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With the advancement of terahertz band applications, extensive research has been conducted on terahertz devices. Terahertz band biosensors find widespread use in biomedical microdetection; however, predicting terahertz spectrum and designing structures pose complex and time-consuming challenges. This article proposes an efficient deep learning method for optimizing the design of terahertz metasurface biosensors. The method employs three neural networks, utilizing spectral response as an intermediary to effectively map customized performance indicators onto geometric structural parameters. Test results demonstrate that the proposed design scheme can generate suitable structural parameters based on the required frequency and bandwidth of the analyte. These output parameters were subsequently simulated and validated using electromagnetic simulation software, yielding results consistent with predictions. This method of using neural networks instead of electromagnetic simulation can be applied to the study of spectrum prediction and inverse design of terahertz devices, providing more possibilities for the future application of terahertz devices.

Abstract Background This project aimed to research the significance of THRIL in the diagnosis of benign and malignant solitary pulmonary nodules (SPNs) and to investigate the role of THRIL/miR-99a in malignant SPNs. Methods The study groups consisted of 169 patients with SPN and 74 healthy subjects. The differences in THRIL levels were compared between the two groups and the healthy group. The receiver operating characteristic curve (ROC) was utilized to analyze the THRIL’s significance in detecting benign and malignant SPN. Pearson correlation and binary regression coefficients represented the association between THRIL and SPN. CCK-8 assay, Transwell assay, and flow cytometry were utilized to detect the regulatory effect of THRIL silencing. The interaction between THRIL, miR-99a, and IGF1R was confirmed by the double luciferase reporter gene. Results There were differences in THRIL expression in the healthy group, benign SPN group, and malignant SPN group. High accuracy of THRIL in the diagnosis of benign SPN and malignant SPN was observed. THRIL was associated with the development of SPN. The expression of THRIL was upregulated and miR-99a was downregulated in lung cancer cells. The double luciferase report experiment confirmed the connections between THRIL/miR-99a/IGF1R. Silencing THRIL could suppress cell proliferation, migration, and invasion and promote cell apoptosis by binding miR-99a. Conclusion The detection of THRIL in serum is useful for the assessment of malignant SPN. THRIL can regulate the expression of IGF1R through miR-99a, thereby promoting the growth of lung cancer cells and inhibiting apoptosis.

When constructing hollow prestressed high-strength concrete (PHC) pipe piles in soft soil foundations, the generation and dissipation of pore water pressure can induce negative friction on the pile. This phenomenon increases the settlement of the pile foundation and, in severe cases, can lead to pile deflection and flotation. To further investigate the development characteristics of pore water pressure during PHC hollow pipe pile driving in soft soil, this study combined existing theories and numerical models to analyze the generation and influence areas of pore water pressure. Field tests were conducted at three different sites: an untreated site, a surcharge preloading site, and a site treated with cement mixing piles and well dewatering. These tests monitored and analyzed the horizontal and vertical development and behavior of pore water pressure during pile driving at each site. The results indicate that during the pile driving process, when the horizontal distance from the pile center is 3d and 9d, the peak values of the excess pore water pressure in the site treated with cement mixing piles and well dewatering are 117 kPa and 100 kPa. After pile driving is completed, they decrease to 50 kPa and 48 kPa, respectively. The peak values of excess pore water pressure in the surcharge preloading site are 122 kPa and 97 kPa, and after pile driving, they decreased to 80 kPa and 21 kPa, respectively. The peak values of excess pore water pressure in untreated sites are 140 kPa and 121 kPa; after pile driving, they decreased to 82 kPa and 60 kPa, respectively. Pore water pressure increases with the depth of pile driving and decreases with distance from the pile driving location. The peak pore water pressure and dissipation rate during construction were found to be higher at the untreated site compared to the other two sites. Therefore, during pile sinking in soft soil foundations, dewatering and driving drainage boards are effective methods for reducing pore water pressure and accelerating its dissipation. These findings provide a theoretical basis and technical support for ensuring the safety of engineering constructions.

Graves’ ophthalmopathy (GO) is a hyperthyroidism-related and immune-mediated disease that poses a significant threat to human health. The pathogenesis of GO primarily involves T cells, B cells, and fibroblasts, suggesting a pivotal role for the thyrotropin-antibody-immunocyte-fibroblast axis. Traditional treatment approaches for Graves’ disease (GD) or GO encompass antithyroid drugs (ATDs), radioactive iodine, and beta-blockers. However, despite decades of treatment, there has been limited improvement in the global incidence of GO. In recent years, promising therapies, including immunotherapy, have emerged as leading contenders, demonstrating substantial benefits in clinical trials by inhibiting the activation of immune cells like Th1 and B cells. Furthermore, the impact of diet, gut microbiota, and metabolites on GO regulation has been recognized, suggesting the potential of non-pharmaceutical interventions. Moreover, as traditional Chinese medicine (TCM) components have been extensively explored and have shown effective results in treating autoimmune diseases, remarkable progress has been achieved in managing GO with TCM. In this review, we elucidate the pathogenesis of GO, summarize current and prospective therapies for GO, and delve into the mechanisms and prospects of TCM in its treatment.

Abstract 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.

The gap plasmon resonance can generate a local enhanced electric field and make the electromagnetic field energy mostly confined in the microfluidic, thereby increasing the interaction between the detection sample and terahertz wave. In this paper, a five-layer microfluidic terahertz biosensor based on gap plasmon resonance is presented. The simulation results show that the designed biosensor can realize a resonant absorption peak with near-perfect absorption at the frequency of 0.655 THz and high refractive index sensitivity of 191.3 GHz/RIU. In addition, the biosensor possesses the characteristics of polarization insensitivity and 50° incidence angle insensitivity due to the symmetry of the metal metasurface, which make the biosensor can be widely used in the biological label-free detection, medical trace element detection.

Abstract 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.

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.

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.

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 conventional ultrasonic thickness measurement method is ineffective in detecting the measured specimen with a step change in thickness as it is easy to cause multimode acoustic mixing in the ultrasonic detection process. To solve this problem, this paper presented an electromagnetic acoustic resonance (EMAR) moving scan identification method based on a frequency–frequency energy density precipitation (FFEDP) algorithm, which uses a standing wave resonance mode to accurately extract step thickness information and employs the algorithm to separate step thickness information. According to the simulation results, the ratio of the highest energy density of the spectrum signal on both sides of the step area to the total energy density had an opposite linear change rule with the equidistant movement of the transducer coil. The thickness step area can be identified by analyzing the crossover point of the contrast value change. The experimental results showed that the proposed method can accurately extract the thickness information under millimeter-level stepping distance for sector-notched specimens with step surfaces of different thicknesses, and at the same time realize the effective identification of the step surface.

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.

Multiple compartments exist inside the composite bucket foundation (CBF), and each compartment can be adjusted individually to adjust air pressure. The CBF tilts and sinks because of environmental load during offshore transportation, and the differential air pressure between compartments produces unbalanced forces and deforms the bulkhead structure. Considering different influencing factors, the finite element calculation method was used to analyze the law of the allowable differential air pressure during offshore transportation. The results showed that the effect of differential air pressure on the deformation of the bulkhead is the key factor for controlling the differential air pressure. The maximum allowable differential air pressure increases linearly with increasing external draft and bulkhead thickness during the offshore transportation of the CBF and is more sensitive to the change in external draft. Finally, the optimal thickness of the bulkhead for different CBF conditions was obtained, providing technical support for engineering safety and economy. [ABSTRACT FROM AUTHOR]

This paper presents a design of a gyro‐TWT operating in the large‐orbit electron beam mode, with the aim of reducing the working magnetic field while ensuring operational efficiency. The periodic dielectric‐loaded structure, which has been successfully applied in the development of small‐orbit devices, is adopted as the high‐frequency interaction circuit. This paper conducts a comprehensive study and analysis of this structure and achieves stable operation in the Ka‐band after the optimization of the tube. This tube works at second harmonic of electron frequency in the mode of large‐orbit electron beam. The required magnetic field is only 5100 gauss, which can be generated using electromagnetic coils instead of superconducting magnets. The operational parameters include voltage of 75 kV, current of 9A, and velocity spread of 3.5%. Under these conditions, the device presents stable operation, with −3 dB bandwidth of 4.3 GHz, and maximum output power of 165 kW. This result meets the expected requirements for magnetic field and operational efficiency, thus validating the feasibility of practical fabrication of large‐orbit gyro‐TWT with periodic dielectric‐loaded structure. [ABSTRACT FROM AUTHOR]