The Relationship Between Meaning in Life and Health Behaviors in Adults Aged 55 Years and Over During the COVID-19 Pandemic: the Mediating Role of Risk Perception and the Moderating Role of Powerful Others Health Locus of Control.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has impacted many people's meaning in life and health behaviors. This study aimed to verify the relationship among meaning in life (MIL), epidemic risk perception, health locus of control (HLC), and preventive health behaviors among older adults after the COVID-19 outbreak was declared a pandemic. METHOD: In this longitudinal study, 164 participants aged 55 years and above completed the following measures at time 1 (February 19, 2021) and one month later at time 2 (March 19, 2021): Meaning in Life in the Epidemic Questionnaire, Epidemic Risk Perception Questionnaire, Multidimensional Health Locus of Control Scale, and Health Behaviors Before and After the Epidemic Survey. Hayes' SPSS Process Macro was used to analyze the mediating effect of epidemic risk perception (model 4) and the moderating role of powerful others HLC in the mediation model (model 14). RESULTS: The results showed that after controlling for gender, age, education level, and health behaviors at the baseline, risk perception had a significant mediating effect on the relationship between MIL and preventive health behaviors (ß = .02, SE = .01, 95% CI [.00, .04]). In addition, powerful others HLC had a moderating effect on the second half of the mediating effect (ß = .02, p = .02, 95% CI [.00, .03]). Specifically, compared to the older adults with low powerful others HLC, the risk perception of older adults with high powerful others HLC increased preventive health behaviors. CONCLUSION: Practitioners should adequately cultivate older adults' risk awareness and reinforce the importance of advice from doctors and professionals, thereby effectively enhancing the preventive health behaviors of older adults in China during the COVID-19 pandemic.

Noncoding RNAs involved in DNA methylation and histone methylation, and acetylation in diabetic vascular complications.

Diabetes is a metabolic disorder and its incidence is still increasing. Diabetic vascular complications cause major diabetic mobility and include accelerated atherosclerosis, nephropathy, retinopathy, and neuropathy. Hyperglycemia contributes to the pathogenesis of diabetic vascular complications via numerous mechanisms including the induction of oxidative stress, inflammation, metabolic alterations, and abnormal proliferation of EC and angiogenesis. In the past decade, epigenetic modifications have attracted more attention as they participate in the progression of diabetic vascular complications despite controlled glucose levels and regulate gene expression without altering the genomic sequence. DNA methylation and histone methylation, and acetylation are vital epigenetic modifications and their underlying mechanisms in diabetic vascular complication are still urgently needed to be investigated. Non-coding RNAs (nc RNAs) such as micro RNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circ RNAs) were found to exert transcriptional regulation in diabetic vascular complication. Although nc RNAs are not considered as epigenetic components, they are involved in epigenetic modifications. In this review, we summarized the investigations of non-coding RNAs involved in DNA methylation and histone methylation and acetylation. Their cross-talks might offer novel insights into the pathology of diabetic vascular complications.

Pro-inflammatory role of cell-free mitochondrial DNA in cardiovascular diseases.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Inflammation contributes to the pathogenesis and progression of CVD. Circulating cell-free mitochondrial DNA (ccf-mtDNA) is that mtDNA fragments are released outside the cell and into the circulation by cell necrosis and secretion. The levels of ccf-mtDNA are increased in CVD and associated risk conditions, including hypercholesterolemia, diabetes mellitus, and arterial hypertension. MtDNA containing unmethylated CpG dinucleotides and can trigger inflammation that aggravates tissue injury by activating toll-like receptor 9, inflammasomes, and the stimulator of interferon genes pathway. Here, we review the expanding field of ccf-mtDNA-mediated inflammation and its role in the progression of CVD.

The protective effect of interfering TLR9-IRF5 signaling pathway on the development of CVB3-induced myocarditis.

Since toll-like receptor 9 (TLR9) or interferon regulatory factor 5 (IRF5) was reported to be associated with the development of myocarditis, we wondered if the TLR9-IRF5 pathway could contribute to the development of coxsackievirus B3 (CVB3)-induced myocarditis. We detected signaling molecules of TLR9-IRF5 pathway in CVB3-infected patients and mice. The results showed that TLR9, IRF5 and its downstream molecules such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased, and the increase was correlated with the severity of heart injury during CVB3 infection. In addition, we demonstrated that an AAAG ODN with IRF5 interfering activities significantly decreased the levels of the TLR9-IRF5 pathway molecules in hearts, spleens as well as white blood cells, and alleviated the myocarditis in CVB3-infected mice. The data suggest that interfering TLR9-IRF5 pathway could be an approach to treat CVB3-induced myocarditis.

An AAAG-Rich Oligodeoxynucleotide Rescues Mice from Bacterial Septic Peritonitis by Interfering Interferon Regulatory Factor 5.

A previous study found that an AAAG-rich Oligodeoxynucleotide (ODN), designated as MS19, could lessen the acute lung inflammatory injury (ALII) in mice infected by influenza viruses. Bioinformatics analysis found that MS19 is consensus with the binding site of interferon regulatory factor 5 (IRF5) in the regulatory elements of pro-inflammatory genes. This study established a septic peritonitis model in Institute of Cancer Research (ICR) mice infected with Escherichia coli (E. coli), and found that MS19 prolonged the survival of the mice and down-regulated the expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). In cultured RAW264.7 cells, MS19 significantly reduced the expression of iNOS, IRF5, IL-6, and TNF-α and inhibited the nuclear translocation of IRF5. This data may provide a new insight for understanding how MS19 reduces the excessive inflammatory responses in sepsis.

Formation of hexagonal and cubic ice during low-temperature growth.

From our daily life we are familiar with hexagonal ice, but at very low temperature ice can exist in a different structure--that of cubic ice. Seeking to unravel the enigmatic relationship between these two low-pressure phases, we examined their formation on a Pt(111) substrate at low temperatures with scanning tunneling microscopy and atomic force microscopy. After completion of the one-molecule-thick wetting layer, 3D clusters of hexagonal ice grow via layer nucleation. The coalescence of these clusters creates a rich scenario of domain-boundary and screw-dislocation formation. We discovered that during subsequent growth, domain boundaries are replaced by growth spirals around screw dislocations, and that the nature of these spirals determines whether ice adopts the cubic or the hexagonal structure. Initially, most of these spirals are single, i.e., they host a screw dislocation with a Burgers vector connecting neighboring molecular planes, and produce cubic ice. Films thicker than ~20 nm, however, are dominated by double spirals. Their abundance is surprising because they require a Burgers vector spanning two molecular-layer spacings, distorting the crystal lattice to a larger extent. We propose that these double spirals grow at the expense of the initially more common single spirals for an energetic reason: they produce hexagonal ice.

Four-fold Raman enhancement of 2D band in twisted bilayer graphene: evidence for a doubly degenerate Dirac band and quantum interference.

We report the observation of a strong 2D band Raman in twisted bilayer graphene (tBLG) with large rotation angles under 638 nm and 532 nm visible laser excitations. The 2D band Raman intensity increased four-fold as opposed to the two-fold increase observed in single-layer graphene. The same tBLG samples also exhibited rotation-dependent G-line resonances and folded phonons under 364 nm UV laser excitation. We attribute this 2D band Raman enhancement to the constructive interference between two double-resonance Raman pathways, which were enabled by a nearly degenerate Dirac band in the tBLG Moiré superlattices.

Clusters, molecular layers, and 3D crystals of water on Ni(111).

We examined the growth and stability of ice layers on Ni(111) up to ∼7 molecular layers (ML) thick using scanning tunneling microscopy. At low coverage, films were comprised of ∼1 nm wide two-dimensional (2D) clusters. Only above ∼0.5 ML did patches of continuous 2D layers emerge, coexisting with the clusters until the first ML was complete. The structure of the continuous layer is clearly different from that of the 2D clusters. Subsequently, a second molecular layer grew on top of the first. 3D crystallites started to form only after this 2nd ML was complete. 2D clusters re-appeared when thicker films were partially evaporated, implying that these clusters represent the equilibrium configuration at low coverage. Binding energies and image simulations computed with density functional theory suggest that the 2D clusters are partially dissociated and surrounded by H adatoms. The complete 2D layer contains only intact water molecules because of the lack of favorable binding sites for H atoms. We propose molecular structures for the 2D layer that are composed of the same pentagon-heptagon binding motif and water density observed on Pt(111). The similarity of the water structures on Pt and Ni suggests a general prescription for generating low-energy configurations on close-packed metal substrates.

The efficiency and safety of low-dosage isotretinoin therapy for Chinese acne vulgaris patients.

BACKGROUND: Acne vulgaris is one of the most common skin conditions in dermatology clinics. Accumulating evidence has implicated oral low-dosage isotretinoin was an effective treatment for acne with fewer side effects. Currently, the data on low-dosage isotretinoin use in Chinese is limited. AIMS: To investigate the efficiency and safety of low-dosage isotretinoin therapy for Chinese acne patients. METHODS: Three hundred and eighty-eight patients treated with low-dosage isotretinoin (0.2-0.4 mg/kg/d) and who completed the course (120 mg/kg) were enrolled. Medical information on the severity, duration, adverse effects, and outcome of acne was reviewed. RESULTS: The majority (90.2%, n = 350) of patients achieved complete remission, and on average, patients received 13.5 months of treatment. The time between isotretinoin start and the clear date between the mild and moderate groups was not significantly different (74 ± 24 vs. 84 ± 24 days). However, it took longer to resolve for the severe acne group (112 ± 25 days). Follow-up 1 year after completion of the isotretinoin course, 37/350 (10.6%) patients relapsed, but there was no difference in the severity of acne. There were 133 (34.3%), 40 (10.3%), and 14 (2.6%) patients who developed hypercholesterolemia, hypertriglyceridemia, and high LDL, respectively. Thirty-two (8.2%) and 28 patients (7.2%) had elevated serum levels of alanine and aspartate aminotransferases. No values above grade 2 were detected. CONCLUSIONS: This study reaffirms the efficacy and safety of low-dosage oral isotretinoin in Chinese patients with acne vulgaris. Lab investigation could be performed after 2 months of therapy in healthy patients with normal baseline liver function and lipid panel tests.

Dysregulated tryptophan metabolism and AhR pathway contributed to CXCL10 upregulation in stable non-segmental vitiligo.

BACKGROUND: Tryptophan metabolism dysregulation has been observed in vitiligo. However, drawing a mechanistic linkage between this metabolic disturbance and vitiligo pathogenesis remains challenging. OBJECTIVE: Aim to reveal the characterization of tryptophan metabolism in vitiligo and investigate the role of tryptophan metabolites in vitiligo pathophysiology. METHODS: LC-MS/MS, dual-luciferase reporter assay, ELISA, qRT-PCR, small interfering RNA, western blotting, and immunohistochemistry were employed. RESULTS: Kynurenine pathway activation and KYAT enzyme-associated deviation to kynurenic acid (KYNA) in the plasma of stable non-segmental vitiligo were determined. Using a public microarray dataset, we next validated the activation of kynurenine pathway was related with inflammatory-related genes expression in skin of vitiligo patients. Furthermore, we found that KYNA induced CXCL10 upregulation in keratinocytes via AhR activation. Moreover, the total activity of AhR agonist was increased while the AhR concentration per se was decreased in the plasma of vitiligo patients. Finally, higher KYAT, CXCL10, CYP1A1 and lower AhR expression in vitiligo lesional skin were observed by immunohistochemistry staining. CONCLUSION: This study depicts the metabolic and genetic characterizations of tryptophan metabolism in vitiligo and proposes that KYNA, a tryptophan-derived AhR ligand, can enhance CXCL10 expression in keratinocytes.

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies.

Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.

Ultrasound elastography predicts anticoagulation in lower extremity deep vein thrombosis.

OBJECTIVE: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE). METHODS: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves. RESULTS: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively. CONCLUSIONS: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.

Insight into magnetite's redox catalysis from observing surface morphology during oxidation.

We study how the (100) surface of magnetite undergoes oxidation by monitoring its morphology during exposure to oxygen at ~650 °C. Low-energy electron microscopy reveals that magnetite's surface steps advance continuously. This growth of Fe3O4 crystal occurs by the formation of bulk Fe vacancies. Using Raman spectroscopy, we identify the sinks for these vacancies, inclusions of α-Fe2O3 (hematite). Since the surface remains magnetite during oxidation, it continues to dissociate oxygen readily. At steady state, over one-quarter of impinging oxygen molecules undergo dissociative adsorption and eventual incorporation into magnetite. From the independence of growth rate on local step density, we deduce that the first step of oxidation, dissociative oxygen adsorption, occurs uniformly over magnetite's terraces, not preferentially at its surface steps. Since we directly observe new magnetite forming when it incorporates oxygen, we suggest that catalytic redox cycles on magnetite involve growing and etching crystal.

Atrophic dermatofibrosarcoma protuberans: Two case reports and literature review.

Dermatofibrosarcoma protuberans is a rare, locally aggressive, slowly growing cutaneous fibroblastic sarcoma with a high recurrence rate and low metastatic potential. Atrophic dermatofibrosarcoma protuberans is a rare variant usually presents as atrophic plaques, easily neglected and misdiagnosed as benign lesions by patients and dermatologists. Here we report two cases of atrophic dermatofibrosarcoma protuberans, one of which was accompanied by pigment, and review other cases have been reported in the literature. Understanding the most up-to-date literature and early identification of these dermatofibrosarcoma protuberans variants can help clinicians avoid delayed diagnosis and improve prognosis.

TMT-Based Quantitative Proteomic and Physiological Analyses on Serums of Chinese Patients with Active Vitiligo.

Purpose: Vitiligo is an acquired depigmented skin disorder. Though genetic background, autoimmune dysregulation, and oxidative stress were reported involved in the development of vitiligo, the exact pathogenesis remains largely unknown. This study aimed to investigate potential functional proteins, pathways, and serum biomarkers involved in active vitiligo. Patients and Methods: Tandem Mass Tags (TMT) method was used to determine differentially expressed proteins (DEPs) in serum samples between 11 active vitiligo patients and 7 healthy controls of Chinese Han population. Results: A total of 31 DEPs were identified (P < 0.05, fold change >1.2), with 21 proteins upregulated and 10 proteins downregulated in the vitiligo group. DEPs were enriched in GO terms such as "extracellular exosome" and "immunoglobulin receptor binding", as well as KEGG pathways including "cysteine and methionine metabolism" and other immune-related pathways. Furthermore, ALDH1A1 and EEF1G achieved areas under receiver-operating characteristic (ROC) curve of 0.9221 and 0.8571, respectively. The expression levels of these 2 proteins were validated in another active vitiligo patient group. Conclusion: Our research provided novel insight into serum proteomic profile for vitiligo patients, detecting ALDH1A1 and EEF1G as potential biomarkers for active vitiligo and therapeutic intervention. Our work also detected several DEPs and associated pathways in the serum of active vitiligo patients, reinforcing the roles of retinoic acid and exosome processes in vitiligo pathogenesis.

COVID-19 risk perception and negative emotional symptoms: Mediating role of self-control and moderating role of life history strategy.

The coronavirus disease 2019 (COVID-19) has emerged as a significant public health crisis, posing threats to physical health and mental well-being. This study, grounded in the Risk-Resilience Model, sought to elucidate how COVID-19 risk perception impacts negative emotional symptoms. Specifically, we examined the mediating role of self-control and the moderating role of life history strategies. We conducted a two-wave longitudinal survey in October 2020 (N = 334) and November 2020 (N = 249), targeting residents across 14 provinces (24 cities) in China. After controlling for sex and age, the results supported the moderated mediation model, illustrating that (1) self-control mediated the relationship between COVID-19 risk perception and negative emotional symptoms, (2) life history strategy moderated the first segment of the mediation process, and (3) life history strategies also moderated the mediating effect of self-control on the link between COVID-19 risk perception and negative emotional symptoms. Furthermore, compared to a fast life history strategy, a slow life history strategy mitigated the effect of COVID-19 risk perception on self-control, thereby reducing negative emotional symptoms. This study sheds light on how COVID-19 risk perception affects negative emotional symptoms and identifies potential targets (i.e., self-control and life history strategy) for addressing emotional distress during pandemics.

Roflumilast enhances the melanogenesis and attenuates oxidative stress-triggered damage in melanocytes.

BACKGROUND: The management of vitiligo is challenging due to limited treatment options, and therapeutic strategy varies according to the active or stable stage of vitiligo. PDE4 inhibitor has been used to treat various skin diseases, but the efficacy in vitiligo treatment is mixed. OBJECTIVE: In this study, we aimed to investigate whether roflumilast, a PDE4 inhibitor, induces melanogenesis and attenuates oxidative stress-triggered damage in melanocytes, and if so, what is the mechanism. METHODS: Melanin content assay, qRT-PCR, western blotting, ELISA, immunofluorescence assays, immunohistochemistry, small interfering RNA, flow cytometry, and transmission electron microscopy were employed. RESULTS: Our results demonstrated that roflumilast alone only slightly increased melanogenesis, however, the combination of roflumilast and forskolin could boost cAMP levels, hence promoting melanogenesis more significantly. Moreover, roflumilast attenuated H2O2-induced apoptosis and mitochondrial morphological changes in melanocytes by reducing ROS levels. Furthermore, roflumilast activated AhR/Nrf2 pathway via cAMP whereas AhR silencing blocked roflumilast-induced Nrf2 nuclear translocation and reversed the inhibitory effect of roflumilast on H2O2-induced ROS production. Finally, we observed that the lesional skin of active vitiligo patients exhibited higher PDE4 expression levels. CONCLUSION: roflumilast enhances the melanogenesis effect of forskolin and protects melanocytes from H2O2-induced apoptosis by cAMP/AhR/Nrf2-activated ROS inhibition, highlighting its therapeutic potential in vitiligo treatment.