Functional properties and skin care effects of sodium trehalose sulfate.

BACKGROUND: It is known that heparinoid, a mucopolysaccharide polysulfate, is effective in improving rough skin and promoting blood circulation as medicines for diseased areas. However, heparinoid has a molecular weight of more than 5000 and cannot penetrate healthy stratum corneum. OBJECTIVE: We tested the efficacy of sulfated oligosaccharides with a molecular weight of less than 2000 on the human skin barrier function and moisturizing function. METHODS: We measured the transepidermal water loss (TEWL) of a three-dimensional human epidermis model cultured for 3 days after topical application of sulfated oligosaccharides, then observed the effects on TEWL suppression. The mRNA levels of proteins involved in intercellular lipid transport and storage in the stratum corneum, and moisture retention were measured using RT-qPCR. RESULTS: An increase in the mRNA levels of the ATP-binding cassette subfamily A member 12 (ABCA12), which transports lipids into stratum granulosum, was confirmed. Increases were also observed in the mRNA levels of filaggrin (FLG), which is involved in the generation of natural moisturizing factors, and of caspase-14, calpain-1 and bleomycin hydrolase, which are involved in the degradation of FLG. Antibody staining confirmed that the application of sodium trehalose sulfate to 3D model skin resulted in more ABCA12, ceramide, transglutaminase1, and FLG than those in controls. In a randomized, placebo-controlled, double-blind study, participants with low stratum corneum water content applied a lotion and emulsion containing sodium trehalose sulfate to their faces for 4 weeks. Sodium trehalose sulfate decreased the TEWL and increased the stratum corneum water content. CONCLUSION: These results suggest that cosmetics containing sodium trehalose sulfate act on the epidermis by increasing barrier factors and moisturizing factors, thereby ameliorating dry skin.

TacPrint: Visualizing the Biomechanical Fingerprint in Table Tennis.

Table tennis is a sport that demands high levels of technical proficiency and body coordination from players. Biomechanical fingerprints can provide valuable insights into players' habitual movement patterns and characteristics, allowing them to identify and improve technical weaknesses. Despite the potential, few studies have developed effective methods for generating such fingerprints. To address this gap, we propose TacPrint, a framework for generating a biomechanical fingerprint for each player. TacPrint leverages machine learning techniques to extract comprehensive features from biomechanics data collected by inertial measurement units (IMU) and employs the attention mechanism to enhance model interpretability. After generating fingerprints, TacPrint provides a visualization system to facilitate the exploration and investigation of these fingerprints. In order to validate the effectiveness of the framework, we designed an experiment to evaluate the model's performance and conducted a case study with the system. The results of our experiment demonstrated the high accuracy and effectiveness of the model. Additionally, we discussed the potential of TacPrint to be extended to other sports.

High Sensitivity and Wide Linear Range Flexible Piezoresistive Pressure Sensor with Microspheres as Spacers for Pronunciation Recognition.

Flexible piezoresistive pressure sensors have received great popularity in flexible electronics due to their simple structure and promising applications in health monitoring and artificial intelligence. However, the contradiction between sensitivity and detection range limits the application of the sensors in the medium-pressure regime. Here, a flexible piezoresistive pressure sensor is fabricated by combining a hierarchical spinous microstructure sensitive layer and a periodic microsphere array spacer. The sensor achieves high sensitivity (39.1 kPa-1) and outstanding linearity (0.99, R2 coefficient) in a medium-pressure regime, as well as a wide range of detection (100 Pa-160.0 kPa), high detection precision (<0.63‰ full scale), and excellent durability (>5000 cycles). The mechanism of the microsphere array spacer in improving sensitivity and detection range was revealed through finite element analysis. Furthermore, the sensors have been utilized to detect muscle and joint movements, spatial pressure distributions, and throat movements during pronouncing words. By means of a full-connect artificial neural network for machine learning, the sensor's output of different pronounced words can be precisely distinguished and classified with an overall accuracy of 96.0%. Overall, the high-performance flexible pressure sensor based on a microsphere array spacer has great potential in health monitoring, human-machine interface, and artificial intelligence of medium-pressure regime.

Long non-coding RNA LIP interacts with PARP-1 influencing the efficiency of base excision repair.

In recent years, various long non-coding RNAs (lncRNAs) involved in DNA damage response (DDR) have been identified and studied to deepen our understanding. However, there are rare reports on the association between lncRNAs and base excision repair (BER). Our designed DNA microarray identified dozens of functionally unknown lncRNAs, and their transcription levels significantly increased upon exposure to DNA damage inducers. One of them, named LIP (Long noncoding RNA Interacts with PARP-1), exhibited a significant alteration in transcription in response to methyl methanesulfonate (MMS) and temozolomide (TMZ) treatments. LIP knockdown or knockout cell lines are sensitive to MMS and TMZ, indicating that LIP plays a crucial role in DDR. The loss or insufficiency of LIP significantly influences the efficiency of BER in human cells, and it suggests that LIP participates in the BER pathway. The interaction between LIP and a key factor in BER, poly (ADP-ribose) polymerase 1 (PARP-1), has been confirmed. We identified and characterized LIP, a lncRNA, which is involved in DDR, significantly influences BER efficiency, and interacts with the BER key factor PARP-1. This advances our understanding of the connection between lncRNAs and BER, presenting the potential for the discovery of new drug targets.

Regulation of the growth performance and the gastrointestinal microbiota community by the addition of defective pear fermentation to feed of small-tailed Han sheep.

This study investigated the effects of defective pear fermentation (DPF) diets on growth performance and gastrointestinal microbial communities in 60 healthy male small-tailed Han sheep, aged 90 days. The sheep were randomly divided into four groups, each consisting of three replicates with five sheep per replicate. Initially, all groups received a basal diet for seven days during the adaptation stage. Subsequently, for 60 days, group C (control) was fed a basal diet, group X received a basal diet with 2% DPF, group Y had a basal diet with 4% DPF, and group Z was fed a basal diet with 6% DPF. The results indicated that group Y experienced a significant increase in average daily gain (ADG) and average daily feed intake (ADFI). The addition of DPF significantly elevated the levels of GSH-Px and notably reduced MDA content compared to group C. Analysis of gastrointestinal microbiota showed that groups receiving DPF had increased relative abundances of Lachnospiraceae_NK3A20_group, norank_f p-2534-18B5_gut_group, Acetitomaculum, Actinobacteriota, Bacteroidota and Ruminococcus_gauvreauii_group, and decreased abundances of Proteobacteria, Prevotella, Staphylococcus, and Psychrobacter compared to group C. Group X exhibited the highest relative abundance of Olsenella, while group Y showed a significant increase in unclassified_f Lachnospiraceae compared to the other groups. Bacterial function prediction indicated that pathways related to energy metabolism were more prevalent in group X and Y. This study preliminarily confirms the feasibility of using DPF as feed additives, providing a foundation for further research and evaluation of DPF's application in animal production.

Association of Ultraprocessed Food Consumption with Risk of Cardiovascular Disease Among Individuals with Type 2 Diabetes: Findings from the UK Biobank.

SCOPE: Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association. METHODS AND RESULTS: This study includes 5405 participants with T2D who provided at least one 24-h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A, C-reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD. CONCLUSION: Higher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.

Improving the Performance of Si/PEDOT:PSS Hybrid Solar Cells with More Economical and Environmentally Friendly Alcohol Ether Solvents.

The photoelectric characteristics of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) films significantly affect the power conversion efficiency and stability of Si/PEDOT:PSS hybrid solar cells. In this paper, we investigated PEDOT:PSS modification with alcohol ether solvents (dipropylene glycol methyl ether (DPM) and propylene glycol phenyl ether (PPH)). The reduction of PSS content and the transformation of the PEDOT chain from benzene to a quinone structure in PEDOT:PSS induced by doping with DPM or PPH are the reasons for the improved conductivity of PEDOT:PSS films. DPM and PPH doping improves the quality of silicon with the PEDOT:PSS heterojunction and silicon surface passivation, thereby reducing the surface recombination of charge carriers, which improves the photovoltaic performance of Si/PEDOT:PSS solar cells. Comparing the power conversion performance (PCE) and air stability of Si/PEDOT:PSS solar cells with DPM (13.24%), DPH (13.51%), ethylene glycol (EG, 13.07%), and dimethyl sulfoxide (DMSO, 12.62%), it is suggested that doping with DPM and DPH can replace DMSO and EG to enhance the performance of Si/PEDOT:PSS solar cells. The EG and DMSO solvents not only have a certain toxicity to the human body but also are not environmentally friendly. In comparison to DMSO and EG, DPM and DPH are more economical and environmentally friendly, helping to reduce the manufacturing cost of Si/PEDOT:PSS solar cells and making them more conducive to their commercial applications.

Enhancing Dielectric Properties of (CaCu3Ti4O12 NWs-Graphene)/PVDF Ternary Oriented Composites by Hot Stretching.

Using high-dielectric inorganic ceramics as fillers can effectively increase the dielectric constant of polymer-based composites. However, a high percentage of fillers will inevitably lead to a decrease in the mechanical toughness of the composite materials. By introducing high aspect ratio copper calcium titanate (CaCu3Ti4O12) nanowires (CCTO NWs) and graphene as fillers, the ternary poly(vinylidene fluoride) (PVDF)-based composites (CCTO NWs-graphene)/PVDF with a significant one-dimensional orientation structure were prepared by hot stretching. CCTO NWs and graphene are arranged in a directional manner to form a large number of microcapacitor structures, which significantly improves the dielectric constant of the composites. When the ratio of CCTO NWs and graphene is 0.2 and 0.02, the oriented composites have the highest dielectric constant, which is 19.3% higher than the random composites, respectively. Numerical simulations reveal that the introduction of graphene and the construction of the one-dimensional oriented microstructure have a positive effect on improving the dielectric properties of the composites. This study provides a strategy to improve the dielectric properties of composite materials by structural design without changing the filler content, which has broad application prospects in the field of electronic devices.

Deep Learning-Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease.

Alzheimer's disease (AD) is a pressing concern in neurodegenerative research. To address the challenges in AD drug development, especially those targeting Aß, this study uses deep learning and a pharmacological approach to elucidate the potential of pyrroloquinoline quinone (PQQ) as a neuroprotective agent for AD. Using deep learning for a comprehensive molecular dataset, blood-brain barrier (BBB) permeability is predicted and the anti-inflammatory and antioxidative properties of compounds are evaluated. PQQ, identified in the Mediterranean-DASH intervention for a diet that delays neurodegeneration, shows notable BBB permeability and low toxicity. In vivo tests conducted on an Aß1₋42-induced AD mouse model verify the effectiveness of PQQ in reducing cognitive deficits. PQQ modulates genes vital for synapse and anti-neuronal death, reduces reactive oxygen species production, and influences the SIRT1 and CREB pathways, suggesting key molecular mechanisms underlying its neuroprotective effects. This study can serve as a basis for future studies on integrating deep learning with pharmacological research and drug discovery.

Lichen pectin-containing polysaccharide from Xanthoria elegans and its ability to effectively protect LX-2 cells from H2O2-induced oxidative damage.

Xanthoria elegans, a drought-tolerant lichen, is the original plant of the traditional Chinese medicine "Shihua" and effectively treats a variety of liver diseases. However, thus far, the hepatoprotective effects of polysaccharides, the most important chemical constituents of X. elegans, have not been determined. The aim of this study was to screen the polysaccharide fraction for hepatoprotective activity by using free radical scavenging assays and a H2O2-induced Lieming Xu-2 cell (LX-2) oxidative damage model and to elucidate the chemical composition of the bioactive polysaccharide fraction. In the present study, three polysaccharide fractions (XEP-50, XEP-70 and XEP-90) were obtained from X. elegans by hot-water extraction, DEAE-cellulose anion exchange chromatography separation and ethanol gradient precipitation. Among the three polysaccharide fractions, XEP-70 exhibited the best antioxidant activity in free radical scavenging capacity and reducing power assays. Structural studies showed that XEP-70 was a pectin-containing heteropolysaccharide fraction that was composed mainly of (1 â†’ 4)-linked and (1 â†’ 4,6)-linked α-D-Glcp, (1 â†’ 4)-linked α-D-GalpA, (1 â†’ 2)-linked, (1 â†’ 6)-linked and (1 â†’ 2,6)-linked α-D-Manp, and (1 â†’ 6)-linked and (1 â†’ 2,6)-linked ß-D-Galf. Furthermore, XEP-70 exhibited effectively protect LX-2 cells against H2O2-induced oxidative damage by enhancing cellular antioxidant capacity by activating the Nrf2/Keap1/ARE signaling pathway. Thus, XEP-70 has good potential to protect hepatic stellate cells against oxidative damage.

Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17.

Improving the function of the blood-spinal cord barrier (BSCB) benefits the functional recovery of mice following spinal cord injury (SCI). The death of endothelial cells and disruption of the BSCB at the injury site contribute to secondary damage, and the ubiquitin-proteasome system is involved in regulating protein function. However, little is known about the regulation of deubiquitinated enzymes in endothelial cells and their effect on BSCB function after SCI. We observed that Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells. In vitro Sox17 knockdown attenuated endothelial cell proliferation, migration, and tube formation, while in vivo Sox17 knockdown inhibited endothelial regeneration and barrier recovery, leading to poor functional recovery after SCI. Conversely, in vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury. Additionally, immunoprecipitation-mass spectrometry revealed the interaction between the deubiquitinase UCHL1 and Sox17, which stabilized Sox17 and influenced angiogenesis and BSCB repair following injury. By generating UCHL1 conditional knockout mice and conducting rescue experiments, we further validated that the deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17. Collectively, our findings present a novel therapeutic target for treating SCI by revealing a potential mechanism for endothelial cell regeneration and BSCB repair after SCI.

Outcomes for patients undergoing transcatheter aortic valve replacement with ascending aorta dilation.

BACKGROUND: We aim to compare the short and long-term outcomes for aortic stenosis (AS) patients undergone TAVR with and without ascending aorta dilation (AAD). METHODS: Consecutive patients diagnosed with native severe AS who underwent TAVR from September 2012 to September 2021 were enrolled. They were stratified into the moderate/severe dilation group (greatest ascending aorta width ≥ 45 mm) and the non/mild dilation group. Survival outcomes were illustrated using Kaplan-Meier curves and evaluated with the log-rank test. Data from patients with CT follow-up of >6 months was used to investigate the progression rate of AAD. RESULTS: The study cohort comprised 556 patients, with a mean age of 75.5 ± 7.3 years. Among them, 107 patients (19.2%) had a moderate/severe AAD (≥45 mm), with an average diameter of 48.6 mm (±2.8). During hospitalization, both groups witnessed two cases of ascending aortic dissection (1.9% vs 0.4%, P = 0.380). The median follow-up duration was 3.9 years (95% CI: 3.8-4.0 years). No deaths were caused by aortic events and no patients experienced a new aortic dissection. The AAD cohort's 4-year all-cause and cardiovascular mortality rates were not significantly different to the non/mild dilation group's (log-rank test, P = 0.109 and P = 0.698, respectively). Follow-up CT data revealed that the rate of aortic dilation progression in the moderate/severe dilation group was not significantly different from that in the non/mild group (0.0 mm/year, 25-75%th: -0.3-0.2 vs 0.1 mm/year, 25-75%th: -0.3-0.4, P = 0.122). CONCLUSION: This study found no significant difference regarding short-term and long-term outcomes in AS patients with/without moderate/severe AAD undergoing TAVR.

Occurrence, distribution and sources of microplastics in typical marine recirculating aquaculture system (RAS) in China: The critical role of RAS operating time and microfilter.

Industrial mariculture, a vital means of providing high quality protein to humans, is a potential source of microplastics (MPs) which have recently received increasing attention. This study investigated the occurrence and distribution of microplastics in feed, source water and recirculating aquaculture system (RAS) with long & short operating times as well as in fish from typical industrial mariculture farms in China. Results showed that microplastics occurred in all samples with the average concentration of 3.53 ± 1.39 particles/g, 0.70 ± 0.17 particles/L, 1.53 ± 0.21 particles/L and 2.21 ± 0.62 particles/individual for feed, source water, RAS and fish, respectively. Microplastics were mainly fiber in shape, blue in color and 20-500 µm in size. Compared with short operated RAS, long operating time led to higher microplastic concentration in RAS, especially that of microplastic in 20-500 µm, granular and blue. Regardless of short or long operating time, microplastics in RAS mainly gathered in culture tank, tank before microfilter and fixed-bed biological filter, and the microfilter removed efficiently the microplastic with the shape of film, granule, fragment as well as those with size > 1000 µm. As for the polymer types, polyamide (PA, 71.9 %) and polyethylene terephthalate (PET, 65.7 %) dominated in feed and source water, respectively, which may be the reason for the high proportion of PA (38.8 % and 26.4 %) and PET (31.8 % and 30.2 %) in RAS and fish. In addition, polypropylene (PP) was also detected in RAS (18.7 %) and fish (22.6 %), indicating that other plastic facilities such as PP brush carrier also made a contribution. Positive matrix factorization (PMF) model revealed three sources of MP in RAS, namely plastic facilities, industrial sewage and plastic packaging products. Our results provided a theoretical basis for the management of MP in RAS.

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial.

INTRODUCTION: Frailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown. METHODS AND ANALYSIS: This prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition. DISCUSSION: This study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions. CLINICAL TRIAL REGISTRATION: https://beta. CLINICALTRIALS: gov/study/NCT05635877 , NCT05635877.

Bending a Cumulene with Electrons: Stepwise Chemical Reduction and Structural Study of a Tetraaryl[4]Cumulene.

Chemical reduction of a [4]cumulene with cesium metal was explored, and the structural changes stemming from electron acquisition are detailed using X-ray crystallography. It is found that the [4]cumulene undergoes dramatic geometric changes upon stepwise reduction, including bending of the cumulenic core and twisting of the endgroups from orthogonal to planar. The structural deformation is consistent with early theoretical reports that suggest that the twisting should occur upon reduction of both even and odd [n]cumulenes. The current results, on the other hand, are inconsistent with a previous experimental study of a [3]cumulene in which the predicted twisting is not observed upon reduction. DFT calculations reveal that the barrier to deformation is an order of magnitude lower in a [3]cumulene than a [4]cumulene, allowing the barrier to be overcome in the solid-state.

Clinical Outcomes of Arthroscopic Surgery in Patients with Gluteal Muscle Contracture: Single-Institution Results from a High-Volume Cohort.

BACKGROUND The aim of this study was to assess clinical outcomes of arthroscopic surgery for gluteal muscle contracture (GMC) with at least 2 years of follow-up in a large sample. MATERIAL AND METHODS A total of 665 patients who underwent arthroscopic release procedure at our institution between March 2014 and December 2018 and met the inclusion criteria were included in this study. All the patients were operated on by the same surgeon and the surgeon released the contracture band from anterior to posterior starting from the anterior edge of the ITB, the contracture band of the gluteus maximus, and vastus medialis tensor. After exclusion, 544 patients (218 males and 326 females) were finally included. Clinical outcomes at 2 years of postoperative follow-up were evaluated by a combination of several methods, including a new criterion we proposed for postoperative assessment, which included the cross-leg test, difficulty in squatting with legs together, and abnormal gait, the visual analogue scale (VAS), the modified Harris hip score (mHHS), and the satisfaction of patients. RESULTS The average follow-up time was 48.2±14.9 months. Based on the new criteria, 513 (94.3%) patients were evaluated as good, 25 (4.6%) as fair, and 6 (1.1%) as poor. The mHHS increased from 72.1±6.0 (range, 56.0-81.3) to 97.3±2.2 (range, 92.3-100.0) (P<0.001). The VAS decreased from 3.3±1.1 (range, 0-5) to 0.062±0.13 (range, 0-1) (P<0.001). For subjective satisfaction, 526 (96.7%) patients were satisfied, 14 (2.6%) patients were neutral, and 4 (0.7%) patients were dissatisfied. CONCLUSIONS In a large sample, favorable and durable clinical outcomes were observed after the arthroscopic procedure. Clinical symptoms and mHHS showed significant improvement with a minimum 2-year follow-up.

Characterization of tumor microbiome and associations with prognosis in intrahepatic cholangiocarcinoma.

BACKGROUND: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC. METHODS: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC. RESULTS: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS. CONCLUSION: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC.

Effects of sitagliptin activation of the stromal cell-derived factor-1/CXC chemokine receptor 4 signaling pathway on the proliferation, apoptosis, inflammation, and osteogenic differentiation of human periodontal ligament stem cells induced by lipopolysaccharide.

OBJECTIVES: This study aimed to investigate the effects of sitagliptin on the proliferation, apoptosis, inflammation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in lipopolysaccharide (LPS)-induced inflammatory microenvironment and its molecular mechanism. METHODS: hPDLSCs were cultured in vitro and treated with different concentrations of sitagliptin to detect cell viability and subsequently determine the experimental concentration of sitagliptin. An hPDLSCs inflammation model was established after 24 h of stimulation with 1 µg/mL LPS and divided into blank, control, low-concentration sitagliptin (0.5 µmol/L), medium-concentration sitagliptin (1 µmol/L), and high-concentration sitagliptin (2 µmol/L), high-concentrationsitagliptin+stromal cell derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) pathway inhibitor (AMD3100) (2 µmol/L+10 µg/mL) groups. A cell-counting kit-8 was used to detect the proliferation activity of hPDLSCs after 24, 48, and 72 h culture. The apoptosis of hPDLSCs cultured for 72 h was detected by flow cytometry. After inducing osteogenic differentiation for 21 days, alizarin red staining was used to detect the osteogenic differentiation ability of hPDLSCs. The alkaline phosphatase (ALP) activity in hPDLSCs was determined using a kit. The levels of inflammatory factors [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6] in the supernatant of hPDLSCs culture were detected by enzyme-linked immunosorbent assay. The mRNA expressions of osteogenic differentiation genes [Runt-associated transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN)], SDF-1 and CXCR4 in hPDLSCs were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western blot analysis was used to determine SDF-1 and CXCR4 protein expression in hPDLSCs. RESULTS: Compared with the blank group, the proliferative activity, number of mineralized nodules, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in the control group significantly decreased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 significantly increased (P<0.05). Compared with the control group, the proliferative activity, number of mineralized nodule, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in low-, medium-, and high-concentration sitagliptin groups increased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 decreased (P<0.05). AMD3100 partially reversed the effect of high-concentration sitagliptin on LPS-induced hPDLSCs (P<0.05). CONCLUSIONS: Sitagliptin may promote the proliferation and osteogenic differentiation of hPDLSCs in LPS-induced inflammatory microenvironment by activating the SDF-1/CXCR4 signaling pathway. Furthermore, it inhibited the apoptosis and inflammatory response of hPDLSCs.

Role of GABAB receptors in cognition and EEG activity in aged APP and PS1 transgenic mice.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Recent evidence suggests that gamma-aminobutyric acid B (GABAB) receptor-mediated inhibition is a major contributor to AD pathobiology, and GABAB receptors have been hypothesized to be a potential target for AD treatment. The aim of this study is to determine how GABAB regulation alters cognitive function and brain activity in an AD mouse model. Early, middle and late stage (8-23 months) amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice were used for the study. The GABAB agonist baclofen (1 and 2.5 mg/kg, i. p.) and the antagonist phaclofen (0.5 mg/kg, i. p.) were used. Primarily, we found that GABAB activation was able to improve spatial and/or working memory performance in early and late stage AD animals. In addition, GABAB activation and inhibition could regulate global and local EEG oscillations in AD animals, with activation mainly regulating low-frequency activity (delta-theta bands) and inhibition mainly regulating mid- and high-frequency activity (alpha-gamma bands), although the regulated magnitude at some frequencies was reduced in AD. The cognitive improvements in AD animals may be explained by the reduced EEG activity in the theta frequency band (2-4 Hz). This study provides evidence for a potential therapeutic effect of baclofen in the elderly AD brain and for GABAB receptor-mediated inhibition as a potential therapeutic target for AD.