Comparison of the difference in the anti-inflammatory activity of two different color types of Farfarae Flos based on in vitro, in vivo experiments and untargeted metabolomics.

Introduction: Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored. Methods: This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms. Results: Our findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos. Discussion: This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos.

Roboticized AI-assisted microfluidic photocatalytic synthesis and screening up to 10,000 reactions per day.

The current throughput of conventional organic chemical synthesis is usually a few experiments for each operator per day. We develop a robotic system for ultra-high-throughput chemical synthesis, online characterization, and large-scale condition screening of photocatalytic reactions, based on the liquid-core waveguide, microfluidic liquid-handling, and artificial intelligence techniques. The system is capable of performing automated reactant mixture preparation, changing, introduction, ultra-fast photocatalytic reactions in seconds, online spectroscopic detection of the reaction product, and screening of different reaction conditions. We apply the system in large-scale screening of 12,000 reaction conditions of a photocatalytic [2 + 2] cycloaddition reaction including multiple continuous and discrete variables, reaching an ultra-high throughput up to 10,000 reaction conditions per day. Based on the data, AI-assisted cross-substrate/photocatalyst prediction is conducted.

Fiber Bragg Grating Pulse and Systolic Blood Pressure Measurement System Based on Mach-Zehnder Interferometer.

A fiber Bragg grating (FBG) pulse and systolic blood pressure (SBP) measurement system based on the edge-filtering method is proposed. The edge filter is the Mach-Zehnder interferometer (MZI) fabricated by two fiber couplers with a linear slope of 52.45 dBm/nm. The developed system consists of a broadband light source, an edge filter, fiber Bragg gratings (FBGs), a coarse wavelength-division multiplexer (CWDM), and signal-processing circuits based on a field-programmable gate array (FPGA). It can simultaneously measure pulse pulsations of the radial artery in the wrist at three positions: Cun, Guan and Chi. The SBP can be calculated based on the pulse transit time (PTT) principle. The measurement results compared to a standard blood pressure monitor showed the mean absolute error (MAE) and standard deviation (STD) of the SBP were 0.93 ± 3.13 mmHg. The system meets the requirements of the Association for the Advancement of Medical Instrumentation (AAMI) equipment standards. The proposed system can achieve continuous real-time measurement of pulse and SBP and has the advantages of fast detection speed, stable performance, and no compression sensation for subjects. The system has important application value in the fields of human health monitoring and medical device development.

Randomized Controlled Trial Comparing Training of Transseptal Puncture With or Without Intracardiac Echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) has been widely used in the catheter ablation of atrial fibrillation (AF). However, the value of ICE in the training of transseptal puncture (TSP) is unclear. METHODS: ICE-Training Study was a single-center, parallel-group, unmasked, randomized controlled trial registered in ChineseClinicalTrials.gov. Participants were randomly assigned (1:1) to different groups (1) the ICE simulator training group (ICE-ST), in which TSP was trained and performed under the guidance of both ICE and x-ray; and (2) the conventional simulator training group (Con-ST), in which TSP was trained and performed only under the guidance of x-ray. The trainees need to undergo the training stage and the evaluation stage. RESULTS: From October 2022 to December 2022, 18 consecutive fellows (age 32.4 ± 4.4 years, 12 males) without experience of TSP were included. The training period (16.9 ± 6.6 vs. 29.6 ± 8.7 times, p = 0.003) and the fluoroscopy time (120.3 ± 25.3 vs. 189.3 ± 40.2 s, p < 0.001) of the ICE-ST group was significantly shorter than that of the Con-ST group. No significant difference was found in the comprehensive performance of TSP in the ICE-ST group (composite score 96.7 ± 5.7) and the Con-ST group (composite score 95.9 ± 6.3, p = 0.62), but the selection of TSP sites in the ICE-ST group was commonly better than that in the Con-ST group. CONCLUSIONS: ICE could improve the efficiency of TSP training and optimize the site of TSP to facilitate catheter manipulation in the ablation. TRIAL REGISTRATION: ChineseClinicalTrials.gov identifier: ChiCTR2200058377.

Hydrogen sulfide ameliorated endothelial dysfunction in hyperhomocysteinemia rats: Mechanism of IRE1α/JNK pathway-mediated autophagy.

Previous studies showed that hyperhomocysteinemia (HHcy) induced endothelial dysfunction by endoplasmic reticulum (ER) stress induction and autophagy stimulation. This study aimed to determine the effect of hydrogen sulfide (H2S) in homocysteine (Hcy)-induced endothelial dysfunction and observe the possible mechanism involved. Male Wistar rats (160-180g) were used and randomly divided into four groups: Control group, HHcy group, HHcy+Sodium hydrosulfide (NaHS) group and NaHS group. Rats were fed with 2% high methionine diet for 8 weeks to set up HHcy model. Plasma concentration of Hcy was measured by ELISA. Endothelium-dependent and non-endothelium-dependent vasodilation of rat renal arteries were determined by myograph. The protein expression of cystathionine-γ-lyase (CSE), ER stress- and autophagy-related proteins in renal arteries or human umbilical vein endothelial cells (HUVECs) were analyzed by western blotting. The endothelial function was impaired in HHcy rats and HUVECs. NaHS supplementation could improve the ACh-induced vasodilation, however it was eliminated by ER stress inducer Tunicamycin (TM) or autophagy inducer Rapamycin. Western blotting in renal arteries showed that Glucose-regulated protein 78 (GRP78) and three branches of ER stress (p-IRE1α, p-PERK, ATF6) , p-JNK1+p-JNK2 were downregulated, simultaneously the autophagy marker Beclin1, LC3BII/LC3BI ratio were decreased and p62 was increased with NaHS treatment in HHcy rats. In HUVECs, IRE1α-JNK induced autophagy was involved in HHcy-induced endothelial dysfunction, while NaHS stimulation reversed the protein expression in IRE1α/JNK-autophagy pathway with Hcy incubation. This study might suggest that endothelial dysfunction induced by HHcy might be correlated with IRE1α-JNK-autophagy axis pathway, which was suppressed by exogenous supplementation of H2S donor, NaHS.

Indoor air pollution by solid fuel usages for cooking is longitudinally associated with possible sarcopenia in middle-aged Chinese population.

Objectives: The Asia Working Group of Sarcopenia (AWGS) 2019 consensus proposed a new concept named "possible sarcopenia". The present study was to estimate the association between indoor air pollution by solid fuel usages for cooking and possible sarcopenia among middle-aged and older Chinese population. Methods: A longitudinal cohort analysis was carried out using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 17,708 participants were recruited and followed up in the CHARLS. Cox proportional hazards models were used to estimate the effects of cooking fuel usages on the new onset of possible sarcopenia. Stratified analyses were performed according to gender and age, and sensitivity analyses were performed using the complete dataset. Results: A total of 4,653 participants were included in the final cohort analysis. During the follow-up of 4 years (2011-2015), a total of 1,532 (32.92%) participants developed new-onset possible sarcopenia. Compared with clean fuel usages for cooking, solid fuel usages were associated with a higher risk of possible sarcopenia (HR = 1.37, 95% CI = 1.23-1.52, p-value < 0.001). After adjusting for potential confounders, there was a trend for association between solid fuel usages and an increased risk of possible sarcopenia. Stratified analyses by gender and age demonstrated a stronger association of the solid fuel usages with possible sarcopenia in the middle-aged female participants (Model 1: HR = 1.83, 95% CI = 1.24-2.69, p-value = 0.002; Model 2: HR = 1.65, 95% CI = 1.10-2.47, p-value = 0.016). Sensitivity analyses indicated that the results were robust. Conclusion: Indoor air pollution from solid fuel usages for cooking was a modifiable risk factor for sarcopenia, especially in middle-aged female population. These findings provide a new prevention strategy to reduce the growing burden of sarcopenia, especially for middle-aged female individuals using solid fuels for cooking.

Correction: Indoor air pollution by solid fuel usages for cooking is longitudinally associated with possible sarcopenia in middle-aged Chinese population.

[This corrects the article DOI: 10.1007/s40201-024-00911-3.].

Biocontrol activity of Kluyveromyces marxianus YG-4 against Penicillium expansum LPH9 on apples.

Penicillium expansum (P. expansum), a widespread fungal pathogen, causes serious economic loss and public health concerns. The aim of this research is to investigate the antifungal effect of Kluyveromyces marxianus YG-4 (K. marxianus YG-4) against P. expansum and possible mechanism. The results showed that competition for nutrients and space, as well as the release of volatile organic compounds (VOCs), are the antifungal mechanisms. Citronellol may be the antifungal component of K. marxianus YG-4 VOCs based on GC-MS analysis. Further experiments had shown that citronellol inhibited the growth of P. expansum LPH9 by damaging the cell structure, disrupting the redox system, reducing antioxidant enzyme activity, and causing oxidative damage. K. marxianus YG-4, K. marxianus YG-4 VOCs and citronellol can effectively inhibit the spore germination of P. expansum on apples. The above results indicated that K. marxianus YG-4 had strong biocontrol activity and can be used as an excellent candidate strain for fruit preservation.

Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis.

AIM: Sepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms. METHODS: Patients with sepsis and healthy controls were included. Sepsis in rats was induced by lipopolysaccharide. Dexmedetomidine, a α2-adrenergic receptor agonist, was used in patients and rats with sepsis to evaluate the role of the sympathetic nervous system in sepsis. Holter monitoring was used to detect heart rate variability, while plasma samples were obtained to measure levels of norepinephrine and inflammatory markers. Mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded. Immunofluorescence was used to detect the activation of neurons in the rostral ventrolateral medulla (RVLM). RESULTS: In patients with sepsis, plasma levels of norepinephrine and interleukin-1ß were higher compared with those in controls and positively correlated with acute physiology and chronic health evaluation (APACHE) II. SDNN and SDANN were significantly reduced as well as negatively correlated with APACHE II. Meanwhile, rats with sepsis showed increased of sympathetic outflow and plasma levels of norepinephrine, with increased c-fos levels in the RVLM. Treatment with dexmedetomidine could improve prognosis. Lesion of tyrosine hydroxylase-positive neurons in the RVLM attenuated sympathetic activation and target organs damage in septic rats as well as improved survival. CONCLUSION: The results suggest that tyrosine hydroxylase-positive neurons in the RVLM might contribute to the prognosis of sepsis via activation of the sympathetic nervous system, while dexmedetomidine could ameliorate sepsis via inhibiting sympathetic activation.

Association between cumulative intake of sugar-sweetened and artificially sweetened beverages and progression of coronary calcification: Insights from the CARDIA study.

BACKGROUND AND AIMS: This study investigates the relationship between the cumulative intake of artificially sweetened beverages (ASBs) and sugar-sweetened beverages (SSBs) during young adulthood and the progression of coronary artery calcium (CAC) by midlife, using data from the Coronary Artery Risk Development in Young Adults study. METHODS AND RESULTS: We included 2,466 participants with CAC measurement via computed tomography at the 15th, 20th, and 25th year follow-ups. Dietary intake was assessed using the CARDIA Diet History at baseline and years 7. Cumulative average beverage intake was calculated and categorized. Multivariable Cox regression models adjusted for demographic, lifestyle, and cardiovascular risk factors assessed associations between beverages consumption and CAC progression. Among the included participants, 1107 (44.9 %) were male, 1439 (58.4 %) were white, and the average age was 40.4 years with a standard deviation of 3.5 years. Over a 9.2±1.8-year follow-up, CAC progression was recorded in 715 participants. Higher cumulative ASBs intake was associated with increased CAC progression risk, with hazard ratios (95%CI, P-value) for low and high ASBs consumption being 1.35 (1.14, 1.60; P < 0.001) and 1.54 (1.15, 2.07; P < 0.001) compared to non-consumers. Participants consuming >2 servings/day of SSBs had a 37 % higher CAC progression risk (HR 1.37, 95 % CI 1.14-1.64, P < 0.001). However, no significant association was found between SSB consumption and CAC progression after adjusting for confounders. CONCLUSIONS: Prolonged consumption of beverages, especially ASBs, in young adults is linked to an increased risk of CAC progression.

The influence of physical literacy of student with different obesity levels on physical fitness: the mediating effect of MVPA.

Background: Perceived physical literacy (PL) is a potential factor for improving health and physical activity, but the relationship between PL and physical fitness (PF) among college students with different obesity levels has not yet been determined. Purpose: The aim of this study was to explore the correlation between PL, moderate-to-vigorous physical activity (MVPA), and PF among college students with different obesity levels. Methods: We recruited Chinese university students to complete a questionnaire and conducted a survey using the Perceived Physical Literacy Instrument Scale (PPLI-SC) and the International Physical Activity Questionnaire Short Form (IPAQ-SF). The physical fitness test data were used for data analysis. The direct and indirect impacts were analyzed using Pearson correlation and the SPSS Hayes process macro (Model 4). Results: The study surveyed 909 boys and 1,668 girls for a total of 2,577 valid questionnaires. Similarly, the MVPA and perceived PL of boys were significantly greater than those of girls (p < 0.01), but the opposite was true for the PF score. The correlation analysis showed that MVPA, perceived PL, and PF were significantly correlated (p < 0.01). For normal weight student, the results showed that the direct effect of PL on PF was still statistically significant (ß = 0.076, p < 0.01) after adding MVPA; MVPA had a positive effect on PF after controlling for perceived PL (ß = 0.055, p < 0.05). Perceived PL has a positive effect on MVPA (ß = 0.123, p < 0.01). The mediating effect of MVPA was notably significant, with a mediation effect percentage of 7.9%. However, it has been found that among the underweight population, there is an absence of a significant relationship between PL, PF, and MVPA (p > 0.05). Contrarily, in the overweight and obese groups, the mediating role of MVPA in the relationship between PL and PF was not statistically supported (-0.002, 0.033). Conclusion: For normal weight student, perceived PL has a positive impact on PF and can also be promoted by increasing the pathway of MVPA. For both underweight individuals and obese populations, further investigation is needed into methods for promoting PA and improving PF.

Revealing the distinct impacts of effectiveness recognition and memory retention on the transfer of creative cognitive reappraisal.

Previous research has shown that creative cognitive reappraisal is highly effective in regulating negative emotions. We conducted three experiments to explore its transferability. In Experiment 1, we observed that free recall performance was better for creative reappraisal compared to non-creative reappraisal. Memory retention of reappraisals was associated with creativity ratings, but not with perceived effectiveness ratings. In Experiment 2, participants generated reappraisals for newly introduced unpleasant images before (pre-session) and after (post-session) exposure to creative reappraisal, non-creative reappraisal, and descriptive control interpretation. Results showed increased reflective effectiveness of self-generated reappraisals in the post-session. The level of creativity of the self-generated reappraisals was associated with differences in perceived effectiveness between creative and non-creative exposed reappraisals. In Experiment 3, we investigated how two processing approaches (effectiveness-oriented vs. memory-oriented) influenced the transferability of creative reappraisal. We observed creativity levels of self-generated reappraisals increased in both conditions. The reflective effectiveness of the self-generated reappraisals tended to increase only in the effectiveness-oriented processing condition. Our findings demonstrate that recognising the effectiveness of creative reappraisal plays a crucial role in its transfer across different situations.

RNA-binding protein YBX3 promotes PPARγ-SLC3A2 mediated BCAA metabolism fueling brown adipogenesis and thermogenesis.

OBJECTIVE: Activating brown adipose tissue (BAT) thermogenesis is a promising approach to combat obesity and metabolic disorders. The post-transcriptional regulation of BAT thermogenesis mediated by RNA-binding proteins (RBPs) is still not fully understood. This study explores the physiological role of novel RBPs in BAT differentiation and thermogenesis. METHODS: We used multiple public datasets to screen out novel RBPs responsible for BAT differentiation and thermogenesis. In vitro loss- and gain-of-function experiments were performed in both C3H10T1/2 preadipocytes and mature brown adipocytes to determine the role of Y-box binding protein 3 (YBX3) in brown adipocyte differentiation and thermogenesis. Adeno-associated virus (AAV)-mediated BAT-specific knockdown or overexpression of Ybx3 was applied to investigate the function of YBX3 in vivo. RESULTS: YBX3 is a brown adipocyte-enriched RBP induced by cold stimulation and ß-adrenergic signaling. Both in vitro loss- and gain-of-function experiments demonstrate that YBX3 is essential for brown adipocyte differentiation and thermogenesis. BAT-specific loss of Ybx3 dampens thermogenesis and exacerbates diet-induced obesity in mice, while overexpression of Ybx3 promotes thermogenesis and confers protection against diet-induced metabolic dysfunction. Transcriptome analysis and mitochondrial stress test indicate that Ybx3 deficiency compromises the mitochondrial oxidative phosphorylation, leading to thermogenic failure. Mechanistically, YBX3 stabilizes the mRNA of Slc3a2 and Pparg, which facilitates branched-chain amino acid (BCAA) influx and catabolism and fuels brown adipocyte differentiation and thermogenesis. CONCLUSIONS: YBX3 facilitates BAT fueling BCAA to boost thermogenesis and energy expenditure, which protects against obesity and metabolic dysfunction. Thus, YBX3 could be a promising therapeutic target for obesity.

Buckling cluster-based H-bonded icosahedral capsules and their propagation to a robust zeolite-like supramolecular framework.

Hydrogen-bonded assembly of multiple components into well-defined icosahedral capsules akin to virus capsids has been elusive. In parallel, constructing robust zeolitic-like cluster-based supramolecular frameworks (CSFs) without any coordination covalent bonding linkages remains challenging. Herein, we report a cluster-based pseudoicosahedral H-bonded capsule Cu60, which is buckled by the self-organization of judiciously designed constituent copper clusters and anions. The spontaneous formation of the icosahedron in the solid state takes advantage of 48 charge-assisted CH···F hydrogen bonds between cationic clusters and anions (PF6-), and is highly sensitive to the surface protective ligands on the clusters with minor structural modification inhibiting its formation. Most excitingly, an extended three-periodic robust zeolitic-like CSF, is constructed by edge-sharing the resultant icosahedrons. The perpendicular channels of the CSF feature unusual 3D orthogonal double-helical patterns. The CSF material not only keeps its single-crystal character in the desolvated phase, but also exhibits excellent chemical and thermal stabilities as well as long-lived phosphorescence emission.

Objectively measured levels of moderate to vigorous intensity physical activity are associated with cognitive impairment in diabetic hemodialysis patients: a cross-sectional study.

Objective: The purpose of this study was to observe the relationship between objectively measured levels of physical activity and cognitive impairment (CI) in the presence or absence of diabetes in middle-aged and elderly hemodialysis patients. Methods: In this multicenter cross-sectional study, 339 clinically stable hemodialysis patients (210 males; mean age: 67.38 ± 8.07 years) aged ≥55 years were included from 7 dialysis units in Shanghai, China. The Chinese version of the Modified Mini-Mental State Examination (MMSE) was used to assess the CI. The duration of physical activity at different intensities, including moderate to vigorous physical activity (MVPA) as well as light physical activity (LPA), was measured using a triaxial accelerometer (ActiGraph GT3X+, Pensacola, FL, USA). Logistic regression and multiple linear regression were used for analyses. Results: The prevalence of CI was higher in hemodialysis patients with comorbid diabetes (24.3%). In diabetic patients, MVPA (increase per 10 min/day) was negatively associated with CI after adjusting for covariates [(OR = 0.89, 95%CI = 0.79-0.99), p = 0.042]. However, no significant association between physical activity and CI was found in non-diabetic hemodialysis patients. Further analyses revealed that MVPA was positively associated with temporal orientation, attention and calculation and recall in diabetic hemodialysis patients. Conclusion: Physical activity was associated with CI in diabetic hemodialysis patients rather than the non-diabetes group. This study is important for early differential diagnosis of CI and improvement of cognitive status in hemodialysis patients.

Enzyme-Mimetic, Cascade Catalysis-Based Triblock Polypeptide-Assembled Micelles for Enhanced Chemodynamic Therapy.

Peptides and their conjugates are appealing as molecular scaffolds for constructing supramolecular biomaterials from the bottom up. Through strategic sequence design and interaction modulation, these peptides can self-assemble into diverse nanostructures that can, in turn, mimic the structural and catalytic functions of contemporary proteins. Here, inspired by the histidine brace active site identified in the metalloenzyme, we developed a triblock polypeptide with a hydrophobic polyleucine segment, a hydrophilic polylysine segment, and a terminal oligohistidine segment. This polypeptide demonstrates tunable and adaptive self-assembly morphologies. Moreover, copper ions can interact with the oligohistidine chelator and mediate the supramolecular assembly, generating metal-ligand centers for redox flow. The triblock polypeptide-based peptide micelles show Fenton-type activity with high substrate affinity when coassembled with copper ions. We have also engineered therapeutic micelles by coassembling two polypeptides, one integrated with copper ions and the other conjugated with glucose oxidase. This coassembled nanoplatform shows high in vitro and in vivo antitumor efficacy through a mechanism that combines triggered starvation and chemodynamic therapy. The versatility of this polypeptide sequence, which is compatible with various metal ions and functional ligands, paves the way for a broad spectrum of therapeutic and diagnostic applications.

The Cumulative Variations of Respiratory Syncytial Virus Fusion Protein (F) in Ten Consecutive Years in China.

BACKGROUND: Variations in the fusion (F) protein of respiratory syncytial virus (RSV) with main antigenic sites I-V and Ø may affect the development of RSV vaccines and therapies. METHODS: In the study, 30 respiratory specimens positive for RSV were randomly selected from children with acute lower respiratory infections (ALRI) in Beijing every year from 2012 to 2021 for F gene sequencing. Then, 300 F gene sequences and 508 uploaded to GenBank from China were subjected to phylogenetic analysis. RESULTS: The results indicated the nucleotide identities were 95.4-100% among 446 sequences of RSV A, and 96.3-100% among 362 of RSV B. The most common variant loci were N80K (100.00%) and R213S (97.76%) for site Ø, and V384I/T (98.43%) for site I among sequences of RSV A, and M152I (100.00%), I185V (100.00%), and L172Q/H (94.48%) for site V, and R202Q (99.45%) for site Ø among sequences of RSV B. N276S appears in 95.29% sequences of RSV A, while S276N and N262 I/S appear in 1.38% and 0.55% sequences of RSV B, respectively. No variation was found in all sequences at the binding sites of 14N4 and motavizumab. CONCLUSIONS: There were cumulative variations of the RSV F gene, especially at some binding sites of antigenic sites.

Efficacy of vitamin D supplementation on depressive symptoms in older patients: a meta-analysis of randomized controlled trials.

Background: The relationship between vitamin D and depression has garnered significant attention in recent years. However, the efficacy of vitamin D in ameliorating depression among specific subgroups of older patients remains controversial. This study aimed to assess the impact of vitamin D supplementation on depressive symptoms and the prevalence of depression in older adults. Additionally, the study sought to examine potential moderating factors, including differences among population subgroups and various supplementation strategies. Methods: A systematic literature search was conducted in the databases PubMed, EMBASE, Web of Science, and the Cochrane Library up to March 2024. The RevMan 5.3 software was utilized to calculate the standardized mean difference (SMD) and to evaluate the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The objective was to determine the efficacy of vitamin D supplementation in alleviating depressive symptoms or treating depression in older adults. Results: This meta-analysis encompassed eleven studies, comprising a total of 21,561 participants. The findings did not indicate a statistically significant therapeutic benefit of vitamin D supplementation for depression in older patients [SMD: -0.10; 95% CI: (-1.19, 0.00); p = 0.05]. Subgroup analyses revealed that the efficacy of vitamin D intervention in geriatric depression correlated with several factors, including baseline serum 25(OH)D levels, the dosage of the intervention, gender, and the initial presence of depressive symptoms or a diagnosis of depression. Conclusion: The current evidence is insufficient to conclusively establish the significant efficacy of vitamin D supplementation in alleviating depressive symptoms among older patients. Consequently, additional randomized controlled trials are warranted to further validate the relationship between vitamin D supplementation and depression in the older adults.

Heparin-enriched plasma proteome is significantly altered in Alzheimer's disease.

INTRODUCTION: Heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to ß-amyloid (Aß) and tau pathology in Alzheimer's disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry-based proteomic approaches. METHODS: We employed heparin-affinity chromatography, followed by off-line fractionation and tandem mass tag mass spectrometry (TMT-MS), to enrich HBPs from plasma obtained from AD (n = 62) and control (n = 47) samples. These profiles were then correlated to Aß, tau and phosphorylated tau (pTau) CSF biomarkers and plasma pTau181 from the same individuals, as well as a consensus brain proteome network to assess the overlap with AD brain pathophysiology. RESULTS: Heparin enrichment from plasma was highly reproducible, enriched well-known HBPs like APOE and thrombin, and depleted high-abundant proteins such as albumin. A total of 2865 proteins, spanning 10 orders of magnitude in abundance, were measured across 109 samples. Compared to the consensus AD brain protein co-expression network, we observed that specific plasma proteins exhibited consistent direction of change in both brain and plasma, whereas others displayed divergent changes, highlighting the complex interplay between the two compartments. Elevated proteins in AD plasma, when compared to controls, included members of the matrisome module in brain that accumulate with Aß deposits, such as SMOC1, SMOC2, SPON1, MDK, OLFML3, FRZB, GPNMB, and the APOE4 proteoform. Additionally, heparin-enriched proteins in plasma demonstrated significant correlations with conventional AD CSF biomarkers, including Aß, total tau, pTau, and plasma pTau181. A panel of five plasma proteins classified AD from control individuals with an area under the curve (AUC) of 0.85. When combined with plasma pTau181, the panel significantly improved the classification performance of pTau181 alone, increasing the AUC from 0.93 to 0.98. This suggests that the heparin-enriched plasma proteome captures additional variance in cognitive dementia beyond what is explained by pTau181. CONCLUSION: These findings support the utility of a heparin-affinity approach coupled with TMT-MS for enriching amyloid-associated proteins, as well as a wide spectrum of plasma biomarkers that reflect pathological changes in the AD brain.