Immunomodulatory potential of primary cilia in the skin.

Primary cilia (PC) are essential signaling hubs for proper epithelial formation and the maintenance of skin homeostasis. Found on most cells in the human body, including skin cells, PC facilitate signal transduction that allows ciliated cells to interact with the immune system via multiple pathways, helping to maintain immune system homeostasis. PC can be altered by various microenvironmental stimuli to develop corresponding regulatory functions.

Mass Balance, Metabolic Pathways, Absolute Bioavailability, and Pharmacokinetics of Giredestrant in Healthy Subjects.

Giredestrant is a potent and selective small-molecule estrogen receptor degrader. The objectives of this study were to assess the absolute bioavailability (aBA) of giredestrant and to determine the mass balance, routes of elimination, and metabolite profile of [C]giredestrant. In part 1 (mass balance), a single 30.

TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis.

Osteoarthritis (OA) is the most prominent chronic arthritic disease, affecting over 3 billion people globally. Synovial macrophages, as immune cells, play an essential role in cartilage damage in OA. Therefore, regulating macrophages is crucial for controlling the pathological changes in OA.

Membrane-assisted tariquidar access and binding mechanisms of human ATP-binding cassette transporter P-glycoprotein.

The human multidrug transporter P-glycoprotein (P-gp) is physiologically essential and of key relevance to biomedicine. Recent structural studies have shed light on the mode of inhibition of the third-generation inhibitors for human P-gp, but the molecular mechanism by which these inhibitors enter the transmembrane sites remains poorly understood. In this study, we utilized all-atom molecular dynamics (MD) simulations to characterize human P-gp dynamics under a potent inhibitor, tariquidar, bound condition, as well as the atomic-level binding pathways in an explicit membrane/water environment.

Intratumoral injection of interferon gamma promotes the efficacy of anti-PD1 treatment in colorectal cancer.

Immune checkpoint inhibitors (ICIs) offer new options for the treatment of patients with solid cancers worldwide. The majority of colorectal cancers (CRC) are proficient in mismatch-repair (pMMR) genes, harboring fewer tumor antigens and are insensitive to ICIs. These tumors are often found to be immune-deserted.

The role of primary cilia in thyroid diseases.

Primary cilia (PC) are non-motile and microtube-based organelles protruding from the surface of almost all thyroid follicle cells. They maintain homeostasis in thyrocytes and loss of PC can result in diverse thyroid diseases. The dysfunction of structure and function of PC are found in many patients with common thyroid diseases.

NLRP3 neuroinflammatory intervention of Mahuang-Lianqiao-Chixiaodou decoction for mental disorders in atopic dermatitis mice.

Ethnopharmacological Relevance: Mahuang-Lianqiao-Chixiaodou decoction (MLCD) is a traditional Chinese medicinal (TCM) formula recorded in the Treatise on Febrile Diseases. It is commonly used for clinical treatment of atopic dermatitis (AD). However, the potential mechanisms of MLCD intervention in AD combined with mental disorders behaviors such as anxiety and depression remain elusive and deserves further investigation.

Mechanism of Chinese botanical drug Dizhi pill for myopia: An integrated study based on bioinformatics and network analysis.

To identify the active constituents, core targets, immunomodulatory functions and potential mechanisms of Dizhi pill (DZP) in the treatment of myopia. The active constituents and drug targets of DZP were searched in the TCMSP, Herb databases and correlational studies. The targets of myopia were searched in the TTD, Genecards, OMIM and Drugbank databases.

The Future of Process Industry: A Cyber-Physical-Social System Perspective.

The process industry is an industrial field of interdisciplinary nature involving electrical engineering, energy, petroleum, chemical, and metallurgy, which play a key role in the sustainable development. As a main source of CO2 emissions, the process industry will undertake a large part of the emission reduction task. In order to incorporate the impact of social factors, such as environment, society, and human to support the future process industry, the cyber-physical-social system (CPSS) framework should be considered as a promising way to enhance the transformation of the process industry.

Evaluation of the mRNA release assay for diagnosis of TB in HIV-infected individuals.

HIV-infected individuals are susceptible to () infection and are at high risk of developing active tuberculosis (TB). Interferon-gamma release assays (IGRAs) are auxiliary tools in the diagnosis of TB. However, the performance of IGRAs in HIV-infected individuals is suboptimal, which limits clinical application.

Catechins: Protective mechanism of antioxidant stress in atherosclerosis.

Tea has long been valued for its health benefits, especially its potential to prevent and treat atherosclerosis (AS). Abnormal lipid metabolism and oxidative stress are major factors that contribute to the development of AS. Tea, which originated in China, is believed to help prevent AS.

A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.

Photoperiod controls plant seed size in a CONSTANS-dependent manner.

Photoperiodic plants perceive changes in day length as seasonal cues to orchestrate their vegetative and reproductive growth. Although it is known that the floral transition of photoperiod-sensitive plants is tightly controlled by day length, how photoperiod affects their post-flowering development remains to be clearly defined, as do the underlying mechanisms. Here we demonstrate that photoperiod plays a prominent role in seed development.

Characterization of fatty acid metabolism-related lncRNAs in lung adenocarcinoma identifying potential novel prognostic targets.

Lung adenocarcinoma (LUAD), a malignant respiratory tumor with an extremely poor prognosis, has troubled the medical community all over the world. According to recent studies, fatty acid metabolism (FAM) and long non-coding RNAs (lncRNAs) regulation have shown exciting results in tumor therapy. In this study, the original LUAD patient data was obtained from the TCGA database, and 12 FAM-related lncRNAs (AL390755.

Global trends and prospects of blue carbon sinks: a bibliometric analysis.

Blue carbon sinks (mangroves, saltmarshes, and seagrasses) are considered an effective nature-based approach for climate change mitigation. Despite growing interest, a systematic review of this topic is still scarce. This study evaluated 1348 blue carbon sink-related articles from 1990 to 2020 using bibliometric technology.

Oblique laser shock peening effect of the FGH95 superalloy with a PCA and comprehensive index.

As a metal surface strengthening technology, oblique laser shock peening uses the force effect of pulsed laser beams to significantly improve the mechanical properties of materials and prolong service life. However, the processing of metal parts still requires a high cost for testing the quality of the finished product. At present, there is no systematic and complete measurement method or evaluation system for the finished products of oblique laser shock peening technology.

Head-to-Tail Cross-Linking to Generate Bicyclic Helical Peptides with Enhanced Helicity and Proteolytic Stability.

We report a new pattern of a bicyclic helical peptide constructed through head-to-tail cross-linking. The described bicyclic helical peptide has a head-to-tail cross-linking arm and a C-terminal , + 4 cross-linking arm. This scaffold will provide a promising scaffold for designing a proteolytically resistant helix-constrained peptide.

Multifunctional Composite Nanosystems for Precise/Enhanced Sonodynamic Oxidative Tumor Treatment.

Ultrasound-activated therapies have been regarded as the efficient strategy for tumor treatment, among which sonosensitizer-enabled sonodynamic oxidative tumor therapy features intrinsic advantages as compared to other exogenous trigger-activated dynamic therapies. Nanomedicine-based nanosonosensitizer design has been extensively explored for improving the therapeutic efficacy of sonodynamic therapy (SDT) of tumor. This review focuses on solving two specific issues, i.

Engineering Chameleon Prodrug Nanovesicles to Increase Antigen Presentation and Inhibit PD-L1 Expression for Circumventing Immune Resistance of Cancer.

Immune evasion is the major obstacle for T-cell-based cancer immunotherapy. The insufficient expression of the tumor-rejection antigen causes the intrinsic immune resistance and high expression of programmed death ligand 1 (PD-L1) induced by interferon gamma (IFN-γ), which accounts for the inducible immune resistance. To deal with both the intrinsic and inducible immune resistance of cancer, a multifunctional prodrug nanovesicle is sequentially developed.

Cancer-Associated Fibroblasts Suppress Cancer Development: The Other Side of the Coin.

Cancer-associated fibroblasts (CAFs) are the main stromal components of cancer, representing a group of heterogeneous cells. Many studies indicate that CAFs promote tumor development. Besides, evidence of the tumor suppression effects of CAFs keeps on merging.

Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer.

Loss of Hippo tumor-suppressor activity and hyperactivation of YAP are commonly observed in cancers. Inactivating mutations of Hippo kinases MST1/2 are uncommon, and it remains unclear how their activity is turned off during tumorigenesis. We identified STRN3 as an essential regulatory subunit of protein phosphatase 2A (PP2A) that recruits MST1/2 and promotes its dephosphorylation, which results in YAP activation.

A deep learning, image based approach for automated diagnosis for inflammatory skin diseases.

Background: As the booming of deep learning era, especially the advances in convolutional neural networks (CNNs), CNNs have been applied in medicine fields like radiology and pathology. However, the application of CNNs in dermatology, which is also based on images, is very limited. Inflammatory skin diseases, such as psoriasis (Pso), eczema (Ecz), and atopic dermatitis (AD), are very easily to be mis-diagnosed in practice.

Stepwise selection on homeologous PRR genes controlling flowering and maturity during soybean domestication.

Adaptive changes in plant phenology are often considered to be a feature of the so-called 'domestication syndrome' that distinguishes modern crops from their wild progenitors, but little detailed evidence supports this idea. In soybean, a major legume crop, flowering time variation is well characterized within domesticated germplasm and is critical for modern production, but its importance during domestication is unclear. Here, we identify sequential contributions of two homeologous pseudo-response-regulator genes, Tof12 and Tof11, to ancient flowering time adaptation, and demonstrate that they act via LHY homologs to promote expression of the legume-specific E1 gene and delay flowering under long photoperiods.

Secreted stromal protein ISLR promotes intestinal regeneration by suppressing epithelial Hippo signaling.

The Hippo-YAP signaling pathway plays an essential role in epithelial cells during intestinal regeneration and tumorigenesis. However, the molecular mechanism linking stromal signals to YAP-mediated intestinal regeneration and tumorigenesis is poorly defined. Here, we report a stroma-epithelium ISLR-YAP signaling axis essential for stromal cells to modulate epithelial cell growth during intestinal regeneration and tumorigenesis.