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Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. Transfer RNA fragments (tRFs) are tRNA-derived small RNAs (tsRNAs), which possess regulatory functions in many diseases. Their potential roles in the pathological development of psoriasis have not been established. We first identified differentially expressed (DE) tRFs from psoriatic skin lesions using small RNA sequencing, and collected additional clinical samples for validation. Then, we investigated the function and mechanism of target tRFs in vitro. As a result of our investigation: we identified 234 DE transcripts in psoriatic skin lesions compared with normal controls. Further functional analysis showed the downregulation of tRF-Ile-AAT-019 in psoriatic lesions plays a critical role in pathogenesis since it could target 3'UTR of the serine protease serpin protein E1 (SERPINE1) gene. We next demonstrated that tRF-Ile-AAT-019 could suppress SERPINE1, thus leading to decreased expressions of vascular endothelial growth factor but increased expressions of keratinocytes (KCs) differentiation markers including Keratin1 and Involucrin. In conclusion, tRF-Ile-AAT-019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1, resulting in regulation of KCs differentiation and vascular proliferation biomarkers and providing a potential novel targeting pathway for the disease treatment.

Background: As the pandemic persists, post-acute sequelae of CoV-2 (PACS) including cardiovascular manifestations have emerged as a new health threat. Obesity is an established risk factor for acute COVID-19 severity. Evolving evidence has suggested its contributive roles in the pathogenesis of PACS. However, whether and how obesity can exacerbate PACS-related cardiomyopathy is unknown. Methods: A Spike protein-pseudotyped (Spp) virus with the proper surface tropism of SARS-CoV- 2 was developed for viral entry assay in vitro and administration into high fat diet (HFD)-fed mice. The systemic viral loads and cardiac transcriptomes were analyzed at 2 and 24 hrs, 3, 6, and 24 weeks post infection (wpi) using RNA-seq or real time RT-PCR. Echocardiography was used to monitor cardiac functions. Results: Low-density lipoprotein cholesterol enhanced viral uptake in endothelial cells, macrophages, and cardiomyocyte-like H9C2 cells. Selective cardiac and adipose viral depositions were observed in HFD mice but not in normal-chow-fed mice. The cardiac transcriptional signatures in HFD mice at 3, 6, and 24 wpi showed systemic suppression of mitochondria respiratory gene families including ATP synthases and nicotinamide adenine dinucleotide:ubiquinone oxidoreductase gene members, upregulation of stress pathway-related crucial factors such as nuclear factor-erythroid 2-related factor 1, and increases in expression of glucose metabolism-associated genes. Cardiac ejection fraction and fractional shortening were significantly decreased, while left ventricular end-systolic diameter and volume were significantly increased, in HFD mice at 24 wpi as compared with the age-matched HFD control mice. Conclusion: Our data demonstrated that chronic cardiac inflammations were persisted and exaggerated in HFD mice after viral infection, leading to mitochondrial metabolic perturbations and myocardial contractile impairment. This work was supported by grants from the National Institutes of Health (AR073172 and NIH COBRE (P20GM109091) pilot study to W.T., NSF EPSCoR (OIA1736150) to H.K., HL160541 to T.C.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

In this paper, a two-dimensional (2D) direction of arrival (DOA) estimation algorithm with a staggered two-parallel linear array has been proposed. The proposed array consists of two staggered linear arrays, any one of which is determined by two consecutive positive integers. The distance between any two sensors of the proposed array is larger than half-wavelength of incident signal, so it has strong robustness to mutual coupling. Using this array, a segmented propagator method (PM) algorithm is proposed to get automatic matching 2D DOA estimation. Compared with some similar PM algorithms based on two-parallel linear array, the proposed segmented PM algorithm has higher estimation accuracy and approaching complexity. Not only that, the proposed algorithm can detect more signals than the similar algorithms without using virtual elements. Complexity analysis and simulation results can prove the advantage of the proposed algorithm.

As the latest information exchange model, ontology is favored by information systems, but the heterogeneity of ontology has seriously influenced the interaction and cooperation between these systems. Ontology matching is considered an effective method to solve the ontology heterogeneity problem whose kernel technology is a similarity measure. However, a single measure cannot achieve satisfactory ontology alignments. To this end, integrating different similarity measures is feasible. First of all, due to the difference in user preferences for alignment quality, the ontology matching problem is modeled as a continuous multi-objective optimization model. Particle Swarm Optimization (PSO) is suitable for solving continuous optimization problems and previous studies have found that decomposition-based methods are more suitable for solving ontology matching. Then, considering the user’s preference, a knee solution-driven, decomposition-based multi-objective particle swarm algorithm (K-MOPSO/D) is designed to solve the ontology matching. Finally, the effectiveness of our proposed method is verified by standard test cases from the well-known OAEI (Ontology Alignment Evaluation Initiative), and its performance is compared with the state-of-the-art matching methods.

The recognition of denatured biological tissue is an indispensable part in the process of high intensity focused ultrasound treatment. As a nonlinear method, multi-scale permutation entropy (MPE) is widely used in the recognition of denatured biological tissue. However, the traditional MPE method neglects the amplitude information when calculating the time series complexity. The disadvantage will affect the recognition effect of denatured tissues. In order to solve the above problems, the method of multi-scale rescaled range permutation entropy (MRRPE) is proposed in this paper. The simulation results show that the MRRPE not only includes the amplitude information of the signal when calculating the signal complexity, but also extracts the extreme volatility characteristics of the signal effectively. The proposed method is applied to the HIFU echo signals during HIFU treatment, and the support vector machine (SVM) is used for recognition. The results show that compared with MPE and the multi-scale weighted permutation entropy (MWPE), the recognition rate of denatured biological tissue based on the MRRPE is higher, up to 96.57%, which can better recognize the non-denatured biological tissues and the denatured biological tissues.

Background COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients. Objective In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients. Methods A 3–6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up. Results LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p p p p p Conclusions Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3–6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.

Nuclear factor-erythroid factor 2–related factor 2 (Nrf2) may either ameliorate or worsen diabetic cardiomyopathy. However, the underlying mechanisms are poorly understood. Herein we report a novel mechanism of Nrf2-mediated myocardial damage in type 1 diabetes (T1D). Global Nrf2 knockout (Nrf2KO) hardly affected the onset of cardiac dysfunction induced by T1D but slowed down its progression in mice independent of sex. In addition, Nrf2KO inhibited cardiac pathological remodeling, apoptosis, and oxidative stress associated with both onset and advancement of cardiac dysfunction in T1D. Such Nrf2-mediated progression of diabetic cardiomyopathy was confirmed by a cardiomyocyte-restricted (CR) Nrf2 transgenic approach in mice. Moreover, cardiac autophagy inhibition via CR knockout of autophagy-related 5 gene (CR-Atg5KO) led to early onset and accelerated development of cardiomyopathy in T1D, and CR-Atg5KO–induced adverse phenotypes were rescued by additional Nrf2KO. Mechanistically, chronic T1D leads to glucolipotoxicity inhibiting autolysosome efflux, which in turn intensifies Nrf2-driven transcription to fuel lipid peroxidation while inactivating Nrf2-mediated antioxidant defense and impairing Nrf2-coordinated iron metabolism, thereby leading to ferroptosis in cardiomyocytes. These results demonstrate that diabetes over time causes autophagy deficiency, which turns off Nrf2-mediated defense while switching on an Nrf2-operated pathological program toward ferroptosis in cardiomyocytes, thereby worsening the progression of diabetic cardiomyopathy.

We aimed to evaluate the efficacy and safety of the 1,565 nm non-ablative fractional laser (NAFL) in combination with isotretinoin and pricking blood therapy (PBT) for treatment of AV.A retrospective analysis of 60 patients with moderate-to-severe AV was performed. Four groups (The triple therapy showed the highest improvement rate of inflammatory papules and boxcar atrophic scars. The patients receiving oral isotretinoin alone, double or triple therapy showed a significant decrease in volume of boxcar atrophic scars. The NAFL alone, double or triple therapy significantly decreased index of hemoglobin. Furthermore, the triple therapy significantly decreased indexes of hemoglobin and red areas as compared to the other three treatments. All four treatments significantly decreased indexes of pore sizes and wrinkles.This study showed that the triple therapy is effective for treatment of AV, which is worthy of further evaluation and investigation.

Since Internet of Everything (IoE) makes all the connections that come online more relevant and valuable, they are subject to numerous security and privacy concerns. Cybersecurity ontology is a shared knowledge model for tackling the security information heterogeneity issue on IoE, which has been widely used in the IoE domain. However, the existing CSOs are developed and maintained independently, yielding the CSO heterogeneity problem. To address this issue, we need to use the similarity measure (SM) to calculate two entities’ similarity value in two CSOs and, on this basis, determine the entity correspondences, i.e., CSO alignment. Usually, it is necessary to integrate various SMs to enhance the result’s correctness, but how to combine and tune these SMs to improve the alignment’s quality is still a challenge. To face this challenge, this work first models CSO matching problem as a Constrained Multiobjective Optimization Problem (CMOOP) and then proposes a Coevolutionary Multiobjective Evolutionary Algorithm (CE-MOEA) to effectively address it. In particular, CE-MOEA uses the multiobjective evolutionary paradigm to avoid the solutions’ bias improvement and introduces the coevolutionary mechanism to trade off Pareto Front’s (PF’s) diversity and convergence. The experiment uses Ontology Alignment Evaluation Initiative’s (OAEI’s) bibliographic track and conference track and five real CSO matching tasks to test CE-MOEA’s performance. Comparisons between OAEI’s participants and EA- and MOEA-based matching techniques show that CE-MOEA is able to effectively address various heterogeneous ontology matching problems and determine high-quality CSO alignments.

Alterations in the accumulation and composition of the extracellular matrix are part of the normal tissue repair process. During fibrosis, this process becomes dysregulated and excessive extracellular matrix alters the biomechanical properties and function of tissues involved. Historically fibrosis was thought to be progressive and irreversible; however, studies suggest that fibrosis is a dynamic process whose progression can be stopped and even reversed. This realization has led to an enhanced pursuit of therapeutic agents targeting fibrosis and extracellular matrix-producing cells. In many organs, fibroblasts are the primary cells that produce the extracellular matrix. In response to diverse mechanical and biochemical stimuli, these cells are activated or transdifferentiate into specialized cells termed myofibroblasts that have an enhanced capacity to produce extracellular matrix. It is clear that interactions between diverse cells of the heart are able to modulate fibroblast activation and fibrosis. Exosomes are a form of extracellular vesicle that play an important role in intercellular communication via the cargo that they deliver to target cells. While relatively recently discovered, exosomes have been demonstrated to play important positive and negative roles in the regulation of fibroblast activation and tissue fibrosis. These roles as well as efforts to engineer exosomes as therapeutic tools will be discussed.

Vein graft failure (VGF) is associated with vein graft (VG) intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (SMCs). The majority of neointimal SMCs are derived from pre-existing vascular SMCs via a process of vascular SMC dedifferentiation; however, the underlying mechanisms remain poorly understood. Here, we tracked down the fate of vascular stem cells (VSCs) expressing stem cell antigen 1 (SCA1) in VG remodeling. After transplantation, most of the donor venous cells including endothelial cells, SMCs, and VSCs died within 3 days, and the recipient arterial SCA1+ VSCs were recruited to repopulate the adventitia and the intima but did not differentiate into neointimal SMCs in VGs. However, ablation of the SCA1+ VSCs ameliorated intimal hyperplasia in VGs. Single-Cell RNA sequencing (scRNA-seq) analysis revealed a unique subset of VSCs expressing Sca1 and cyclin-dependent kinase 8 (Cdk8) in the artery. Notably, the number of SCA1+CDK8+ cells was increased in the adventitia prior to dramatic proliferation of SMCs in the media and neointima in VGs. Inactivation of CDK8 intensified SCA1+ VSC naïve stemness but suppressed SCA1+ VSC proliferation, migration, and exosome release for paracrine enforcement of vascular SMC dedifferentiation. A short-time perivascular delivery of CDK8 inhibitors ameliorated adventitial SCA1+ VSC accumulation associated with a long-term efficacy in suppressing intimal hyperplasia in VGs. There findings uncover that a novel subset of adventitial VSCs paracrine control media SMC dedifferentiation for intimal hyperplasia in VGs toward VGF.

Ozone therapy has been widely used to treat many skin diseases, including infections, allergic dermatosis, and skin ulcers. However, its efficacy as a treatment for psoriasis is unclear. In this study, we explored the clinical efficacy and the underlying molecular mechanisms of ozone therapy on psoriasis. We found that topical ozone treatment significantly decreased patients' psoriasis area and severity index (PASI) scores and the expression of psoriasis-associated cytokines in their peripheral blood CD4+ T cells. In the IMQ-induced psoriasis mouse model, topical ozone treatment significantly inhibited the formation of IMQ-induced psoriasis-like lesions and the expression of psoriasis-associated inflammatory factors. High-throughput sequencing confirmed that IMQ-induced activation of toll-like receptor 2 (TLR2)/ nuclear factor-κB (NF-κB) signaling pathway was significantly suppressed in psoriasis-like lesions after topical ozone treatment. Furthermore, the activation of spleen T helper (Th) 17 cells was blocked in the mouse model; this was associated with the downregulation of cytokines and NF-κB pathways upon topical ozone treatment. Ozone therapy can attenuate local inflammatory reactions and the activation of Th17 cells in psoriasis by inhibiting the NF-κB pathway. Our results show that ozone therapy is effective in treating psoriasis. We recommend further evaluations for its clinical applications.

Background Facial telangiectasia is one of the common skin vascular lesions characterized by dilated cutaneous vasculatures. The variety of diameters and difference in depths of lesional blood vessels are the major challenges for effective treatments for Facial telangiectasia. Aims To compare the efficacy and safety profiles of pulsed dye laser (PDL, 595 nm) with intense pulsed light (IPL) configured by three different wavelength bands in the treatment for facial telangiectasia in Asian populations. Patients/methods A retrospective analysis of hospital records and review on photographs were performed for those subjects with facial telangiectasia (n = 160) who were treated in our department from January 2017 to January 2019. Patients were received two sessions of one of the four following laser treatments: PDL (595 nm, n = 38), IPL with M22 vascular filter (530-650 nm and 900-1200 nm, n = 39), M22 560 (560-1200 nm, n = 42), and M22 590 (590-1200 nm, n = 41). Results The patients in all the four groups showed an overall and significant improvement of indexes of lesional severity and subjective discomfort as well as improvement score of facial telangiectasia after treatment as compared to baseline. In addition, PDL (595 nm) and IPL with vascular filter (530-650 nm and 900-1200 nm) treatments showed significantly better indexes of lesional severity, subjective discomfort, and improvement score of facial telangiectasia as compared with other two treatments. Conclusion Light devices with various wavelength ranges showed different efficacies of treatment for facial telangiectasia, among which PDL (595 nm) and IPL with M22 vascular filter (530-650 nm and 900-1200 nm) had similar and the best clinical efficacy as compared to IPL with other wavelength bands.

Author(s): Fu, Zhibing; Huang, Jinhua; Xiang, Yaping; Huang, Jian; Tang, Zhen; Chen, Jing; Nelson, J Stuart; Tan, Wenbin; Lu, Jianyun | Abstract: Background and objectivesPort wine stain (PWS) is a congenital vascular malformation of the human skin. Laser is the treatment of choice for PWS. Laser-resistant PWS is one crucial factor accounting for inadequate treatment outcome, which needs to be fully characterized. This study aims to quantitatively characterize the morphology of laser-resistant PWS blood vessels in the upper papillary dermis using in vivo reflectance confocal microscopy (RCM).Study design/materials and methodsA total of 42 PWS subjects receiving laser treatment from August 2016 through July 2018 were enrolled into this study. Thirty-three subjects had facial PWS; nine had extremity PWS. All subject's PWS received multiplex 585/1,064 nm laser treatment. RCM images were taken before and after treatment. The density, diameter, blood flow, and depth of PWS blood vessels were analyzed.ResultsWe found 44.4% PWS on the extremities (four out of nine subjects) were laser-resistant, which was significantly higher (P l 0.001) when compared with those PWS on the face (15.2%, 5 out of 33 subjects). The laser-resistant facial PWS blood vessels had significantly higher blood flow (1.35 ± 0.26 U vs. 0.89 ± 0.22 U, P l 0.001), larger blood vessel diameters (109.60 ± 18.24 µm vs. 84.36 ± 24.04 µm, P = 0.033) and were located deeper in the skin (106.01 ± 13.87 µm vs. 87.82 ± 12.57 µm, P l 0.001) in the skin when compared with laser-responsive PWS on the face. The average PWS blood vessel density (17.01 ± 4.63/mm2 vs. 16.61 ± 4.44/mm2 , P = 0.857) was not correlated to the laser resistance.ConclusionsLaser-resistant PWS blood vessels had significantly higher blood flow, larger diameters, and were located deeper in the skin. RCM can be a valuable tool for a prognostic evaluation on laser-resistant lesions before treatment, thereby providing guidance for tailored laser treatment protocols, which may improve the therapeutic outcome. The limitations for this study include relative small sample size and acquisitions of different blood vessels before and after 2 months of treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Background: Nasopharyngeal carcinoma (NPC) is the common malignant tumor of nasopharynx in southern China and other southeastern Asian countries. MicroRNAs (miRNAs) have been shown to play important roles in carcinogenesis. Recently, miR-34c-3p and miR-18a-5p have been found to be involved in carcinogenesis of NPC. Furthermore, platelets in NPC patients may acquire RNAs from NPC cells and turn into "tumor-educated platelet (TEP)", which may serve as potential biomarkers for a diagnosis of NPC. However, the expression profiles of TEP miR-34c-3p and miR-18a-5p in NPC patients and their diagnostic values are yet to be determined. Aims: To investigate expression levels of TEP miR-34c-3p and miR-18a-5p and determine their diagnostic values for NPC. Materials and methods: Relative quantitative real-time PCR was used to determine the expression levels of TEP miR-34c-3p and miR-18a-5p in NPC patients (n=54) as compared to normal subjects (n=36). The receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic values of TEP miR-34c-3p and miR-18a-5p for NPC. Results: The expression levels of TEP miR-34c-3p and miR-18a-5p were significantly higher in NPC patients as compared to healthy subjects. The ROC analysis showed that the area under the ROC curve (AUC), sensitivity, specificity and accuracy for TEP miR-34c-3p, miR-18a-5p, or a combination of both miRNAs for NPC diagnostic tests were 0.952, 94.44%, 86.11%, 91.11%, or 0.884, 85.19%, 86.11%, 85.55%, or 0.954, 92.59%, 86.11%, 90.00%, respectively. No correlation was found between expression levels of TEP miR-34c-3p or miR-18a-5p and patients' demographic variables and their NPC tumor/node/metastasis stages. The positive rates of TEP miR-34c-3p and miR-18a-5p for NPC diagnosis were 93.8% and 87.5%, respectively, which were significantly higher than Epstein-Barr virus DNA with a positive rate of 66.7%. Conclusion: The expression levels of TEP miR-34c-3p and miR-18a-5p are upregulated in NPC, rendering a significant clinical value for NPC diagnosis. The TEP miRNAs might serve as a novel type of liquid biopsies for NPC diagnosis.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein–pseudotyped (Spp) lentivirus with the proper tropism of the SARS‐CoV‐2 spike protein on the surface and determined the distribution of the Spp lentivirus in wild‐type C57BL/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV‐G) or with a deletion of the receptor‐binding domain (RBD) in the spike protein [Spp (∆RBD)] were used as controls. Two hours postinfection (hpi), there were 27‐75 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3‐5 times more viral burden from Spp lentivirus than from VSV‐G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC+ and LDLR+ pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR‐γ were quickly upregulated in response to infection in the lungs as well as in macrophage‐like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS‐CoV‐2 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2‐independent viral entry pathway may be recruited in the heart and aorta.

Background Coronavirus disease 2019 (COVID‐19) patients exhibit multiple organ malfunctions with a primary manifestation of acute and diffuse lung injuries. The Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyper‐inflammations in COVID‐19 is not well known. Methods and Findings In this study, we developed a Spike protein‐pseudotyped (Spp) lentivirus with the proper tropism of SARS‐CoV‐2 Spike protein on the surface and tracked down the fate of Spp in wild type C57BL/6J mice receiving intravenous injection of the virus. A lentivirus with vesicular stomatitis virus glycoprotein (VSV‐G) was used as the control. Two hours post‐infection (hpi), Spp showed more than 27‐75 times more viral burden in the lungs than other organs; it also exhibited about 3‐5 times more viral burden than VSV‐G lentivirus in the lungs, liver, kidney and spleen. Acute pneumonia was evident in animals 24 hpi. Spp lentivirus was mainly found in LDLR+ macrophages and pneumocytes in the lungs, but not in MARC1+ macrophages. IL6, IL10, CD80 and PPAR‐γ were quickly upregulated in response to infection of Spp lentivirus in the lungs in vivo as well as in macrophage‐like RAW264.7 cells in vitro. We further confirmed that forced expression of the Spike protein in RAW264.7 cells could significantly increase the mRNA levels of the same panel of inflammatory factors. Conclusions Our results demonstrate that the Spike protein of SARS‐CoV‐2 alone can induce cellular pathology, e.g. activating macrophages and contributing to induction of acute inflammatory responses.

This study investigated the mechanism and efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis (AO). A total of 32 AO patients were enrolled in this study. In the initial pilot study, 20 patients were double-blindly, randomly divided into acidified aliphatic ester or aliphatic ester treatment groups, followed by efficacy evaluation after 4 weeks. Then, all patients (n = 32) were treated with topical acidified aliphatic ester for 16 weeks. Efficacy was evaluated at every 4 weeks, and at 3- and 6-month follow-ups. Changes of pH values and microecology at targeting sites were analyzed. In the first cohort (n = 20) of pilot study, acidified aliphatic ester showed significantly higher curative rate (60% vs 10%, P < .05) and effective rate (90% vs 30%; P < .05) than aliphatic ester. For the next 16 weeks, 25 of 32 cases completed treatment. Curative rate showed gradual and significant increases from 64% to 96% during the treatment courses (P = .001); it slightly but insignificantly decreased at 3- and 6- month follow-ups. Abundance of Corynebacterium and Anaerobic bacteria decreased while Staphylococcus increased after treatments. Axillary pH values negatively correlated with Staphylococcus abundance (r = -.40, P = .01) and positively with Corynebacterium abundance (r = .64, P = .01). We concluded that topical acidified aliphatic ester could effectively alleviate conditions of AO patients by reducing value of axillary pH and rebalancing axillary microecology.

Background: COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved in recovered patients.Objective: In this follow-up study, we evaluated serum lipidemia and other physiopathological laboratory values in recovered patients.Methods: A 3–6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). 61 patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up.Results: LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p < 0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p < 0.05). With adjustment of the factor of traditional Chinese medicine, LDL-c and HDL-c levels were significantly improved at follow-up than at admission in severe/critical cases (p < 0.05). Coagulation and liver laboratory values were significantly lower at follow-up than at admission for patients (p < 0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (pp < 0.05) during patients’ recovery. Residue lesions were observed in CT images in 69% (42 of 61) of follow-up patients.Conclusions: Improvements of LDL-c, HDL-c and incomplete absorption of lung lesions were observed at 3–6 month follow-up for recovered patients, indicating that a long-term recovery process could be required.

Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) may either ameliorate or worsen diabetic cardiomyopathy. However, the underlying mechanisms are poorly understood. Herein we report a novel mechanism of Nrf2-mediated myocardial damage in type 1 diabetes (T1D). Global Nrf2 knockout (Nrf2KO) hardly affected the onset of cardiac dysfunction induced by T1D but slowed down its progression in mice independent of sex. In addition, Nrf2KO inhibited cardiac pathological remodeling, apoptosis and oxidative stress associated with both onset and advancement of cardiac dysfunction in T1D. Such Nrf2-mediated progression of diabetic cardiomyopathy was confirmed by cardiomyocyte-restricted (CR) Nrf2 transgenic (Tg) approach in mice. Moreover, cardiac autophagy inhibition via CR KO of autophagy related 5 gene (CR-Atg5KO) led to early onset and accelerated development of cardiomyopathy in T1D, and CR-Atg5KO-induced adverse phenotypes were rescued by additional Nrf2KO. Mechanistically, chronic T1D leads to glucolipotoxicity inhibiting autolysosome efflux, which in turn intensifies Nrf2-driven transcription to fuel lipid peroxidation while inactivating Nrf2-mediated antioxidant defense and impairing Nrf2-coordinated iron metabolism, thereby leading to ferroptosis in cardiomyocytes. These results demonstrate that diabetes over time causes autophagy deficiency, which turns off Nrf2-mediated defense while switching on Nrf2-operated pathological program toward ferroptosis in cardiomyocytes, thereby worsening the progression of diabetic cardiomyopathy.

Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

Background Many patients with coronavirus disease 2019 (COVID-19) suffer multiple organ dysfunctions. However, whether patients develop dyslipidemia is unknown. Objective In this study, we aimed to investigate the pathological alterations of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol (TC) in COVID-19 patients and their relationships with the disease severity. Methods A retrospective study was performed to examine serum levels of LDL-c, HDL-c, and TC on 597 COVID-19 patients (mild: 394; severe, 171; critical: 32) who were hospitalized in our center between February 1 and March 3, 2020. Age and gender-matched normal subjects (n=50) who had routine laboratory lipid tests between October 1 and November 1, 2019 in our center were included as the control group. Results LDL-c and TC levels were significantly lower in COVID-19 patients as compared with normal subjects (p, Highlights • SARS-COV-2 causes multiple types of pathophysiologies including hypolipidemia • Decrease in LDL-c is observed as early as in patients with mild symptoms • Hypolipidemia positively correlates with the disease severity in patients • Hypolipidemia raises awareness to frontline physicians against this pandemic

In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID‐19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 versus 46.5 ± 14.7, p

The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. The lipid pathophysiology in COVID-19 is unknown.In this retrospective longitudinal study, we monitored the serum lipids in 17 surviving and 4 non-surviving COVID-19 cases prior to their viral infections and duration the entire disease courses.In surviving cases, the low-density lipoprotein (LDL) levels decreased significantly on admission as compared with the levels before infection; the LDL levels remained constantly low during the disease progression and resumed to the original levels when patients recovered (pre-infection: 3.5 (3.0-4.4); on admission: 2.8 (2.3-3.1), p 0.01; progression: 2.5 (2.3-3.0); discharge: 3.6 (2.7-4.1); median (IQR), in mmol/L). In non-surviving patients, LDL levels showed an irreversible and continuous decrease until death (1.1 (0.9-1.2), p = 0.02 versus the levels on admission). The ratio changes of LDL levels inversely correlated with ratio changes of high-sensitivity C-reactive protein levels. Logistic regression analysis showed increasing odds of lowered LDL levels associated with disease progression (odds ratio: 4.48, 95% IC: 1.55-12.92, p = 0.006) and in-hospital death (odds ratio: 21.72, 95% IC: 1.40-337.54, p = 0.028).LDL levels inversely correlated to disease severities, which could be a predictor for disease progress and poor prognosis.

Author(s): Lu, Jianyun; Anvari, Radean; Wang, Jinwei; Huang, Jian; Pei, Shiyao; Xiang, Yaping; Huang, Jinhua; Yin, Zhaoqi; Chen, Jing; Nelson, J Stuart; Tan, Wenbin

Port wine stain (PWS) is a congenital vascular malformation of human skin involving the superficial vascular plexus,1-4 but the molecular pathogenesis of these lesions remains incompletely understood.5-8 We herein performed a transmission electron microscopy (TEM) study to determine the main pathological characteristics and ultrastructure of various cell types, including endothelial cells (ECs), pericytes, fibroblasts and keratinocytes, in hypertrophic and nodular PWS. The study was approved by the Investigational Review Board at the Xijing Hospital, Xi'an, China. This article is protected by copyright. All rights reserved.

Author(s): Tan, W; Zakka, LR; Gao, L; Wang, J; Zhou, F; Selig, MK; Anvari, R; Sukanthanag, A; Wang, G; Mihm, MC; Nelson, JS