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The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.

Whey acidic protein four-disulfide core domain protein 12 (WFDC12) has been implicated in the pathogenesis of psoriasis but the specific molecular mechanism is not clearly defined. In this study, we found the expression of WFDC12 protein closely correlated with psoriasis. WFDC12 in keratinocyte might increase infiltration of Langerhans cells (LCs) and monocyte-derived dendritic cells (moDDCs), up-regulating the co-stimulation molecular CD40/CD86. Th1 cells in lymph nodes were higher in K14-WFDC12 transgenic psoiasis-like mice. Meanwhile, the mRNA of IL-12 and IFN-γ in the lesion skin was significantly increased in transgenic mice. Moreover, we found that the expression of the proteins that participated in the retinoic acid–related pathway and immune signaling pathway was more changed in the lesion skin of K14-WFDC12 transgenic psoriasis-like mice. Collectively, the results implied that WFDC12 might affect the activation of the retinoic acid signaling pathway and regulate the infiltration of DC cells in the skin lesions and lymph nodes, thereby inducing Th1 cells differentiation and increasing the secretion of IFN-γ to exacerbate psoriasis in mice.

In this brief, a 400 kW-level 95-GHz gyrotron has been designed and measured. By linear analysis, TE+22.6 mode is selected as the operating mode. Through the time-dependent multimode self-consistent analysis, main mode TE+22.6 can steadily operate at the conditions: beam voltage of 51.6 kV, beam current of 24 A, beam radius of 11.75 mm, and magnetic field of 3.62 T. With the help of CST microwave studio and numerical calculation code, the single-disk vacuum window has been designed for the transmission of the main mode. The measured results show that the output power of 430 kW and the frequency of 95.3 GHz are obtained at the current of 24 A, the voltage of 51.6 kV, and the magnetic field of 3.615 T.

Psoriasis is a common inflammatory skin disease involving interactions between keratinocytes and immune cells that significantly affects the quality of life. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes and excessive infiltration of immune cells in the dermis and epidermis. The immune mechanism underlying this disease has been elucidated in the past few years. Research shows that psoriasis is regulated by the complex interactions among immune cells, such as keratinocytes, dendritic cells, T lymphocytes, neutrophils, macrophages, natural killer cells, mast cells, and other immune cells. An increasing number of signaling pathways have been found to be involved in the pathogenesis of psoriasis, which has prompted the search for new treatment targets. In the past decades, studies on the pathogenesis of psoriasis have focused on the development of targeted and highly effective therapies. In this review, we have discussed the relationship between various types of immune cells and psoriasis and summarized the major signaling pathways involved in the pathogenesis of psoriasis, including the PI3K/AKT/mTOR, JAK-STAT, JNK, and WNT pathways. In addition, we have discussed the results of the latest omics research on psoriasis and the epigenetics of the disease, which provide insights regarding its pathogenesis and therapeutic prospects; we have also summarized its treatment strategies and observations of clinical trials. In this paper, the various aspects of psoriasis are described in detail, and the limitations of the current treatment methods are emphasized. It is necessary to improve and innovate treatment methods from the molecular level of pathogenesis, and further provide new ideas for the treatment and research of psoriasis.

Interleukin-38 (IL-38) is strongly associated with chronic inflammatory diseases; however, its role in tumorigenesis is poorly understood. We demonstrated that expression of IL-38, which exhibits high expression in the skin, is downregulated in human cutaneous squamous cell carcinoma and 7,12-dimethylbenzanthracene/12-O-tetradecanoyl phorbol-13-acetate-induced mouse skin tumorigenesis. IL-38 keratinocyte-specific knockout mice displayed suppressed skin tumor formation and malignant progression. Keratinocyte-specific deletion of IL-38 was associated with reduced expression of inflammatory cytokines, leading to reduced myeloid cell infiltration into the local tumor microenvironment. IL-38 is dispensable for epidermal mutagenesis, but IL-38 keratinocyte-specific deletion reduces proliferative gene expression along with epidermal cell proliferation and hyperplasia. Mechanistically, we first demonstrated that IL-38 activates the c-Jun N-terminal kinase (JNK)/activator protein 1 signal transduction pathway to promote the expression of cancer-related inflammatory cytokines and proliferation and migration of tumor cells in an IL-1 receptor-related protein 2 (IL-1Rrp2)-dependent manner. Our findings highlight the role of IL-38 in the regulation of epidermal cell hyperplasia and pro-tumorigenic microenvironment through IL-1Rrp2/JNK and suggest IL-38/IL-1Rrp2 as a preventive and potential therapeutic target in skin cancer.

Patients with psoriasis tend to have significant comorbidities, such as hyperlipemia, diabetes mellitus, and obesity, which belong to metabolic disorders. The specific mechanism through which psoriasis increases the metabolic disorder risk is uncertain. In this study, we demonstrated that the dysbiotic gut microbiota of 6-month-old psoriasis-like model mice (K14-VEGF-A-transgenic) exacerbated psoriasis disease and induced metabolic disorder when transferred into 2-month-old mice. By 16S rRNA gene sequencing, we confirmed that the Parabacteroides distasonis decreased with age in K14-VEGF mice, and P. distasonis also decreased in the transferred mice. Metabolomic screening identified an altered bile acid profile, including a decrease in chenodeoxycholic acid (CDCA) in the feces of transferred mice. Additionally, CDCA supplements prevented metabolic disorders in K14-VEGF-A-transgenic mice. Consequently, we found that aberrant bile acid metabolism may contribute to metabolic disorder in K14-VEGF-A-transgenic mice, indicating the possibility to prevent and treat the metabolic disorder in psoriasis mice by targeting gut microbial metabolites.

The term ferroptosis coined in 2012 causes acute kidney injury (AKI). However, its pathway mechanism in AKI is poorly understood. In this study, we conducted an RNA-sequence analysis of kidneys in AKI and normal mice to explore the pathway mechanism of ferroptosis. Consequently, differentially expressed genes highlighted Acyl-CoA synthetase long-chain family (ACSL4), a known promotor for ferroptosis. Besides, RT-PCR, Western blot, and immunohistochemical analyses confirmed its upregulation. HIF-1α was downregulated in I/R-AKI mice, and in vitro studies confirmed a negative regulation of HIF-1α on ACSL4. To explore the role of ACSL4 in AKI, we constructed ACSL4 knockout in kidney tubules of mice-as Cdh16Cre-ACSL4F/F mice. Results revealed that ACSL4 knockout significantly reduced ferroptosis and inhibited the functional and pathological injury of AKI mice. Meanwhile, the kidneys of Cdh16Cre-ACSL4F/F mice demonstrated a significantly decreased inflammation and macrophage infiltration. Further, additional explorations were explored to decipher a more thorough understanding of ferroptotic immunogenicity. As a result, neutrophils were not directly recruited by ferroptotic cells, but by ferroptotic cell-induced macrophages. Further, ACSL4 inhibitor rosiglitazone significantly inhibited AKI. Collectively, these data provide novel insights into the AKI pathogenesis, and defined ACSL4 as an effective target in AKI.

Defective execution of proteases and protease inhibitors that mediate abnormal signaling cascades is emerging as a key contributor to skin diseases, such as psoriasis. SerpinB7 is identified as a skin-specific endogenous protease inhibitor, but the role and underlying mechanism in psoriasis are poorly understood. Here we found that SerpinB7 is highly expressed in psoriatic keratinocytes of patients and imiquimod-induced psoriatic lesions in mice. SerpinB7-/- mice showed abnormal epidermal barrier integrity and skin architecture in homeostasis, and aggravated psoriatic lesion with inhibiting terminal differentiation and increasing inflammatory cells infiltration compared to SerpinB7+/+ mice after Imiquimod treatment. Mechanistically, SerpinB7 deficiency results in excessive proliferation and impaired differentiation, as well as increased chemokines and antimicrobial peptide expression in normal human epidermal keratinocyte and mouse primary keratinocyte. Transcriptomics and proteomics results showed that the SeprinB7 deficiency affected keratinocyte differentiation and proinflammatory cytokines, possibly by affecting the calcium ion channel-related proteins. Notably, we demonstrated that SerpinB7 deficiency prevented the increase in intracellular Ca2+ influx, which was partly eliminated by the intracellular Ca2+ chelator BAPTA-AM. Our findings first described the critical role of SerpinB7 in the regulation of keratinocyte differentiation and psoriatic microenvironment mediated via keratinocytes' intracellular calcium flux, proposing a new candidate for therapeutic targets in psoriasis.

The transient receptor potential canonical (TRPC) channels, encoded in seven non-allelic genes, are important contributors to calcium fluxes, are strongly associated with various diseases. Here we explored the consequences of ablating all seven TRPCs in mice focusing on colitis. We discovered that absence of all seven TRPC proteins in mice (TRPC HeptaKO mice) promotes the development of dextran sulfate sodium (DSS)-induced colitis. RNA-sequence analysis highlighted an extremely pro-inflammatory profile in colons of DSS-treated TRPC HeptaKO mice, with an amount of increased pro-inflammatory cytokines and chemokines. Flow cytometry analysis showed that the infiltration of Ly6C

BackgroundThe intestinal microbiota has been associated with host immunity, however, a link with psoriasis has not been demonstrated. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis.ResultsWe performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis. Psoriasis severity was accompanied with changes in the composition of the intestinal microbiota. Furthermore, FMT from mice with severe psoriasis exacerbated psoriasis in mice with mild symptoms, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Indeed, oral administration of oleic and stearic acids exacerbated psoriasis and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas.ConclusionOverall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis pathogenesis in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.

The tension legs are the essential parts of the tension legs platform-type (TLP-type) floating offshore wind turbine (FOWT) against the extra buoyancy of FOWT. Therefore, the TLP-type FOWT will face the risk of tension leg failure. However, there are seldom analyses on the hydrodynamic response and tension leg failure performance of FOWT with inclined tension legs. In this paper, a hydrodynamic model was established using three-dimensional hydrodynamic theory and applied in the motion response and tension analyses of FOWT with conventional and new tension leg arrangements on Moses. The influence of draft and tension leg arrangement on the performance of FOWT with inclined tension legs were studied. The optimum draft was the height of the column and lower tensions were obtained for the new tension leg arrangement. Moreover, the tension leg failure performance of FOWT with inclined tension legs was evaluated under different failure conditions. The results illustrated that the FOWT with the new tension leg arrangement can still operate safely after one tension leg fails.

A graphene metamaterials based on plasmon-induced transparent has been proposed, which is composed of graphene split rings and graphene nanostrip. Split ring and nanostrip can generate resonance points at different frequencies under the excitation of terahertz waves. When these two structures are combined, two transparent windows are generated due to the destructive interference. Via tuning the Fermi energy of graphene of MaSRR, the amplitude of the first transmission peak increased from 0.64 to 0.86, and the amplitude of the second transmission peak decreased from 0.97 to 0.85. Via tuning the Fermi energy of graphene of MiSRR, the amplitude of the first transmission peak remains unchanged, and the amplitude of the second transmission peak ranges from 0 to 0.85. This study provides a good theoretical basis for the diversity of terahertz wave modulation.

A large orbit gyrotron capable of operating from the 4th to the 9th harmonic is investigated. With the assistance of the 3-D particle-in-cell simulation, the beam-wave interaction dynamics and high harmonics operation regimes are studied. It is shown that by tuning the external magnetic field intensity, successive excitation of the oscillation at a number of neighboring harmonics can be achieved, corresponding to radiation frequencies between 240 GHz to 460 GHz. Then, a study of the competition among the 7th, 8th and 9th harmonics are conducted, providing an insight into the multi-modes, multi-harmonics behavior of the high-harmonic LOG.

Psoriasis is a common chronic inflammatory skin disease mediated by innate and adaptive immune systems, characterized by abnormal proliferation and differentiation of epidermal keratinocytes and infiltration of inflammatory cells. Skin-specific keratinocytes are key participants in innate immunity, responding to immune cells and environmental stimulation, thereby serving an important role in the immunopathogenesis of psoriasis. Here, we present a method for inducing psoriasiform keratinocytes inflammation at transcription level with HaCaT cell line using five proinflammatory cytokines combination (M5 combination), including IL-17A, IL-22, IL-1α, TNF-α, and oncostatin M. Results demonstrate that M5 combination induced HaCaT cells showed increased levels of antimicrobial peptides (BD2, S100A7, S100A8, and S100A9), chemokines, and cytokines (CXCL1, CXCL2, CXCL8, CCL20, IL-1β, IL-6 and, IL-18). The mRNA levels of keratinocytes differentiation markers (Keratin1, Keratin10, Filaggrin, and Loricrin) were down regulated, which was consistent with the transcriptome data derived from psoriasis-like keratinocytes. The method described here, therefore, establishes an in vitro psoriasiform cutaneous inflammation at transcription level and contributes to the research for molecular pathogenesis of psoriasis.

The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivation. The impairment of autophagic flux alleviated psoriasisform inflammation. We also found that an autophagy-based unconventional secretory pathway (autosecretion) dependent on ATG5 (autophagy related 5) and GORASP2 (golgi reassembly stacking protein 2) promoted psoriasiform KC inflammation. Moreover, the alarmin HMGB1 (high mobility group box 1) was more effective than other autosecretory proteins in regulating psoriasiform cutaneous inflammation. HMGB1 neutralization in autophagy-efficient KCs eliminated the differences in psoriasiform inflammation between Krt14(+/+)-Atg5(f/f) KCs and Krt14(Cre/+)-atg5(f/f) KCs, and conversely, recombinant HMGB1 almost completely restored psoriasiform inflammation in Krt14(Cre/+)-atg5(f/f) KCs in vivo. These results suggest that HMGB1-associated autosecretion plays a pivotal role in cutaneous inflammation. Finally, we demonstrated that Krt14(Cre/+)-hmgb1(f/f) mice displayed attenuated psoriatic inflammation due to the essential crosstalk between KC-specific HMGB1-associated autosecretion and γδT cells. Thus, this study uncovered a novel autophagy mechanism in psoriasis pathogenesis, and the findings imply the clinical significance of investigating and treating psoriasis. Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AGER: advanced glycosylation end-product specific receptor; Anti-HMGB1: anti-HMGB1 neutralizing antibody; Anti-IL18: anti-IL18 neutralizing antibody; Anti-IL1B: anti-IL1B neutralizing antibody; ATG5: autophagy related 5; BAF: bafilomycin A(1); BECN1: beclin 1; CASP1: caspase 1; CCL: C-C motif chemokine ligand; CsA: cyclosporine A; ctrl shRNA: lentivirus harboring shRNA against control; CXCL: C-X-C motif chemokine ligand; DCs: dendritic cells; DMEM: dulbecco’s modified Eagle’s medium; ELISA: enzyme-linked immunosorbent assay; EM: electron microscopy; FBS: fetal bovine serum; GORASP2 shRNA: lentivirus harboring shRNA against GORASP2; GORASP2/GRASP55: golgi reassembly stacking protein 2; GR1: a composite epitope between LY6 (lymphocyte antigen 6 complex) locus C1 and LY6 locus G6D antigens; H&E: hematoxylin and eosin; HMGB1: high mobility group box 1; HMGB1 shRNA: lentivirus harboring shRNA against HMGB1; IFNG/IFN-γ: interferon gamma; IL17A: interleukin 17A; IL18: interleukin 18; IL1A/IL-1α: interleukin 1 alpha; IL1B/IL-1β: interleukin 1 beta; IL22/IL-22: interleukin 22; IL23A: interleukin 23 subunit alpha; IL23R: interleukin 23 receptor; IMQ: imiquimod; ITGAM/CD11B: integrin subunit alpha M; ITGAX/CD11C: integrin subunit alpha X; IVL: involucrin; KC: keratinocyte; KD: knockdown; KO: knockout; Krt14(+/+)-Atg5(f/f) mice: mice bearing an Atg5 flox allele, in which exon 3 of the Atg5 gene is flanked by two loxP sites; Krt14(+/+)-Hmgb1(f/f): mice bearing an Hmgb1 flox allele, in which exon 2 to 4 of the Hmgb1 gene is flanked by two loxP sites; Krt14(Cre/+)-atg5(f/f) mice: keratinocyte-specific atg5 knockout mice generated by mating Atg5-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt4; Krt14(Cre/+)-hmgb1(f/f) mice: keratinocyte-specific hmgb1 knockout mice generated by mating Hmgb1-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt14; Krt14-Vegfa mice: mice expressing 164-amino acid Vegfa splice variant recombinase under the control of promoter of Krt14; LAMP1: lysosomal associated membrane protein 1; LDH: lactate dehydrogenase; LORICRIN: loricrin cornified envelope precursor protein; M5: TNF, IL1A, IL17A, IL22 and OSM in combination; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MKI67: marker of proliferation Ki-67; MTT: thiazolyl blue tetrazolium bromide; NFKB/NF-κB: nuclear factor kappa B; NHEKs: primary normal human epidermal keratinocytes; NS: not significant; OSM: oncostatin M; PASI: psoriasis area and severity index; PtdIns3K: class III phosphatidylinositol 3-kinase; qRT-PCR: quantitative RT-PCR; RELA/p65: RELA proto-oncogene, NF-kB subunit; rHMGB1: recombinant HMGB1; rIL18: recombinant interleukin 18; rIL1B: recombinant interleukin 1 beta; S100A: S100 calcium binding protein A; SQSTM1/p62: sequestosome 1; T17: IL17A-producing T; TCR: T-cell receptor; tcrd KO mice: tcrd (T cell receptor delta chain) knockout mice, which show deficient receptor expression in all adult lymphoid and epithelial organs; TLR: toll-like receptor; TNF/TNF-α: tumor necrosis factor; WOR: wortmannin; WT: wild-type; γδT17 cells: IL17A-producing γδ T cells.

The realization of electromagnetically induced transparency (EIT) on metamaterials has special properties, such as strong slow-light, frequency-selection and so on, which have allowed EIT to be widely used in the fields of slow-light, optical storages and filters. In this paper, a metamaterial with two pairs of split ring resonators and one cut-wire is designed to achieve dual-band EIT effect at 0.5–2.14 GHz and 0.4–2.10 GHz with independently tunable bandwidths of 1.64 GHz and 2.7 GHz, respectively. The coupled Lorentz model is adopted to principally study the coupling characteristics between dark and bright modes. It is shown that the coupling strength between the dark and bright modes could be modulated by the coupling distance, which make the dual-band transparent window could be independently modulated by only changing the coupling distance between the bright and dark mode. The group delay and energy storage are also simulated by setting the Gaussian pulse signal passing through the EIT structure. The results show that the group delay of the designed EIT structure is 16.9 times that of the same thickness of dielectric material. The manufactured metamaterial is tested in a microwave anechoic chamber. The experimental and theoretical results are well consistent. These results could be beneficial for the development of EIT research toward some up-and-coming novel slow-light, optical storage, sensor and optical filter applications.

Both decreased autophagy positive regulator AMP activated protein kinase (AMPK) level and promoted mitophagy are observed in oxygen‐glucose deprivation (OGD) cardiomyocytes treated with pigment epithelium‐derived factor (PEDF). This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Our previous study reveals that PEDF increases the protein kinase Cα (PKCα) and phospho‐PKCα (p‐PKCα) contents to promote mitophagy. Thus, we investigated the association between PKCα and mitophagy. Here we identify an interaction between PKCα and Unc‐51‐like kinase 1 (ULK1), essential component of mitophagy. Further analyses show this is a direct interaction within a domain of ULK1 that termed the serine/threonine‐rich domain (S/T domain). Notably, a deletion mutant ULK1 that lacks the binding domain is defective in mediating PEDF‐induced mitophagy. Furthermore, we demonstrate that ULK1 is phosphorylated at Ser317/555/777 and Raptor is also phosphorylated by phospho‐PKCα. Phospho‐ULK1 (p‐ULK1) at these sites are all essential for PEDF‐induced mitophagy and reduce the release of mitochondrial ROS and DNA. This study therefore identifies a previously uncharacterized interaction between the ULK1 and PKCα that can replace the AMPK‐dependent mitophagy processes.

Aims The activated AMP activated protein kinase (AMPK) serves as a transient protective cardiovascular kinase via preserving adenosine triphosphate (ATP) production under ischemic conditions. However, recent studies reveal that inhibition of AMPK in stroke is neuroprotection. Pigment epithelium derived factor (PEDF) is also known for the protection of ischemic cardiomyocytes. However, the relationship between PEDF and AMPK in cardiomyocytes is poorly understood. Methods and results Rat neonatal and adult left ventricular cardiomyocytes were isolated and subjected to oxygen-glucose deprivation (OGD). During OGD, PEDF significantly reduced AMPKα levels to decrease ATP production and reduced ATP expenditure both in neonatal and adult cardiomyocytes, which increased energy reserves and cell viability. Importantly, pharmacological AMPK inhibitor reduced ATP production but failed to decrease ATP expenditure, thus leading cells into death. Furthermore, AMPKα was degraded by a ubiquitin-dependent proteasomal degradation pathway, which is associated with a PEDF/PEDFR/peroxisome proliferator activated receptor γ (PPARγ) axis. Inhibition of PPARγ or proteasome disrupted the interaction of AMPKα and PPARγ, which abolished AMPKα degradation. Importantly, the decrease of AMPKα and ATP level was normalized after recovery of oxygen and glucose. Conclusions We demonstrate a novel mechanism for regulation of cardiac ATP production by PEDF involving AMPKα and PPARγ. PEDF promotes proteasomal degradation of AMPK and, subsequently, reduces ATP production. The reduction of ATP production associated with the decrease of ATP expenditure completed by PEDF increase energy reserves and reduces cell energy failure, prolonging the cell activity during OGD.

The lack of terahertz sources, especially the high-power ones, is one of the main obstacles in the developments of terahertz science and technology. A gyrotron, based on the electron cyclotron masers, is one of the most promising sources to generate high-power terahertz radiation. Therefore, a 0.42-THz gyrotron with a gradually tapered complex cavity operating at the second harmonic is designed and experimentally tested in this paper. Experimental results show that the designed gyrotron can generate high-power THz radiation of 19.2 kW at 0.42 THz with the beam voltage ${V}_{\textsf {0}}$ of 51 kV, beam current ${I}_{\textsf {0}}$ of 4.4 A and the external magnetic field ${B}_{\textsf {0}}$ of 8.03 T, corresponding to an efficiency of 8.6%. By comparison with theoretical results, it can be shown that the operating mode in the designed gyrotron is confirmed as the TE17.4 mode. At the same time, the excitation of the fundamental TE0.5 mode is also observed in the experiment when the beam current is increased to 7.3 A, where the operating frequency is 216.143 GHz. Through extensive experimental efforts, it is found that the designed gyrotron can operate stably at the desired TE17.4 mode when the beam current is in the range of 3–7 A.

Titanium nickel nitride (TiNiN) decorated three-dimensional (3D) carbon nanotubes-reduced graphene oxide (CNT-rGO), a fancy 3D platinum (Pt)-based catalyst hybrid support, is prepared by a solvothermal process followed by a nitriding process, which is tested as anodic catalyst support for the methanol oxidation reaction (MOR). The structure, morphology and composition of the synthesized TiNiN/CNT-rGO exhibits a uniform particle dispersion with high purity and interpenetrating 3D network structure. Notably, Pt/TiNiN/CNT-rGO catalyst exhibits significantly improved catalytic activity and durability for methanol oxidation in comparison with Pt/CNT-rGO and conventional Pt/C (JM). The outstanding electrochemical performance was attributed to structure and properties. That is, the 3D CNT-rGO provided a fast transport network for charge-transfer and mass-transfer as well as TiNiN NPs with good synergistic effect and the strong electronic coupling between different domains in TiNiN/CNT-rGO, thus the catalytic activity of the novel catalyst is greatly improved. These results evidences 3D TiNiN/CNT-rGO as a promising catalyst support for a wide range of applications in fuel cells.

The application of direct methanol fuel cells (DMFCs) is hampered by not only low activity but also poor stability and poor CO tolerance by the Pt catalyst. Herein, a novel titanium nitride coated multi-walled carbon nanotubes (CNTs@TiN) hybrid support was successfully synthesized by a facile solvothermal process followed by a nitriding process, and this hybrid support was used as Pt support for the oxidation of methanol. The structure, morphology and composition of the synthesized CNTs@TiN exhibits a uniform particle perfect coating with high purity and interpenetrating network structure. Notably, Pt/CNTs@TiN also showed excellent stability, experiencing only a slight performance loss after 5000 potential cycles. The onset potential (0.34 V) of CO oxidation on Pt/CNTs@TiN is obviously more negative than that on the Pt/TiN (0.38 V) and Pt/CNTs (0.48 V) in the first forward scan. In the Pt 4f XPS spectra, plentiful Pt atoms existed as Pt(II) in the Pt/CNTs and Pt/TiN catalysts, while a relatively smaller amount of Pt(II) was observed in the Pt/CNTs@TiN catalyst. The synthetic Pt/CNTs@TiN catalyst was studied with respect to its electrocatalytic activity and durability and CO tolerance toward methanol oxidation might be mainly attributed to the strongly coupled Pt–TiN and the fast electron-transport network structure. This work may provide more insight into developing novel catalyst supports of various transition metal nitrides coated CNTs for DMFCs with high activity and good durability and excellent CO tolerance.

Terahertz (THz) and sub-THz science and technology are very hot today. However, it is difficult to obtain high-power source of THz wave. Gyrotrons are well known as one of the most promising source for powerful THz radiation. In this paper, a 0.42-THz second harmonic gyrotron with complex cavity operating at TE17.4 is numerically simulated and designed by adopting self-consistent nonlinear theory with the first-order transmission line equations. Meanwhile, the mode competitions in the designed gyrotron have been investigated carefully by using time-dependent multimode nonlinear theory. It is proved that the operating mode can be first excited and other competing modes are well suppressed in the complex cavity. Based on these numerical simulations, the designed complex cavity gyrotron has been manufactured and measured in the Terahertz Science and Technology Research Center at the University of Electronic Science and Technology of China. The measured results show that the designed gyrotron can stably operate at TE17.4 with pulsed output power of 19.3 kW when the beam current ${I}_{{0}}$ is 4.4 A, beam voltage ${U}_{{0}}$ is 51 kV, and magnetic field ${B}_{{0}}$ is 8.03 T. The corresponding frequency and interaction efficiency are 421.645 GHz and 8.6%, respectively.

Myocardial edema is divided into cellular edema and interstitial edema; however, the dynamic change of cardiomyocyte edema has not been described in detail. Pigment epithelium‑derived factor (PEDF) is known for its protective effects on ischemic cardiomyocytes; however, the association between PEDF and cardiomyocyte edema remains to be fully elucidated. In the present study, rat neonatal left ventricular cardiomyocytes were isolated and treated with oxygen‑glucose deprivation (OGD) and recovery. During OGD and recovery, the cardiomyocytes exhibited significant edema following 30 min of OGD (OGD 30 min) and OGD 30 min with recovery for 6 h. PEDF significantly decreased the lactate content and extracellular acidification rate of the OGD‑treated cardiomyocytes, thereby reducing cellular osmotic gradients and preventing the occurrence of cell edema. In addition, the glycolytic agonist, fructose‑1, 6‑diphosphate, eliminated the effect of PEDF on inhibiting edema in the OGD‑treated cardiomyocytes. Furthermore, PEDF reduced the protein and mRNA expression of aquaporin 1 (AQP1), and thus downregulated cardiomyocyte edema during the OGD/recovery period. The addition of AQP1 agonist, arginine vasopressin, inhibited the inhibitory effect of PEDF on cardiomyocyte edema during OGD/recovery. In conclusion, the present study revealed a novel mechanism for the regulation of cardiomyocyte edema by PEDF involving lactate levels and the expression of AQP1 during OGD/recovery. The reduction of lactate content during OGD was associated with a decrease in the protein level of AQP1 during OGD/recovery; therefore, PEDF decreased cardiomyocyte edema and cellular apoptosis, prolonging the viability of the cells.

Patients with psoriasis tend to have significant comorbidities, such as hypertension, diabetes mellitus and obesity, which belong to metabolic disorder. The specific pathways through which psoriasis increases metabolic disorder risk is uncertain. The gut microbiome and gut associated metabolites as important regulators of host energy and substrate metabolism are intricately linked to host metabolic homeostasis. Here we demonstrated that the dysbiotic gut microbiota of aged psoriasis-like model mice(6 months K14-VEGF) exacerbated psoriasis disease and induced the emergence of metabolic disorder when transferred into young mice(2 months K14-VEGF). We used 16S rRNA gene sequencing detected the decrease of Parabacteroides distasonis, an intestinal bacterium, in aged K14-VEGF mice. It has been reported that Parabacteroides distasonis can affect the distribution of bile acid metabolism and benefits the metabolism of host. Metabolomic screening identified an altered distribution of bile acid metabolites, including a decrease in chenodeoxycholic acid(CDCA) in the feces of transferred mice. In addition, supplement with dietary CDCA prevented metabolic disease in K14-VEGF mice. Consequently, we found that aberrant bile acid metabolism may contribute to metabolic disorder in K14-VEGF mice, indicating the possibility to prevent and treat the metabolic disorder by targeting gut microbial metabolites in psoriasis mice.

Stable operation in a single mode is an important goal of high-power gyrotron. Both multimoding and switching into unwanted modes can lead to lower efficiency. Based on the multimode, multifrequency, and time-dependent fixed field theory, a numerical code has been written for simulating the mode competition in the complex cavity gyrotron operating at the second harmonic, which is confirmed to be correct by comparison with the self-consistent simulation. With the help of the code, the mode competition in the designed complex gyrotron with the frequency of 0.42 THz is simulated by tracking several competition modes without considering ohmic losses, whose influence is roughly estimated. Through mode competition simulations, it is verified that the complex gyrotron with gradually tapered cavity has a good capability to suppress the mode competition, especially the competition from the fundamental modes. Meanwhile, the simulations show that the single mode oscillation of the desired mode TE17.4 at 150-kW level can be expected when the optimal operating condition is that the beam voltage is 50 kV, the beam current is 6 A, and the applied magnetic field is 7.98 T.

High-power terahertz gyrotrons always operate at high-order modes to avoid damage from Ohmic heating. However, the spectral densities of these modes are very high, especially when gyrotrons operate at high-order harmonics. Therefore, the self-excitation condition can be satisfied for several modes simultaneously. Correspondingly, in order to determine which mode will be excited first in the designed terahertz gyrotron, the starting currents of competing modes should be calculated more accurately to predict the operating status. In this paper, an existing linear theory is generalized to take into account the influences of the field profile, finite beam thickness, and velocity spread. Starting currents are calculated for the operating and the most dangerous competing mode in a 0.42-THz second harmonic gyrotron with a complex cavity, which is recently under development at the Terahertz Science and Technology Research Center. The calculations show that the radial and velocity spreads play a critical role in the starting current and prove that the measured output terahertz radiation in the designed device is generated from the interaction between the desired mode and the electron beam.

Gyrotron oscillators are one of promising sources to generate high power terahertz radiation. To achieve high power at high frequency, gyrotrons have to operate at high order modes to alleviate the problem of wall heating and the miniaturization of interaction structures at these frequencies. Due to high order modes, the mode spectrum is very dense and the electron beam is likely to interact with several modes. Mode competition is a major hurdle in achieving stable and efficient operation of a gyrotron at cyclotron harmonics. The gradually tapered complex cavity could suppress mode competition by locking a pair of operating modes in two single cavities. Starting from the general transmission line equations with an electron beam, self-consistent nonlinear simulations on the second harmonic complex cavity gyrotron operating at 0.42 THz are presented. The influences of the electron beam parameters on the interaction efficiency are analyzed. The experimental results show that the designed complex cavity gyrotron is operationally stable at TE 17.4 with pulse output power of 22.25 kW when the beam current is 4.8 A, beam voltage is 45 kV, and applied magnetic field is 8.185 T. The corresponding frequency and interaction efficiency are 421.60 GHz and 10.27%, respectively.

Pigment epithelial-derived factor (PEDF) is a multifunctional secreted glycoprotein, which exerts a variety of physiological activities. PEDF may protect against hypoxia-induced cell death associated with its antioxidative effects and p53 mitochondrial translocation in cultured cardiomyocytes and H9c2 cells. Additionally, previous studies have suggested that autophagy is an important cell survival mechanism. However, the effect of PEDF on autophagy and the associated pathway in hypoxic H9c2 cells has not been fully established. Autophagy has been reported to regulate lipid metabolism; however, little is known about whether PEDF is able to regulate lipid metabolism by promoting autophagy. In the present study, western blotting results revealed that PEDF increased the level of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II. Transmission electron microscopy (TEM) and LC3 fluorescence demonstrated that PEDF increased the number of autophagosomes. PEDF also increased the viability of hypoxic H9c2 cells and decreased the level of cleaved caspase-3 protein, as evidenced by CCK-8 assays and western blotting, respectively. TEM and a triglyceride assay kit demonstrated that PEDF-induced autophagy may stimulate lipid degradation. Western blotting results revealed a novel mechanism underlying PEDF-induced H9c2 cell autophagy via the PEDF-R-mediated Atg5 pathway under hypoxic conditions. Furthermore, the results also suggest that PEDF-induced autophagy may stimulate lipid degradation. The survival function of autophagy suggests that modulation of PEDF-induced autophagy may be used as a therapeutic strategy to protect cells against lipid-associated metabolic diseases.

The prevention and management of myocardial ischemia/reperfusion (MI/R) injury is an essential part of coronary heart disease surgery and is becoming a major clinical problem in the treatment of ischemic heart disease. Previous studies by our group have demonstrated that pigment epithelium-derived factor (PEDF) improves cardiac function in rats with acute myocardial infarction and reduces hypoxia-induced cell injury. However, the protective function and mechanisms underlying the effect of PEDF in MI/R injury remain to be fully understood. In the present study, the positive effect of PEDF in MI/R injury was confirmed by construction of the adult Sprague-Dawley rat MI/R model. PEDF reduced myocardial infarct size and downregulated cardiomyocyte apoptosis in the I/R myocardium in this model. In addition, PEDF improved cardiac function and increased cardiac functional reserve in rats subjected to MI/R Injury. To further study the protective effect of PEDF and the underlying mechanisms in MI/R injury, a H9c2 cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed. PEDF was confirmed to decrease H/R-induced apoptosis in H9c2 cells, and this anti-apoptotic function was abolished by pigment epithelium-derived factor-receptor (PEDF R) small interfering (si)RNA. Furthermore, administration of PEDF decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in H/R H9c2 cells. Compared with the H/R group, PEDF decreased mitochondrial ROS, increased the mitochondrial DNA copy number, reduced xanthine oxidase and NADPH oxidase activity, as well as RAC family small GTPase 1 protein expression. However, these effects of PEDF were markedly attenuated by PEDF-R siRNA. To the best of our knowledge, the present study is the first to identify the protective effect of PEDF in MI/R injury, and confirm that the antioxidative effect PEDF occurred via inhibition of ROS generation via PEDF-R under MI/R conditions.

Pigment epithelial-derived factor (PEDF) is known to exert diverse physiological activities. Previous studies suggest that hypoxia could induce mitophagy. Astoundingly, under hypoxic condition, we found that PEDF decreased the mitochondrial density of cardiomyocytes. In this study, we evaluated whether PEDF could decrease the mitochondrial density and play a protective role in hypoxic cardiomyocytes via promoting mitophagy. Immunostaining and western blotting were used to analyze mitochondrial density and mitophagy of hypoxic cardiomyocytes. Gas chromatography‑mass spectrometry and ELISA were used to analyze levels of palmitic acid and diacylglycerol. Transmission Electron Microscopy was used to detect mitophagy and the mitochondrial density in adult male Sprague-Dawley rat model of acute myocardial infarction. Compared to the control group, we observed that PEDF decreased mitochondrial density through promoting hypoxic cardiomyocyte mitophagy. PEDF increased the levels of palmitic acid and diacylglycerol, and then upregulated the levels of protein kinase Cα (PKC-α) and its activation. Furthermore, inhibition of PKC-α by Go6976 could effectively suppress PEDF-induced mitophagy. Besides, we found that PEDF promoted FUNDC1-mediated cardiomyocyte mitophagy via ULK1, which depended on the activation of PKC-α. Finally, we discovered that mitophagy was increased and mitochondrial density was reduced in adult male Sprague-Dawley rat model of acute myocardial infarction. We concluded that PEDF promotes mitophagy to protect hypoxic cardiomyocytes, through PEDF/PEDF-R/PA/DAG/PKC-α/ULK1/FUNDC1 pathway.

The problem of mode competition can present a major hurdle for gyrotron to achieve stable and efficient operation, especially when the gyrotron operates at electron cyclotron harmonics. Therefore, an effective theoretical investigation of the mode competition is an essential first step to the implementation of gyrotron. In this paper, the nonlinear dynamics of the mode competition in the terahertz gyrotron operating at high-order mode are studied using a multifrequency time-dependent model. Based on the model, the simulations of mode competition in the designed gyrotron are presented by the corresponding code. The influence of the velocity spread on the mode competition is also studied. The simulations tracking five competing modes show that stable excitation of the second harmonic oscillation can be realized with a proper choice of the operation parameters. The results show that a single-mode second harmonic radiation with a power of over 120 kW at a frequency of 0.4 THz could be achieved.

A double anode magnetron injection gun (MIG) for a 0.42 THz second harmonic gyrotron has been presented in this paper. Through design, simulation and optimization by the particle-in-cell code, a double-anode electron gun with maximum transverse velocity spread of 3.19 % is obtained, the beam acceleration voltage is 50 kV, operating current is 5.5 A and the ratio of the transverse velocity to the axial velocity is equal to 1.4. A comprehensive analysis of MIG for 0.42 THz second harmonic gyrotron is presented, and the designed electron gun well satisfies the requirement of the 0.42 THz gyrotron.

In this paper, the results of theoretical study on a 0.4-THz second harmonic gyrotron operating at TE19.3 are presented. A gradually tapered cavity is adopted to alleviate the problem of parasitic mode competition. It is proved that the amplitudes of spurious modes in the gradually tapered cavity could be kept lower than that in the line-joint cavity, especially that in the line-joint cavity with large angle. Based on the self-consistent nonlinear theory, a code is written to simulate the process of beam–wave interaction. Through optimizing the operating parameters, the beam–wave interaction efficiency can reach 35% and an output power of 100 kW can be obtained. In addition, the mode competition in the designed gyrotron is studied using multifrequency time-dependent nonlinear theory. Simulations tracking five competition modes show that stable excitation of the desired operating mode TE19.3 at 100 kW level can be realized with proper choice of operating parameters.

Confocal gyrotron traveling-wave tube (gyro-TWT) is a novel gyrotron amplifier capable of operating in higher order modes while generating high power at the same time. So far, confocal gyro-TWT has been studied by MIT both in theory and experiment at 140 GHz. In this paper, a center frequency of 170-GHz $\mathrm{TE}_{06}$ -mode confocal gyro-TWT is designed theoretically, and it features high power and broadband capabilities. Theoretical investigation predicts that, when the magnetic injection gun is optimized to generate an electron beam of 65 kV, current of 7 A, with a pitch factor of 1.2, this gyro-TWT is of an excellent performance. At a given operating magnetic field of 6.11 T, with an input power of 10 W, a saturated gain of at least 30 dB, 3-dB bandwidth of over 4 GHz and highest efficiency of 17.1% are achieved.

A Denisov launcher operating at 420 GHz with TE17,4 mode is designed and optimized through theoretical analysis and numerical simulations. The launcher consists of a mode converted waveguide and a helical cut. Instead of using the conventional perturbations, a sinusoid type perturbation is used in this converted waveguide. Operations of the launcher are analyzed by the coupled mode theory. The field at the output aperture of the launcher has a nice Gaussian profile distribution. The conversion efficiency is more than 98.1 %. The parasitic modes in the launcher and the aperture field profile were analyzed. The wall field of the launcher is analyzed in case that the input wave is rotating left-hand. A full 3D electromagnetic field analysis of the integrated launcher has been done. The results are in good agreement with the numerical calculation results.

Confocal gyrotron traveling wave tube (gyro-TWT) is a novel gyrotron amplifier capable of operating in higher order modes while generating high power at the same time. Confocal gyro-TWT suppresses lower-order modes at the cost of reduction of efficiency. According to the characteristics of confocal system, in this paper, we theoretically design a special magnetron injection gun (MIG) for a 170 GHz confocal gyro-TWT, and then compare it with the traditional MIG. The efficiency is found to be as high as 33 %, deservedly higher than the traditional less than 10 %. The output power increases trebly accordingly.

The mode competition and beam wave interaction in a gradually tapered cavity are studied for achieving high efficiency of a 0.6-THz second harmonic (SH) gyrotron. In order to obtain high power and stable radiation, the TE32,5 mode is selected as the operating mode of the desired gyrotron to realize a single-mode oscillation. The issues of studying the high-order mode gyrotron are solved effectively by transforming the generalized telegraphist's equations. The efficiency and the output power of the gyrotron under different conditions have been calculated by the code, which is based on the transformed equations. The results show that a single-mode SH radiation with a power of over 100 kW at frequency of 0.6 THz could be achieved.

In this paper, a coaxial resonator with inner-outer corrugation is studied. By the surface impedance theory, its eigenequation is derived; by the energy balance equation, its ohmic quality factor is obtained. Research shows that for a coaxial resonator with outer, inner, and inner-outer corrugation, slot depth can influence eigenvalue, ohmic quality factor, and wall loading loss in comparison with coaxial smoothing resonator; in the region of eigencurve with positive slope, ohmic quality factor, and wall loading loss of outer slot bottom attain the minimum. However, wall loading loss of inner slot bottom attains the maximum and wall loading loss of inner slot bottom is larger than one of outer slot bottom. These results can help us to research mode selection and mode competition of coaxial resonator with inner-outer corrugation.