Relationship between prognostic nutritional index and post-stroke cognitive impairment.

BACKGROUND: The Prognostic Nutritional Index (PNI) has been described as a useful screening tool for patient prognosis in several diseases. As a potential diagnostic index, it has attracted the interest of many physicians. However, the correlation between the PNI and post-stroke cognitive impairment (PSCI) remains unclear. METHODS: A total of 285 patients with acute ischemic stroke were included. PNI was assessed as serum albumin (g/L) + 5× lymphocyte count (109/L) and was dichotomized according to the prespecified cut-off points 48.43 for the high and low groups. PSCI was defined as Mini-Mental State Examination (MMSE) < 27 at the 6-10 months follow-up. Multiple logistic regression and linear regression analyses were performed to examine the association between PNI and cognitive outcomes. RESULTS: A low PNI was independently associated with PSCI after adjusting for age, sex, education, National Institutes of Health Stroke Scale (NIHSS), deep white matter hyperintensity (DWMH), and stroke history (odds ratio [OR]: 2.158; 95% confidence interval [CI]: 1.205-3.863). The PNI scores were significantly associated with MMSE and attention domain (ß = 0.113, p = 0.006; ß = 0.109, p = 0.041, respectively). The PNI improved the model's discrimination when added to the model with other clinical risk factors. CONCLUSIONS: A low PNI was independently associated with the occurrence of PSCI and the PNI scores were specifically associated with the scores of global cognition and attention domain. It can be a promising and straightforward screening indicator to identify the person with impaired immune-nutritional status at higher risk of PSCI.

Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

Gastric Cancer Mesenchymal Stem Cells Trigger Endothelial Cell Functional Changes to Promote Cancer Progression.

Our previous studies have highlighted the pivotal role of gastric cancer mesenchymal stem cells (GCMSCs) in tumor initiation, progression, and metastasis. In parallel, it is well-documented that endothelial cells (ECs) undergo functional alterations in response to challenging tumor microenvironment. This study aims to elucidate whether functional changes in ECs might be induced by GCMSCs and thus influence cancer progression. Cell proliferation was assessed through CCK-8 and colony formation assays, while cell migration and invasion capabilities were evaluated by wound-healing and Transwell assays. Immunohistochemistry was employed to examine protein distribution and expression levels. Additionally, quantitative analysis of protein and mRNA expression was carried out through Western blotting and qRT-PCR respectively, with gene knockdown achieved using siRNA. Our findings revealed that GCMSCs effectively stimulate cell proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs), both in vitro and in vivo. GCMSCs promote the migration and invasion of gastric cancer cells by inducing the expression of Slit2 in HUVECs. Notably, the inhibition of phosphorylated AKT partially mitigates the aforementioned effects. In conclusion, GCMSCs may exert regulatory control over Slit2 expression in ECs via the AKT signaling pathway, thereby inducing functional changes in ECs that promote tumor progression.

Accelerating Elastic Property Prediction in Fe-C Alloys through Coupling of Molecular Dynamics and Machine Learning.

The scarcity of high-quality data presents a major challenge to the prediction of material properties using machine learning (ML) models. Obtaining material property data from experiments is economically cost-prohibitive, if not impossible. In this work, we address this challenge by generating an extensive material property dataset comprising thousands of data points pertaining to the elastic properties of Fe-C alloys. The data were generated using molecular dynamic (MD) calculations utilizing reference-free Modified embedded atom method (RF-MEAM) interatomic potential. This potential was developed by fitting atomic structure-dependent energies, forces, and stress tensors evaluated at ground state and finite temperatures using ab-initio. Various ML algorithms were subsequently trained and deployed to predict elastic properties. In addition to individual algorithms, super learner (SL), an ensemble ML technique, was incorporated to refine predictions further. The input parameters comprised the alloy's composition, crystal structure, interstitial sites, lattice parameters, and temperature. The target properties were the bulk modulus and shear modulus. Two distinct prediction approaches were undertaken: employing individual models for each property prediction and simultaneously predicting both properties using a single integrated model, enabling a comparative analysis. The efficiency of these models was assessed through rigorous evaluation using a range of accuracy metrics. This work showcases the synergistic power of MD simulations and ML techniques for accelerating the prediction of elastic properties in alloys.

Association of cardiovascular disease prevalence with BMD and fracture in men with T2DM.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. METHODS: In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. RESULTS: A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. CONCLUSIONS: The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.

Combining brief recall and ketamine treatment prevents stress-primed methamphetamine memory reinstatement via heightening mPFC GABA activity.

This study aimed to assess whether brief recall of methamphetamine (MA) memory, when combined with ketamine (KE) treatment, may prevent stress-primed MA memory reinstatement. Combining 3-min recall and KE facilitated MA memory extinction and resistance to subsequent stress-primed reinstatement. Such combination also produced glutamate metabotropic receptor 5 (mGluR5) upregulation in animals' medial prefrontal cortex (mPFC) γ-amino-butyric acid (GABA) neuron. Accordingly, chemogenetic methods were employed to bi-directionally modulate mPFC GABA activity. Following brief recall and KE-produced MA memory extinction, intra-mPFC mDlx-Gi-coupled-human-muscarinic-receptor 4 (hM4Di)-infused mice receiving compound 21 (C21) treatment showed eminent stress-primed reinstatement, while their GABA mGluR5 expression seemed to be unaltered. Intra-mPFC mDlx-Gq-coupled-human-muscarinic-receptor 3 (hM3Dq)-infused mice undergoing C21 treatment displayed MA memory extinction and resistance to stress-provoked reinstatement. These results suggest that combining a brief recall and KE treatment and exciting mPFC GABA neuron may facilitate MA memory extinction and resistance to stress-primed recall. mPFC GABA neuronal activity plays a role in mediating brief recall/KE-produced effects on curbing the stress-provoked MA seeking.

Effect of magnetic field coupled magnetic biochar on membrane bioreactor efficiency, membrane fouling mitigation and microbial communities.

The excitation by magnetic field was established to mitigate the membrane fouling of magnetic biochar (MB)-supplemented membrane bioreactor (MBR) in this study. The results showed that the transmembrane pressure (TMP) increase rates decreased by about 8 % after introducing the magnetic field compared with the magnetic biochar-MBR (MB-MBR). Membrane characterization suggested that the flocs in the magnetic field-magnetic biochar-MBR (MF-MB-MBR) formed a highly permeable developed cake layer, and a fluffier and more porous deposited layer on membrane surface, which minimized fouling clogging of the membrane pores. Further mechanistic investigation revealed that the decrease in contact angle of fouled membrane surface in MF-MB-MBR, i.e. an enhanced membrane hydrophilicity, is considered important for forming highly permeable layers. Additionally, the magnetic field was demonstrated to have a positive effect on the improvement of the magneto-biological effect, the enhancement of charge neutralization and adsorption bridging between sludge and magnetic biochar, and the reduction of formation of extracellular polymeric substances (EPSs), which all yielded sludge flocs with a large pore structure conducive to form a fluffy and porous deposited layer in the membrane surface. Furthermore, high-throughput sequencing analysis revealed that the magnetic field also led to a reduction in microbial diversity, and that it promoted the enrichment of specific functional microbial communities (e.g. Bacteroidetes and Firmicutes) playing an important role in mitigating membrane fouling. Taken together, this study of magnetic field-enhanced magnetic biochar for MBR membrane fouling mitigation provides insights important new ideas for more effective and sustainable operation strategies.

Na+-Mg2+ ion effects on conformation and translocation dynamics of single-stranded RNA: Cooperation and competition.

The nanopore-based translocation of a single-stranded RNA (ssRNA) in mixed salt solution has garnered increasing interest for its biological and technological significance. However, it is challenging to comprehensively understand the effects of the mixed ion species on the translocation dynamics due to their cooperation and competition, which can be directly reflected by the ion screening and neutralizing effects, respectively. In this study, Langevin dynamics simulation is employed to investigate the properties of ssRNA conformation and translocation in mixed Na+-Mg2+ ion environments. Simulation results reveal that the ion screening effect dominates the change in the ssRNA conformational size, the ion neutralizing effect controls the capture rate of the ssRNA by the nanopore, and both of them take charge of the different changes in translocation time of the ssRNA under various mixed ion environments. Under high Na+ ion concentration, as Mg2+ concentration increases, the ion neutralizing effect strengthens, weakening the driving force inside the nanopore, leading to longer translocation time. Conversely, at low Na+ concentration, an increase in Mg2+ concentration enhances the ion screening effect, aiding in faster translocation. Furthermore, these simulation results will be explained by quantitative analysis, advancing a deeper understanding of the complicated effects of the mixed Na+-Mg2+ ions.

Extracellular vesicles in cancer therapy: Roles, potential application, and challenges.

Extracellular vesicles (EVs) have emerged as a novel cell-free strategy for the treatment of many diseases including cancer as they play important roles in cancer development and progression. Considering their natural capacity to facilitate cell-to-cell communication as well as their high physiochemical stability and biocompatibility, EVs serve as superior delivery systems for a wide range of therapeutic agents, including medicines, nanomaterials, nucleic acids, and proteins. Therefore, EVs-based cancer therapy is of greater interest to researchers. Mounting studies indicate that EVs can be improved in efficiency, specificity, and safety for cancer therapy. However, their heterogeneity of physicochemical properties and functions is not fully understood, hindering the achievement of bioactive EVs with high yield and purity. Herein, we paid more attention to the EVs applications and their significance in cancer therapy.

[Effect of Spatholobi Caulis extract from ethyl acetate on immune killing function of NK cells].

This study aims to investigate the regulatory effect of the Spatholobi Caulis extract from ethyl acetate(SEA) on natural killer(NK) cells under physiological conditions and elucidate the underlying mechanism. The C57BL/6 mice were randomized into NC and SEA groups, and NK-92 cells were respectively treated with 0, 25, 50, and 100 µg·mL~(-1) SEA. The body weight and immune organ index of the mice were compared between groups. The lactate dehydrogenase(LDH) assay was employed to examine the cytotoxicity of NK-92 cells treated with SEA and the killing activity of mouse NK cells against YAC-1 cells. The cell-counting kit-8(CCK-8) was used to examine the impact of SEA on the proliferation of NK-92 cells. Flow cytometry was employed to measure the number of NK cells in the peripheral blood as well as the expression levels of natural killer group 2 member A(NKG2A) and natural killer group 2 member D(NKG2D). The enzyme-linked immunosorbent assay(ELISA) was performed to determine the interferon(IFN)-γ secretion in the serum. Semi-quantitative PCR was conducted to determine the mRNA levels of NKG2A, NKG2D, and IFN-γ in spleen cells. Western blot was employed to investigate the involvement of phosphoinositide 3-kinase(PI3K)/extracellular regulated protein kinase 1(ERK1) signaling pathway. The results showed that SEA exhibited no adverse effects on the body, while significantly enhance the number of NK cells and augment the cytotoxicity of NK-92 cells against YAC-1 cells. Moreover, it suppressed the expression of NKG2A, enhanced the expression of NKG2D, promoted IFN-γ secretion, and upregulated the protein levels of PI3K and ERK. The findings suggest that SEA has the potential to enhance the immune recognition and effector function of NK cells by increasing the cell number, modulating the expression of functional receptors, and promoting IFN-γ secretion via the PI3K/ERK signaling pathway.

[Chaihu Sanshen Capsules protect rats from myocardial ischemia reperfusion injury via PKCßâ ¡/NOX2/ROS signaling pathway].

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cß(PKCßⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCßⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCßⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCßⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.

A new strategy for accelerating recovery of anaerobic granular sludge after low-temperature shock: In situ regulation of quorum sensing microorganisms embedded in polyvinyl alcohol sodium alginate.

Low-temperature could inhibit the performance of anaerobic granular sludge (AnGS). Quorum sensing (QS), as a communication mode between microorganisms, can effectively regulate AnGS. In this study, a kind of embedded particles (PVA/SA@Serratia) based on signal molecule secreting bacteria was prepared by microbial immobilization technology based on polyvinyl alcohol and sodium alginate to accelerate the recovery of AnGS system after low temperature. Low-temperature shock experiment verified the positive effect of PVA/SA@Serratia on restoring the COD removal rate and methanogenesis capacity of AnGS. Further analysis by metagenomics analysis showed that PVA/SA@Serratia stimulated higher QS activity and promoted the secretion of extracellular polymeric substance (EPS) in AnGS. The rapid construction of EPS protective layer effectively accelerated the establishment of a robust microbial community structure. PVA/SA@Serratia also enhanced multiple methanogenic pathways, including direct interspecies electron transfer. In conclusion, this study demonstrated that PVA/SA@Serratia could effectively strengthen AnGS after low-temperature shock.

[Prenatal diagnosis of fetal microdeletion and microduplication syndromes among pregnant women with advanced maternal ages].

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes. METHODS: A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children's Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out. RESULTS: CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%). CONCLUSION: The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

Impact of Drp1-regulated changes in T cell activity on the combined antitumor effects of PARPi and PD-1 inhibitors.

This study aimed to investigate the influence of dynamin-related protein 1 (Drp1)-regulated T cells on the antitumor effects of poly (ADP-ribose) polymerase inhibitors (PARPi) combined with programmed cell death protein 1 (PD-1) inhibitors to identify potential targets for enhancing immunotherapy efficacy. We found that T cells with high expression of Drp1 promoted the inhibitory and killing effects of the PARPi and PD-1 inhibitor combination on lung cancer cells in vivo and in vitro. This synergistic mechanism involves Drp1-regulated promotion of activation, migration, and intratumor infiltration of effector T cells; inhibition of negative immunomodulatory cells in the tumor microenvironment; and suppression of PARPi-induced upregulation of PD-L1 expression in tumor cells. These findings suggest that Drp1 could serve as a new target for comprehensively improving the tumor microenvironment, enhancing immunotherapy efficacy, and reversing immunotherapy resistance.

Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness.

BACKGROUND: To successfully replicate within the host cell, Toxoplasma gondii employs several mechanisms to overcome the host cell defenses and mitigate the harmful effects of the free radicals resulting from its own metabolic processes using effectors such as thioredoxin proteins. In this study, we characterize the location and functions of a newly identified thioredoxin in T. gondii, which was named Trx4. METHODS: We characterized the functional role of Trx4 in T. gondii Type I RH and Type II Pru strains by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The enzyme-catalyzed proximity labeling technique, the TurboID system, was employed to identify the proteins in proximity to Trx4. RESULTS: Trx4 was identified as a dense granule protein of T. gondii predominantly expressed in the parasitophorous vacuole (PV) and was partially co-localized with GRA1 and GRA5. Functional analysis showed that deletion of trx4 markedly influenced the parasite lytic cycle, resulting in impaired host cell invasion capacity in both RH and Pru strains. Mutation of Trx domains in Trx4 in RH strain revealed that two Trx domains were important for the parasite invasion. By utilizing the TurboID system to biotinylate proteins in proximity to Trx4, we identified a substantial number of proteins, some of which are novel, and others are previously characterized, predominantly distributed in the dense granules. In addition, we uncovered three novel proteins co-localized with Trx4. Intriguingly, deletion of trx4 did not affect the localization of these three proteins. Finally, a virulence assay demonstrated that knockout of trx4 resulted in a significant attenuation of virulence and a significant reduction in brain cyst loads in mice. CONCLUSIONS: Trx4 plays an important role in T. gondii invasion and virulence in Type I RH strain and Type II Pru strain. Combining the TurboID system with CRISPR-Cas9 technique revealed many PV-localized proximity proteins associated with Trx4. These findings suggest a versatile role of Trx4 in mediating the processes that occur in this distinctive intracellular membrane-bound vacuolar compartment.

Utility Scores for Risk-Reducing Mastectomy and Risk-Reducing Salpingo-Oophorectomy: Mapping to EQ-5D.

BACKGROUND: Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are the most effective breast and ovarian cancer preventive interventions. EQ-5D is the recommended tool to assess the quality of life and determine health-related utility scores (HRUSs), yet there are no published EQ-5D HRUSs after these procedures. These are essential for clinicians counselling patients and for health-economic evaluations. METHODS: We used aggregate data from our published systematic review and converted SF-36/SF-12 summary scores to EQ-5D HRUSs using a published mapping algorithm. Study control arm or age-matched country-specific reference values provided comparison. Random-effects meta-analysis provided adjusted disutilities and utility scores. Subgroup analyses included long-term vs. short-term follow-up. RESULTS: Four studies (209 patients) reported RRM outcomes using SF-36, and five studies (742 patients) reported RRSO outcomes using SF-12/SF-36. RRM is associated with a long-term (>2 years) disutility of -0.08 (95% CI -0.11, -0.04) (I2 31.4%) and a utility of 0.92 (95% CI 0.88, 0.95) (I2 31.4%). RRSO is associated with a long-term (>1 year) disutility of -0.03 (95% CI -0.05, 0.00) (I2 17.2%) and a utility of 0.97 (95% CI 0.94, 0.99) (I2 34.0%). CONCLUSIONS: We present the first HRUSs sourced from patients following RRM and RRSO. There is a need for high-quality prospective studies to characterise quality of life at different timepoints.

Boosting Formate Electrooxidation by Heterostructured PtPd Alloy and Oxides Nanowires.

Direct formate fuel cells (DFFCs) receive increasing attention as promising technologies for the future energy mix and environmental sustainability, as formate can be made from carbon dioxide utilization and is carbon neutral. Herein, heterostructured platinum-palladium alloy and oxides nanowires (PtPd-ox NWs) with abundant defect sites are synthesized through a facile self-template method and demonstrated high activity toward formate electrooxidation reaction (FOR). The electronic tuning arising from the heterojunction between alloy and oxides influence the work function of PtPd-ox NWs. The sample with optimal work function reveals the favorable adsorption behavior for intermediates and strong interaction in the d-p orbital hybridization between Pt site and oxygen in formate, favoring the FOR direct pathway with a low energy barrier. Besides the thermodynamic regulation, the heterostructure can also provide sufficient hydroxyl species to facilitate the formation of carbon dioxide due to the ability of combining absorbed hydrogen and carbon monoxide at adjacent active sites, which contributes to the improvement of FOR kinetics on PtPd-ox NWs. Thus, heterostructured PtPd-ox NWs achieve dual regulation of FOR thermodynamics and kinetics, exhibiting remarkable performance and demonstrating potential in practical systems.

Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES.

BACKGROUND: Age-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults. METHODS: This study used a dataset derived from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman' s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients. RESULTS: Multivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (ß = 0.37, 95% confidence interval [CI] = 0.01, 0.73; ß = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (ß = 0.82, 95% CI = 0.36, 1.3 and ß = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests. CONCLUSIONS: The study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.

Biomarker profiling to determine clinical impact of microRNAs in cognitive disorders.

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI.

Bruceantinol works as a CDK2/4/6 inhibitor to inhibit the growth of breast cancer cells.

Bruceantinol (BOL), isolated from the dried fruit of the Brucea javanica (L.) Merr., exhibits cytotoxic effects on breast cancer cells. However, the underlying mechanism remains to be fully addressed. In this paper, the MCF-7 and MDA-MB-231 human breast cancer cell lines were used as experimental models to uncover how BOL inhibits breast cancer cell growth. The effects of BOL on cell growth, proliferation, the cell cycle, and apoptosis were investigated using the MTT assays, EdU incorporation assays, and flow cytometry, respectively. Bioinformatics techniques were applied to predict the key targets of BOL in breast cancer. Subsequent validation of these targets and the anti-breast cancer mechanism of BOL was conducted through Western blotting, RT-PCR, siRNA transfection, and molecular docking analysis. The results demonstrated that BOL dose- and time-dependently reduced the growth of both cell lines, impeded cell proliferation, disrupted the cell cycle, and induced necrosis in MCF-7 cells and apoptosis in MDA-MB-231 cells. Furthermore, CDK2/4/6 were identified as BOL targets, and their knockdown reduced cell sensitivity to BOL. BOL was found to potentially bind with CDK2/4/6 to facilitate protein degradation through the proteasome pathway. Additionally, BOL activated ERK in MDA-MB-231 cells, and this activation was required for BOL's functions in these cells. Collectively, BOL may act as an inhibitor of CDK2/4/6 to exert anti-breast cancer effects. Its effects on cell growth and CDK2/4/6 expression may also depend on ERK activation in HRs-HER2- breast cancer cells. These results suggest the potential of using BOL for treating breast cancer.