Visible-light-driven photoelectrochemical sensor based on conjugated microporous polymer-grafted graphene for o-aminophenol detection.

The pollutant o-aminophenol (o-AP) presents considerable risk to environmental safety, and its detection is therefore critical. Although various optical and electrochemical methods have been proposed for the detection of o-AP, there are a limited number of detection methods based on photoelectrochemical (PEC) sensors. In this study, a sensitive visible-light-driven PEC sensor was developed for o-AP detection in water. A conjugated microporous polymer (CMP)-coated graphene heterostructure (CMP-rGO) was synthesized and used to develop a PEC sensor. Under optimal conditions, the proposed sensor exhibited a high sensitivity of 0.03 µM with a wide linear range of 0.0034-37.6 µM. The PEC sensor also displayed acceptable repeatability and reproducibility, good long-term stability, and excellent recovery (98-102%). In addition, the binding patterns of CMP to o-AP and o-AP analog molecules were analyzed by molecular docking. Therefore, this study provides a new and feasible PEC sensor-based detection scheme for o-AP detection.

Irreversible coherent matching bonding of van der Waals heterostructure lattice by pressure.

The key of heterostructure is the combinations created by stacking various vdW materials, which can modify interlayer coupling and electronic properties, providing exciting opportunities for designer devices. However, this simple stacking does not create chemical bonds, making it difficult to fundamentally alter the electronic structure. Here, we demonstrate that interlayer interactions in heterostructures can be fundamentally controlled using hydrostatic pressure, providing a bonding method to modify electronic structures. By covering graphene with boron nitride and inducing an irreversible phase transition, the conditions for graphene lattice-matching bonding (IMB) were created. We demonstrate that the increased bandgap of graphene under pressure is well maintained in ambient due to the IMB in the interface. Comparison to theoretical modeling emphasizes the process of pressure-induced interfacial bonding, systematically generalizes, and predicts this model. Our results demonstrate that pressure can irreversibly control interlayer bonding, providing opportunities for high-pressure technology in ambient applications and IMB engineering in heterostructures.

Layer-by-layer self-assembly of PLL/CPP-ACP multilayer on SLA titanium surface: Enhancing osseointegration and antibacterial activity in vitro and in vivo.

Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca2+ ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material's antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0)10 implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0)10 surface was able to continuously release Ca2+ ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants.

Sex difference in nocturnal blood pressure dipping in adolescents with varying degrees of adiposity.

BACKGROUND: For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. METHODS: 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th-95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. RESULTS: 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. CONCLUSIONS: Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.

Uptake, accumulation, translocation and transformation of seneciphylline (Sp) and seneciphylline-N-oxide (SpNO) by Camellia sinensis L.

Pyrrolizidine alkaloids (PAs) and their N-oxide (PANOs), as emerging environmental pollutants and chemical hazards in food, have become the focus of global attention. PAs/PANOs enter crops from soil and reach edible parts, but knowledge about their uptake and transport behavior in crops is currently limited. In this study, we chose tea (Camellia sinensis L.) as a representative crop and Sp/SpNO as typical PAs/PANOs to analyze their root uptake and transport mechanism. Tea roots efficiently absorbed Sp/SpNO, utilizing both passive and active transmembrane pathways. Sp predominantly concentrated in roots and SpNO efficiently translocated to above-ground parts. The prevalence of SpNO in cell-soluble fractions facilitated its translocation from roots to stems and leaves. In soil experiment, tea plants exhibited weaker capabilities for the uptake and transport of Sp/SpNO compared to hydroponic conditions, likely due to the swift degradation of these compounds in the soil. Moreover, a noteworthy interconversion between Sp and SpNO in tea plants indicated a preference for reducing SpNO to Sp. These findings represent a significant stride in understanding the accumulation and movement mechanisms of Sp/SpNO in tea plants. The insights garnered from this study are pivotal for evaluating the associated risks of PAs/PANOs and formulating effective control strategies.

Multi-omics reveals the molecular mechanism of the combined toxic effects of PFOA and 4-HBP exposure in MCF-7 cells and the key player: mTORC1.

With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10-8 M to 4 × 10-7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.

Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism.

The pathophysiology of atopic dermatitis (AD) is complex. CD4+ T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4+ T memory cells (p < 0.01). We then identified 13 hub genes with a strong association with CD4+ T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4+ T subcluster, CD4+ tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4+ TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4+ TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (p < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4+ TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4+ TRM may be involved in the pathogenesis of adult AD.

Dynamic performance of combined biochar from co-pyrolysis of pig manure with invasive weed: Effect of natural aging on Pb and As mobilization in polluted mining soil.

Due to the natural biochar aging, the improvement of soil quality and immobilization of soil pollutants achieved by biochar may change; understanding the dynamic evolution of the in situ performance of biochar in these roles is essential to discuss the long-term sustainability of biochar remediation. Therefore, in this study, combined biochar from co-pyrolysis of pig manure and invasive Japanese knotweed - P1J1, as well as pure pig manure - PM - and pure Japanese knotweed - JK - derived biochar were applied to investigate their remediation performance in a high As- and Pb-polluted soil with prolonged incubation periods (up to 360 days). Biochar application, especially P1J1 and PM, initially promoted soil pH, dissolved organic carbon, and EC, but the improvements were not constant through time. The JK-treated soil exhibited the highest increase of soil organic matter (OM), followed by P1J1 and then PM, and OM did not change with aging. Biochar, especially P1J1, was a comprehensive nutrient source of Ca, K, Mg, and P to improve soil fertility. However, while soluble cationic Ca, K, and Mg increased with time, anionic P decreased over time, indicating that continuous P availability might not be guaranteed with the aging process. The total microorganism content declined with time; adding biochars slowed down this tendency, which was more remarkable at the later incubation stage. Biochar significantly impeded soil Pb mobility but mobilized soil As, especially in PM- and P1J1-treated soils. However, mobilized As gradually re-fixed in the long run; meanwhile, the excellent Pb immobilization achieved by biochars was slightly reduced with time. The findings of this study offer fresh insights into the alterations in metal(loid)s mobility over an extended duration, suggesting that the potential mobilization risk of As is reduced while Pb mobility slightly increases over time.

A reference profile of N-glycosylation for human kidney and the identification of cell-cell interactions between parietal epithelial cells and capillary endothelial cells by single-cell glycosylation-sequencing.

Background N-glycosylation is one of the most common post-translational modifications in humans, and these alterations are associated with kidney diseases. Methods A novel technological approach, single-cell N-acetyllactosamine sequencing (scLacNAc-seq), was applied to simultaneously detect N-glycosylation expression and the transcriptome at single-cell resolution in three human kidney tissues from zero-time biopsy. Cell clusters, glycation abundance in each cell cluster, functional enrichment analysis, cell-cell crosstalk, and Pseudotime analysis were applied. Results Using scLacNAc-seq, 24,247 cells and 22 cell clusters were identified, and N-glycan abundance in each cell was obtained. Transcriptome analysis revealed a close connection between capillary endothelial cells (CapECs) and parietal epithelial cells (PECs). PECs and CapECs communicate with each other through several pairs of ligand receptors (e.g., TGFB1-EGFR, GRN-EGFR, TIMP1-FGFR2, VEGFB-FLT1, ANGPT2-TEK, and GRN-TNFRSF1A). Finally, a regulatory network of cell-cell crosstalk between PECs and CapECs was constructed, which is involved in cell development. Conclusions We here, for the first time, constructed the glycosylation profile of 22 cell clusters in the human kidney from time-zero biopsy. Moreover, cell-cell communication between PECs and CapECs through the ligand-receptor system may play a crucial regulatory role in cell proliferation.

Intelligent wireless power transfer via a 2-bit compact reconfigurable transmissive-metasurface-based router.

With the rapid development of the Internet of Things, numerous devices have been deployed in complex environments for environmental monitoring and information transmission, which brings new power supply challenges. Wireless power transfer is a promising solution since it enables power delivery without cables, providing well-behaved flexibility for power supplies. Here we propose a compact wireless power transfer framework. The core components of the proposed framework include a plane-wave feeder and a transmissive 2-bit reconfigurable metasurface-based beam generator, which constitute a reconfigurable power router. The combined profile of the feeder and the beam generator is 0.8 wavelengths. In collaboration with a deep-learning-driven environment sensor, the router enables object detection and localization, and intelligent wireless power transfer to power-consuming targets, especially in dynamic multitarget environments. Experiments also show that the router is capable of simultaneous wireless power and information transfer. Due to the merits of low cost and compact size, the proposed framework may boost the commercialization of metasurface-based wireless power transfer routers.

Synergistic developmental effects of zebrafish exposed to combined perfluorooctanoic acid and atrazine.

Perfluorooctanoic acid (PFOA) and atrazine are two endocrine disruptors that are widely found in waters. Negative effects of PFOA and atrazine have been studied individually, but few data have focused on their combined effects. Here, zebrafish embryos were used as model to investigate the combined toxicity of PFOA and atrazine. The acute toxicity of atrazine (11.9 mg/L) to zebrafish embryos was much higher than that of perfluorooctanoic acid (224.6 mg/L) as shown by the 120h-LC50 value. Developmental effects, including delayed yolk sac absorption, spinal curvature, and liver abnormalities, were observed in both one- and two-component exposures. Notably, the rate of embryonic malformations in the co-exposure group was more than twice as high as that of single component exposure in the concentration range of 1/8-1/2 EC50, which indicated a synergistic effect of the binary mixture. The synergistic effect of PFOA-atrazine was further validated by combinatorial index (CI) modeling. In addition, changes of amino acid metabolites, reactive oxygen species and superoxide dismutase indicated that oxidative stress might be the main pathway for enhanced toxicity under co-exposure condition. Overall, co-exposure of PFOA and atrazine resulted in stronger developmental effects and more complicated amino acid metabolic response toward zebrafish, compared with single component exposure.

Monitoring Changes in Biochemical and Metabolite Profiles in Garlic Cloves during Storage.

Storage is important for the garlic cloves industry because it is critical to enabling a year-round supply. This study aimed to investigate the changes in biochemical and metabolic profiles in garlic cloves in terms of different temperatures and cultivars during storage using nontargeted and targeted metabolomics. The results showed that the storage temperatures and times were important factors affecting the composition and metabolite content of garlic cloves. In detail, the metabolic profiling of garlic cloves changed significantly at 22 °C, which was mainly related to sprouting. Furthermore, γ-glutamyl peptide was converted into the corresponding flavor precursors or free amino acids, leading to the fluctuation in the amount of nutrients in garlic cloves. In contrast, the quality of garlic cloves remained stable for 290 days at 0 °C though metabolism still occurred, which indicated that the slight chemical changes did not impact the quality significantly and low temperature could prolong their dormancy.

Comprehensive analysis of phospholipid in milk and their biological roles as nutrients and biomarkers.

Phospholipids (PL) have garnered significant attention due to their physiological activities. Milk and other dairy products are important dietary sources for humans and have been extensively used to analyze the presence of PL by various analytical techniques. In this paper, the analysis techniques of PL were reviewed with the eight trigrams of phospholipidomics and a comprehensive fingerprint of 1295 PLs covering 8 subclasses in milk and other dairy products, especially. Technology is the primary productive force. Based on phospholipidomics technology, we further review the relationship between the composition of PL and factors that may be involved in processing and experimental operation, and emphasized the significance of the biological role played by PL in dietary supplements and biomarkers (production, processing and clinical research), and providing the future research directions.

Alterations of the amplitude of low-frequency fluctuation induced by repetitive transcranial magnetic stimulation combined with antidepressants treatment for major depressive disorder.

We investigated the neuroimaging changes and clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants in major depressive disorder (MDD) patients. We scanned 35 patients with MDD and 27 healthy controls (HC) with resting-state functional magnetic resonance imaging (fMRI) before and after treatment. We analyzed amplitude of low-frequency fluctuation (ALFF) and the correlation with clinical variables. The rate of significant efficacy after treatment was higher in the combination treatment group than in the antidepressant group, although not statistically significant. At baseline, ALFF increased in the left middle temporal, brain stem, and left cerebellum and decreased in the right anterior cingulate (ACC), right orbital frontal cortex (OFC), and right caudate. ALFF increased in the left fusiform and decreased in the right lingual gyrus, left middle occipital gyrus, and left superior occipital gyrus after antidepressants. ALFF increased in the right ACC, right OFC, and right rectus after combination treatment. ALFF changes in the right ACC/OFC were negatively correlated with HAMD changes. After treatment, abnormal activity in some brain regions normalized, but these regions differed between the two treatment groups. rTMS combined with antidepressants therapy may improve MDD symptoms by improving neuronal activity levels in the right ACC and right OFC.

Sedum aizoon L.: a review of its history, traditional uses, nutritional value, botany, phytochemistry, pharmacology, toxicology, and quality control.

In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.

Serum secreted phosphoprotein 1 level is associated with plaque vulnerability in patients with coronary artery disease.

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Enhanced osteogenic and antibacterial properties of titanium implant surface modified with Zn-incorporated nanowires: Preclinical in vitro and in vivo investigations.

OBJECTIVE: This study aimed to synthesize zinc-incorporated nanowires structure modified titanium implant surface (Zn-NW-Ti) and explore its superior osteogenic and antibacterial properties in vitro and in vivo. MATERIALS AND METHODS: Zn-NW-Ti was synthesized via displacement reactions between zinc sulfate solutions and the titanium (Ti) surface, which was pretreated by hydrofluoric acid etching and hyperthermal alkalinization. The physicochemical properties of the Zn-NW-Ti surface were examined. Moreover, the biological effects of Zn-NW-Ti on MC3T3-E1 cells and its antibacterial property against oral pathogenic bacteria (Staphylococcus aureus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) compared with sandblasted and acid-etched Ti (SLA-Ti) and nanowires modified Ti (NW-Ti) surface were assessed. Zn-NW-Ti and SLA-Ti modified implants were inserted into the anterior extraction socket of the rabbit mandible with or without exposure to the mixed bacterial solution (S. aureus, P. gingivalis, and A. actinomycetemcomitans) to investigate the osteointegration and antibacterial performance via radiographic and histomorphometric analysis. RESULTS: The Zn-NW-Ti surface was successfully prepared. The resultant titanium surface appeared as a nanowires structure with hydrophilicity, from which zinc ions were released in an effective concentration range. The Zn-NW-Ti surface performed better in facilitating the adhesion, proliferation, and differentiation of MC3T3-E1 cells while inhibiting the colonization of bacteria compared with SLA-Ti and NW-Ti surface. The Zn-NW-Ti implant exhibited enhanced osseointegration in vivo, which was attributed to increased osteogenic activity and reduced bacterial-induced inflammation compared with the SLA-Ti implant. CONCLUSIONS: The Zn-incorporated nanowires structure modified titanium implant surface exhibited improvements in osteogenic and antibacterial properties, which optimized osteointegration in comparison with SLA titanium implant surface.

Comparative analysis of Deinagkistrodon acutus venom from Taiwan and China utilizing chromatographic, electrophoretic, and bioinformatic approaches, along with ELISA employing a monospecific antivenom.

Deinagkistrodon acutus is a medically important pitviper inhabiting mainly South China and Taiwan. The hemorrhagic effects of its envenoming are compatible to its venom, which is abundant in metalloproteases (svMPs) and C-type lectin-like proteins. In this study, we investigated geographic variations in the venom of D. acutus collected from Taiwan and four Mainland Chinese provinces: Fujian, Jiangxi, Anhui, and Hunan. The variations were assessed through high-performance liquid chromatography, non-metric multidimensional scaling analysis, gel electrophoresis, and enzyme-linked immunosorbent assay (ELISA) with a monospecific antivenom (DaMAV) generated against the Taiwanese D. acutus venom, and discussed based on venom-protein sequences in databases and literature related to D. acutus venom. Additionally, the cross-reactivity of DaMAV against Crotalus horridus and Calloselasma rhodostoma venoms was investigated. We noted differential abundances of D. acutus venom metalloproteases, C-type lectin-like proteins, and phospholipase A2, along with point mutations and selective expression of serine protease isoforms. The ELISA results revealed that the venom from Taiwan was more reactive toward Taiwanese DaMAV than the four Mainland Chinese venoms, consistent with chromatographic profile differences, whereas C. horridus venom presented moderate cross-reactivity with DaMAV. The observed immunoreactivities of these venom with DaMAV can be attributed to the high prevalence of their PIII-svMPs, which are the dominant antigens, and the conservation of PIII-svMP epitopes.

PI3Kδ inhibition alleviates the brain injury during cerebral ischemia reperfusion via suppressing pericyte contraction in a TNF-α dependent manner.

The pericytes (PCs) surrounding capillaries are vital regulators of capillary constriction. Persistent PC contraction results in the increased capillary constriction, therefore leading to the impaired cerebral blood flow (CBF) recovery after reperfusion and worsening the clinical outcomes in stroke patients. However, the potential determinants of PC functions during ischemia/reperfusion are poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit Delta (PIK3CD/PI3Kδ) is a crucial factor involved with neuronflammation during ischemic stroke. PI3Kδ has shown the expression in PCs, while its effect on PC functions has not been explored yet. In this study, a rodent ischemia/reperfusion model was established in C57BL/6 mice via transient middle cerebral artery occlusion and reperfusion (MCAO/R). The PI3Kδ expression in ischemic penumbra was remarkably upregulated following MCAO/R induction. PI3Kδ inhibitor CAL-101 improved the CBF recovery, ischemic brain injury, and suppressed capillary constriction in MCAO/R mice. Besides, the production of tumor necrosis factor alpha (TNF-α), an inducer for tissue injury, and the expression of transient receptor potential vanilloid type 2 (TRPV2), a channel protein permitting calcium (Ca2+) uptake, were significantly reduced in ischemic penumbra after CAL-101 treatment. In vitro, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of PI3Kδ and TRPV2 in primary mouse PCs. CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke.

Persistence of antibody to 23-valent pneumococcal polysaccharide vaccine: a 5-year prospective follow-up cohort study.

BACKGROUND: Pneumococcal vaccines are effective in preventing pneumococcal diseases in adults. The evaluation of the antibodies persistence to the 23-valent pneumococcal polysaccharide vaccine (PPV23) could provide evidence on PPV23 revaccination. RESEARCH DESIGN AND METHODS: Adults aged ≥ 60 years were selected and vaccinated with PPV23 in Shanghai, and followed up for 5 years with blood samples collection of a 1-year interval. The geometric mean concentrations (GMC) of the IgG against 23 pneumococcal serotypes covered by PPV23 were detected using enzyme-linked immunosorbent assay. The antibodies to 23 pneumococcal serotypes among different groups was analyzed using statistical analysis. RESULTS: Overall, 517 participants completed all six visits over a 5-year period (2013-2018). The GMC of 23 serotypes in adults aged ≥ 60 years decreased slowly after PPV23 vaccination compared to baseline pre-vaccination (P < 0.05), except serotype 3. Additionally, the multiplicative increase in the antibody concentration after PPV23 vaccination was greater, and the antibody levels of serotypes 1 and 6B were significantly higher at visit 5 than at visit 4 (P < 0.05). CONCLUSIONS: The pneumococcal antibodies in elderly after PPV23 vaccination could sustain high levels over long-term follow-up, which suggested that the interval of revaccination with PPV23 in elderly should be at least 5 years after the first vaccination.