The causal relationship between physical activity, sedentary behavior and brain cortical structure: a Mendelian randomization study.

Physical activity and sedentary behavior, both distinct lifestyle behaviors associated with brain health, have an unclear potential relationship with brain cortical structure. This study aimed to determine the causal link between physical activity, sedentary behavior, and brain cortical structure (cortical surface area and thickness) through Mendelian randomization analysis. The inverse-variance weighted method was primarily utilized, accompanied by sensitivity analyses, to confirm the results' robustness and accuracy. Analysis revealed nominally significant findings, indicating a potential positive influence of physical activity on cortical thickness in the bankssts (ß = 0.002 mm, P = 0.043) and the fusiform (ß = 0.002 mm, P = 0.018), and a potential negative association of sedentary behavior with cortical surface area in the caudal middle frontal (ß = -34.181 mm2, P = 0.038) and the pars opercularis (ß = -33.069 mm2, P = 0.002), alongside a nominally positive correlation with the cortical surface area of the inferior parietal (ß = 58.332 mm2, P = 0.035). Additionally, a nominally significant negative correlation was observed between sedentary behavior and cortical thickness in the paracentral (ß = -0.014 mm, P = 0.042). These findings offer insights into how lifestyle behaviors may influence brain cortical structures, advancing our understanding of their interaction with brain health.

Semiquantitative Fingerprinting Based on Pseudotargeted Metabolomics and Deep Learning for the Identification of Listeria monocytogenes and Its Major Serotypes.

The rapid identification of pathogenic microorganism serotypes is still a bottleneck problem to be solved urgently. Compared with proteomics technology, metabolomics technology is directly related to phenotypes and has higher specificity in identifying pathogenic microorganism serotypes. Our study combines pseudotargeted metabolomics with deep learning techniques to obtain a new deep semiquantitative fingerprinting method for Listeria monocytogenes identification at the serotype levels. We prescreened 396 features with orthogonal partial least-squares discrimination analysis (OPLS-DA), and 200 features were selected for deep learning model building. A residual learning framework for L. monocytogenes identification was established. There were 256 convolutional filters in the initial convolution layer, and each hidden layer contained 128 filters. The total depth included seven layers, consisting of an initial convolution layer, a residual layer, and two final fully connected classification layers, with each residual layer containing four convolutional layers. In addition, transfer learning was used to predict new isolates that did not participate in model training to verify the method's feasibility. Finally, we achieved prediction accuracies of L. monocytogenes at the serotype level exceeding 99%. The prediction accuracy of the new strain validation set was greater than 97%, further demonstrating the feasibility of this method. Therefore, this technology will be a powerful tool for the rapid and accurate identification of pathogens.

[Efficacy of compound Dendrobium on PI3K/AKT/eNOS signaling pathway in hypertensive rats induced by "dietary disorders"].

To observe the efficacy of compound Dendrobium on Sprague Dawley rats (SD) hypertension model induced by "dietary disorders" and its relevant mechanism, totally 50 SD rats were fed with high-sugar, high-fat diet and alcohol for four weeks. According to the blood pressure after modeling, the rats were divided into model group, valsartan group (8 mg·kg⁻¹), low, medium and high-dose Dendrobium candidum compound groups (1.65, 3.30, 5.00 g·kg⁻¹), with 10 rats in each group, and the other 10 SD rats were also taken as the normal group. After four weeks of treatment, blood pressure was measured. Orbital blood was collected for the determination of serum cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL), calculation of atherosclerosis index (AI). Nitric acid reductase method was used to detect serum nitric oxide (NO); the levels of serum endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by ELISA. The rats were put to death after the last administration, and the protein expressions of PI3K/AKT/eNOS in thoracic aorta of rats in each group were detected by Western blot. The aorta was separated and stained with hematoxylin-eosin (HE) to observe the changes in the endothelium and blood vessels in the thoracic aorta. Masson staining was used to observe the formation of aortic collagen. The expressions of nitric oxide synthase (eNOS) and ICAM-1 in aortic endothelial cells were observed by immunohistochemistry. In contrast, the results show D. candidum compound can significantly reduce the blood pressure in hypertensive rats, increase HDL-c, and reduce AI, while increasing serum NO content, decreasing ET-1 and ICAM-1 levels and promoting PI3K/AKT/NOS protein expressions. The lesion degree of the D. candidum compound group was reduced, and the collagen deposition was significantly reduced. Meanwhile, D. candidum compound can significantly increase the expression of eNOS, and reduce the formation of ICAM-1.Therefore, D. candidum compound has an obvious antihypertensive effect on hypertensive rats, which may be related to the increase in PI3K/AKT/eNOS signaling pathways and NO generation, the inhibition of the secretion of ICAM-1 and ET-1, the protection of the vascular endothelium and the improvement of aortic disease.

The association between physical activity intensity and frailty risk among older adults across different age groups and genders: Evidence from four waves of the China Health and Retirement Longitudinal Survey.

"Exercise is the best medicine" is well known, but the optimal dose of physical activity (PA) for males and females across different age groups is still unknown. This study, using data from the four waves of CHARLS, aimed to determine the optimal PA dose that reduces frailty risks among older adults across various age groups and both sexes. We created a frailty index score using 63 health-related variables and used 0.21 as the frailty cut point. Binary logistic regression was used to compare the effect of vigorous, moderate, and light intensity PA under IPAQ criteria on frailty risk. The study found that regardless of whether males or females, the optimal effect of vigorous-intensity PA in reducing the risk of frailty is consistently observed throughout the entire old age career. Moreover, the age groups at which moderate-intensity PA reduces the risk of frailty were from age 70 for males and from age 80 for females. And light-intensity PA had no effect on reducing the risk of frailty. Moderate and vigorous intensity of PA in older adults should be promoted, but guidelines and recommendations must account for optimal associations with PA dose across genders and age groups.

Pseudotargeted Metabolomic Fingerprinting and Deep Learning for Identification and Visualization of Common Pathogens.

Matrix-assisted laser desorption/ionization time-of-flight mass (MALDI-TOF) spectrometry fingerprinting has reduced turnaround times, costs, and labor as conventional procedures in various laboratories. However, some species strains with high genetic correlation have not been directly distinguished using conventional standard procedures. Metabolomes can identify these strains by amplifying the minor differences because they are directly related to the phenotype. The pseudotargeted metabolomics method has the advantages of both non-targeted and targeted metabolomics. It can provide a new semi-quantitative fingerprinting with high coverage. We combined this pseudotargeted metabolomic fingerprinting with deep learning technology for the identification and visualization of the pathogen. A variational autoencoder framework was performed to identify and classify pathogenic bacteria and achieve their visualization, with prediction accuracy exceeding 99%. Therefore, this technology will be a powerful tool for rapidly and accurately identifying pathogens.

Corticolimbic brain anomalies are associated with cognitive subtypes in psychosis: A longitudinal study.

BACKGROUND: Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes ("preserved," "deteriorated," and "compromised") seen in psychotic spectrum disorders. METHODS: Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group. RESULTS: Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in "deteriorated" cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in "compromised" than "preserved" subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in "deteriorated" compared with healthy controls and "preserved" subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes. CONCLUSION: These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.

Plasticity of DNA methylation, functional brain connectivity and efficiency in cognitive remediation for schizophrenia.

Cognitive remediation (CR) is predicated on principles of neuroplasticity, but the actual molecular and neurocircuitry changes underlying cognitive change in individuals with impaired neuroplastic processes is poorly understood. The present study examined epigenetic-neurocircuitry-behavioral outcome measures in schizophrenia, before and after participating in a CR program that targeted higher-order cognitive functions. Outcome measures included DNA methylation of genes central to synaptic plasticity (CpG sites of Reelin promoter and BDNF promoter) from buccal swabs, resting-state functional brain connectivity and topological network efficiency, and global scores of a cognitive battery from 35 inpatients in a rehabilitative ward (18 CR, 17 non-CR) with similar premorbid IQ to 15 healthy controls. Baseline group differences between healthy controls and schizophrenia, group-by-time effects of CR in schizophrenia, and associations between the outcome measures were tested. Baseline functional connectivity abnormalities within the frontal, fronto-temporal and fronto-parietal regions, and trending decreases in global efficiency, but not DNA methylation, were found in schizophrenia; the frontal and fronto-temporal connectivity, and global efficiency correlated with global cognitive performance across all individuals. Notably, CR resulted in differential changes in Reelin promoter CpG methylation levels, altered within-frontal and fronto-temporal functional connectivity, increasing global efficiency and improving cognitive performance in schizophrenia, when compared to non-CR. In the CR inpatients, positive associations between the micro to macro measures: Reelin methylation changes, higher global efficiency and improving global cognitive performance were found. Present findings provide a neurobiological insight into potential CR-led epigenetics-neurocircuitry modifications driving cognitive plasticity.

The Amygdala in Schizophrenia and Bipolar Disorder: A Synthesis of Structural MRI, Diffusion Tensor Imaging, and Resting-State Functional Connectivity Findings.

Frequently implicated in psychotic spectrum disorders, the amygdala serves as an important hub for elucidating the convergent and divergent neural substrates in schizophrenia and bipolar disorder, the two most studied groups of psychotic spectrum conditions. A systematic search of electronic databases through December 2017 was conducted to identify neuroimaging studies of the amygdala in schizophrenia and bipolar disorder, focusing on structural MRI, diffusion tensor imaging (DTI), and resting-state functional connectivity studies, with an emphasis on cross-diagnostic studies. Ninety-four independent studies were selected for the present review (49 structural MRI, 27 DTI, and 18 resting-state functional MRI studies). Also selected, and analyzed in a separate meta-analysis, were 33 volumetric studies with the amygdala as the region-of-interest. Reduced left, right, and total amygdala volumes were found in schizophrenia, relative to both healthy controls and bipolar subjects, even when restricted to cohorts in the early stages of illness. No volume abnormalities were observed in bipolar subjects relative to healthy controls. Shape morphometry studies showed either amygdala deformity or no differences in schizophrenia, and no abnormalities in bipolar disorder. In contrast to the volumetric findings, DTI studies of the uncinate fasciculus tract (connecting the amygdala with the medial- and orbitofrontal cortices) largely showed reduced fractional anisotropy (a marker of white matter microstructure abnormality) in both schizophrenia and bipolar patients, with no cross-diagnostic differences. While decreased amygdalar-orbitofrontal functional connectivity was generally observed in schizophrenia, varying patterns of amygdalar-orbitofrontal connectivity in bipolar disorder were found. Future studies can consider adopting longitudinal approaches with multimodal imaging and more extensive clinical subtyping to probe amygdalar subregional changes and their relationship to the sequelae of psychotic disorders.

Beneficial Effects of Paeoniflorin Enriched Extract on Blood Pressure Variability and Target Organ Damage in Spontaneously Hypertensive Rats.

Blood pressure variability (BPV) is associated with the development and progression of severe target organ damage (TOD). This study aims to evaluate the protective effect of paeoniflorin enriched extract from Radix Paeoniae Alba (PG) on BPV and TOD in spontaneously hypertensive rats (SHR). All SHR were orally treated with distilled water, metoprolol (MP, 20 mg/kg), and PG (PG-H, 90 mg/kg or PG-L, 30 mg/kg) for a single time or daily for 7 weeks. The 24-hour dynamic blood pressure was monitored and then calculated BPV including long- and short-term systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV), mean blood pressure variability (MBPV), and heart rate variability (HRV) as well as the 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP. The protective effects of PG on TOD were observed by histopathologic and biochemical detection. The results indicated that long- and short-term SBPV, DBPV, MBPV, and HRV as well as 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP showed no significant changes after single-dose administration of PG and significantly decreased after administration with PG for 7 weeks. PG could also markedly improve the damage of aorta, heart, kidney, and brain. This study suggested that PG could notably reduce BPV, stabilize blood pressure, and mitigate TOD in SHR.

[Studies on the saliva adsorption and the salivary film property on the hydroxyapatite surface].

OBJECTIVE: To evaluate the thickness and viscoelasticity of whole saliva (WS), parotid saliva (PS) and submandibular/sublingual gland saliva (SMSLS) film adsorption on the hydroxyapatite (HA) surface. METHODS: Ultra-thin layer of HA nanocrystals was coated on the dissipation TiO(2) sensor of gold quartz crystal microbalance using electrophoretic deposition technique. The thickness of the HA layer was measured by the ellipsometer, and element analysis was conducted using X-ray photoelectron spectroscopy. Atomic force microscopy and scanning electron microscope were used to observe its morphology. The in-situ adsorption thickness, the shear elastic modulus and the shear viscosity of salivary layers (WS, PS and SMSLS) on HA surfaces were investigated. The statistical data were analysed by an one-way ANOVA analysis followed by a SNK-q test. RESULTS: The results show that the HA layer was a plate-like morphology with 1.53 ± 0.12 in Ca/P molar ratio, (19.1 ± 0.9) nm in the thickness and (6.5 ± 1.6) nm in the roughness. The thickness of salivary film was SMSLS [(21.84 ± 1.25) nm] > WS[(17.91 ± 1.35) nm] > PS [(14.30 ± 1.03 nm) (P < 0.05). The shear elastic modulus of salivary film was PS [(0.61 ± 0.01) MPa] > SMSLS [(0.31 ± 0.09) MPa] and WS [(0.25 ± 0.03) MPa] (P < 0.05). The trend of the shear viscosity was opposite to one of thickness. CONCLUSIONS: The characteristics of saliva adsorption on HA surface suggest that the thicker, softer and more hydrated properties for the SMSLS and WS films are likely to afford a stronger lubrication to protect oral surfaces from wear and dehydration. The viscoelasticity of the PS film is probably related to the retention covering the oral cavity.

The interactions of epigallocatechin-3-gallate with human whole saliva and parotid saliva.

OBJECTIVE: The aim of the present study was to assess the null hypothesis that the astringency and loss of lubrication in the oral cavity are not related to the properties of the epigallocatechin-3-gallate (EGCG) adlayer, the affinity and the entropy-drive of EGCG binding to saliva. METHODS: The mass, thickness, and viscoelasticity of the EGCG adlayer and the temperature dependence of EGCG adsorption onto saliva surfaces were determined by quartz crystal microbalance with dissipation (QCM-D). The affinities of EGCG to human whole saliva (WS) and to parotid saliva (PS) were carried out by QCM-D monitoring and fluorescence quenching. RESULTS: The stiffer and more compact EGCG adlayers were formed on saliva surfaces at various concentrations of EGCG. The affinity for EGCG binding to WS was higher than that to PS. The precipitation of EGCG/saliva was temperature-dependent. The driving force of EGCG binding to saliva is dominated by the hydrogen bond, the hydrophobic reaction, and the entropy-drive, which were confirmed by the FTIR spectra and the measurement of temperature- dependence, respectively. CONCLUSION: The viscoelasticity of the EGCG adlayer, the affinity of EGCG to saliva, and the priority of EGCG binding to hydrophobic proteins on the mucosa may account for the oral astringency and loss of lubrication.