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BackgroundThe outbreak of COVID-19 has profoundly influenced people’s lifestyles; these impacts have varied across subgroups of people. The pandemic-related impacts on the health outcomes of people with dermatological conditions are unknown. ObjectiveThe aim of this paper was to study the association of COVID-19 pandemic–related impacts with health-related quality of life in patients with skin diseases. MethodsThis was a cross-sectional study among Chinese patients with skin diseases. A self-administered web-based questionnaire was distributed through social media. Demographic and clinical data and pandemic-related impacts (isolation status, income changes, and employment status) were collected. The main outcomes included perceived stress (Visual Analog Scale), symptoms of anxiety (Generalized Anxiety Disorder-7) and depression (9-Item Patient Health Questionnaire), quality of life (Dermatology Life Quality Index), and health utility mapping based on the EQ-5D-3L descriptive system. Multivariable logistic regression was used to investigate the associations. ResultsA total of 506 patients with skin diseases completed the survey. The mean age of the patients was 33.5 years (SD 14.0), and 217/506 patients (42.9%) were male. Among the 506 respondents, 128 (25.3%) were quarantined, 102 (20.2%) reported unemployment, and 317 (62.6%) reported decrease or loss of income since the pandemic. The pandemic-related impacts were significantly associated with impaired mental well-being and quality of life with different effects. Unemployment and complete loss of income were associated with the highest risks of adverse outcomes, with increases of 110% to 162% in the prevalence of anxiety, depression, and impaired quality of life. ConclusionsIsolation, income loss, and unemployment are associated with impaired health-related quality of life in patients with skin diseases during the COVID-19 pandemic.

As research progresses, there has been growing interest in the association between Alopecia areata (AA) and anxiety, as well as depression. However, there have been limited reports on the genetic variation level of AA in relation to mental disorders. We performed large-scale Two sample Mendelian randomization (MR) analyses to examine whether there is a association between AA with anxiety and depression. The data utilized for AA analysis were sourced from the FinnGen release 9 databases, including 682 cases and 361,822 controls. Summary statistics for major depression disorder (MDD) were obtained from a genome-wide meta-analysis dataset, incorporating 170,756 cases and 329,443 controls. The anxiety disorder data was conducted by the Anxiety Neuro Genetics Study Consortium, including 5580 cases and 11,730 controls. We employed four distinct approaches, including MR-Egger, weighted median, random-effect inverse variance weighted (IVW), and weighted mode, to conduct the MR analysis. Genetic liability to AA was associated with an increased risk of Major depression disorder (MDD) and anxiety demonstrated an odds ratio (OR) of 1.01 (βivw = 0.011, PIVW = 0.023) and OR of 1.16 (βivw = 0.150, PIVW = 0.002). Upon conducting the Bonferroni correction, the P -values were 0.046 and 0.004, respectively. For reverse analysis, we observed no significant association between anxiety and MDD with the risk of AA. Our research unveil a unidirectional causal association whereby AA exerts a risk effect against MDD and anxiety, which serves as a valuable complement to prior meta-analyses, enriching the existing body of knowledge on the subject matter. • Unidirectional causal link found between AA and MDD/anxiety. • GRM8 may be a significant gene associated with AA, MDD, and anxiety. • Comorbidity due to combined environmental and genetic factors. [ABSTRACT FROM AUTHOR]

Psoriasis (PsO) and atopic dermatitis (AD) are chronic skin disorders that may be associated with erectile dysfunction (ED). However, a Mendelian randomization study found that there was no significant genetic association between PsO and ED. On the other hand, the study showed that genetically predicted increase in AD was associated with a lower risk of ED. The study also identified specific genes and the JAK-STAT signaling pathway as potential factors linking AD and ED. Further research is needed to validate and expand upon these findings. [Extracted from the article]

Autophagy and apoptosis are essential processes that participate in cell death and maintain cellular homeostasis. Dysregulation of these biological processes results in the development of diseases, including cancers. Therefore, targeting the interaction between apoptosis and autophagy offers a potential strategy for cancer therapy. Melanoma is the most lethal skin cancer. We previously found that tumor necrosis factor receptor‐associated factor 6 (TRAF6) is overexpressed in melanoma and benefits the malignant phenotype of melanoma cells. Additionally, TRAF6 promotes the activation of cancer‐associated fibroblasts in melanoma. However, the role of TRAF6 in autophagy and apoptosis remains unclear. In this study, we found that knockdown of TRAF6 induced both apoptosis and autophagy in melanoma cells. Transcriptomic data and real‐time PCR analysis demonstrated reduced expression of autophagy related 16 like 2 (ATG16L2) in TRAF6‐deficient melanoma cells. ATG16L2 knockdown resulted in increased autophagy and apoptosis. Mechanism studies confirmed that TRAF6 regulated ATG16L2 expression through c‐Jun. Importantly, targeting TRAF6 with cinchonine, a TRAF6 inhibitor, effectively suppressed the growth of melanoma cells by inducing autophagy and apoptosis through the TRAF6/c‐Jun/ATG16L2 signaling pathway. These findings highlight the pivotal role of TRAF6 in regulating autophagy and apoptosis in melanoma, emphasizing its significance as a novel therapeutic target for melanoma treatment. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca2+) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment. [ABSTRACT FROM AUTHOR]

Background: Gamma delta (γδ) T lymphocytes are promising candidate for adoptive T cell therapy, however, their treatment efficacy is not satisfactory. Vδ2 T cells are unique to primates and few suitable models are available to assay their anti‐tumour function. Methods: We tested human γδ T cell activation, tumour infiltration, and tumour‐killing in four three‐dimensional (3D) models, including unicellular, bicellular and multicellular melanoma spheroids, and patient‐derived melanoma organoids. We studied the effects of checkpoint inhibitors on γδ T cells and performed a small molecule screen using these platforms. Results: γδ T cells rapidly responded to melanoma cells and infiltrated melanoma spheroids better than αβ T cells in PBMCs. Cancer‐associated fibroblasts (CAFs) in bicellular spheroids, stroma cells in multicellular melanoma spheroids and inhibitory immune cells in organoids significantly inhibited immune cell infiltrates including γδ T cells and lessened their cytotoxicity to tumour cells. Tumour‐infiltrating γδ T cells showed exhausted immunophenotypes with high checkpoints expression (CTLA‐4, PD‐1 and PD‐L1). Immune checkpoint inhibitors increased γδ T cell infiltration of 3D models and killing of melanoma cells in all four 3D models. Our small molecule screen assay and subsequent mechanistic studies demonstrated that epigenetic modifiers enhanced the chemotaxis and cytotoxicity of γδ T cells through upregulating MICA/B, inhibiting HDAC6/7 pathway and downregulating the levels of PD‐L1 and PD‐L2 in CAFs and tumour cells. These compounds increased CXCR4 and CD107a expression, IFN‐γ production and decreased PD‐1 expression of γδ T cells. Conclusions: Tumour‐infiltrating γδ T cells show exhausted immunophenotypes and limited anti‐tumour capacity in melanoma 3D models. Checkpoint inhibitors and epigenetic modifiers enhance anti‐tumour functions of γδ T cells. These four 3D models provided valuable preclinical platforms to test γδ T cell functions for immunotherapy. [ABSTRACT FROM AUTHOR]

Biological neurons can be approached by using some functional neural circuits, and the biophysical mechanism for signal processing can be explained. Chemical stimulus can adjust the intracellular and extracellular ions concentration, and thus the channel current can be regulated to trigger appropriate firing modes in the neural activities. A physical stimulus often injects kinds of energy, and the energy can be encoded in the components for generating a certain channel current. The energy driving on the cell can be effective to enhance the pumping of ions and mode transition is induced. Based on a simple neural circuit exposed to the external magnetic field, the mode selection is investigated to explore the biophysical mechanism of energy absorption by applying periodic, and stochastic magnetic fields, respectively. The external field energy is encoded in the induction coil of the neural circuit, and the channel current is induced. Two identical neural circuits are exposed to the same magnetic field and the synchronization approach is investigated without synapse coupling. It is found that two neurons in periodic firings can be synchronized under the same periodic or noise-like magnetic field even applying different initials, while intermittent phase lock is induced between two chaotic neurons. Stochastic variation in the external magnetic field can induce noisy induced electromotive force (IEF) and the firing mode is regulated effectively. When both noisy IEF and periodic stimulus are applied, synchronization stability between periodic neurons with initials diversity is enhanced while synchronization approach between chaotic neurons becomes difficult. In addition, the Hamilton energy in each neuron can keep pace with another neuron when complete synchronization is stabilized within a finite transient period. These results provide new insights to know the energy encoding mechanism in neural circuits and neurons exposed to external magnetic field. [ABSTRACT FROM AUTHOR]

Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme of glycolysis, is a critical regulator in tumor metabolism. PKM2 has been demonstrated to overexpressed in various cancers and promoted proliferation and metastasis of tumor cells. The errant expression of PKM2 has inspired people to investigate the function of PKM2 and the therapeutic potential in cancer. In addition, some studies have shown that the upregulation of PKM2 in tumor tissues is associated with the altered expression of lncRNAs and the poor survival. Therefore, researchers have begun to unravel the specific molecular mechanisms of lncRNA-mediated PKM2 expression in cancer metabolism. As the tumor microenvironment (TME) is essential in tumor development, it is necessary to identify the role of PKM2 in TME. In this review, we will introduce the role of PKM2 in different cancers as well as TME, and summarize the molecular mechanism of PKM2-related lncRNAs in cancer metabolism. We expect that this work will lead to a better understanding of the molecular mechanisms of PKM2 that may help in developing therapeutic strategies in clinic for researchers. [ABSTRACT FROM AUTHOR]

Autophagy, or self-eating, is an evolutionarily conserved process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for the degradation and recycling of cytoplasmic components in eukaryotes. It is well recognized that autophagy plays an important role in maintaining cellular homeostasis under physiological and pathophysiological con-ditions and the upregulation of autophagy may serve as an adaptive process to provide nutrients and energy when under stresses. Recently, studies have illustrated that autophagy is intricately related to skin diseases. This review provides a brief synopsis of the process of autophagy and aims to elucidate the roles of autophagy in different skin diseases and to highlight the need for increased research in the field. [ABSTRACT FROM AUTHOR]

Skin cancer can be classified as cutaneous malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Due to the high level of morbidity and mortality, skin cancer has become a global public health issue worldwide while the pathogenesis of skin cancer is still unclear. It is necessary to further identify the pathogenesis of skin cancer and find candidate targets to diagnose and treat skin cancer. A variety of factors are known to be associated with skin cancer including N-glycosylation, which partly explained the malignant behaviors of skin cancer. In this review, we retrieved databases such as PubMed and Web of Science to elucidate its relationship between glycosylation and skin cancer. We summarized some key glycosyltransferases and proteins during the process of N-glycosylation related to skin cancer, which was helpful to unmask the additional mechanism of skin cancer and find some novel targets of skin cancer. [ABSTRACT FROM AUTHOR]

The stress tolerance of wetland plants is crucial for their appropriate application in constructed wetland (CW). Ammonia, one of the major pollutants in wastewater, is nutrition for plants at low concentrations but could be toxic at excess concentrations. This study aimed to investigate the effect of external ammonia at different concentrations (0, 1, 2, 4, 8, 10 mg L) to a specific submerged plant Potamogeton crispus ( P. crispus), which has been used widely in CW. Results showed that the threshold value of ammonia for P. crispus was 4 mg L, under which no obvious variations from the control group were detected in all associated observations. When ammonia concentration exceeded 4 mg L, plants displayed significant increase in lipid peroxidation product contents (MDA, O and HO), antioxidant enzyme activities (T-SOD, POD, and CAT), and a corresponding increase in the percentages of electrolyte leakage. However, external ammonia only had slight effect on the chlorophyll synthesis of P. crispus under the studied concentration range. Excess ammonia exposure (≥4 mg L) could affect the physiological responses of P. crispus, by inducing oxidative stress and by limitedly altering permeability of cell membrane and plant photosynthesis. The results of this study supplied useful information for the aquatic vegetation collocation in CW design, and it is suggested to take proper application of P. crispus in CW when treating eutrophication or other relatively heavily polluted water. [ABSTRACT FROM AUTHOR]