Association between C-reactive protein, Life's Essential 8, and mortality in American adults: Insights from NHANES 2005-2010 data analysis.

Objective: To evaluate the independent, mediating, interactive, and associated effects of C-reactive protein (CRP) and Life's Essential 8 (LE8) on all-cause and cardiovascular mortality.

Methods: Utilizing data from 10,043 participants in the NHANES 2005-2010, we employed Cox proportional hazards regression models and causal mediation analysis to investigate the joint and interactive effects of Life's Essential 8 (LE8) and C-reactive protein (CRP) on mortality risk.

Results: During an average follow-up of 137.

Effect of robotic exoskeleton training on lower limb function, activity and participation in stroke patients: a systematic review and meta-analysis of randomized controlled trials.

Background: The current lower limb robotic exoskeleton training (LRET) for treating and managing stroke patients remains a huge challenge. Comprehensive ICF analysis and informative treatment options are needed. This review aims to analyze LRET' s efficacy for stroke patients, based on ICF, and explore the impact of intervention intensities, devices, and stroke phases.

MAPK pathway orchestrates gallid alphaherpesvirus 1 infection through the biphasic activation of MEK/ERK and p38 MAPK signaling.

Therapies targeting virus-host interactions are seen as promising strategies for treating gallid alphaherpesvirus 1 (ILTV) infection. Our study revealed a biphasic activation of two MAPK cascade pathways, MEK/ERK and p38 MAPK, as a notably activated host molecular event in response to ILTV infection. It exhibits antiviral functions at different stages of infection.

IFNγ at the early stage induced after cryo-thermal therapy maintains CD4 Th1-prone differentiation, leading to long-term antitumor immunity.

Introduction: Recently, more and more research illustrated the importance of inducing CD4 T helper type (Th)-1 dominant immunity for the success of tumor immunotherapy. Our prior studies revealed the crucial role of CD4 Th1 cells in orchestrating systemic and durable antitumor immunity, which contributes to the satisfactory outcomes of the novel cryo-thermal therapy in the B16F10 tumor model. However, the mechanism for maintaining the cryo-thermal therapy-mediated durable CD4 Th1-dominant response remains uncovered.

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D-Ligand Interaction after Cryo-Thermal Therapy.

In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy.

Insight into the High Mobility and Stability of In O :H Film.

Wide bandgap semiconductors, particularly In O :Sn (ITO), are widely used as transparent conductive electrodes in optoelectronic devices. Nevertheless, due to the strohave beenng scattering probability of high-concentration oxygen vacancy (V ) defects, the mobility of ITO is always lower than 40 cm  V  s . Recently, hydrogen-doped In O (In O :H) films have been proven to have high mobility (>100 cm  V  s ), but the origin of this high mobility is still unclear.

Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer.

Immunosuppression plays a significant role in tumor recurrence and metastasis, ultimately causing poor survival outcomes. Overcoming immunosuppression and stimulating durable antitumor immunity are essential for tumor treatment. In our previous study, a novel cryo-thermal therapy involving liquid nitrogen freezing and radiofrequency heating could reduce the proportion of Myeloid-derived suppressor cells (MDSCs), but the remaining MDSCs produced IL-6 by the NF-κB pathway, resulting in an impaired therapeutic effect.

Therapeutic Potential of Perillaldehyde in Ameliorating Vulvovaginal Candidiasis by Reducing Vaginal Oxidative Stress and Apoptosis.

Vulvovaginal candidiasis (VVC) is one of the most frequent diseases induced by () during pregnancy, which results in enormous pain to women and their partners in daily life. Perillaldehyde (PAE), a natural monoterpenoid, has significant anti-microbial, anti-inflammatory and anti-oxidation effects. Reactive oxygen species (ROS) are key factors for the host to resist the invasion of fungi.

A 13-Bit, 12-ps Resolution Vernier Time-to-Digital Converter Based on Dual Delay-Rings for SPAD Image Sensor.

A three-dimensional (3D) image sensor based on Single-Photon Avalanche Diode (SPAD) requires a time-to-digital converter (TDC) with a wide dynamic range and fine resolution for precise depth calculation. In this paper, we propose a novel high-performance TDC for a SPAD image sensor. In our design, we first present a pulse-width self-restricted (PWSR) delay element that is capable of providing a steady delay to improve the time precision.

Accelerating Faceting Wide-Field Imaging Algorithm with FPGA for SKA Radio Telescope as a Vast Sensor Array.

The SKA (Square Kilometer Array) radio telescope will become the most sensitive telescope by correlating a huge number of antenna nodes to form a vast array of sensors in a region over one hundred kilometers. Faceting, the wide-field imaging algorithm, is a novel approach towards solving image construction from sensing data where earth surface curves cannot be ignored. However, the traditional processor of cloud computing, even if the most sophisticated supercomputer is used, cannot meet the extremely high computation performance requirement.

Immunoaffinity microflow liquid chromatography/tandem mass spectrometry for the quantitation of PD1 and PD-L1 in human tumor tissues.

Rationale: High tumor expression of programmed cell death protein (PD1) and programmed death-ligand 1 (PD-L1) is thought to be associated with positive clinical outcomes after treatment with anti-PD1 or anti-PD-L1 agents. Several sensitive methods based on immunohistochemistry, ligand binding assay (LBA), and liquid chromatography/mass spectrometry involving the measurement of PD1 and PD-L1 expression have been reported. Here, we expand on the characterization of different tumor types using a highly specific, sensitive, and robust immunoaffinity liquid chromatography/tandem mass spectrometry (IA-LC/MS/MS)-based method for the simultaneous quantitation of PD1 and PD-L1 in tumor tissues.

LncRNA XIST knockdown ameliorates oxidative low-density lipoprotein-induced endothelial cells injury by targeting miR-204-5p/TLR4.

Oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell injury is a key contributor to atherosclerosis development. However, the role and mechanism of long noncoding RNA X-inactive specific transcript (XIST) in atherosclerosis remain largely unknown. The ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury was analyzed by cell viability, apoptosis, inflammatory cytokines secretion and oxidative stress.

Antibody Drug-Target Engagement Measurement in Tissue Using Quantitative Affinity Extraction Liquid Chromatography-Mass Spectrometry: Method Development and Qualification.

We demonstrate a novel strategy using affinity extraction (AE) LC-MS to directly measure drug exposure and target engagement, two critical pharmacological questions, with a single assay. The assay measures total drug and target concentration at the site of therapeutic action, as well as the amount of target bound to drug. The case study presented applies the strategy to measure drug engagement of a membrane bound receptor (CD40) that is critical to immune regulation in colon biopsies collected from monkey dosed with an anti-CD40 antibody.

In Vitro Metabolite Formation in Human Hepatocytes and Cardiomyocytes and Metabolism and Tissue Distribution in Monkeys of the 2'-C-Methylguanosine Prodrug BMS-986094 : Potential Role in Clinical Cardiovascular Toxicity.

BMS-986094, a 2'-C-methylguanosine prodrug for the treatment of chronic hepatitis C virus infection, was withdrawn from phase 2 clinical trials because of unexpected cardiac and renal toxicities. To better understand these toxicities, the in vitro metabolism of BMS-986094 in human hepatocytes (HHs) and human cardiomyocytes (HCMs) and the measurement of BMS-986094 and selected metabolites in monkey plasma and tissues were assessed. BMS-986094 was extensively metabolized by HHs and HCMs, resulting in more efficient formation and accumulation of the active triphosphorylated metabolite, INX-09114, and less efficient efflux of metabolites in HCMs.

Discovery of the Selective CYP17A1 Lyase Inhibitor BMS-351 for the Treatment of Prostate Cancer.

Efforts to identify a potent, reversible, nonsteroidal CYP17A1 lyase inhibitor with good selectivity over CYP17A1 hydroxylase and CYPs 11B1 and 21A2 for the treatment of castration-resistant prostate cancer (CRPC) culminated in the discovery of BMS-351 (compound 18), a pyridyl biaryl benzimidazole with an excellent in vivo profile. Biological evaluation of BMS-351 at a dose of 1.5 mg in castrated cynomolgus monkeys revealed a remarkable reduction in testosterone levels with minimal glucocorticoid and mineralcorticoid perturbation.

LC-MS/MS multiplexed assay for the quantitation of a therapeutic protein BMS-986089 and the target protein Myostatin.

Background: Therapeutic protein discovery study highlights the need for the development of quantitative bioanalytical methods for determining the levels of both the therapeutic protein and the target protein, as well.

Results: For the quantitation of BMS-986089, both accuracy (99-103%) and precision (2.4-12%) were obtained for the analysis of the surrogate peptide (ITYGGNSPVQEFTVPGR), in addition to the accuracy (100-108%) and precision (0.

Application and challenges in using LC-MS assays for absolute quantitative analysis of therapeutic proteins in drug discovery.

As more protein therapeutics enter the drug-discovery pipeline, the traditional ligand-binding assay (LBA) faces additional challenges to meet the rapid and diverse bioanalytical needs in the early drug-discovery stage. The high specificity and sensitivity afforded by LC-MS, along with its rapid method development, is proving invaluable for the analysis of protein therapeutics in support of drug discovery. LC-MS not only serves as a quantitative tool to complement LBA in drug discovery, it also provides structural details at a molecular level, which are used to address issues that cannot be resolved using LBA alone.

Ex vivo delta opioid receptor autoradiography: CNS receptor occupancy of two novel compounds over their antihyperalgesic dose range.

Discovered as part of an effort to identify delta opioid (DOPr or DOR) agonist analgesics, JNJ-20788560 and JNJ-39204880 exhibited high DOR affinity, with K(i) values of 1.7 and 2.0nM, respectively, and were selective for DOR over the mu opioid receptor (MOPr or MOR), with 596- and 122-fold selectivity, respectively.

Pharmacokinetics of green tea catechins in extract and sustained-release preparations.

Catechins are a major constituent of green tea. For green tea to have cancer therapeutic benefit, catechin concentrations in the range of 100 nM are required continuously until apoptosis (programmed cell death) is induced. To prolong elevated plasma and interstitial concentrations of catechins, a sustained-release formulation of green tea extract was tested and compared to a commercial green tea extract (Tegreen97®).

Effect of long-term oral administration of green tea extract on weight gain and glucose tolerance in Zucker diabetic (ZDF) rats.

There have been some claims that green tea reduces weight and lowers blood glucose in diabetes. Intraperitoneal injections of green tea catechins in diabetic rats have shown beneficial effects. To determine if oral administration of green tea would prevent development of diabetes, young Zucker diabetic rats were dosed with green tea extract containing 50-125 mg/kg of Epigallocatechin gallate (EGCG) starting at 7 weeks of age, before the appearance of excessive weight gain and glucose elevation.

Liquid chromatography/tandem mass spectrometry for the determination of carbamazepine and its main metabolite in rat plasma utilizing an automated blood sampling system.

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of carbamazepine and its main metabolite carbamazepine 10,11-epoxide in rat plasma is described. The method consists of a liquid-liquid extraction procedure and electrospray LC/MS/MS analysis. The chromatographic separation was achieved within 5 min using a C(8) (150 mm x 2.

Identification of the major vanilloid component in Capsicum extract by HPLC-EC and HPLC-MS.

A sensitive multi-channel HPLC-electrochemical (EC) method has been developed to determine the vanilloid content in the complex Capsicum annuum extract Capsibiol. Chromatographic separation was achieved within 10 min using a YMC Basic S5 column with a mobile phase containing chloroacetic acid, heptane sulphonic acid and acetonitrile. The multi-channel detector simultaneously applied four potentials between +500 and +800 mV (referenced to a silver/silver chloride electrode) to four glassy carbon working electrodes.