Diagnostic and grading criteria for androgenetic alopecia using dermoscopy.

OBJECTIVES: To establish accurate and objective dermoscopic diagnostic criteria and grading standards for males and females with androgenetic alopecia (AGA). METHODS: Twenty patients each with AGA, diffuse alopecia areata, telogen effluvium, and healthy controls were enrolled in the current study. In addition, 60 patients with grades F1/V1, F2/V2, and F3/V3 AGA (20 cases each) were enrolled. The patients underwent dermoscopic examinations. The sensitivity and specificity of the diagnostic criteria were based on the 60 AGA and 60 non-AGA. In addition, 150 patients diagnosed with AGA clinically and by dermoscopy were enrolled to calculate the accuracy of the grading criteria. RESULTS: The diagnostic criteria included primary, secondary, and exclusion criteria. The grading criteria included three indices, which divided the severity of AGA into grades 1, 2, and 3. The sensitivity and specificity of the diagnostic criteria were 98.3% and 96.7% respectively. The accuracy of grade 1, 2, and 3 dermoscopic grading criteria were 96%, 92%, and 100% respectively, with a total accuracy of 96%. LIMITATIONS: To test the diagnostic and grading criteria, more patients need to be collected. CONCLUSIONS: The dermoscopic diagnostic and grading criteria are objective with good accuracy, which could provide a reasonable basis for the early diagnosis, grading treatment, and improved prognosis for AGA.

HCN1 in the lateral habenula contributes to morphine abstinence-induced anxiety-like behaviors in male mice.

Anxiety disorders, common symptoms during morphine withdrawal, are important negative reinforcement factors leading to relapse. Lateral habenula serves as a negative reinforcement center, however its role in morphine withdrawal-induced anxiety remains uncovered. The hyperpolarization activated cyclic nucleotide-gated (HCN) channels have been reported to be important in emotion processing and addiction, but the role of HCN in anxiety from drug protracted abstinence remains elusive. In this study, by using behavioral test, Western blot, immunofluorescence, electrophysiology and virus-mediated regulation of HCN, we found that: (1) Intra-LHb injection of selective HCN blocker ZD7288 alleviated anxiety-like behaviors in morphine protracted abstinent male mice. (2) The LHb neuronal activity was increased by morphine protracted abstinence. (3) LHb neurons were inhibited by ZD7288 and activated by 8-Br-cAMP respectively, which were enhanced by morphine withdrawal. (4) HCN1 in the LHb was upregulated by morphine withdrawal. (5) Virus-mediated overexpression of HCN1 in the LHb was sufficient to produce anxiety-like behaviors in male mice and virus-mediated knockdown of HCN1 in the LHb prevented the anxiety-like behaviors in male mice. The findings reveal that selective blockade of HCN1 channels in the LHb may represent a therapeutic approach to morphine withdrawal-induced anxiety.

HCMV IE1/IE1mut Therapeutic Vaccine Induces Tumor Regression via Intratumoral Tertiary Lymphoid Structure Formation and Peripheral Immunity Activation in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine. In addition, immunofluorescence data demonstrated that the treated group exhibited significantly more and larger tertiary lymphoid structures (TLSs) than the untreated group. The presence of TLS was associated with enhanced T cell infiltration, and a large number of proliferating T cells were found in the treated group. Furthermore, the flow cytometry results showed that in the treatment group, cytotoxic T lymphocytes exhibited partial polarization toward effector memory T cells and were activated to play a lethal role in the peripheral immunological organs. Furthermore, a substantial proportion of B cells in the draining lymph nodes expressed CD40 and CD86. Surprisingly, quantitative polymerase chain reaction indicated that a high expression of cytokines, including chemokines in brain tumors and immune tissues, induced the differentiation, development, and chemokine migration of immune cells in the treated group. Our study data demonstrate that IE1 or IE1mut vaccination has a favorable effect in glioma mice models. This study holds substantial implications for identifying new and effective therapeutic targets within GBM.

Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer's-Like Disease in Transgenic Mice.

    Although multiple factors are known to concur with Alzheimer's disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2.

Patient Needs in Psoriasis Treatment and their Influencing Factors: A Nationwide Multicentre Cross-Sectional Study in China.

Background: The management and treatment of psoriasis has rarely considered patient needs, which are numerous, multi-dimensional and are of great importance to improving treatment outcomes. Objectives: This study aimed to evaluate and compare the patients' needs for psoriasis treatment and identify factors predicting the need to make patient-centred decisions about treatment. Materials and Methods: This nationwide multicentre cross-sectional study included subjects between October 2020 and August 2021. The status quo of the needs in psoriasis treatment and their influencing factors were analysed mainly using the Chi-square test and binary logistic regression. Results: Information on sociodemographic and clinical characteristics were obtained. Factor analysis of a specially designed questionnaire showed that rapid skin clearance, reduced treatment expense and fewer hospital visits or treatment time were the first three patient needs in psoriasis treatment. Several influencing factors were important including the sociodemographic characteristics of gender, marital status, education level and family history, special location of skin lesions, dermatology life quality index (DLQI), Investigator's Global Assessment modified 2011 (IGA mod 2011), condition of the episode, clinical type of psoriasis, seasonal exacerbation and therapy. Conclusions: Patients with psoriasis pursued a wide range of treatment goals, with the most desired being rapid skin clearance, reduced treatment expense and time-saving. Paying attention to sex, marital status, education level, the special location of skin lesions and the DLQI will help dermatologists develop patient-centred treatment, meet the patient's needs and eventually improve the treatment outcomes.

A Photocurable Polysaccharide-Based Hydrogel Delivery of Polydeoxyribonucleotide-Loaded Vectors for Wound Treatment.

The wounds caused by war, accidents, and diseases require timely and effective treatment. Polysaccharides, as natural macromolecules, have good biocompatibility and unique functions, and are excellent substrates for constructing new wound dressings. Short-chain chitosan (SCS) has good water solubility and, importantly, retains a large number of active amino groups. We first introduce double bonds to SCS. This chitosan derivative can be entangled with sodium alginate (SA) through electrostatic interaction. The flowing sol can be applied to a wound with an irregular shape. Under the initiation of a photoinitiator, the internal double bonds are broken and cross-linked to form a gel. The prepared hydrogel wound dressing exhibited good antibacterial properties and can provide a microenvironment conducive to wound repair. A polydeoxyribonucleotide (PDRN) has been proven to have encouraging therapeutic effects for wound healing. PDRN can be condensed by branched polyethylenimine (PEI) to form a nucleic acid delivery system, which can be efficiently uptaken by cells. The cooperation of hydrogel and nucleic-acid-based therapy presented good results in a mouse full-thickness skin wound model.

The in vitro and in vivo antiviral effects of aloperine against Zika virus infection.

Zika virus (ZIKV) infection poses a significant threat to global public health and is associated with microcephaly. There are no approved ZIKV-specific vaccines or drugs for the clinical treatment of the infection. Currently, there are no approved ZIKV-specific vaccines or drugs for the clinical treatment of the infection. In this study, we investigated the antiviral potential of aloperine, a quinolizidine alkaloid, against ZIKV infection in vivo and in vitro. Our results demonstrate that aloperine effectively inhibits ZIKV infection in vitro, with a low nanomolar half maximal effective concentration (EC50 ). Specifically, aloperine strongly protected cells from ZIKV multiplication, as indicated by decreased expression of viral proteins and virus titer. Our further investigations using the time-of-drug-addition assay, binding, entry, and replication assays, detection of ZIKV strand-specific RNA, the cellular thermal shift assay, and molecular docking revealed that aloperine significantly inhibits the replication stage of the ZIKV life cycle by targeting the domain RNA-dependent RNA polymerase (RDRP) of ZIKV NS5 protein. Additionally, aloperine reduced viremia in mice and effectively lowered the mortality rate in infected mice. These findings highlight the potency of aloperine and its ability to target ZIKV infection, suggesting its potential as a promising antiviral drug against ZIKV.

CRM197-conjugated multi antigen dominant epitope for effective human cytomegalovirus vaccine development.

Human cytomegalovirus (HCMV) infection is a major cause of neonatal neurodevelopmental disorders and serious complications in organ transplantation. Previous HCMV vaccines focused on humoral immunity but had limited effect on viral infection. T-cell responses are essential to prevent HCMV infection, indicating that effective vaccines require T cells activation. In this study, we designed a novel polypeptides vaccine conjugated to a CRM197 carrier protein, encoding 15 CD8+ T-cell epitopes, five CD4+ T-cell epitopes, and four B-cell epitopes from gB287-320 and pp150311-325 of HCMV to induce T-cell immune responses. To evaluate the effectiveness of vaccines, we subsequently measured the expression of surface molecule markers and proinflammatory cytokines from antigen presenting cells in vivo and in vitro as well as the activation of T cells and antibodies. The results demonstrated that this polypeptide vaccine could activate innate immunity including up-regulating MHCI, II, CD80, CD86, and cytokine expression through the TLR4/NF-κB pathway. Meanwhile, vaccinations elicited potent neutralizing antibody and cellular immune responses producing TNF-α, INF-γ and IL-2, indicating Th1-biased polarization. This finding underlines that CRM197-conjugated polypeptide vaccines facilitate a synergism of humoral and cellular immunity, providing enhanced protection against HCMV, which could be a potential strategy to prevent CMV-associated diseases.

Liver transcriptomics reveals features of the host response in a mouse model of dengue virus infection.

Background: Dengue virus (DENV) infection induces various clinical manifestations and even causes organ injuries, leading to severe dengue haemorrhagic fever and dengue shock syndrome. Hepatic dysfunction was identified as a risk predictor of progression to severe disease during the febrile phase of dengue. However, the underlying mechanisms of hepatic injury remain unclear. Methods: A model of dengue disease was established in IFNAR -/- C57BL/6 mice by challenge with DENV-2. Body weight, symptoms, haematological parameters and liver pathological observations in mice were used to determine the effects of DENV infection. Liver transcriptome sequencing was performed to evaluate the features of the host response in IFNAR -/- mice challenged with DENV. Functional enrichment analysis and analysis of significantly differentially expressed genes (DEGs) were used to determine the critical molecular mechanism of hepatic injury. Results: We observed haemoconcentration, leukopenia and liver pathologies in mice, consistent with findings in clinical dengue patients. Some differences in gene expression and biological processes were identified in this study. Transcriptional patterns in the liver indicated that antiviral responses to DENV and tissue damage via abnormal expression of proinflammatory cytokines were induced. Further analysis showed that the upregulated DEGs were significantly enriched in the leukocyte transendothelial migration, complement and coagulation cascades, and cytokine-cytokine receptor interactions signalling pathways, which are considered to be closely associated with the pathogenic mechanism of dengue. IL6, IL 10, ICAM-1, VCAM-1, MMP9 and NLRP3 were identified as biomarkers of progression to severe disease. Conclusions: The interactions of these cytokines, which activate inflammatory signalling, may lead to organ injury and haemoconcentration and even to vascular leakage in tissues, including the mouse liver. Our study identifies candidate host targets that could be used for further functional verification.

Cinnamic acid inhibits Zika virus by inhibiting RdRp activity.

In recent years, Zika virus (ZIKV), which causes severe diseases such as congenital microcephaly and Guillain-Barré syndrome, bringing serious harm to humans, has spread throughout the world. However, there are currently no effective drugs against the virus, and the need to develop anti-ZIKV drugs is thus urgent. In this study, we evaluated the antiviral efficacy of cinnamic acid against ZIKV by using reverse transcription-quantitative real-time PCR (qRT-PCR), plaque--forming, immunofluorescence and Western blotting. Additionally, Cinnamic acid possessed anti-ZIKV properties against the post-entry stage of the ZIKV replication cycle, and inhibited RdRp activity. In vivo, we found that cinnamic acid reduced the mortality of mice, viral load in the blood and ZIKV protein levels in the brain. Based on our experiments, cinnamic acid was found to be a potential effective anti-ZIKV drug.

Research progress and challenges to coronavirus vaccine development.

Coronaviruses (CoVs) are nonsegmented, single-stranded, positive-sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models.

Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear. Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology. Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology. Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05). Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

Study of Mechanical Properties and Durability of Alkali-Activated Coal Gangue-Slag Concrete.

Herein, a new geopolymer is recognized as a potential alternative cementing material of ordinary Portland cement (OPC), which is used for reducing carbon emissions and efficiently recycling the waste. Therefore this paper mainly studied the alkali-activated coal gangue-slag concrete (ACSC) was prepared by using the coal gangue-slag and Na2SiO3 and NaOH complex activator. The ratio of coal gangue (calcined and uncalcined) coarse aggregate replacing the gravel was 0%, 30%, 50%, 70%, and 100%. The water and salt freeze-thaw resistance, compressive strength, chloride permeation, microstructure, performance mechanism, inner freeze-thaw damage distribution, and mechanics models of ACSC were investigated. Results show that ACSC displayed excellent early age compressive strength, and the compact degree and uniformity of structure were better compared with the ordinary Portland cement (OPC) when the coal gangue replacement rate was less than 50%. The ACSC demonstrated the best chloride penetration resistance under 30% uncalcined coal gangue content, which was less than 27.75% lower than that of using OPC. At the same number cycles, especially in the salt freezing, the calcined coal gangue had lowered advantages of improving resistance freeze-thaw damage resistance. Water and salt accumulative freeze-thaw damage mechanics models of ACSC were established by using the relative dynamic elasticity modulus. The exponential function model was superior to the power function model with better precision and relativity, and the models accurately reflected the freeze-thaw damage effect.

Coronavirus infections and immune responses.

Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

Subcutaneous Panniculitis-Like T-Cell Lymphoma in Children: A Review of the Literature.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a type of skin lymphoma. Pleomorphic T-cells infiltrate the subcutaneous tissue and mimic lobular panniculitis. We report a case occurring in a 12-year-old Chinese boy who presented with multiple indolent erythematous subcutaneous nodules on both extremities without systemic symptoms. He had a protracted course of multiple erythematous subcutaneous nodules for 1 year and underwent biopsy of lesional skin for histology and T-cell receptor (TCR) gene analysis. Histopathology showed infiltration of medium to large atypical pleomorphic cells involving the subcutis with characteristic rimming of fat spaces. TCR gene rearrangement shows monoclonal rearrangements of the TCR ß and γ chains. Immunophenotypic studies showed that CD3, CD4, and CD8 were strongly and diffusely positive in lesional cells and that CD56 was focally positive. In contrast, these cells were negative for CD20, CD30, and CD68. The combined morphology, characteristic histologic features, and positive T-CR gene rearrangement supported a diagnosis of SPTCL. He is being treated with combination chemotherapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone.

Molecular "light switch" for G-quadruplexes and i-motif of human telomeric DNA: [Ru(phen)2(dppz)]2+.

[Ru(phen)(2)(dppz)](2+)can serve as a prominent molecular "light switch" for G-quadruplexes and i-motif, but it preferentially binds to G-quadruplexes over i-motif.

[Research of the surface oxide film on anodizing Ni-Cr porcelain alloy].

OBJECTIVE: To study the shape, thickness and oxide percentage of major metal element of oxide film on Ni-Cr porcelain alloy after anodizing pretreatment. METHODS: 10 samples were made and divided into 2 groups at random. Then after surface pretreatment, the oxide films of two samples of each group were analyzed using electronic scanning microscope. The rest 3 samples were measured by X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES). RESULTS: Lightly selective solution appeared because the different component parts of the alloy have dissimilar electrode, whose dissolve velocity were quite unlike. The sample's metal surface expanded, so the mechanical interlocking of porcelain and metal increased bond strength. The thickness of oxide film was 1.72 times of the control samples. The oxide percentage of major metal elements such as Cr, Ni and Mo were higher, especially Cr. It initially involved the formation of a thin oxide bound to the alloy and second, the ability of the formed oxide to saturate the porcelain, completing the chemical bond of porcelain to metal. CONCLUSION: The method of anodizing Ni-Cr porcelain alloy can easily control the forming of oxide film which was thin and its surface pattern was uniform. It is repeated and a good method of surface pretreatment before firing cycle.

[Study on the compositions in the interface of corrosion inhibition membrane/copper plating layer/iron substrate by depth etching and photoelectron spectroscopy].

In order to explore the reason for the weak bond intensity between pyro-phosphate copper plating layer and iron substrate, spectrum technology was adopted. The compositions of various elements in the perpendicular interface were analyzed. The effect of surface roughness in the metal substrate on various elements distribution was discussed. According to etching time, the membrane layer was divided into three portions: surface layer with nitrogen and oxygen content decreasing quickly, mesosphere of basic fixed composition, and mix disturbing layer with substrate element appearing and occupying a half thickness. Through analyzing oxygen content in the mix layer, it was concluded that the oxygen layer in the interface of copper layer/iron substrate was the main cause of influencing the bond intensity between the plating layer and substrate.