Discovery of Biaryl Amide Derivatives as Potent, Selective, and Orally Bioavailable RORγt Agonists for Cancer Immunotherapy.

The master transcription factor receptor retinoic acid receptor-related orphan receptor γt (RORγt) regulates the differentiation of T-helper 17 (Th17) cells and the production of interleukin-17 (IL-17). Activation of RORγt T cells in the tumor microenvironment promotes immune infiltration to more effectively inhibit tumor growth. Therefore, RORγt agonists provide a reachable approach to cancer immunotherapy.

The effect of health literacy, self-efficacy, social support and fear of disease progression on the health-related quality of life of patients with cancer in China: a structural equation model.

Background: Health literacy (HL), self-efficacy (SE), social support (SS) and fear of disease progression (FOP) are all important factors affecting health-related quality of life (HRQoL) in cancer patients. However, their synergistic effects and underlying mechanisms on HRQoL in cancer patients remain unclear. Therefore, the purpose of this study was to construct a structural equation model (SEM) to explore the underlying mechanism of factors affecting HRQoL.

Broadband and Spectrally Selective Photothermal Conversion through Nanocluster Assembly of Disordered Plasmonic Metasurfaces.

Plasmonic metasurfaces have been realized for efficient light absorption, thereby leading to photothermal conversion through nonradiative decay of plasmonic modes. However, current plasmonic metasurfaces suffer from inaccessible spectral ranges, costly and time-consuming nanolithographic top-down techniques for fabrication, and difficulty of scale-up. Here, we demonstrate a new type of disordered metasurface created by densely packing plasmonic nanoclusters of ultrasmall size on a planar optical cavity.

Discovery of novel triazine derivatives as potent retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonists.

Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) has been exploited as a promising target for the new small molecule therapeutics to treat inflammatory and autoimmune diseases via modulating the interleukin-17 (IL-17) production by T helper 17 (Th17) cells. Herein, we reported a series of triazine-based derivatives as novel RORγt inverse agonists. By screening of our in-house compound library, the hit compound 1 was identified with weak RORγt inhibitory activity.

Gas phase fabrication of morphology-controlled ITO nanoparticles and their assembled conductive films.

ITO nanoparticles were generated in the gas phase with a magnetron plasma gas aggregation cluster source. Their morphologies were modified by modulating the discharging power of magnetron sputtering. The shape of the nanoparticles changed from rough spheroid formed with a higher discharging power to multi-branch formed with a lower discharging power.

Investigation of health literacy status and related influencing factors in military health providers of Chinese People's liberation Army, a cross-sectional study.

Objective: The aim of this study was to investigate health literacy and analyze its influencing factors in military health providers of the Chinese People's Liberation Army (PLA Army).

Methods: From November to December 2018, cluster sampling was used to select 1512 military health providers from the Army Medical University. Health literacy was measured by using the Chinese Citizen Health Literacy Questionnaire (HLQ) (2015 edition).

Maternal rodent exposure to di-(2-ethylhexyl) phthalate decreases muscle mass in the offspring by increasing myostatin.

Background: Di-(2-ethylhexyl) phthalate (DEHP) and its metabolites can cross the placenta and may cause birth defects and developmental disorders. However, whether maternal DEHP exposure affects skeletal muscle development in the offspring and the pathways involved are unknown. This study investigated the effects of maternal DEHP exposure and the contribution of myostatin (MSTN) to skeletal muscle development in the offspring.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

Background And Aims: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time.

Approach And Results: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology.

Discovery of Orally Available Retinoic Acid Receptor-Related Orphan Receptor γ-t/Dihydroorotate Dehydrogenase Dual Inhibitors for the Treatment of Refractory Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a multifactorial autoimmune disease, representing a major clinical challenge. Herein, a strategy of dual-targeting approach employing retinoic acid receptor-related orphan receptor γ-t (RORγt) and dihydroorotate dehydrogenase (DHODH) was proposed for the treatment of IBD. Dual RORγt/DHODH inhibitors are expected not only to reduce RORγt-driven Th17 cell differentiation but also to mitigate the expansion and activation of T cells, which may enhance anti-inflammatory effects.

Two orders of magnitude extra SERS enhancement on silver nanoparticle-based substrate induced by laser irradiation in nitrogen ambient.

Photo-reduction of silver oxide and light-induced Ag nanoparticle (NP) generations have been applied for Surface-enhanced Raman spectroscopy (SERS) substrate fabricated for years. In this paper, we demonstrate a general method to enhance the SERS activity of conventional Ag NPs-based SERS substrates by performing Raman scattering measurement in a nitrogen ambient after a period of laser irradiation (photoactivation). The Raman characteristic peak intensity of carbonaceous impurities adsorbed on the surfaces of Ag NPs display an additional enhancement of 93 times after photoactivation in nitrogen ambient.

Association of serum microcystin levels with neurobehavior of school-age children in rural area of Southwest China: A cross-sectional study.

To investigate whether microcystin-LR (MC-LR) influences children's cognitive function and memory ability, we measured serum MC-LR and whole blood lead levels in 697 primary students, and collected their academic and neurobehavioral test scores. The median of serum MC-LR levels was 0.80 µg/L (the value below the limit of detection to 1.

Realizing the enhanced cyclability of a cactus-like NiCoO nanocrystal anode fabricated by molecular layer deposition.

Lithium-ion batteries with conversion-type anode electrodes have attracted increasing interest in providing higher energy storage density than those with commercial intercalation-type electrodes. However, conversion-type materials exhibit severe structural instability and capacity fade during cycling. In this work, a molecular layer deposition (MLD)-derived conductive AlO/carbon layer was employed to stabilize the structure of the cactus-like NiCoO nanocrystal (NC) anode.

Controllable Fabrication of Percolative Metal Nanoparticle Arrays Applied for Quantum Conductance-Based Strain Sensors.

We use gas phase deposition of well-defined nanoparticles (NPs) to fabricate closely-spaced Pd NP arrays on flexible membranes prepatterned with interdigital electrodes (IDEs). The evolution of the morphology and electron conductance of the NP arrays during deposition is analyzed. The growth of two-dimensional percolation clusters of interconnected NPs, which correlate with the percolation pathway for electron conduction in the NP deposits, is demonstrated.

Ghrelin ameliorates tumor-induced adipose tissue atrophy and inflammation Ghrelin receptor-dependent and -independent pathways.

Adipose tissue (AT) atrophy is a hallmark of cancer cachexia contributing to increased morbidity/mortality. Ghrelin has been proposed as a treatment for cancer cachexia partly by preventing AT atrophy. However, the mechanisms mediating ghrelin's effects are incompletely understood, including the extent to which its only known receptor, GHSR-1a, is required for these effects.

Imaging of Senescent Vascular Cells in Atherosclerotic Mice Using a β-Galactosidase-Activatable Nanoprobe.

Senescence-associated diseases have severely diminished the quality of life and health of patients. However, a sensitive assay of these diseases remains limited due to a lack of straightforward methods. Considering that senescence-associated β-galactosidase (SA-β-Gal) is overexpressed in senescent cells, the detection of SA-β-Gal in senescent cells and tissues might be a feasible strategy for the early diagnosis of SA diseases.

Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists.

GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties.

Rational design of fluorescent probes for targeted in vivo nitroreductase visualization.

Nitroreductase (NTR) has been recognized as a biomarker for identifying the hypoxic status of cancers. Therefore, it is of high scientific interest to design effective fluorescent probes for tracking NTR activity. However, studies on elucidation of the structure-performance relationship of fluorescent probes and those providing valuable insight into optimized probe design have rarely been reported.

Imaging of ovarian cancers using enzyme activatable probes with second near-infrared window emission.

We herein develop two β-galactosidase (β-Gal) activatable NIR fluorescent probes for visualizing ovarian cancers. Particularly, probe BOD-M-βGal produced NIR-II emission light at 900-1300 nm upon β-Gal activation. By using our activatable and target specific NIR-II probe for deep-tissue imaging of β-Gal overexpressed ovarian cancer cells, rapid and accurate imaging of ovarian tumors in nude mice was achieved.

A Novel Rhynchophylline Analog, Y396, Inhibits Endothelial Dysfunction Induced by Oxidative Stress in Diabetes Through Epidermal Growth Factor Receptor.

Endothelial dysfunction appears in early diabetes mellitus partially because of epidermal growth factor receptor (EGFR) abnormal activation and downstream oxidative stress. The aim of this study was to determine whether Y396, a synthesized analog of rhynchophylline, could protect against endothelial dysfunction in diabetes and the underlying molecular mechanism. Y396 could directly target the EGFR and inhibit its phosphorylation induced by high glucose and EGF, downstream translocation to the nucleus of E2F1, and its transcriptional activity and expression of Nox4.

A molecular design strategy toward enzyme-activated probes with near-infrared I and II fluorescence for targeted cancer imaging.

The advance of cancer imaging requires innovations to establish novel fluorescent scaffolds that are excitable and emit in the near-infrared region with favorable Stokes shifts. Nevertheless, the lack of probes with these optimized optical properties presents a major bottleneck in targeted cancer imaging. By coupling of boron dipyrromethene platforms to enzymic substrates a self-immolative benzyl thioether linker, we here report a strategy toward enzyme-activated fluorescent probes to satisfy these requirements.

Levels of phthalate acid esters and sex hormones and their possible sources in traffic-patrol policemen in Chongqing.

To investigate the correlation between the air phthalate acid ester (PAE) exposure and serum PAE concentration and the effects of PAE exposure on reproductive health among Chongqing traffic-patrol policemen. In 2013, 32 traffic-patrol policemen working in an area with poor air quality in Chongqing and 28 traffic-patrol policemen working in an area with good air quality were selected. Their blood levels of 14 PAEs and six reproductive hormones were determined.

Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased Gankyrin in Vitro and in Vivo.

Background/aims: Our recent study indicated that the serum microcystin-LR (MC-LR) level is positively linked to the risk of human hepatocellular carcinoma (HCC). Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether MC-LR induces tumor formation and the role of gankyrin in this process is unclear.

Methods: We induced malignant transformation of L02 liver cells via 35 passages with exposure to 1, 10, or 100 nM MC-LR.

Mitochondria-targeting BODIPY-loaded micelles as novel class of photosensitizer for photodynamic therapy.

In this paper, a series of novel BODIPY-based photosensitizers have been designed and synthesized for photodynamic therapy. BODIPY3 was screened out as the most potential photosensitizer due to its excellent optical properties, high singlet oxygen efficiency and good photostability. However, as an organic photosensitizer, BODIPY3 still suffered from the drawbacks of insolubility and instability in aqueous system.

Interaction Effects of AFB1 and MC-LR Co-exposure with Polymorphism of Metabolic Genes on Liver Damage: focusing on SLCO1B1 and GSTP1.

AFB1 and MC-LR are two major environmental risk factors for liver damage worldwide, especially in warm and humid areas, but there are individual differences in health response of the toxin-exposed populations. Therefore, we intended to identify the susceptible genes in transport and metabolic process of AFB1 and MC-LR and find their effects on liver damage. We selected eight related SNPs that may affect liver damage outcomes in AFB1 and MC-LR exposed persons, and enrolled 475 cases with liver damage and 475 controls of healthy people in rural areas of China.