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Over the past few decades, cellular senescence has been identified in cancer patients undergoing chemotherapy and radiotherapy. Senescent cells are generally characterized by permanent cell cycle arrest as a response to endogenous and exogenous stresses. In addition to exiting the cell cycle process, cellular senescence also triggers profound phenotypic changes such as senescence-associated secretory phenotype (SASP), autophagy modulation, or metabolic reprograming. Consequently, cellular senescence is often considered as a tumor-suppressive mechanism that permanently arrests cells at risk of malignant transformation. However, accumulating evidence shows that therapy-induced senescence can promote epithelial-mesenchymal transition and tumorigenesis in neighboring cells, as well as re-entry into the cell cycle and activation of cancer stem cells, thereby promoting cancer cell survival. Therefore, it is particularly important to rapidly eliminate therapy-induced senescent cells in patients with cancer. Here we review the hallmarks of cellular senescence and the relationship between cellular senescence and cancer. We also discuss several pathways to induce senescence in tumor therapy, as well as strategies to eliminate senescent cells after cancer treatment. We believe that exploiting the intersection between cellular senescence and tumor cells is an important means to defeat tumors. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a common multisystem, multiorgan heterozygous autoimmune disease. The main pathological features of the disease are autoantibody production and immune complex deposition. Autophagy is an important mechanism to maintain cell homeostasis. Autophagy functional abnormalities lead to the accumulation of apoptosis and induce the autoantibodies that result in immune disorders. Therefore, improving autophagy may alleviate the development of SLE. For SLE, glucocorticoids or immunosuppressive agents are commonly used in clinical treatment, but long-term use of these drugs causes serious side effects in humans. Immunosuppressive agents are expensive. Traditional Chinese medicines (TCMs) are widely used for immune diseases due to their low toxicity and few side effects. Many recent studies found that TCM and its active ingredients affected the pathological development of SLE by regulating autophagy. This article explains how autophagy interferes with immune system homeostasis and participates in the occurrence and development of SLE. It also summarizes several studies on TCM-regulated autophagy intervention in SLE to generate new ideas for basic research, the development of novel medications, and the clinical treatment of SLE. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene which encodes membrane receptor PKD1 and cation channel PKD2, respectively. PKD2, also called transient receptor potential polycystin-2 (TRPP2), is a Ca2+-permeable channel located on the membrane of cell surface, primary cilia, and endoplasmic reticulum (ER). Ca2+ is closely associated with diverse cellular functions. While ER Ca2+ homeostasis depends on different Ca2+ receptors, channels and transporters, the role of PKD2 within the ER remains controversial. Whether and how PKD2- mediated ER Ca2+ leak relates to ADPKD pathogenesis is not well understood. Here, we reviewed current knowledge about the biophysical and physiological properties of PKD2 and how PKD2 contributes to ER Ca2+ homeostasis. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM), one of the most prevalent brain tumor types, is correlated with an extremely poor prognosis. The extracellular matrix (ECM) genes could activate many crucial pathways that facilitate tumor development. This study aims to provide online models to predict GBM survival by ECM genes. Methods: The associations of ECM genes with the prognosis of GBM were analyzed, and the significant prognosis-related genes were used to develop the ECM index in the CGGA dataset. Furthermore, the ECM index was then validated on three datasets, namely, GSE16011, TCGA-GBM, and GSE83300. The prognosis difference, differentially expressed genes, and potential drugs were obtained. Multiple machine learning methods were selected to construct the model to predict the survival status of GBM patients at 6, 12, 18, 24, 30, and 36 months after diagnosis. Results: Five ECM gene signatures (AEBP1, F3, FLNC, IGFBP2, and LDHA) were recognized to be associated with the prognosis. GBM patients were divided into high– and low–ECM index groups with significantly different overall survival rates in four datasets. High–ECM index patients exhibited a worse prognosis than low–ECM index patients. Four small molecules (podophyllotoxin, lasalocid, MG-262, and nystatin) that might reduce GBM development were predicted by the Cmap dataset. In the independent dataset (GSE83300), the maximum values of prediction accuracy at 6, 12, 18, 24, 30, and 36 months were 0.878, 0.769, 0.748, 0.720, 0.705, and 0.868, respectively. These machine learning models were provided on a publicly accessible, open-source website (https://ospg.shinyapps.io/OSPG/). Conclusion: In summary, our findings indicated that ECM genes were prognostic indicators for patient survival. This study provided an online server for the prediction of survival curves of GBM patients. [ABSTRACT FROM AUTHOR]

In a dielectric tube partially surrounded by distilled water, a propagating discontinuity is observed in a cold argon plasma jet at atmospheric pressure in both the laminar and turbulent flow regimes. Through electrical and optical diagnostics, the mechanism of formation for this phenomenon is investigated. Results show that the strong polarization of the distilled water, the constraint from the electric field (or a sufficiently high electric field), and the transport of the active species are in combination responsible for the propagating plasma discontinuity. Indeed, smaller surface areas of the tube surrounded by distilled water, shorter distances between the distilled water and the ground electrodes, as well as larger gas flow rates can together make the discontinuous discharge channel appear more readily. In particular, when the flow switches from laminar to turbulent, the plasma behavior of the discontinuity no longer depends on the gas flow rate. This is mostly attributed to the extreme instability of turbulence which further suppresses the transport of active species. [ABSTRACT FROM AUTHOR]

PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a single-residue hydrophobic gate in PKD2. We find that a PKD2 gain-of-function gate mutant effectively rescues PKD2 knockdown-induced phenotypes in embryonic zebrafish. The structure of a PKD2 activating mutant F604P by cryo-electron microscopy reveals a π- to α-helix transition within the pore-lining helix S6 that leads to repositioning of the gate residue and channel activation. Overall the results identify hydrophobic gates and a gating mechanism of PKD2 and PKD2L1. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5- bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues. PIP2 bound to cationic residues in TRPP3, including K568, thereby disrupting the N-C interaction and negatively regulating TRPP3. PIP2 had similar negative effects on TRPP2. Interestingly, we found that PIP2 facilitates the N-C interaction in TRPM8/-V1, resulting in channel potentiation. The intramolecular N-C interaction might represent a shared mechanism underlying the gating and PIP2 regulation of TRP channels. [ABSTRACT FROM AUTHOR]

Nutritional or classical rickets (here labeled as "rickets") is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule's important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region. [ABSTRACT FROM AUTHOR]

A single-electrode atmospheric pressure nonequilibrium plasma jet surrounded with different ambient dielectrics is investigated driven by AC power supply. Another three ambient dielectrics, distilled water, ethanol, and carbon tetrachloride, are adopted to compare with air. By examining electrical and optical characteristics, it was found that the molecular polarity of ambient dielectrics had its significant effect on the propagation of atmospheric pressure nonequilibrium plasma jets. When the polarization of molecules was enhanced, the discharge current and the bullet velocity were also increased. For nonpolar dielectric of carbon tetrachloride, this was mainly resulted from the electron polarization in the built-in electric field. For polar dielectrics of ethanol and distilled water, in addition to the electron polarization, orientation polarization was the main cause for the further increase in discharge current and bullet velocity. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-associated disease exhibits distinct gene expression patterns characterized by the transcription of EBV nuclear antigen (EBNA) 1, EBNA2, latent membrane protein (LMP) 1, LMP2A, and BZLF1 (Zebra). A series of visual reverse transcript loop-mediated isothermal amplification (RT-LAMP) assays were performed to examine the expression of EBNA1, EBNA2, LMP1, LMP2A and BZLF1. The sensitivity of RT-LAMP for these transcripts was approximately equivalent to real-time RT-PCR (RT-qPCR), which was developed to quantify relative levels of EBV transcripts, and 10 to 100-fold more sensitive than conventional RT-PCR. Cross-reactions to other viruses were not observed upon examination of cell lines infected with herpes simplex viruses-1 and -2 (HSV-1 and -2), varicella zoster virus (VZV), human cytomegalovirus (HCMV) or Kaposi's sarcoma-associated herpesvirus. When applied to 146 specimens, RT-LAMP exhibited high clinical sensitivity and specificity, with an excellent agreement (κ > 0.92) compared to RT-qPCR. These assays are convenient for rapid early diagnosis and for surveillance of EBV-infected individuals by evaluating the EBV transcriptional profile, because the results can be visualized with the naked eye. These assays may be employed in further investigations because they can aid the design of improved therapeutic regimens and can be used specifically in resource-poor settings. [ABSTRACT FROM AUTHOR]

In this letter, the effect of the dielectric wall temperature on the length and volume of an atmospheric pressure plasma jet (APPJ) is investigated using a single-electrode configuration driven with an AC power supply. To distinguish the APPJ status from the argon flow rate, the three modes, laminar, transition, and turbulent, are separated. When the dielectric wall is heated, the APPJ length and volume are enhanced. Also, the transition regions remarkably expand over a large range of flow rates. The results indicate that different factors contribute to the expansion of the transition region. The increase in the radial and axial velocities is the main cause of the expansion of the transition region to the low-velocity region. The expansion to the high-velocity region is dominantly induced by a change in the viscosity. [ABSTRACT FROM AUTHOR]