2-AS1 promotes phyllodes tumor progression by binding to CDC42 and inhibiting STAT1 activation.

Breast phyllodes tumor (PT) is a rare fibroepithelial neoplasm with potential malignant behavior. Long non-coding RNAs (lncRNAs) play multifaceted roles in various cancers, but their involvement in breast PT remains largely unexplored. In this study, microarray was leveraged for the first time to investigate the role of lncRNA in PT. We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT, and its overexpression endowed PT with high tumor grade and adverse prognosis. Furthermore, we elucidated that ZFPM2-AS1 promotes the proliferation, migration, and invasion of malignant PT in vitro. Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft (PDX) model could effectively inhibit tumor progression in vivo. Mechanistically, our findings showed that ZFPM2-AS1 is competitively bound to CDC42, inhibiting ACK1 and STAT1 activation, thereby launching the transcription of TNFRSF19. In conclusion, our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT, and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA + DHA (FA 800 µg/d + DHA 800 mg/d), FA (800 µg/d), DHA (800 mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow-up, scores of full intelligence quotient (ßDHA: 1.302, 95% CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95% CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95% CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA + DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA, and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone.

A Comparative Study Evaluating the Effectiveness of Folate-Based B Vitamin Intervention on Cognitive Function of Older Adults under Mandatory Folic Acid Fortification Policy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The policies regarding the mandatory fortification of food with folic acid (FA) may impact the effectiveness of folate-based B vitamin treatment on cognitive function in older adults. We critically and systematically review the literature to assess whether food fortification policies affect folate-based B vitamin treatment efficacy on cognition function in older adults. Electronic databases, including PubMed, Web of Science, and CNKI, were searched for "Cognitive Function", "Folate", and "Older Adults". The study had specific criteria for inclusion, which were as follows: (1) the studies should initially have randomized controlled trials that were conducted on older adults aged 60 or above; (2) the studies must assess the relationship between folate status and cognitive performance; and (3) the studies should clarify the policies regarding food fortification with FA. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Two reviewers independently extracted all the data, and any discrepancies were resolved by consensus. All the data collected were compiled, compared, and analyzed critically. Random effects models were used to assess the effects of interventions. The systematic review included fifty-one articles involving 42,768 participants. Of these, the 23 articles were included in the meta-analysis. The meta-analysis on the effects of folate-based B vitamin supplementation on cognitive function showed a significant overall impact (Z = 3.84; p = 0.0001; SMD, 0.18; 95% CI, 0.09, 0.28). Further analysis revealed that FA food fortification policies were not implemented in countries where folate-based B vitamin supplementation improved cognitive impairment in older adults (Z = 3.75; p = 0.0002; SMD, 0.27; 95% CI, 0.13, 0.40). However, the FA intervention did not have significant outcomes in areas where FA food fortification policies were mandatory (Z = 0.75; p = 0.45; SMD, 0.03; 95% CI, -0.06, 0.13). Supplementing with oral folic acid, alone or in combination, has been linked to improved cognitive performance in older adults. While mandatory FA fortification has the improved folic acid status, additional folate-based B vitamin supplements do not appear to influence cognitive function.

Medium-chain triglycerides combined with DHA improve cognitive function by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Socioeconomic disparities and green space associated with myopia among Chinese school-aged students: A population-based cohort study.

Background: There is increasing evidence on the link between environmental factors and myopia in children and adolescents, yet with inconsistent conclusions. We investigated the associations between socioeconomic inequalities and green space with myopia in school-aged students participating in the Tianjin Child and Adolescent Research of Eye (TCARE) study. Methods: We obtained data from a population-based dynamic cohort study conducted in Tianjin, China, in 2021 and followed up in 2022. We included 1 245 271 participants from 16 districts with an average age of 11.6 years (standard deviation = 3.3) in our analysis. We synthesized their area-level SES through a prediction model that combined economic, educational, and health care variables and assessed the greenness levels surrounding the school using the Normalized Difference Vegetation Index (NDVI) based on data obtained through satellite remote sensing. We performed generalised linear mixed effects analyses for each myopia outcome separately, with adjustments for students' sex, years of education completed, and the school's geographical location. Results: We observed that students living in low SES areas had the highest prevalence of myopia (60.7%) in the last screening in 2022, as well as a higher incidence of one-year myopia (26.4%) compared to those residing in middle SES areas (22.7%). With a 0.1 increase in the 250, 500, and 1000 m buffer NDVI, the prevalence of myopia dropped by 6.3% (odds ratio (OR) = 0.937; 95% confidence interval (CI) = 0.915, 0.960), 7.7% (OR = 0.923; 95% CI = 0.900, 0.946), and 8.7% (OR = 0.913; 95% CI = 0.889, 0.937), respectively. The interaction analysis showed that low SES and low greenness exacerbate the prevalence of myopia. Findings from longitudinal analyses consistently demonstrated a correlation between higher values of NDVI and a slower progression of myopia. These findings remained robust across sensitivity analyses, including for variables on parental myopia and students' behaviors. Conclusions: Exposure to green spaces could play a crucial role in slowing the progression of myopia among school-aged students. Myopia control policies should prioritise young populations residing in low SES areas with limited access to green spaces, as they face the highest potential risks.

The Myopia Prevalence and Association With Physical Activity Among Primary School Students Aged 6-12 Years: A Cross-Sectional Study in Tianjin, China.

Purpose: This study aimed to investigate the prevalence of myopia and determine the association between physical activity and risk of myopia among primary school students in Tianjin, China. Methods: A cross-sectional study was conducted among subjects from nine primary schools. All of the subjects underwent visual acuity and spherical equivalent (SE) with noncycloplegic autorefraction measurement. Myopia was defined as an SE refraction ≤-0.50D and an uncorrected visual acuity <5.0 in either eye. Physical activity was measured via the Physical Activity Questionnaire for Children. Data were analyzed using the Pearson χ2 test and binary logistic regression. Stratification analysis by sex was also performed. Results: A total of 2976 participants (1408 boys and 1568 girls) aged six to 12 years (mean age 8.82 years) were included in this study. The overall prevalence of myopia was 52.92%. When stratified according to physical activity, myopia prevalence significantly decreased with increasing physical activity levels (χ2 trend test = 127.63, P < 0.001). In the binary logistic regression analysis, after adjusting for age, sex, and school region, the odds ratio for the association between physical activity and myopia was 0.762 (95% confidence interval, 0.675-0.862, P < 0.001). When stratified by sex, the significant statistical association between physical activity and myopia both can be found in two groups (P < 0.05). Conclusions: Higher levels of physical activity were independently associated with decreased risk of myopia. The significant reverse statistical association between physical activity and myopia can be found in male or female groups. Translational Relevance: Taking part in physical activities may be an effective way to reduce the prevalence of myopia.

Reactive oxygen species produced by photodynamic therapy enhance docosahexaenoic acid lipid peroxidation and induce the death of breast cancer cells.

Breast cancer remains a serious threat to women's physical and emotional health. The combination therapies can overcome the deficiency of single therapy, enhance the therapeutic effects and reduce the side effects at the same time. In this study, we synthesize a novel nanomedicine that enhanced the therapeutic effects of breast cancer treatment by combining photodynamic therapy and chemotherapy. The doxorubicin (DOX) and photosensitizer methyl pyropheophorbide-a (MPPa) are loaded into the nano-drug delivery system as DPSPFA/MPPa/DOX. In response to near-infrared (NIR) laser, the drugs were quickly released to the cancer cells. The MPPa produces reactive oxygen species (ROS) under the action of photodynamics. Unsaturated fatty acids with ROS promotes lipid peroxidation and the combination of chemotherapy and photodynamic therapy. The data shows that the DPSPFA/MPPa/DOX has a spherical shape, good dispersibility and stability, and the particle size is roughly 200 nm. The drug loading capability of DOX is about 13 %. Both of MCF7 cell model in vitro and breast cancer model in vivo, DPSPFA/MPPa/DOX showed an excellent anti-tumor effect of 86.9 % and without any obvious side effects. These findings might offer potential for a new approach for breast cancer treatment.

Mental health difficulties and related factors in Chinese children and adolescents during the COVID-19 pandemic: a cross-sectional study.

OBJECTIVE: To examine the mental health status and related factors in children and adolescents, and to assess age groups and sexes differences in factors influencing mental health. METHODS: This cross-sectional study was performed on Chinese children aged 6-18 years from November 2021 to January 2022. Mental health difficulties were accessed by the Strengths and Difficulties Questionnaire. Multivariate logistic regression was used to analyze factors associated with mental health status. Multiple linear regression was used to evaluate factors associated with the scores of the Strengths and Difficulties Questionnaire. RESULTS: The prevalence of mental health difficulties was 12.98% (n =1348). Age (OR, 0.909, [95%CI, 0.830-0.996]), sex (OR, 1.424, [95%CI, 1.033-1.963]) and screen time on weekdays ("≥2" h/d vs "< 1" h/d: OR, 2.001, [95%CI, 1.300-3.080]) were related factors for mental health difficulties. For children (year ≤ 12), the strongest related factor for mental health difficulties was screen time on weekdays ("≥ 2" h/d vs "< 1" h/d: OR, 1.821 [95%CI, 1.203-2.755]). The risk of mental health difficulties in females with ≥ 2 h/d screen time on weekends was 3.420 times higher than those with < 1 h/d (OR, 3.420, [95%CI, 1.923-6.081]). CONCLUSION: The prevalence of mental health difficulties among children and adolescents was relatively high. The lower age, female sex and excessive screen time were associated with a higher risk of mental health difficulties. The factors influencing mental health varied by different age groups and sexes. Thus, specific measures for different age groups and sexes should be adopted to mitigate the impact.

circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

Protocol for evaluating the effects of the Reducing Cardiometabolic Diseases Risk dietary pattern in the Chinese population with dyslipidaemia: a single-centre, open-label, dietary intervention study.

INTRODUCTION: Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found. METHODS/DESIGN: The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35-45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases. ETHICS AND DISSEMINATION: The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300072472).

Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging via mitochondria-associated membrane-mediated calcium homeostasis regulation.

BACKGROUND: Sarcopenia, an age-related disease, is characterized by a gradual loss of muscle mass, strength, and function. It has been linked to abnormal organelle function in myotubes, including the mitochondria and endoplasmic reticulum (ER). Recent studies revealed that mitochondria-associated membranes (MAM), the sites connecting mitochondria and the ER, may be implicated in skeletal muscle aging. In this arena, the potential of Polygonatum sibiricum polysaccharide (PSP) emerges as a beacon of hope. PSP, with its remarkable antioxidant and anti-senescence properties, is on the cusp of a therapeutic revolution, offering a promising strategy to mitigate the impacts of sarcopenia. PURPOSE: The objective of this research is to explore the effects of PSP on age-related muscle dysfunction and the underlying mechanisms involved both in vivo and in vitro. METHODS: In this investigation, we used in vitro experiments using D-galactose (D-gal)-induced aging in C2C12 myotubes and in vivo experiments on aged mice. Key indices were assessed, including reactive oxygen species (ROS) levels, mitochondrial function, the expression of aging-related markers, and the key proteins of mitochondria and MAM fraction. Differentially expressed genes (DEGs) related to mitochondria and ER were identified, and bioinformatic analyses were performed to explore underlying mechanisms. Muscle mass and function were determined to evaluate the quantity and quality of skeletal muscle in vivo. RESULTS: PSP treatment effectively mitigated oxidative stress and mitochondrial malfunction caused by D-gal in C2C12 myotubes, preserving mitochondrial fitness and reducing MAM formation. Besides, PSP attenuated D-gal-induced increases in Ca2+ concentrations intracellularly by modulating the calcium-related proteins, which were also confirmed by gene ontology (GO) analysis of DEGs. In aged mice, PSP increased muscle mass and improved grip strength, hanging time, and other parameters while reducing ROS levels and increasing antioxidant enzyme activities in skeletal muscle tissue. CONCLUSION: PSP offers protection against age-associated muscle impairments. The proposed mechanism suggests that modulation of calcium homeostasis via regulation of the MAM results in a favorable functional outcome during skeletal muscle aging. The results of this study highlight the prospect of PSP as a curative intervention for sarcopenia and affiliated pathological conditions, warranting further investigation.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma.

Introduction: The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. Methods: We assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively. Results: MUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells in vitro, in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. Conclusion: The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

IGFBP5, as a Prognostic Indicator Promotes Tumor Progression and Correlates with Immune Microenvironment in Glioma.

Background: Insulin-like growth factor binding protein 5 (IGFBP5) is highly expressed in multiple human cancers, including glioma. Despite this, it remains unclear what role it plays in glioma. The aim of the present study was to analyze whether IGFBP5 could be used as a predictor of prognosis and immune infiltration in glioma. Methods: Glioma patients' clinical information was collected from the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), Rembrandt, and Gravendeel databases. The diagnostic and prognostic roles of IGFBP5 were assessed by the Kaplan-Meier survival curves, diagnostic receiver operating characteristic (ROC) curves, nomogram model, Cox regression analysis and Enrichment analysis by R software. Moreover, the correlation between IGFBP5 expression and immune cell infiltration, and immune checkpoint genes was conducted. Immunohistochemistry staining, CCK8, colony formation, scratch and transwell assays and western blot were used to interrogate the expression and function of IGFBP5 in glioma. Results: IGFBP5 levels were obviously increased in glioma with higher malignancy and predicted poor outcomes by Univariate and multivariate Cox analysis. The biological function analysis revealed that IGFBP5 correlated closely with immune signatures. Moreover, IGFBP5 expression was associated with tumor infiltration of B cells, T cells, macrophages, and NK cells. IGFBP5 affected glioma cell proliferation, migration, and invasion probably involved in the epithelial-to-mesenchymal transition (EMT) and Hippo-YAP signaling pathway. Further study showed that IGFBP5 induced the expression of PD-L1 and CXCR4. Conclusions: IGFBP5 as an oncogene is a useful biomarker of prognosis and correlates with progression and immune infiltration in glioma.

Exploring the Effect Mechanism of Alkyl Chain Lengths on the Tribological Performance of Ionic Liquids.

In this work, four kinds of imidazole phosphate ionic liquids (ILs) with different anionic and cationic alkyl chain lengths were synthesized. The physicochemical properties and tribological performance of ILs were evaluated. The experimental results revealed that the tribological properties of ILs were positively correlated with the cationic chain length and negatively correlated with the anionic chain length. The effect mechanism can be summarized in two aspects: on the one hand, anions with shorter alkyl chain lengths possess stronger adsorption performance and better film forming ability on the friction pair surfaces, which makes the ILs form more robust and stable lubricating film; on the other hand, ILs with longer cationic alkyl chain lengths possess milder tribo-chemical reactions, which can effectively enhance the tribological performance and decrease the corrosion wear.