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Ni Zeng,1,2 Yueyue Li,2 Qian Wang,3 Yihe Chen,2 Yan Zhang,1 Lanfang Zhang,1 Feng Jiang,4,5 Wei Yuan,1 Dan Luo2 1Department of Dermatology, Affiliated Hospital of Zunyi Medical University,149 Dalian Road, Huichuan District, Guizhou, 563003, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, People’s Republic of China; 4Neonatal Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China; 5Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 21000, People’s Republic of ChinaCorrespondence: Wei YuanDepartment of Dermatology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Guizhou, 563003, People’s Republic of ChinaTel/Fax +86 13655187928Email dryuanweihua@sina.comDan LuoDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of ChinaTel/Fax +86 13655187928Email daniluo2005@163.comPurpose: To identify potential risk factors for herpes zoster infection in type 2 diabetes mellitus in southeast Chinese population.Patients and Methods: We built a model involving 266 herpes zoster patients collecting data from January 2018 to December 2019. The least absolute shrinkage and selection operator (Lasso) predictive model was used to test herpes zoster virus risk using the patient data. Multivariate regression was conducted to decide which variable would be the strongest to decrease the Lasso penalty. The predictive model was tested using the C-index, a calibration plot, and decision curve study. External validity was verified by bootstrapping by counting probabilities.Results: In the prediction nomogram, the prediction variables included age, sex, weight, length of hospital stay, infection, and blood pressure. The C-index of 0.844 (0.798– 0.896) indicated substantial variability and thus the model was adjusted appropriately. A score of 0.825 was achieved somewhere in the above interval. Examination of the decision curve estimated that herpes zoster nomogram was useful when the intervention was determined at the 16 percent of the herpes zoster infection potential threshold.Conclusion: The herpes zoster nomogram combines age, weight, position of the rash, 2-hour plasma glucose, glycosuria, serum creatinine, length of the hospital stay, and hypertension. This calculator can be used to assess the individual herpes zoster risks in patients diagnosed with type 2 diabetes mellitus.Keywords: glycemic status, herpes zoster, nomogram, type 2 diabetes mellitus, infection

Polymeric micelles have long been considered as promising nanocarrier for hydrophobic drugs and imaging probes, due to their nanoscale particle size, biocompatibility and ability to loading reasonable amount of cargoes. Herein, a facile method for dextran micelles preparation was developed and their performance as carriers of superparamagnetic iron oxide (SPIO) nanocrystals was evaluated. Amphiphilic dextran (Dex-g-OA) was synthesized via the Schiff base reactions between oxidized dextran and oleylamine, and self-assembled in situ into nano-size micelles in the reaction systems. The self-assembling behaviors of the amphiphilic dextran were identified using fluorescence resonance energy transfer technique by detection the energy transfer signal between the fluorophore pairs, Cy5 and Cy5.5. Hydrophobic SPIO nanoparticles (Fe3O4 NPs) were successfully loaded into the dextran micelles via the in situ self-assembly process, leading to a series of Fe3O4 NPs-loaded micelle nanocomposites (Fe3O4@Dex-g-OA) with good biocompatibility, superparamagnetism and strongly enhanced T2 relaxivity. At the magnetic field of 0.5 T, the Fe3O4@Dex-g-OA nanocomposite with particle size of 116.2 ± 53.7 nm presented a higher T2 relaxivity of 327.9 mMFe−1·s−1. The prepared magnetic nanocomposites hold the promise to be used as contrast agents in magnetic resonance imaging.

Background Ultraviolet irradiation (UVR) can induce both cellular senescence and cell apoptosis, which is mainly determined by the DNA damage response. The mechanism that determines the cellular outcome after UVR has not been fully illuminated. Objective To investigate the role of ACTL6A in the response of human dermal fibroblasts to UVR. Methods Human dermal fibroblasts were used to find the function and mechanism of ACTL6A in photoaging and verified in mice. Results ACTL6A expression was significantly increased both in vitro and in vivo after UVR exposure. Interference ACTL6A expression in HDFs inhibited the UVR stress-induced premature senescence, intracellular ROS production and SASP secretion. Meanwhile, knockdown of ACTL6A promotes apoptosis of senescent cells. Conclusion ACTL6A exhibited a critical role in resolving the cell fate under UVR and maybe a potential target for the therapy of UV-induced diseases and UV-needed diseases.

In this paper, the effects of a polarization-modulated quaternary AlInGaN quantum barrier on carrier capture capability and the overlap rate of wave functions in deep-ultraviolet light-emitting diodes (DUV-LEDs) are numerically investigated. By controlling the band bending degree by adjusting polarization intensity (ΔP) in the active region, the band bending is alleviated, and electrons and holes move from both sides of the quantum well to the center, which increases the overlap rate of wave functions and enhances the light output power of DUV-LEDs. Also, there is a limitation on improving the performance of DUV-LEDs by reducing the polarization intensity. This is because the reduced polarization intensity (ΔP) flattens the energy band, reduces the two-dimensional electron gas (2DEG) concentration at the quantum well/quantum barrier (QW/QB) interface, and decreases the effective barrier height. The lower effective barrier height reduces the capability of carrier confinement and carrier concentration in the active region, resulting in the imbalance between the wave function and the carrier concentration, which limits further enhancement of the performance of DUV-LEDs.

Ni Zeng,1,2 Liwen Ma,3 Yuxin Cheng,1 Qingyue Xia,1 Yueyue Li,1 Yihe Chen,1 Zhiyu Lu,1 Qian Lu,1 Feng Jiang,4 Dan Luo1 1Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 3Department of Dermatology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 4Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of ChinaCorrespondence: Dan LuoDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, People’s Republic of ChinaEmail daniluo2005@163.comFeng JiangDepartment of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People’s Republic of ChinaEmail dxyjiang@163.comObjective: In this research, we studied the genes associated with ferroptosis to develop a prognostic model and find out an association with tumor immune microenvironment in skin cutaneous melanoma (SKCM) patients.Methods: To find SKCM-related ferroptosis genes, we used Cox regression and LASSO approach on 60 genes related to ferroptosis and SKCM-related RNA-seq. Following that, a ferroptosis-related gene signature was created. Time-dependent ROC curve and Kaplan–Meier analysis were calculated to determine its capability of prediction. Besides, several assessments were used to evaluate overall survival (OS), accompanied by the creation of a nomogram for the clinicopathologic factors and the ferroptosis-related gene signature we established. We also investigated the relationship between ferroptosis-related gene signature with three immune checkpoints and immune cell infiltration.Results: Our prognostic model included two genes (ALOX5, CHAC1). In both TCGA and GEO cohorts, OS was lower in high-risk category. Using our gene signature, we can reliably predict OS. Additionally, our gene signature can predict immune cell infiltration and SKCM immunotherapy response.Conclusion: Our gene signature has shown to be a reliable predictor of OS, reflect the immune microenvironment, and predict the effectiveness of immunotherapy for SKCM patients.Keywords: skin cutaneous melanoma, SKCM, ferroptosis, immune microenvironment, immune checkpoint

Background Atopic dermatitis is the most common chronic inflammatory skin disease and presents a major public health burden worldwide. Recent observational studies revealed the potential association between atopic dermatitis with autoimmune disorders. However, there is no meta-analysis of the prevalence or incidence of autoimmune diseases in atopic dermatitis. Therefore, considering the potential clinical implications of these associations, we aimed to assess the risk of autoimmune diseases in patients with atopic dermatitis using this method. Methods PubMed, Embase, and Web of Science were searched from inception to October, 2020. Observational studies which provided estimate effects with 95% CI or raw data were included. The quality of selected studies was evaluated using the Newcastle–Ottawa Scale. Odds ratio and relative risks were pooled using a random effects model and expressed with 95% confidence intervals. Results Fourteen observational studies were included in this systematic review and meta-analysis. The random-effects meta-analysis of case–control and cross-sectional studies showed a significant association of atopic dermatitis with mutiple autoimmune diseases, including alopecia areata, celiac disease, Crohn’s disease, rheumatoid arthritis, systematic lupus erythematosus, ulcerative colitis and vitiligo. Furthermore, pooling of the results of cohort studies showed that patients with atopic dermatitis were more likely to develop these autoimmune diseases. Conclusion Our meta-analysis showed that patients with atopic dermatitis were at higher risk of multiple autoimmune diseases including alopecia areata, celiac disease, Crohn’s disease, rheumatoid arthritis, systematic lupus erythematosus, ulcerative colitis and vitiligo. It is important for early detection of the affected group so that timely management can be initiated. Dermatologists and allergists should be aware of the autoimmune diseases in patients with atopic dermatitis and develop interventions if necessary. Also, limited by the present research, we still require more large-scale studies to further establish the association between atopic dermatitis and autoimmune diseases.

Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic core/hydrophilic shell structure and nanoscale. However, the structural stability of polymer micelles can be affected strongly by environmental factors, such as temperature, pH, shear force in the blood and interaction with non-target cells, leading to degradations and drug leakage as drug carriers. Therefore, researches on the structural integrity and in vivo distribution of micelle-based carriers are very important for evaluating their therapeutic effect and clinical feasibility. At present, fluorescence resonance energy transfer (FRET) technology has been widely used in real-time monitoring of aggregation, dissociation and distribution of polymer micelles (in vitro and in vivo). In this review, the polymer micelles, characteristics of FRET technology, structure and properties of the FRET-polymer micelles are briefly introduced. Then, methods and mechanism for combinations of several commonly used fluorescent probes into polymer micelles structures, and progresses on the stability and distribution studies of FRET-polymer micelles (in vitro and in vivo) as drug carriers are reviewed, and current challenges of FRET technology and future directions are discussed.

This study aims to investigate the necessity of nostril retention after secondary unilateral cleft rhinoplasty.Seventy four patients who underwent secondary unilateral cleft rhinoplasty were categorized into control group, nasal retainer group, and nasal clip group. A nasal retainer or nasal clip was applied 7 days after secondary correction and retained in the nostrils of the patients for 6 to 12 months. Measurements from pre- and post-operative photos and patient-reported outcomes were used in this study.After 6 to 12 months, although relapse still occurred in three groups, the nasal retainer group showed a better effect in the ratio of nostril height, whereas the nasal clip group showed a significant improvement in the ratio of nasal base. And both the two groups also showed significant improvement in the ratio of nasal columella. Patients from the control group generally had lower Derriford Appearance Scale (DAS) scores than the nasal retainer group and nasal clip group. Wearing a nasal retainer may negatively influence self-concept, facial self-consciousness of appearance and physical state, and significant differences in mean scores were also found in 9 items.The nostril retention after secondary unilateral cleft rhinoplasty could help preserve nasal morphology and reduce postoperative relapse but worsen the patients' quality of life. The necessity of applying the nostril retention should consider the forms of nasal deformity and the potential influence on the quality of life.3 Laryngoscope, 2022.

Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The CLP-induced sepsis mouse model was established and the septic mice were examined for histopathological changes using HE staining. KLF13 expression in septic mouse heart and LPS-induced cellular inflammation model was detected. Pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 level, inflammatory cytokines (IL-1β, TNF-α, IL-8 and MCP-1) production and IκB-α protein level and p65 phosphorylation in septic mice and LPS-induced cells were detected to evaluate cardiomyocyte apoptosis, inflammatory response and NF-κB pathway activation. KLF13 was overexpressed in vivo and in vitro to explore its specific effect on sepsis-induced myocardial injury. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in myocardial cells. KLF13 was downregulated in the septic mouse heart and LPS-induced cellular inflammation model. Septic heart and LPS-induced cell model showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-κB pathway (increased p65 phosphorylation and decreased IκB-α protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially the NF-κB signalling) and cardiomyocyte apoptosis.

Background Increasingly evidence has shown pulmonary arterial hypertension (PAH) was predisposed to occur in psoriasis, however, the common mechanism of this phenomenon is still not fully clarified. This study aims to further explore the molecular mechanisms of this complication. Methods Four datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the communal DEGs, modules, and hub genes of psoriasis and PAH, subsequent bioinformatic analyses, consisting of function annotation analysis, co-expression analysis, drug-gene interaction prediction, and mRNA–miRNA regulation network construction were conducted. Moreover, Immune cell infiltration analysis and correlation analysis were performed to further uncover the related immune pathogenesis in psoriasis and PAH. Results 170 communal DEGs, 4 modules, and 6 hub genes were identified between GSE15197 and GSE30999, and the expression of hub genes was verified in the GSE41662 and GSE113439 respectively. The function annotation analysis of these genes mainly enriched in the Immune System and associated signal transduction, and the immune cell infiltration analysis highlighted the existence of the overlap in terms of mast cells between PAH and psoriasis. Conclusions The analysis of communal DEGs, modules, and hub genes underlined the potential role of the immune system and associated signal transduction in the common pathogenesis of psoriasis and PAH, and immune Infiltration analysis of two diseases provide us with new perspectives and exploring direction. Moreover, six hub genes (MYO5A, CDT1, ASPM, ACTR2, PTPN11, and SOST) may be used as biomarkers or therapeutic targets in psoriasis and PAH.

The novel coronavirus disease 2019 (COVID-19) vaccination is now an essential strategy for controlling the COVID-19 epidemic. This study included 132 cases of adverse skin reactions after the injection of COVID-19 vaccination from January 2021 to January 2022. The rate of adverse skin reactions after the 1st, 2nd, and 3rd doses of the COVID-19 vaccine were 52%, 40%, and 8% of total adverse skin reactions, respectively. The Urticaria-like rash was the most common manifestation of all adverse skin reactions, accounting for 40.15% of all adverse reactions. The Eczema-like rash was 27.27%. The rates of adverse skin reactions after vaccination with the COVID-19 vaccine in patients with a previous skin disease was 12.12%. Other rare skin adverse reactions after COVID-19 vaccination included herpes zoster, pityriasis rosea, erythema multiforme, chickenpox, herpes simplex, psoriasis, erythrodermatitis, arthus reaction, lichen planus recurrence, measles-like rash, frostbite rash, seborrhea, and vitiligo. There were 23 cases of adverse skin reactions in the same individual after two doses of COVID-19 vaccine. There were three cases of adverse skin reactions in the same person after three doses of the vaccine. Treatment measures are mostly mild regimens, such as oral antihistamines, compounded glycopyrrolate and topical weak to moderately potent corticosteroid creams. The total duration of these skin adverse reactions ranged from 2 weeks to 1 month.

The estrogen-related receptor (ERR) family of orphan nuclear receptors are transcriptional activators for genes involved in mitochondrial bioenergetics and metabolism. The goal of this study was to explore the role of ERRα in lipid metabolism and the potential effect of inhibiting ERRα on the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In the current study, three experimental mouse models: high-fat diet, high-carbohydrate diet, and a genetic model of hepatic insulin resistance where the liver hyperinsulinemia signal is mimicked via hepatic deletion of Pten (phosphatase and tensin homolog deleted on chromosome 10), the negative regulator of the insulin/phosphatidylinositol 3-kinase signaling pathway, were used. A recently developed small-molecule inhibitor for ERRα was used to demonstrate that inhibiting ERRα blocked NAFLD development induced by either high-carbohydrate diet or high-fat diet feeding. ERRα inhibition also diminished lipid accumulation and attenuated NASH development in the Pten null mice. Glycerolipid synthesis was discovered as an additional mechanism for ERRα-regulated NAFLD/NASH development and glycerophosphate acyltransferase 4 was identified as a novel transcriptional target of ERRα. In summary, these results establish ERRα as a major transcriptional regulator of lipid biosynthesis in addition to its characterized primary function as a regulator for mitochondrial function. This study recognizes ERRα as a potential target for NAFLD/NASH treatment and elucidates novel signaling pathways regulated by ERRα.

Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2 (ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPK kinases, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.

Increasing evidence has shown that microRNAs (miRNAs) participate in cardiac fibrosis. We aimed to elucidate the effect of miRNA miR-25-3p on cardiac fibrosis. MiRNA microarray was used to profile miRNAs in the myocardium of angiotensin-II (Ang-II)-infused mice. Effect of miR-25-3p on expression of fibrosis-related genes, including Col1a1, Col3a1, and Acta2, was investigated both in vitro and in vivo. MiR-25-3p was shown increased in the myocardium of Ang-II-infused mice and patients with heart failure. MiR-25-3p enhanced fibrosis-related gene expression in mouse cardiac fibroblasts (mCFs) and in the myocardium of Ang-II-infused mice. Dickkopf 3 (Dkk3) was identified as a target gene of miR-25-3p, and Dkk3 could ameliorate Smad3 activation and fibrosis-related gene expression via enhancing Smad7 expression in mCFs. Additionally, NF-κB signal was proven to mediate upregulation of miR-25-3p in cardiac fibrosis. Our findings suggest that miR-25-3p enhances cardiac fibrosis by suppressing Dkk3 to activate Smad3 and fibrosis-related gene expression.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Brain neuroinflammation plays a role in PD pathogenesis. However, the involvement of the peripheral immune system has not been systematically investigated. Here we analyzed >700 combinatorial immunological features in fresh blood of 28 early-to-mid-stage PD patients and 24 matched controls. We found an enhanced cytotoxic immune profile in idiopathic PD patients (iPD), with a higher frequency of terminally-differentiated effector CD8 T (TEMRA), late-differentiated CD8+ natural killer T cells and neutrophils. This immune profile was intensified by elevated serum granzyme A, reduced percentages of CD8+FOXP3+ regulatory T cells and group 2 innate lymphoid cells with immunosuppressive or tolerance-inducing functions. The frequency of CD8 TEMRA was negatively correlated with disease duration, suggesting a contribution to PD pathogenesis. Our work provides a comprehensive map on disturbed peripheral adaptive and innate immune cells in early-to-mid iPD, proposing easily-accessible candidates for early diagnosis and treatments.

The predominant pathological manifestation of osteoarthritis (OA) is articular cartilage damage. Chondrocytes are the only cell type present in articular cartilage. The proportion of chondrocytes inflammation and apoptosis correlated significantly with the degree of articular cartilage degeneration and progression of OA. Irisin is released from myocytes during physical activity, and acts as a link between muscles and other tissues and organs. Many studies have confirmed the multifunctional role of Irisin and the beneficial effects of this molecule on bone development and regeneration. Little is known about the mechanisms of Irisin on chondrocytes and the development of OA. This study aimed to investigate the mechanisms and effects of Irisin on interleukin-1β (IL-1β)-induced rat chondrocytes. Our results revealed that Irisin improved IL-1β-induced growth inhibition in chondrocytes and attenuated the production of reactive oxygen species (ROS). And Irisin decreased the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and exerted anti-apoptotic effects by the extracellular signal-regulated kinases (ERK) signaling pathway. In conclusion, Irisin acts through the ERK signaling pathway to protect against IL-1β-induced chondrocytes injury by reducing excessive ROS, inhibiting inflammation and apoptosis. The present study sheds new light on the chondroprotective actions of this myokine, and further develops the therapeutic targets of Irisin for bone and cartilage disorders including OA.

Ultraviolet A (UVA) radiation causes skin damage. Recently, natural compounds have become an interest to protect skin from UV-induced photodamages.In this study, we investigated the protective effects of hesperetin, a citrus flavonoid, on UVA-induced oxidative stress, inflammation, apoptosis, and photoaging.Our results showed that hesperetin increased the cell viability, suppressed the intracellular ROS levels, and decreased the expression of MMPs including MMP-1 and MMP-3, pro-inflammatory cytokines including IL-6 and COX-2 in UVA-irradiated HDFs. Besides, hesperetin exerted an anti-apoptotic effect by increasing expression of anti-apoptotic protein Bcl-2 and decreasing expression of pro-apoptotic protein Bax. Moreover, these anti-photodamage effects were mediated by inhibition of ERK, p38/AP-1, and NF-κb/p65 phosphorylation.Therefore, hesperetin may be useful in the prevention of UVA-induced skin damage.

In this work, we investigated the relationship between the modulation bandwidths and the number of quantum wells of GaN-based blue light-emitting diodes (LEDs). The number of quantum wells is designed to be 1, 3, 6, 9 and 12, respectively. Our results show that when the number of quantum wells of the LED is set to be 3 at the same injection current, not only the −3 dB bandwidth of the LED gets its largest, but also the modulation characteristics obtain best responses. Combining results from time-resolved photoluminescence spectroscopy (TRPL), alternating current (AC) impedance spectroscopy and optical output power of the LEDs further concluded that setting the quantum well number of LEDs 3 optimizes visible light communication.

Ultraviolet A (UVA) irradiation can induce cellular senescence and cause skin photoaging, which is mainly driven by the excessive production of reactive oxygen species (ROS). Emerging studies have focused on new strategies for the prevention of skin photoaging. Ultrasmall Prussian blue nanoparticles (USPBNPs) demonstrate an intensive ability to scavenge ROS as nanozymes and exhibit great potential in the treatment of ROS-related diseases. Our goal was to investigate the anti-senescent role of USPBNPs against UVA-induced premature senescence in human dermal fibroblasts (HDFs). Our results showed that the activation of senescence-associated β-galactosidase (SA-β-gal) and the arrest of the cell cycle induced by UVA radiation in HDFs were significantly inhibited by pretreatment of USPBNPs (1 μg ml−1). Furthermore, USPBNPs downregulated the expression of DNA damage marker γH2AX and inhibited the secretion of senescence-associated secretory phenotypes (SASP) including IL-6, TNF-α and matrix metalloproteinases (MMPs). In addition, we found that the antiphotoaging effect of USPBNPs involved the scavenging of ROS as well as the inhibition of the ERK/AP-1 pathway. In conclusion, USPBNPs exhibited great potential to become novel anti-photoaging agents by alleviating UVA-induced cellular senescence and thus delaying the process of skin photoaging.

Ultraviolet B (UVB) is one of the most common exogenous factors in skin aging, especially photoaging. Once a large amount of UVB accumulates within a short period of time, skin tissue can become inflamed. It has also been found in clinics that platelet-rich plasma (PRP) can promote wound repair; therefore, the aim of this study was to identify the mechanism by which PRP repairs UVB-induced skin photodamage. We used PRP of Sprague-Dawley rats with the two-spin technique in the established acute UVB radiation photodamage model and harvested the corresponding skin after 1, 7, and 28 d. Hematoxylin and eosin staining was used to observe tissue inflammation. We found that PRP reduces inflammation in the early stages of UVB-induced acute skin damage, and then promotes the proliferation of collagen in the middle and late stages. Moreover, PRP can stimulate Act A and M1 polarization in the early stage, while inhibiting activin A (Act A) and inducing M2 polarization in the middle and late stages. In conclusion, this study demonstrates that PRP plays an important regulatory role in helping reduce UVB-induced acute skin tissue inflammation by adjusting macrophage polarization, which alleviates skin inflammation and stimulates collagen regeneration.

Background Myocardial infarction (MI) is a common cause of death worldwide. It is characterized by coronary artery occlusion that causes ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. Materials and Methods To explore potential targets for treatment of MI, we reorganized and analyzed two microarray datasets (GSE4648 and GSE775). The GEO2R tool was used to screen for differentially expressed genes (DEGs) between infarcted and normal myocardium. We used the Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform Gene Ontology functional annotation analysis (GO analysis) and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analysis (KEGG analysis). We examined protein–protein interactions to characterize the relationship between differentially expressed genes, and we screened potential hub genes according to the degree of connection. PCR and Western blotting were used to identify the core genes. Results At different times of infarction, a total of 35 genes showed upregulation at all times; however, none of the genes showed downregulation at all 3 times. Similarly, 10 hub genes with high degrees of connectivity were identified. In vivo and in vitro experiments suggested that expression levels of MMP-9 increased at various times after myocardial infarction and that expression increased in a variety of cells simultaneously. Conclusion Expression levels of MMP-9 increase throughout the course of acute myocardial infarction, and this expression has both positive and negative sides. Further studies are needed to explore the role of MMP-9 in MI treatment. The potential values of Il6, Spp1, Ptgs2, Serpine1, Plaur, Cxcl5, Lgals3, Serpinb2, and Cd14 are also worth exploring.

Osteoarthritis is the most prevalent arthritis typically characterized by degradation of cartilage. However, its pathogenesis is not fully understood. Currently, osteoarthritis is best considered a disease of the whole "joint organ". Infrapatellar fat pad (IFP), an adipose tissue near synovium, is now attaching importance to researchers for its inflammatory phenotype. In this narrative review, a large body of evidence has been gathered for the involvement of IFP in the development of knee osteoarthritis. Additionally, the underlying mechanisms of how IFP can be involved in this process have been proposed. However, further investigations are needed to better understand its precise role in this process and its underlying mechanism, and beyond that, to develop new strategies to slow down the degenerative process and explore an effective and timely diagnosis of the disease.

Monitoring the changes in the level of KRAS point mutation (the concentration fraction of the KRAS point mutated DNA to the total DNA) in clinical treatment progress can guide and greatly improve the personalized therapy and therapeutic evaluation of patients with cancer. In this work, based on FRET fluorescence quenching and apyrimidinic site-induced guanine/pterin specific binding, we developed a pterin-FAM-TAMRA tri-color fluorescence sensing system to assess the level of KRAS point mutation in one step. The responses from TAMRA displayed good and similar linear correlations in the range from 60 nM to 2 μM for all four types of DNA, resulting in a common linear equation related to the T-DNA concentration (NΔFTAMRA = 2.908cT-DNA + 0.364). Meanwhile, the responses from pterin showed excellent selectivity to W-DNA and an excellent linear correlation to the W-DNA in the concentration range from 60 nM to 1 μM (NΔFpterin = -0.364cgDNA-G + 0.034). This biosensor has an effective concentration range for detecting KRAS point mutations. Especially, because the apyrimidinic site-induced guanine/pterin binding is selective for the detection of wild-type DNA, the sensing system can be applied for clinical mutation level detection of all kinds of KRAS point mutations (G → A, G → C and G → T) in blood samples, which is crucial for the personalized therapy and therapeutic evaluation of patients with most KRAS-related cancer types.

Face hallucination (FH) aims to reconstruct high-resolution faces from low-resolution face inputs, making it significant to other face-related tasks. Different from general super resolution issue, it often requires facial priors other than general extracted features thus leading to fusion of more than one kind of feature. The existing CNN-based FH methods often fuse different features indiscriminately which may introduce noises. Also the latent relations among different features which may be useful are taken into less consideration. To address the above issues, we propose an end-to-end deep ensemble network which aggregates three extraction sub-nets in attention-based manner. In our ensemble strategy, both relations among different features and inter-dependencies among different channels are dug out through the exploitation of spatial attention and channel attention. And for the diversity of extracted features, we aggregate three different sub-nets, which are the basic sub-net for basic features, the auto-encoder sub-net for facial shape priors and the dense residual attention sub-net for fine-grained texture features. Conducted ablation studies and experimental results show that our method achieves effectiveness not only in PSNR (Peak Signal to Noise Ratio) and SSIM (Structural Similarity Index) metrics but more importantly in clearer details within both key facial areas and whole range. Also results show that our method achieves real-time hallucinating faces by generating one image in 0.0237s.

Hepatic glucose metabolism signaling downstream of insulin can diverge to multiple pathways including AKT. Genetic studies suggest that AKT is necessary for insulin to suppress gluconeogenesis. To specifically address the role of AKT2, the dominant liver isoform of AKT in the regulation of gluconeogenesis genes, we generated hepatocytes lacking AKT2 (Akt2−/−). We found that, in the absence of insulin signal, AKT2 is required for maintaining the basal level expression of phosphoenolpyruvate carboxyl kinase (PEPCK) and to a lesser extent G6Pase, two key rate-limiting enzymes for gluconeogenesis that support glucose excursion due to pyruvate loading. We further showed that this function of AKT2 is mediated by the phosphorylation of cyclic AMP response element binding (CREB). Phosphorylation of CREB by AKT2 is needed for CREB to induce the expression of PEPCK and likely represents a priming event for unstimulated cells to poise to receive glucagon and other signals. The inhibition of gluconeogenesis by insulin is also dependent on the reduced FOXO1 transcriptional activity at the promoter of PEPCK. When insulin signal is absent, this activity appears to be inhibited by AKT2 in manner that is independent of its phosphorylation by AKT. Together, this action of AKT2 on FOXO1 and CREB to maintain basal gluconeogenesis activity may provide fine-tuning for insulin and glucocorticoid/glucagon to regulate gluconeogenesis in a timely manner to meet metabolic needs.

Objective Based on the specific binding of target with aptamer, a portable aptasensor combined with highly sensitive electrochemical methods was designed to complete the rapid detection of biological toxins Okadaic acid (OA) in shellfish. Results A simple aptasensor based on screen-printed carbon electrode (SPCE) with modification of chitosan (CS) and gold nanoparticles (AuNPs) was designed for electrochemical determination of OA, and the electrode surface was modified with AuNPs by potential-sweeping electrodeposition, which greatly improved the electrochemical response. The entire detection and characterization process were carried out by cyclic voltammetry (CV) with a linear correlation in the range from 0.01 ng/mL to 100 ng/mL and a LOD of 6.7 pg/mL. Furthermore, a recovery rate of 92.30-115.98% was obtained demonstrating excellent accuracy through the recovery trial of mussel and scallop samples. Conclusion The current method based the change of spatial structure before and after aptamer binding target showed great potential in rapid on-site and low-cost detection of OA for its simplicity.

Objective This study aimed to investigate the outcomes of using a novel nasal clip designed for nostril retention after primary unilateral cleft rhinoplasty. Design This is a retrospective study. Setting Department of Cleft Lip and Palate in a stomatological hospital. Patients A retrospective study was conducted on 57 patients who had a unilateral complete cleft lip without cleft palate and underwent primary surgical repair. Interventions The patients were categorized into 3 groups: the group in which the conventional nasal retainer was used, that in which the nasal clip was used, and the control group in which no postoperative nasal retainer was used. The nasal retainer or our nasal clip was applied 7 days after primary surgical repair and kept in the nostrils of children from 6 to 12 months. Main Outcome Measures Noses underwent photogrammetry preoperatively, postoperatively, and at follow-up. The nose was also subjectively scored at the follow-up. Results The nasal retainer and the nasal clip significantly minimized relapse as determined by nasal tip deviation. The nasal clip sustained nasal symmetry, as determined by the postoperative nostril width ratio, better than did the conventional retainer. After 6 to 12 months, the nasal clip achieved better columellar morphology and a more symmetric nasal base than did the conventional nasal retainer. Statistical differences in subjective scores between the control and nostril retention groups were noted. Conclusion The application of the novel nasal clip after primary unilateral cleft rhinoplasty preserves nasal morphology and reduces postoperative relapse without the need for adhesive tape.

The aim of this study was to investigate the related influencing factors of neuropathic pain (NP) in patients with spinal cord injury (SCI).Patients diagnosed with SCI between January 2016 and December 2019 in the Department of Rehabilitation Medicine, Affiliated Hospital of Guizhou Medical University, were screened for NP by using the Douleur Neuropathique 4 (DN4) questionnaire. A total of 133 patients diagnosed with SCI with NP were finally included in the study. We collected the patients' basic information, including gender, age, body mass index (BMI), disease course, injury segment, American Spinal Injury Association (ASIA) grade, occupation, educational level, whether painkillers were used, stability of economic support, and pain level. Univariate and multiple ordered logistic regression analyses were used to examine the influencing factors of NP in the patients with SCI.The chi-square test revealed that disease course, injury level, severity of SCI (ASIA classification), stable economic support during hospitalization, and the use of painkillers had statistical significance (In this study, we found no significant correlation between NP after SCI and sex, age, BMI, disease course, injury level, and occupation. However, the injury severity was an independent risk factor, and stable economic support and painkiller use were protective factors.

A novel high-throughput aptamer microarray fluorescent method based on thioflavin T (ThT) was established for the sensitive detection of phoxim, parathion, fensulfothion, and isocarbophos. In this work, the aptamers in binding buffer tended to have the antiparallel G-quadruplex structure, which can bind ThT and release its potential fluorescence signal. However, when the organophosphorus pesticides (OPs) were present, partial aptamers preferred to bind them, forcing the displacement of ThT from the G-quadruplex and resulting in the significant decrease in fluorescence signal. Under optimal experimental conditions (12T spacer, 300 nM aptamer, and 80 μM ThT), the OP aptamer microarray has low limits of detection of 25.4 ng/mL for phoxim, 12.0 ng/mL for parathion, 7.7 ng/mL for fensulfothion, and 9.9 ng/mL for isocarbophos. The accuracy and reliability of the method is further verified by testing the recovery rate of OPs spiked in two different complicated sample matrices (pears and radishes). It is worth mentioning that not only the developed aptamer microarray technology has low sensitivity and a broad spectrum, but it also allows for high-throughput and rapid analysis of a variety OPs, which overcomes some of the shortcomings of other OP detection methods.

Decline in immune function during aging increases susceptibility to different aging-related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T-cell subpopulations, still remain largely elusive. Here, we show that loss of DJ-1 encoded by PARK7/DJ-1, causing early-onset familial Parkinson’s disease (PD), unexpectedly diminished signs of immunoaging in T-cell compartments of both human and mice. Compared with two gender-matched unaffected siblings of similar ages, the index PD patient with DJ-1 deficiency showed a decline in many critical immunoaging features, including almost doubled non-senescent T cells. The observation was further consolidated by the results in 45-week-old DJ-1 knockout mice. Our data demonstrated that DJ-1 regulates several immunoaging features via hematopoietic-intrinsic and naïve-CD8-intrinsic mechanisms. Mechanistically, DJ-1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T-cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ-1 in regulating immunoaging, discovering a potent target to interfere with immunoaging- and aging-associated diseases.

Tomato ripening is a complex and dynamic process coordinated by many regulatory elements, including plant hormones, transcription factors, and numerous ripening-related RNAs and proteins. Although recent studies have shown that some RNA-binding proteins are involved in the regulation of the ripening process, understanding of how RNA-binding proteins affect fruit ripening is still limited. Here, we report the analysis of a glycine-rich RNA-binding protein, RZ1A-Like (RZ1AL), which plays an important role in tomato ripening, especially fruit coloring. To analyze the functions of RZ1AL in fruit development and ripening, we generated knockout cr-rz1al mutant lines via the CRISPR/Cas9 gene-editing system. Knockout of RZ1AL reduced fruit lycopene content and weight in the cr-rz1al mutant plants. RZ1AL encodes a nucleus-localized protein that is associated with Cajal-related bodies. RNA-seq data demonstrated that the expression levels of genes that encode several key enzymes associated with carotenoid biosynthesis and metabolism were notably downregulated in cr-rz1al fruits. Proteomic analysis revealed that the levels of various ribosomal subunit proteins were reduced. This could affect the translation of ripening-related proteins such as ZDS. Collectively, our findings demonstrate that RZ1AL may participate in the regulation of carotenoid biosynthesis and metabolism and affect tomato development and fruit ripening.

Type 2 immunity mediates the immune responses against parasites and allergic stimuli. Evidence from studies of cell lines and animals implies that neuromedin U (NmU) acts as a pro-inflammatory mediator of type 2 inflammation. However, the role of NmU in human type 2 immunity remains unclear. Here we investigated the expression of NmU in human blood and airways, and the expression of NmU receptors by human immune cells in blood and lung tissue. We detected human NmU (hNmU-25) in blood and airways with higher concentrations in the latter. NmU receptor 1 (NmUR1) was expressed by most human immune cells with higher levels in type 2 cells including type 2 T helpers, type 2 cytotoxic T cells, group-2 innate lymphoid cells and eosinophils, and was upregulated in lung-resident and activated type 2 cells. We also assessed the effects of NmU in these cells. hNmU-25 elicited type 2 cytokine production by type 2 lymphocytes and induced cell migration, including eosinophils. hNmU-25 also enhanced the type 2 immune response to other stimuli, particularly prostaglandin D

Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human naïve and memory CD4 T cells, here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 naïve T-cell-intrinsic role in regulating the Th1/Th2 differentiation balance. Both stress hormones reduced the Th1 programme and cytokine production by inhibiting mTORC1 signalling via two parallel mechanisms. Stress hormone signalling inhibited mTORC1 in naïve CD4 T cells (1) by affecting the PI3K/AKT pathway and (2) by regulating the expression of the circadian rhythm gene, period circadian regulator 1 (PER1). Both stress hormones induced the expression of PER1, which inhibited mTORC1 signalling, thus reducing Th1 differentiation. This previously unrecognized cell-autonomous mechanism connects stress hormone signalling with CD4 T-cell differentiation via mTORC1 and a specific circadian clock gene, namely PER1.

Objective. Malignant melanoma (MM) is one of the most malignant types of skin cancer and its incidence and mortality rates are increasing worldwide. Aging is well recognized as a significant risk factor for cancer. However, few studies have analyzed in depth the association between aging-related genes (AGs) and malignant melanoma prognosis with tumor immune microenvironment. Methods. Here, we downloaded 471 MM patients from The Cancer Genome Atlas (TCGA) with RNA sequence and clinicopathological data. 58 AGs from the TCGA dataset were examined using Cox regression and the LASSO assay. As a result, a gene signature for aging-related genes was created. The time-dependent ROC curve and Kaplan–Meier analysis were calculated to determine its predictive capability. Moreover, we created a nomogram for the clinicopathologic variables and the AGs gene signature to determine overall survival (OS). We also explored the association between three immune checkpoints, immune cell infiltration, and the aging-related gene signature. Results. We established an aging risk model to identify and predict the immune microenvironment in malignant melanoma. Then we developed and validated a prognosis risk model using three AGs (CSNK1E, C1QA, and SOD-2) in the GSE65904 dataset. The aging signature was positively associated with clinical and molecular characteristics and can be used as a prognostic factor for malignant melanoma. The low aging risk score was associated with a poor prognosis and indicated an immunosuppressive microenvironment. Conclusions. To summarize, we established and validated a model of aging risk based on three aging-related genes that acted as an independent prognostic predictor of overall survival. Besides, it also characterized the immune response in the malignant melanoma microenvironment and could provide a potential indicator of individualized immunotherapy in malignant melanoma.

Hydrogels loaded with magnetic nanoparticles have been widely researched recently as biomaterials, due to their good biocompatibility and unique magnetic characteristics. In this study, water-soluble superparamagnetic iron oxide nanoparticles (Fe

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor 5 (DR5), participate in pulmonary cell apoptosis. This study aimed to investigate the clinical value of soluble DR5 and TRAIL for prognosis assessment in acute respiratory distress syndrome (ARDS). Serum and bronchoalveolar lavage fluid (BALF) samples were collected from ARDS patients and controls. Patients were followed-up until death or discharge. Soluble DR5, TRAIL, TNF-α, soluble receptor for advanced glycation end-products (sRAGE), and albumin levels were measured using the Magnetic Luminex or enzyme-linked immunosorbent assays. Data were analyzed according to their distributions and statistical purposes. Serum and BALF DR5 levels were elevated in patients with ARDS; TRAIL elevation and reduction was observed in BALF and serum, respectively. Serum DR5 was higher in non-survivors compared to survivors. Serum DR5 was positively correlated with serum TNF-α and critical illness scores and negatively correlated with serum TRAIL. Serum DR5 exhibited potential for predicting mortality in patients with ARDS. Serum soluble DR5 elevation, a valuable prognosis predictor in ARDS, may be associated with alveolar epithelial cell apoptosis. http://www.chictr.org.cn/index.aspx.Uniqueidentifier:ChiCTR-DDD-17013370.

Objective: To investigate the interaction of infrapatellar fat pad/cartilage and related mechanisms in knee osteoarthritis (OA) using the metabolomics method.Method: Fat-conditioned media (FCM) of the infrapatellar fat pad from patients with OA were used to treat human OA chondrocytes. The extracellular metabolites of human OA chondrocytes were detected by nontargeted metabolic footprint analysis based on liquid chromatography and mass spectrometry (LC-MS). Then, the different metabolites were found, and the main metabolic pathways were explored, combined with bioinformatics methods.Results: After treatment with FCM for 48 h, the proliferation of human OA chondrocytes was slowed down, indicating that FCM had a certain inhibitory effect on the proliferation of human OA chondrocytes (P = 0.023). On the pattern diagram of principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA), after FCM treatment, the data sample areas were obviously separated, indicating that FCM can significantly affect the metabolic footprint of human OA chondrocytes. Through metabonomic identification, 131 different metabolites were screened after FCM treatment compared with before treatment. For 4 pathways in total, significantly different activity levels were discovered in pairwise comparisons: alanine, aspartate, and glutamate metabolism; citrate cycle (TCA cycle); arginine and proline metabolism; and phenylalanine metabolism.Conclusion: The infrapatellar fat pad aggravates OA chondrocyte injury and is involved in OA by disturbing the chondrocyte TCA cycle, amino acid metabolism, and glutamine metabolism, among others.

The green-flesh (gf) mutant of the tomato fruit ripen to a muddy brown color and has been demonstrated previously to be a loss-of-function mutant. Here, we provide more evidence to support this view that SlSGR1 is involved in color change in ripening tomato fruits. Knocking out SlSGR1 expression using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 genome editing strategy showed obviously a muddy brown color with significantly higher chlorophyll and carotenoid content compared with wild-type (WT) fruits. To further verify the role of SlSGR1 in fruit color change, we performed transcriptome deep sequencing (RNA-seq) analysis, where a total of 354 differentially expressed genes (124/230 downregulated/upregulated) were identified between WT and slsgr1. Additionally, the expression of numerous genes associated with photosynthesis and chloroplast function changed significantly when SlSGR1 was knocked out. Taken together, these results indicate that SlSGR1 is involved in color change in ripening fruit via chlorophyll degradation and carotenoid biosynthesis.

Purpose: In this study, we investigated the effect of treadmill exercise training on cardiac hypertrophy, collagen deposition, echo parameters and serum levels of cardiac troponin I (cTnI) in rats, and how they differ with various exercise intensities, hence exploring potential signal transduction.Methods: Male Sprague-Dawley rats were randomly divided into sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. Each exercise group had 3 subgroups that were sacrificed for cardiac tissue analyses at 1, 4, and 8 weeks, respectively, and all rats participated in a daily 1 h treadmill routine 5 days per week. Echocardiographic measurements were performed 24 h after the last exercise session. Additionally, myocardium samples and blood were collected for histological and biochemical examinations. Changes in the extracellular signal-regulated kinases 1/2 (ERK1/2) signal pathway were detected by Western blotting.Results: After a week of running, ventricular myocyte size and the phosphorylation of ERK1/2 increased in the HIR group, while left ventricular (LV) diastolic diameter values and LV relative wall thickness increased in the LIR and MIR groups. In addition, we observed heart enlargement, cTnI decrease, and ERK1/2 signal activation in each of the exercise groups after 4 weeks of running. However, the HIR group displayed substantial rupture and increased fibrosis in myocardial tissue. In addition, compared with the LIR and MIR groups, 8 weeks of HIR resulted in structural damage, fiber deposition, and increased cTnI. However, there was no difference in the activation of ERK1/2 signaling between the exercise and SED groups.Conclusion: The effect of running on cardiac hypertrophy was intensity dependent. In contrast to LIR and MIR, the cardiac hypertrophy induced by 8 weeks of HIR was characterized by potential cardiomyocyte injury, which increased the risk of pathological development. Furthermore, the ERK signaling pathway was mainly involved in the compensatory hypertrophy process of the myocardium in the early stage of exercise and was positively correlated with exercise load. However, long-term exercise may attenuate ERK signaling activation.

Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Hypoxia is one of characteristics of cancer leading to tumor progression. For ACC, however, no reliable prognostic signature on the basis of hypoxia genes has been built. Our study aimed to develop a hypoxia-associated gene signature in ACC. Data of ACC patients were obtained from TCGA and GEO databases. The genes included in hypoxia risk signature were identified using the Cox regression analysis as well as LASSO regression analysis. GSEA was applied to discover the enriched gene sets. To detect a possible connection between the gene signature and immune cells, the CIBERSORT technique was applied. In ACC, the hypoxia signature including three genes (CCNA2, COL5A1, and EFNA3) was built to predict prognosis and reflect the immune microenvironment. Patients with high-risk scores tended to have a poor prognosis. According to the multivariate regression analysis, the hypoxia signature could be served as an independent indicator in ACC patients. GSEA demonstrated that gene sets linked to cancer proliferation and cell cycle were differentially enriched in high-risk classes. Additionally, we found that PDL1 and CTLA4 expression were significantly lower in the high-risk group than in the low-risk group, and resting NK cells displayed a significant increase in the high-risk group. In summary, the hypoxia risk signature created in our study might predict prognosis and evaluate the tumor immune microenvironment for ACC.

Purpose: Exercise is an effective intervention for both the prevention and treatment of cardiovascular diseases. In this study, we investigated the structural and functional changes that occur in cardiac response and how they differ with various exercise intensities, hence exploring the potential signal transduction.Methods: Male Sprague–Dawley rats were randomly divided into the sedentary (SED), low-intensity running (LIR), medium-intensity running (MIR), and high-intensity running (HIR) groups. Each exercise group had 3 different operation time subgroups for 1, 4, and 8 weeks, respectively, and all rats observed a daily 1 h treadmill routine 5 days per week. Echocardiographic measurements were performed at the end of the experimental program. Additionally, myocardium samples and blood were collected for histological and biochemical examinations. Changes in the extracellular signal-regulated kinases 1/2 (ERK1/2) signal pathway were detected by Western blotting.Results: After a week of running, ventricular myocyte size and the phosphorylation of ERK1/2 increased in the HIR group, while left ventricular (LV) diastolic diameter values and LV relative wall thickness increased in the LIR and MIR groups. In addition, we observed heart enlargement, cTnI decrease, and ERK1/2 signal activation in each of the exercise groups after 4 weeks of running. However, the HIR group displayed a substantial rupture and increased fibrosis in myocardial tissue. In addition, compared with the LIR and MIR groups, 8 weeks of HIR resulted in structural damage, fiber deposition, and increased cTnI. However, there was no difference in activation of ERK1/2 signaling between the exercise groups and SED group.Conclusions: The effect of running on cardiac hypertrophy was intensity dependent. In contrast to LIR and MIR, 8 weeks of HIR-induced cardiac hypertrophy was characterized by potential cardiomyocyte injury, which increased the risk of pathological development. Furthermore, the ERK signaling pathway was mainly involved in the compensatory hypertrophy process of the myocardium in the early stage of exercise and was positively correlated with exercise load. However, long-term exercise may attenuate ERK signaling activation.

The new development of noninvasive diagnosis in breath analysis requires the fabrication of inexpensive and rapid sensing technologies, whose sensing mechanisms are further encouraged to be studied. Here based on the dramatically enhanced plasma-assisted cataluminescence (PA-CTL) signals, a new sensor was constructed for the detection of acetone, an important biomarker of diabetes mellitus in breath. As demonstrated, the PA-CTL-based sensor showed good sensitivity, repeatability, and selectivity in acetone detection, which also displayed good recovery and stability in exhaled breath. An online ionization system of low-temperature plasma mass spectrometry was designed to couple with the PA-CTL sensor for examining changes of molecules during the sensing. For the first time, some important ions were recorded in real time, which helped to clear the reaction mechanism of radical-based catalytic oxidation combined with the CTL data. By the fabrication and relative comprehensive understanding of the PA-CTL sensor for acetone detection, this work would promote the development of CTL sensing techniques and inspire a potential pathway for rapid and noninvasive diagnosis.

Duck hepatitis A virus (DHAV) causes an infectious disease that mainly affects 1- to 4-week-old ducklings, resulting in considerable loss to the duck industry. Although there have been many studies on DHAV in recent years, the effects on host infection and pathogenesis of DHAV-1 remain largely unknown. This study investigated the effects of the DHAV-1 structural protein VP3 on DHAV-1 virus adsorption and apoptosis to explore the role of VP3 in the viral life cycle. The effects of DHAV-1 VP3 and an antibody against the protein on virion adsorption was analyzed by qRT-PCR. The results showed that the virus copy number for the rabbit anti-VP3 IgG-treated group was significantly lower than that for the negative control group but higher than that for the rabbit anti-DHAV-1 IgG-treated group. This result indicates that VP3 mediates DHAV-1 virus adsorption but that it is not the only protein that involved in this process. In addition, a eukaryotic recombinant plasmid, pCAGGS/VP3, was transfected into duck embryo fibroblasts (DEFs), and the apoptotic rate was determined by DAPI staining, the TUNEL assay and flow cytometry. DAPI staining showed nucleus fragmentation and nuclear edge shifting. TUNEL assay results revealed yellow nuclei, and flow cytometry indicated a significant increase in the apoptotic rate. In addition, qRT-PCR revealed increased in the transcriptional levels of the apoptotic caspase-3, −8 and −9, with the largest increase for caspase-3, followed by caspase-9 and caspase-8. Enzyme activity analysis confirmed these results. Furthermore, the VP3 protein decreased the mitochondrial membrane potential, and the transcriptional levels of the proapoptotic factors Bak, Cyt c and Apaf-1 in the mitochondrial apoptotic pathway were significantly upregulated. These data suggest that expression of VP3 in DEFs induces apoptosis and may primarily activate caspase-3-induced apoptosis through mitochondrion-mediated intrinsic pathways. The findings provide scientific data to clarify DHAV-1 infection and pathogenesis.

Although macrophage migration inhibitory factor (MIF) is known to have antioxidant property, the role of MIF in cardiac fibrosis has not been well understood. We found that MIF was markedly increased in angiotension II (Ang-II)-infused mouse myocardium. Myocardial function was impaired and cardiac fibrosis was aggravated in Mif-knockout (Mif-KO) mice. Functionally, overexpression of MIF and MIF protein could inhibit the expression of fibrosis-associated collagen (Col) 1a1, COL3A1 and α-SMA, and Smad3 activation in mouse cardiac fibroblasts (CFs). Consistently, MIF deficiency could exacerbate the expression of COL1A1, COL3A1 and α-SMA, and Smad3 activation in Ang-II-treated CFs. Interestingly, microRNA-29b-3p (miR-29b-3p) and microRNA-29c-3p (miR-29c-3p) were down-regulated in the myocardium of Ang-II-infused Mif-KO mice but upregulated in CFs with MIF overexpression or by treatment with MIF protein. MiR-29b-3p and miR-29c-3p could suppress the expression of COL1A1, COL3A1 and α-SMA in CFs through targeting the pro-fibrosis genes of transforming growth factor beta-2 (Tgfb2) and matrix metallopeptidase 2 (Mmp2). We further demonstrated that Mif inhibited reactive oxygen species (ROS) generation and Smad3 activation, and rescued the decrease of miR-29b-3p and miR-29c-3p in Ang-II-treated CFs. Smad3 inhibitors, SIS3 and Naringenin, and Smad3 siRNA could reverse the decrease of miR-29b-3p and miR-29c-3p in Ang-II-treated CFs. Taken together, our data demonstrated that the Smad3-miR-29b/miR-29c axis mediates the inhibitory effect of macrophage migration inhibitory factor on cardiac fibrosis.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple molecular mechanisms. To investigate and contrast the molecular processes differing between bronchiolitis and emphysema phenotypes of COPD, we downloaded the GSE69818 microarray data set from the Gene Expression Omnibus (GEO), which based on lung tissues from 38 patients with emphysema and 32 patients with bronchiolitis. Then, weighted gene coexpression network analysis (WGCNA) and differential coexpression (DiffCoEx) analysis were performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis (KEGG) analysis. Modules and hub genes for bronchiolitis and emphysema were identified, and we found that genes in modules linked to neutrophil degranulation, Rho protein signal transduction and B cell receptor signalling were coexpressed in emphysema. DiffCoEx analysis showed that four hub genes (IFT88, CCDC103, MMP10 and Bik) were consistently expressed in emphysema patients; these hub genes were enriched, respectively, for functions of cilium assembly and movement, proteolysis and apoptotic mitochondrial changes. In our re‐analysis of GSE69818, gene expression networks in relation to emphysema deepen insights into the molecular mechanism of COPD and also identify some promising therapeutic targets.

Aims Circular RNAs (circRNAs) are involved in gene regulation in a variety of physiological and pathological processes. The present study aimed to investigate the effect of circRNA_000203 on cardiac hypertrophy and the potential mechanisms involved. Methods and results CircRNA_000203 was found to be up-regulated in the myocardium of Ang-II-infused mice and in the cytoplasma of Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Enforced expression of circRNA_000203 enhances cell size and expression of atrial natriuretic peptide and β-myosin heavy chain in NMVCs. In vivo, heart function was impaired and cardiac hypertrophy was aggravated in Ang-II-infused myocardium-specific circRNA_000203 transgenic mice (Tg-circ203). Mechanistically, we found that circRNA_000203 could specifically sponge miR-26b-5p, -140-3p in NMVCs. Further, dual-luciferase reporter assay showed that miR-26b-5p, -140-3p could interact with 3′-UTRs of Gata4 gene, and circRNA_000203 could block the above interactions. In addition, Gata4 expression is transcriptionally inhibited by miR-26b-5p, -140-3p mimic in NMVCs but enhanced by over-expression of circRNA_000203 in vitro and in vivo. Functionally, miR-26b-5p, -140-3p, and Gata4 siRNA, could reverse the hypertrophic growth in Ang-II-induced NMVCs, as well as eliminate the pro-hypertrophic effect of circRNA_000203 in NMVCs. Furthermore, we demonstrated that NF-κB signalling mediates the up-regulation of circRNA_000203 in NMVCs exposed to Ang-II treatment. Conclusions Our data demonstrated that circRNA_000203 exacerbates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p leading to enhanced Gata4 levels., Graphical Abstract Graphical Abstract