A case of Trousseau syndrome: Screening, detection and complication.

Trousseau syndrome (TS) is a malignant tumor-mediated complication of the hypercoagulable state with an unknown etiology. Laboratory testing results in patients with TS have indicated elevated D-dimer levels. The imaging analysis in patients who had undergone stroke has shown the presence of several cerebral infarction lesions in multiple regions. Since patients have had malignant tumors for a long time when they suffer from a secondary stroke, the optimum time for radical tumor treatment is usually missed. This study reports a case to improve the early screening and detection of TS and reduce the risk of recurrence of cerebral infarction.

Image quality assessment and feasibility of three-dimensional amide proton transfer-weighted imaging for hepatocellular carcinoma.

Background: With the continuous innovation of magnetic resonance imaging (MRI) hardware and software technology, amide proton transfer-weighted (APTw) imaging has been applied in liver cancer. However, to our knowledge, no study has evaluated the feasibility of a three-dimensional amide proton transfer-weighted (3D-APTw) imaging sequence for hepatocellular carcinoma (HCC). This study thus aimed to conduct an image quality assessment of 3D-APTw for HCC and to explore its feasibility. Methods: 3D-APTw MRI examinations were completed in 134 patients with clinically suspected HCC. According to the uniformity of APTw signal in the liver and within the lesion and the proportion of artifact and missing signal regions, APTw images were subjectively scored using a 5-point scale. The scanning success rate of liver APTw imaging was calculated as the ratio of the number of cases with a quality assurance measurement of more than 3 to the total number of HCC cases. The intra- and interobserver quality assurance measurements for APTw images were compared via the Kappa consistency test. Within the HCC cases with a minimum image quality threshold of 3 points, the APT values of HCC and the liver parenchyma, signal-to-noise ratio of APT-weighted images (SNRAPTw), and contrast-to-noise ratio of HCC (CNRHCC) were measured by two observers. The intra- and interobserver agreement was assessed using the intraclass correlation coefficient (ICC). The differences in APT values between HCC and liver parenchyma was determined using the Mann-Whitney test. Results: Sixty-six HCC cases with a quality assurance measurement of APTw imaging were included in the final analysis, and the calculated success rate was 70.21% (66/94). The subjective APT image quality scores of the two observers were consistent (3.66±1.18, 3.50±1.19, and 3.68±1.18), and no intergroup or intragroup statistical differences were found (P=0.594, and P=0.091), but the consistency of inter- and intraobserver was not as satisfactory (κ=0.594 and κ=0.580). The APT values in HCC lesion were significantly higher than those in liver parenchyma (2.73%±0.91% vs. 1.62%±0.55%; P<0.001). The APT values in HCC showed favorable intra- and interobserver consistency between the two observers (ICC =0.808 and ICC =0.853); the APT values in liver parenchyma, SNRAPTw, and CNRHCC values had moderate intraobserver consistency (ICC =0.578, ICC =0.568, and ICC =0.508) and interobserver consistency (ICC =0.599, ICC =0.199, and ICC =0.650). The coefficients of variation of the APTw values in the HCC lesion and in liver parenchyma were 33.4% and 34.4%, respectively. The SNRAPTw and CNRHCC were 30.75±18.74 and 3.56±3.19, with a coefficient of variation of 60.9% and 74.9%, respectively. Conclusions: Liver 3D-APTw imaging was preliminarily demonstrated to be clinically feasible for evaluating HCC.

A signature based on neutrophil extracellular trap-related genes for the assessment of prognosis, immunoinfiltration, mutation and therapeutic response in hepatocellular carcinoma.

BACKGROUND: Liver cancer is a highly lethal and aggressive form of cancer that poses a significant threat to patient survival. Within this category, liver hepatocellular carcinoma (LIHC) represents the most common subtype of liver cancer. Despite decades of research and treatment, the overall survival rate for LIHC has not significantly improved. Improved models are necessary to differentiate high-risk cases and predict possible treatment options for LIHC patients. Recent studies have identified a set of genes associated with neutrophil extracellular traps (NETs) that may contribute to tumor growth and metastasis; however, their prognostic value in LIHC has yet to be established. This study aims to construct a prognostic signature based on a set of NET-related genes (NRGs) for patients diagnosed with LIHC. METHODS: The transcriptomic data and clinical information concerning LIHC patients were procured from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium LIHC (ICLIHC) databases, respectively. To determine the NRG subtypes, the k-means algorithm was employed, along with consensus clustering. The aforementioned analysis aided the construction of a prognostic signature utilizing the last absolute shrinkage and selection operator Cox analysis. To validate the prognostic model, an external dataset, receiver operating characteristic curve, and principal component analysis were utilized. Moreover, the immune microenvironment and the proportion of immune cells between high- and low-risk cases were scrutinized by ESTIMATE and CIBERSORT algorithms. Finally, gene set enrichment analysis was executed to investigate the potential mechanism of NRGs in the pathogenesis and prognosis of LIHC. RESULTS: Two molecular subtypes of LIHC were identified based on the expression patterns of differentially expressed NRGs (DE-NRGs). The two subtypes demonstrated significant differences in survival rates and immune cell expression levels. The study results demonstrated the role of NRGs in antigen presentation, which led to the promotion of tumor immune escape. A risk model was developed and validated with strong overall survival prediction ability. The model, comprising 34 NRGs, showed a strong ability to predict prognosis. CONCLUSION: We built a dependable prognostic signature based on NRGs for LIHC. We identified that NRGs could have a significant interaction in LIHC's immune microenvironment and therapeutic response. This finding offers insight into the molecular mechanisms and targeted therapy for LIHC.

Rational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin.

Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety profiles, likely reflecting variable selectivity for JAK subtypes. Absolute JAK subtype selectivity has not yet been achieved. Here, we rationally design small interfering RNAs (siRNAs) that offer sequence-specific gene silencing of JAK1, narrowing the spectrum of action on JAK-dependent cytokine signaling to maintain efficacy and improve safety. Our fully chemically modified siRNA supports efficient silencing of JAK1 expression in human skin explant and modulation of JAK1-dependent inflammatory signaling. A single injection into mouse skin enables five weeks of duration of effect. In a mouse model of vitiligo, local administration of the JAK1 siRNA significantly reduces skin infiltration of autoreactive CD8+ T cells and prevents epidermal depigmentation. This work establishes a path toward siRNA treatments as a new class of therapeutic modality for inflammatory and autoimmune skin diseases.

TGF-ß/Smads signaling pathway, Hippo-YAP/TAZ signaling pathway, and VEGF: Their mechanisms and roles in vascular remodeling related diseases.

Vascular remodeling is a basic pathological process in various diseases characterized by abnormal changes in the morphology, structure, and function of vascular cells, such as migration, proliferation, hypertrophy, and apoptosis. Various growth factors and pathways are involved in the process of vascular remodeling. The transforming growth factor-ß (TGF-ß) signaling pathway, which is mainly mediated by TGF-ß1, is an important factor in vascular wall enhancement during vascular development and regulates the vascular response to injury by promoting the accumulation of intimal tissue. Vascular endothelial growth factor (VEGF) has an important effect on initiating the formation of blood vessels. The Hippo-YAP/TAZ signaling pathway also plays an important role in angiogenesis. In addition, studies have shown that there is a certain interaction between the TGF-ß/Smads signaling pathway, Hippo-YAP/TAZ signaling pathway, and VEGF. Many studies have shown that in the development of atherosclerosis, hypertension, aneurysm, vertebrobasilar dolichoectasia, pulmonary hypertension, restenosis after percutaneous transluminal angioplasty, and other diseases, various inflammatory reactions lead to changes in vascular structure and vascular microenvironment, which leads to vascular remodeling. The occurrence of vascular remodeling changes the morphology of blood vessels and thus changes the hemodynamics, which is the cause of further development of the disease process. Vascular remodeling can cause vascular smooth muscle cell dysfunction and vascular homeostasis regulation. This review aims to explore the mechanisms of the TGF-ß/Smads signaling pathway, Hippo-YAP/TAZ signaling pathway, and vascular endothelial growth factor in vascular remodeling and related diseases. This paper is expected to provide new ideas for research on the occurrence and development of related diseases and provide a new direction for research on the treatment of related diseases.

Role and mechanism of PVN-sympathetic-adipose circuit in depression and insulin resistance induced by chronic stress.

Chronic stress induces depression and insulin resistance, between which there is a bidirectional relationship. However, the mechanisms underlying this comorbidity remain unclear. White adipose tissue (WAT), innervated by sympathetic nerves, serves as a central node in the interorgan crosstalk through adipokines. Abnormal secretion of adipokines is involved in mood disorders and metabolic morbidities. We describe here a brain-sympathetic nerve-adipose circuit originating in the hypothalamic paraventricular nucleus (PVN) with a role in depression and insulin resistance induced by chronic stress. PVN neurons are labelled after inoculation of pseudorabies virus (PRV) into WAT and are activated under restraint stress. Chemogenetic manipulations suggest a role for the PVN in depression and insulin resistance. Chronic stress increases the sympathetic innervation of WAT and downregulates several antidepressant and insulin-sensitizing adipokines, including leptin, adiponectin, Angptl4 and Sfrp5. Chronic activation of the PVN has similar effects. ß-adrenergic receptors translate sympathetic tone into an adipose response, inducing downregulation of those adipokines and depressive-like behaviours and insulin resistance. We finally show that AP-1 has a role in the regulation of adipokine expression under chronic stress.

Microglia in the context of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that commonly results in nontraumatic disability in young adults. The characteristic pathological hallmark of MS is damage to myelin, oligodendrocytes, and axons. Microglia provide continuous surveillance in the CNS microenvironment and initiate defensive mechanisms to protect CNS tissue. Additionally, microglia participate in neurogenesis, synaptic refinement, and myelin pruning through the expression and release of different signaling factors. Continuous activation of microglia has been implicated in neurodegenerative disorders. We first review the lifetime of microglia, including the origin, differentiation, development, and function of microglia. We then discuss microglia participate in the whole processes of remyelination and demyelination, microglial phenotypes in MS, and the NF-κB/PI3K-AKT signaling pathway in microglia. The damage to regulatory signaling pathways may change the homeostasis of microglia, which would accelerate the progression of MS.

The role of the gut microbiota and fecal microbiota transplantation in neuroimmune diseases.

The gut microbiota plays a key role in the function of the host immune system and neuroimmune diseases. Alterations in the composition of the gut microbiota can lead to pathology and altered formation of microbiota-derived components and metabolites. A series of neuroimmune diseases, such as myasthenia gravis (MG), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), Guillain-Barré syndrome (GBS), and autoimmune encephalitis (AIE), are associated with changes in the gut microbiota. Microecological therapy by improving the gut microbiota is expected to be an effective measure for treating and preventing some neuroimmune diseases. This article reviews the research progress related to the roles of gut microbiota and fecal microbiota transplantation (FMT) in neuroimmune diseases.

RNAi-based modulation of IFN-γ signaling in skin.

Aberrant activation of interferon (IFN)-γ signaling plays a key role in several autoimmune skin diseases, including lupus erythematosus, alopecia areata, vitiligo, and lichen planus. Here, we identify fully chemically modified small interfering RNAs (siRNAs) that silence the ligand binding chain of the IFN-γ receptor (IFNGR1), for the modulation of IFN-γ signaling. Conjugating these siRNAs to docosanoic acid (DCA) enables productive delivery to all major skin cell types local to the injection site, with a single dose of injection supporting effective IFNGR1 protein reduction for at least 1 month in mice. In an ex vivo model of IFN-γ signaling, DCA-siRNA efficiently inhibits the induction of IFN-γ-inducible chemokines, CXCL9 and CXCL10, in skin biopsies from the injection site. Our data demonstrate that DCA-siRNAs can be engineered for functional gene silencing in skin and establish a path toward siRNA treatment of autoimmune skin diseases.

The Efficacy of Fecal Microbiota Transplantation in Experimental Autoimmune Encephalomyelitis: Transcriptome and Gut Microbiota Profiling.

OBJECTIVE: To study the protective effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and reveal its potential intestinal microflora-dependent mechanism through analyses of the intestinal microbiota and spinal cord transcriptome in mice. METHOD: We measured the severity of disease by clinical EAE scores and H&E staining. Gut microbiota alteration in the gut and differentially expressed genes (DEGs) in the spinal cord were analyzed through 16S rRNA and transcriptome sequencing. Finally, we analyzed associations between the relative abundance of intestinal microbiota constituents and DEGs. RESULTS: We observed that clinical EAE scores were lower in the EAE+FMT group than in the EAE group. Meanwhile, mice in the EAE+FMT group also had a lower number of infiltrating cells. The results of 16S rRNA sequence analysis showed that FMT increased the relative abundance of Firmicutes and Proteobacteria and reduced the abundance of Bacteroides and Actinobacteria. Meanwhile, FMT could modulate gut microbiota balance, especially via increasing the relative abundance of g_Adlercreutzia, g_Sutterella, g_Prevotella_9, and g_Tyzzerella_3 and decreasing the relative abundance of g_Turicibacter. Next, we analyzed the transcriptome of mouse spinal cord tissue and found that 1476 genes were differentially expressed between the EAE and FMT groups. The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37. CONCLUSION: Altogether, FMT may selectively regulate gene expression to improve inflammation and maintain the stability of the intestinal environment in a gut microbiota-dependent manner.

scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function.

Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results in CD8+ T cell infiltration of vitiligo lesions, but the full scope of signals required to coordinate autoimmune responses is not completely understood. We performed single-cell RNA sequencing on affected and unaffected skin from patients with vitiligo, as well as healthy controls, to define the role of each cell type in coordinating autoimmunity during disease progression. We confirmed that type 1 cytokine signaling occupied a central role in disease, but we also found that this pathway was used by regulatory T cells (Tregs) to restrain disease progression in nonlesional skin. We determined that CCL5-CCR5 signaling served as a chemokine circuit between effector CD8+ T cells and Tregs, and mechanistic studies in a mouse model of vitiligo revealed that CCR5 expression on Tregs was required to suppress disease in vivo but not in vitro. CCR5 was not required for Treg recruitment to skin but appeared to facilitate Treg function by properly positioning these cells within the skin. Our data provide critical insights into the pathogenesis of vitiligo and uncover potential opportunities for therapeutic interventions.

Follicular Helper CD4+ T Cells, Follicular Regulatory CD4+ T Cells, and Inducible Costimulator and Their Roles in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

Follicular helper CD4+ T (TFH) cells are a specialized subset of effector T cells that play a central role in orchestrating adaptive immunity. TFH cells mainly promote germinal center (GC) formation, provide help to B cells for immunoglobulin affinity maturation and class-switch recombination of B cells, and facilitate production of long-lived plasma cells and memory B cells. TFH cells express the nuclear transcriptional repressor B cell lymphoma 6 (Bcl-6), the chemokine (C-X-C motif) receptor 5 (CXCR5), the CD28 family members programmed cell death protein-1 (PD-1) and inducible costimulator (ICOS) and are also responsible for the secretion of interleukin-21 (IL-21) and IL-4. Follicular regulatory CD4+ T (TFR) cells, as a regulatory counterpart of TFH cells, participate in the regulation of GC reactions. TFR cells not only express markers of TFH cells but also express markers of regulatory T (Treg) cells containing FOXP3, glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte antigen 4 (CTLA-4), and IL-10, hence owing to the dual characteristic of TFH cells and Treg cells. ICOS, expressed on activated CD4+ effector T cells, participates in T cell activation, differentiation, and effector process. The expression of ICOS is highest on TFH and TFR cells, indicating it as a key regulator of humoral immunity. Multiple sclerosis (MS) is a severe autoimmune disease that affects the central nervous system and results in disability, mediated by autoreactive T cells with evolving evidence of a remarkable contribution from humoral responses. This review summarizes recent advances regarding TFH cells, TFR cells, and ICOS, as well as their functional characteristics in relation to MS.

AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma.

The STING and absent in melanoma 2 (AIM2) pathways are activated by the presence of cytosolic DNA, and STING agonists enhance immunotherapeutic responses. Here, we show that dendritic cell (DC) expression of AIM2 within human melanoma correlates with poor prognosis and, in contrast to STING, AIM2 exerts an immunosuppressive effect within the melanoma microenvironment. Vaccination with AIM2-deficient DCs improves the efficacy of both adoptive T cell therapy and anti-PD-1 immunotherapy for "cold tumors," which exhibit poor therapeutic responses. This effect did not depend on prolonged survival of vaccinated DCs, but on tumor-derived DNA that activates STING-dependent type I IFN secretion and subsequent production of CXCL10 to recruit CD8+ T cells. Additionally, loss of AIM2-dependent IL-1ß and IL-18 processing enhanced the treatment response further by limiting the recruitment of regulatory T cells. Finally, AIM2 siRNA-treated mouse DCs in vivo and human DCs in vitro enhanced similar anti-tumor immune responses. Thus, targeting AIM2 in tumor-infiltrating DCs is a promising new treatment strategy for melanoma.

Development of a Laser Gas Analyzer for Fast CO2 and H2O Flux Measurements Utilizing Derivative Absorption Spectroscopy at a 100 Hz Data Rate.

We report the development of a laser gas analyzer that measures gas concentrations at a data rate of 100 Hz. This fast data rate helps eddy covariance calculations for gas fluxes in turbulent high wind speed environments. The laser gas analyzer is based on derivative laser absorption spectroscopy and set for measurements of water vapor (H2O, at wavelength ~1392 nm) and carbon dioxide (CO2, at ~2004 nm). This instrument, in combination with an ultrasonic anemometer, has been tested experimentally in both marine and terrestrial environments. First, we compared the accuracy of results between the laser gas analyzer and a high-quality commercial instrument with a max data rate of 20 Hz. We then analyzed and compared the correlation of H2O flux results at data rates of 100 Hz and 20 Hz in both high and low wind speeds to verify the contribution of high frequency components. The measurement results show that the contribution of 100 Hz data rate to flux calculations is about 11% compared to that measured with 20 Hz data rate, in an environment with wind speed of ~10 m/s. Therefore, it shows that the laser gas analyzer with high detection frequency is more suitable for measurements in high wind speed environments.

Role of Adiponectin-Notch pathway in cognitive dysfunction associated with depression and in the therapeutic effect of physical exercise.

A substantial percentage of late-life depression patients also have an cognitive impairment, which severely affects the life quality, while the co-occurring mechanisms are still unclear. Physical exercise can ameliorate both depressive behaviors and cognitive dysfunction, but the molecular mechanisms underlying its beneficial effects remain elusive. In this study, we uncover a novel adipose tissue to hippocampus crosstalk mediated by Adiponectin-Notch pathway, with an impact on hippocampal neurogenesis and cognitive function. Adiponectin, an adipocyte-derived hormone, could activate Notch signaling in the hippocampus through upregulating ADAM10 and Notch1, two key molecules in the Notch signaling. Chronic stress inhibits the Adiponectin-Notch pathway and induces impaired hippocampal neurogenesis and cognitive dysfunction, which can be rescued by AdipoRon and running. Inhibition Notch signaling by DAPT mimics the adverse effects of chronic stress on hippocampal neurogenesis and cognitive function. Adiponectin knockout mice display depressive-like behaviors, associated with inhibited Notch signaling, impaired hippocampal neurogenesis and cognitive dysfunction. Physical exercise could activate Adiponectin-Notch pathway, and improve hippocampal neurogenesis and cognitive function, while deleting adiponectin gene or inhibiting Notch signaling blocks its beneficial effects. Together, our data not only suggest that Adiponectin-Notch pathway is involved in the pathogenesis of cognitive dysfunction associated with depression, but also contributes to the therapeutic effect of physical exercise. This work helps to decipher the etiology of cognitive impairment associated with depression and hence will provide a potential innovative therapeutic target for these patients.

Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo.

Vitiligo is an autoimmune disease of the skin mediated by CD8+ T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (TRM) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)-deficient mice reportedly have impaired TRM formation, and IL-15 promotes TRM function ex vivo. We found that both human and mouse TRM express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits TRM production of interferon-γ (IFNγ), and long-term treatment depletes TRM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving TRM.

E3 Ligase Trim21 Ubiquitylates and Stabilizes Keratin 17 to Induce STAT3 Activation in Psoriasis.

Keratin 17 (K17), a marker of keratinocyte hyperproliferation, is a type I intermediate filament that is overexpressed in psoriatic epidermis and plays a critical pathogenic role by stimulating T cells. However, the posttranslational modification of K17, which is reversible and targetable, has not been elucidated. Herein, we reported that K17 could be modified through ubiquitination that controlled its stability and led to the phosphorylation and nuclear translocation of its interactor signal transducers and activators of transcription 3 (STAT3), which is a key regulator of cell proliferation in psoriasis. First, we stimulated human keratinocyte cell line HaCaT cells with psoriasis (pso)-mix, which is a cytokine pool (IL-17, IL-22, tumor necrosis factor-α, and IFN-γ) mimicking the in vitro "psoriasis-like" status and found that the ubiquitination of K17 was essential to stabilize its protein expression in pso-mix-treated HaCaT cells. Subsequently, tripartite motif-containing protein 21 was identified as the E3 ligase of K17, which ubiquitylated K17 via K63 linkage to maintain K17 stabilization. More importantly, we uncovered that K17 was a direct interactor of STAT3, and K17 ubiquitination could promote STAT3 activation in pso-mix-treated HaCaT cells. Our study demonstrated that targeting K17 ubiquitination may be a potential therapeutic approach by attenuating STAT3 signaling in psoriasis.

A novel hand gesture recognition method based on 2-channel sEMG.

Hand gesture recognition is getting more and more important in the area of rehabilitation and human machine interface (HMI). However, most current approaches are difficult to achieve practical application because of an excess of sensors. In this work, we proposed a method to recognize six common hand gestures and establish the optimal relationship between hand gesture and muscle by utilizing only two channels of surface electromyography (sEMG). We proposed an integrated approach to process the sEMG data including filtering, endpoint detection, feature extraction, and classifier. In this study, we used one-order digital lowpass infinite impulse response (IIR) filter with the cutoff frequency of 500 Hz to extract the envelope of the sEMG signals. The energy was utilized as a feature to detect the endpoint of motion. The short-time energy, zero-crossing rate and linear predictive coefficient (LPC) with 12 levels were chosen as the features and back propagation (BP) neural network was utilized to classify. In order to test the method, five subjects were involved in the experiment to test the hypothesis. With the proposed method, 96.41% to 99.70% recognition rate was obtained. The experimental results revealed that the proposed method is highly efficient both in sEMG data acquisition and hand motions recognition, and played a role in promoting hand rehabilitation and HMI.

Nrf2 Promotes Keratinocyte Proliferation in Psoriasis through Up-Regulation of Keratin 6, Keratin 16, and Keratin 17.

Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation of epidermis. Although hyperproliferation-associated keratins K6, K16, and K17 are considered to be the hallmarks of psoriasis, the molecular basis underlying the overexpression of these keratins remains unclear. Nrf2 regulates cell proliferation. Therefore, we investigated whether Nrf2 regulates keratinocyte proliferation via promoting expression of K6, K16, and K17 in psoriasis. We initially found that psoriatic epidermis exhibited elevated expression of Nrf2. Furthermore, Nrf2 promoted expression of K6, K16, and K17 in both HaCaT cells and primary human keratinocytes by binding to the ARE domains located in the promoter of these genes. Additionally, upon stimulation with IL-17 or IL-22, Nrf2 translocated to the nucleus and initiated expression of targeted keratins. In mice of imiquimod-induced psoriasis-like dermatitis, topical application of Nrf2 small interfering RNA alleviated the epidermal hyperplasia with reduced expression of these keratins. More importantly, Nrf2 promoted the proliferation of human keratinocytes through up-regulation of K6, K16, or K17. These data suggested that inflammatory cytokines promoted Nrf2 nuclear translocation in psoriatic epidermis, which led to elevated expression of K6, K16, and K17, thus promoting keratinocyte proliferation and contributing to the pathogenesis of psoriasis.

Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells.

The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia. Among differentially expressed proteins identified, Cdc6 is a DNA replication initiation factor and exhibits oncogenic activities when overexpressed. We have recently demonstrated that Cdc6 was required for E7-induced re-replication. Significantly, here we showed that Cdc6 played a role in E7-mediated G1 checkpoint abrogation under hypoxic condition, and the function could possibly be independent from its role in DNA replication initiation. This study uncovered a new function of Cdc6 in regulating cell cycle progression and has important implications in HPV-associated cancers.