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Aiming at the problems of low computing power and limited storage capacity of mobile terminals, a lightweight identity authentication protocol suitable for mobile edge computing environment is proposed. This protocol combines cryptography with the security protection technology of the physical layer. The system is a web software system based on the Internet network, which provides both teachers and students with the necessary network teaching environment and related tools for online teaching. To integrate the text, graphics, voice and video document systems required for the course, relying on Yu Classroom, Xuetangyun, Chuangao APP, WeChat group and other platforms to create "theoretical learning + live teaching + MOOC video + online Q&A" four the integrated teaching mode has achieved teachers' teaching, students' independent learning and multi-channel interaction between teachers and students.

Based on the research on the practical teaching system of ideological and political theory courses in physical education institutions, combined with the practices and experiences accumulated in the practical teaching of ideological and political theory courses in Harbin Institute of Physical Education in recent years, this paper attempts to propose the basic composition, innovative expansion, and operational guarantee of the practical teaching system of ideological and political theory courses in physical education institutions. It is expected to provide valuable reference for the construction and reform of practical teaching of ideological and political theory courses in national universities. The discipline of physical education itself has inherent advantages in ideological and political education work. However, the various problems that have permeated the existing teaching process also require substantive adjustments in the future education process, especially the connection between the current development status of physical education teaching in universities and future education work, which is the core content of the current situation.

Organic nitrates make an important contribution to the formation of secondary organic aerosols, but the formation mechanisms of organic nitrates are not fully understood at the molecular level. In the present work, we explore a new route for the formation of organic nitrates in the reaction of formaldehyde (HCHO) with nitric acid (HNO

Background Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC). Methods Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages. Results We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA)+ fibroblasts at the tumor invasive front positively correlated with the number of macrophages (MØs), but negatively correlated with that of tumor-infiltrating granzyme B+ immune cells, and CD4+ and CD8+ T cells. Spatial analyses uncovered a significant spatial interaction between α-SMA+ fibroblasts and CD163+ MØs in the TME, which resulted in spatially exclusive interactions to anti-tumor immune cells. We further validated the laminin and collagen signaling network contributions to TME remodeling. Moreover, compared with pTNM staging, a molecular prognostic model, based on expression of α-SMA+ fibroblasts at the invasive front, and CD163+ MØs, showed higher accuracy in predicting survival or recurrence in ESCC patients. Regression analysis confirmed this model is an independent predictor for survival, which also identifies a high-risk group of ESCC patients that can benefit from adjuvant therapy. Conclusions Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment.

Supplementary Materials and Methods

Supplementary Table S1-S4. Table S1. Correlation between expression of LOXL2 or its spliced isoform L2Δ13 and clinicopathological characteristics in ESCC patients of cohort 1 (n = 252). Table S2. Patient demographics and clinical characteristics for tissue microarray cohort 2 in ESCC (n = 135). Table S3. Multivariate Cox regression for overall survival and disease-free survival of ESCC patients (n = 252). Table S4. Interacting proteins associated with LOXL2 and L2Δ13 in KYSE150 ESCC cells identified by high-performance liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) analysis.

Supplementary Figure Legends

Lysyl oxidase-like 2 (LOXL2), a copper-dependent enzyme of the lysyl oxidase family and its nonsecreted, catalytically dead spliced isoform L2Δ13, enhance cell migration and invasion, stimulate filopodia formation, modulate the expression of cytoskeletal genes, and promote tumor development and metastasis in vivo. We previously showed that LOXL2 reorganizes the actin cytoskeleton in esophageal squamous cell carcinoma (ESCC) cells, however, the underlying molecular mechanisms were not identified. Here, using interactome analysis, we identified ezrin (EZR), fascin (FSCN1), heat shock protein beta-1 (HSPB1), and tropomodulin-3 (TMOD3) as actin-binding proteins that associate with cytoplasmic LOXL2, as well as with its L2Δ13 variant. High levels of LOXL2 and L2Δ13 and their cytoskeletal partners correlated with poor clinical outcome in patients with ESCC. To better understand the significance of these interactions, we focused on the interaction of LOXL2 with ezrin. Phosphorylation of ezrin at T567 was greatly reduced following depletion of LOXL2 and was enhanced following LOXL2/L2Δ13 reexpression. Furthermore, LOXL2 depletion inhibited the ability of ezrin to promote tumor progression. These results suggest that LOXL2-induced ezrin phosphorylation, which also requires PKCα, is critical for LOXL2-induced cytoskeletal reorganization that subsequently promotes tumor cell invasion and metastasis in ESCC. In summary, we have characterized a novel molecular mechanism that mediates, in part, the protumorigenic activity of LOXL2. These findings may enable the future development of therapeutic agents targeting cytoplasmic LOXL2.Significance:LOXL2 and its spliced isoform L2Δ13 promote cytoskeletal reorganization and invasion of esophageal cancer cells by interacting with cytoplasmic actin-binding proteins such as ezrin.

Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP.Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of −80, −120, −160, and −200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale.Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of −120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales.Conclusion: An NP of −120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.

Strong physically unclonable function (PUF) offers a promising solution to low-cost hardware identification and authentication for Internet of Things (IoT) applications. The continuous advancement of machine learning (ML) technology makes the PUF resilience to ML attacks a major design priority. This paper presents a robust and area-efficient strong PUF design with high ML attack resilience. The proposed PUF architecture based on inverter amplifiers operating in the subthreshold region achieves both low energy consumption and high supply and temperature scalability. The proposed nonlinearity topology effectively enhances PUF resilience to various ML attacks with low implementation area and cost. The proposed strong PUF design was designed and implemented using a 28-nm CMOS process. The measurement results show that the proposed PUF design achieves a nearly ideal ML attack resilience of 49.96 % with a small area of 239,857 F², and demonstrates a stable operation across a wide range of supply voltage from 0.5-1.4 V and temperature from -40-100 °C. This represents 3x improvement in area efficiency, 2.25x and 1.08x improvement in operating voltage and temperature range, respectively, compared to the state-of-the-art results.

BackgroundFatal infantile hypertonic myofibrillar myopathy (FIHMM) is an autosomal recessive hereditary disease characterized by amyotrophy, progressive flexion contracture and ankylosis of the trunk and limb muscles, apnea and respiratory failure, and increased creatine phosphate levels. It is caused by mutations in the CRYAB gene, and only around 18 cases including genetic mutations have been reported worldwide. All patients with FIHMM develop respiratory distress, progressive stiffness of the limbs, and have a poor prognosis. However, no effective treatment for CRYAB-associated respiratory failure has been reported. Here, we report a case of FIHMM with a novel heterozygous missense mutation.Case PresentationA 2-year-old female developed scoliosis of the lumbar spine and restrictive ventilatory dysfunction in infancy. She was admitted to the hospital with labored breathing on the third day after the second injection of inactivated poliomyelitis vaccine. Acute respiratory failure, pneumothorax, and cardiac arrest arose in the patient during hospitalization, and progressive stiffness of the trunk and limb muscles appeared, accompanied by obvious abdominal distension and an increase in phosphocreatine kinase levels. Screenings for genetic metabolic diseases in the blood and urine were normal. Electromyography revealed mild myogenic damage. A muscle biopsy indicated the accumulation of desmin, α-crystallin, and myotilin in the musculus biceps brachii, and dense granules were observed in muscle fibers using electron microscopy. Mutation analysis of CRYAB revealed a novel heterozygous missense mutation in the proband, c.302A > C (p.His101Pro) and c.3G > A (p.Met1Ile), which inherited from her asymptomatic, heterozygous carrier parents, respectively. The proband was finally diagnosed as FIHMM. One month after the FIHMM diagnosis, the child died of respiratory failure.ConclusionWe report a case of FIHMM with a novel heterozygous missense mutation of CRYAB. This finding might improve our understanding of FIHMM and highlight a novel mutation in the Chinese population.

The sulfur oxidation in mixed sodium thiosulfate/sucrose/aqueous micro-droplets by gaseous ozone is studied in this work via aerosol optical tweezers coupled with Ra- man spectroscopy, which can simultaneously determine various physicochemical proper- ties and the heterogeneous reaction kinetics of single optically trapped micro-droplets, allowing for elucidating their complicate interplay. According to the kinetics measure- ment results at different relative humidities, ozone concentrations and stoichiometries of inorganic and organic solutes, this work finds that a high aerosol ionic strength can accelerate the ozone oxidation of thiosulfate at air-water interfaces, while a high aerosol viscosity prolongs the reaction timescales due to diffusion-limited kinetics. The kinetic multilayer model of aerosol surface and bulk chemistry (KM-SUB) is utilized to inves- tigate the observed heterogeneous kinetics results and to retrieve the surface reaction rate coefficients. The KM-SUB simulations results indicate that the observed kinet- ics of sulfur oxidation in binary sodium thiosulfate aqueous micro-droplets with high ionic strengths is dominated by interfacial reactions, and the fitted surface reaction rate coefficients increase one order of magnitude when the droplet ionic strength increases around 40 M. Furthermore, this work demonstrated that including the effects of inter- facial ion depletion in the kinetics simulations can lead to an excellent agreement with the experimental results, implying its potential role in the interfacial kinetics.

Additional file 1. Multiple linear regression analysis showed that operative time and number of reloads correlated with surgical method.

Additional file 1: Fig. S1. Representative images showing the scoring process by the automated quantitative pathology imaging system. Fig. S2. Violin plots displaying the expression level of representative markers in each cell cluster. Fig. S3. Kaplan-Meier survival curves for total α-SMA+ CAFs, lamina propria α-SMA+ CAFs and stromal α-SMA+ CAFs in the generation (n=103) and validation (n=99) dataset of patients with ESCC. Fig. S4. The number of intratumoral macrophages correlates with clinical outcome in ESCC patients. Fig. S5. The density of CD68+ and CD163+ MØs correlates with clinical outcome in patients with ESCC. Fig. S6. Crucial cell-to-cell interaction pathways among the distinct cell populations predicted by CellChat. Fig. S7. Cell-to-cell communication among the CAFs and other cell types. Fig. S8. Differentially-expressed gene (DEG) enrichment analysis for α-SMA+ CAFs. Supplementary Table S1. The clinicopathological parameters of 11 patients profiled by scRNA-seq. Supplementary Table S2. Metal-conjugated antibodies and element-containing reagents used for IMC. Supplementary Table S3. Clinicopathological characteristics in the generation and validation dataset of patients with ESCC. Supplementary Table S4. Correlation between markers and clinicopathological characteristics in the generation and validation datasets. Supplementary Table S5. Differential expressed genes between α-SMA+ CAFs and α-SMA- CAFs. Supplementary Table S6. Univariate and multivariate analyses of factors associated with overall survival (OS) and disease-free survival (DFS) in the generation and validation datasets of patients with ESCC.

Human sparganosis is a food-borne parasitic disease caused by the plerocercoids of Spirometra species. Clinical diagnosis of sparganosis is crucial for effective treatment, thus it is important to identify sensitive and specific antigens of plerocercoids. The aim of the current study was to identify and characterize the immunogenic proteins of Spirometra erinaceieuropaei plerocercoids that were recognized by patient sera. Crude soluble extract of the plerocercoids were separated using 2-dimensional gel electrophoresis coupled with immunoblot and mass spectrometry analysis. Based on immunoblotting patterns and mass spectrometry results, 8 antigenic proteins were identified from the plerocercoid. Among the proteins, cysteine protease protein might be developed as an antigen for diagnosis of sparganosis.

The clinical efficacy of cisplatin in the treatment of esophageal squamous cell carcinoma (ESCC) is undesirable. Signal transducer and activator of transcription 3β (STAT3β), a splice variant of STAT3, restrains STAT3α activity and enhances chemosensitivity in ESCC. However, the underlying molecular mechanisms remain poorly understood. Here, we found that high expression of STAT3β contributes to cisplatin sensitivity and enhances Gasdermin E (GSDME) dependent pyroptosis in ESCC cells after exposure to cisplatin. Mechanistically, STAT3β was located into the mitochondria and its high expression disrupts the activity of the electron transport chain, resulting in an increase of ROS in cisplatin treatment cells. While high levels of ROS caused activation of caspase-3 and GSDME, and induced cell pyroptosis. STAT3β blocked the phosphorylation of STAT3α S727 in mitochondria by interacting with ERK1/2 following cisplatin treatment, disrupting electron transport chain and inducing activation of GSDME. Clinically, high expression of both STAT3β and GSDME was strongly associated with better overall survival and disease-free survival of ESCC patients. Overall, our study reveals that STAT3β sensitizes ESCC cells to cisplatin by disrupting mitochondrial electron transport chain and enhancing pyroptosis, which demonstrates the prognostic significance of STAT3β in ESCC therapy.

The purpose of this study was to investigate whether or not angiotensin II type 1 receptor blocker irbesartan (ARB) with a partial agonist of PPAR-γ could protect against chronic nocturnal intermittent hypoxia (CIH)–induced cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis. Sprague–Dawley rats were in a normoxic control group (CON-G), or rats were in a chronic nocturnal intermittent hypoxia group (HP-G, from 3 to 7% oxygen versus 21% oxygen per forty seconds cycle, nocturnally 8 h per day for 1 month), or rats were in a chronic nocturnal intermittent hypoxia group pretreated with ARB (50 mg/kg/day, S.C.) (ARB-HP-G). Echocardiography, H&E staining, TUNEL staining, and Western blotting were measured in the left ventricle. Hypoxia-induced SIRT1 degradation, Fas receptors, FADD, active caspase-8 and caspase-3 (Fas/FasL apoptotic pathway) and Bax, tBid, active caspase-9 and -3 (mitochondrial apoptotic pathway) and TUNEL-positive apoptosis were reduced in ARB-HP-G when compared with HP-G. IGF-I, IGF1 receptor, p-PI3k, p-Akt, Bcl2, and Bcl-XL (IGF1/PI3K/AKT pro-survival pathway) were increased in ARB-HP-G compared to HP-G. Our findings suggest that the ARB may prevent cardiac Fas/FasL to mitochondrial apoptotic pathways and enhance cardiac IGF1/PI3K/AKT pro-survival pathway in the sleep apnea model associated with JNK de-activation and SIRT1 upregulation. ARB prevents chronic sleep apnea–enhanced cardiac apoptosis via enhancing survival pathways.

Since the rise of E-commerce companies and many other web services, the applications of recommender systems have been adopted more broadly than ever before. Although collaborative filtering is the most well-known approach which utilizes customer’s preference to discover their interest, the problems of data sparsity and similarities selection still exist in it. Thus, this study intends to propose a hybrid metaheuristic with perturbation-based K-nearest neighbors and densest imputation for collaborative filtering (KDI-KNN) algorithm to reduce the effects of data sparsity. A similarities union function is proposed to determine the fittest similarity and enhance the prediction performance. Eventually, the experimental results indicate that hybrid metaheuristics with perturbation-based KDI-KNN algorithms are superior to basic KNN, original KDI-KNN, and most single metaheuristic-based KDI-KNN. In addition, a real-world dataset, fund transaction dataset is adopted in the case study. The analysis reveals that the similarity is seriously affected by the different content of the dataset.

Angiostrongylus cantonensis constitutes a major etiologic agent of eosinophilic meningoencephalitis. The detection methods for angiostrongyliasis mainly depend on morphology or immunology. A firmer diagnosis could be reached by directly detecting the parasite in the cerebrospinal fluid or through laboratory assays that are specific for Angiostrongylus-induced antibodies or the parasite's DNA. A. cantonensis detection could be carried out by larva release from the tissue upon pepsin digestion. However, the procedure requires live mollusks, which might complicate the analysis of large amounts of samples. Since morphological assays are limited, multiple molecular techniques have been put forward for detecting A. cantonensis, including PCR amplification of targets followed by fragment length or DNA sequence analysis. This allows rapid and accurate identification of A. cantonensis for efficient infection management and epidemiological purposes. In this study, we reviewed the current methods, concepts, and applications of molecular approaches to better understand the genetic characterization, molecular detection methods, and practical application of molecular detection in A. cantonensis.

A field experiment was carried out to study the effects of winter cover cropping on soil greenhouse gas emissions in dryland maize. Four cover crop treatments, namely oat, lentil, a mixture of oat and lentil, and no cover crops (CK), were included during the winter fallow period. Greenhouse gas emission fluxes from soil were measured using the static chamber-gas chromatograph technique. The results showed that:both soil CO

It is controversial whether angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) have a potentially beneficial role in the respiratory system. This study investigated the association between ACEI/ARB medications and respiratory-related mortality in hypertensive patients in a real-world nationally representative cohort.This was a retrospective analysis based on a prospective cohort study. A total of 10,530 patients with hypertension aged ≥ 20 years were included. The data was extracted from the US National Health and Nutrition Examination Survey during 1988-1994 and 1999-2006. The study was approved by the Institutional Review Boards. Moreover, inform concent was taken form all the participants.Overall, 27.7% (We discovered no significant link between ACEI or ARB medication and pulmonary-related mortality in hypertensive patients. In hypertensive patients, standard ACEI/ARB administration may have little effect on the respiratory system.

ImportanceTo optimize the integration of artificial intelligence (AI) decision aids and reduce workload in thyroid nodule management, it is critical to incorporate personalized AI into the decision-making processes of radiologists with varying levels of expertise.ObjectiveTo develop an optimized integration of AI decision aids for reducing radiologists’ workload while maintaining diagnostic performance compared with traditional AI-assisted strategy.Design, Setting, and ParticipantsIn this diagnostic study, a retrospective set of 1754 ultrasonographic images of 1048 patients with 1754 thyroid nodules from July 1, 2018, to July 31, 2019, was used to build an optimized strategy based on how 16 junior and senior radiologists incorporated AI-assisted diagnosis results with different image features. In the prospective set of this diagnostic study, 300 ultrasonographic images of 268 patients with 300 thyroid nodules from May 1 to December 31, 2021, were used to compare the optimized strategy with the traditional all-AI strategy in terms of diagnostic performance and workload reduction. Data analyses were completed in September 2022.Main Outcomes and MeasuresThe retrospective set of images was used to develop an optimized integration of AI decision aids for junior and senior radiologists based on the selection of AI-assisted significant or nonsignificant features. In the prospective set of images, the diagnostic performance, time-based cost, and assisted diagnosis were compared between the optimized strategy and the traditional all-AI strategy.ResultsThe retrospective set included 1754 ultrasonographic images from 1048 patients (mean [SD] age, 42.1 [13.2] years; 749 women [71.5%]) with 1754 thyroid nodules (mean [SD] size, 16.4 [10.6] mm); 748 nodules (42.6%) were benign, and 1006 (57.4%) were malignant. The prospective set included 300 ultrasonographic images from 268 patients (mean [SD] age, 41.7 [14.1] years; 194 women [72.4%]) with 300 thyroid nodules (mean [SD] size, 17.2 [6.8] mm); 125 nodules (41.7%) were benign, and 175 (58.3%) were malignant. For junior radiologists, the ultrasonographic features that were not improved by AI assistance included cystic or almost completely cystic nodules, anechoic nodules, spongiform nodules, and nodules smaller than 5 mm, whereas for senior radiologists the features that were not improved by AI assistance were cystic or almost completely cystic nodules, anechoic nodules, spongiform nodules, very hypoechoic nodules, nodules taller than wide, lobulated or irregular nodules, and extrathyroidal extension. Compared with the traditional all-AI strategy, the optimized strategy was associated with increased mean task completion times for junior radiologists (reader 11, from 15.2 seconds [95% CI, 13.2-17.2 seconds] to 19.4 seconds [95% CI, 15.6-23.3 seconds]; reader 12, from 12.7 seconds [95% CI, 11.4-13.9 seconds] to 15.6 seconds [95% CI, 13.6-17.7 seconds]), but shorter times for senior radiologists (reader 14, from 19.4 seconds [95% CI, 18.1-20.7 seconds] to 16.8 seconds [95% CI, 15.3-18.3 seconds]; reader 16, from 12.5 seconds [95% CI, 12.1-12.9 seconds] to 10.0 seconds [95% CI, 9.5-10.5 seconds]). There was no significant difference in sensitivity (range, 91%-100%) or specificity (range, 94%-98%) between the 2 strategies for readers 11 to 16.Conclusions and RelevanceThis diagnostic study suggests that an optimized AI strategy in thyroid nodule management may reduce diagnostic time-based costs without sacrificing diagnostic accuracy for senior radiologists, while the traditional all-AI strategy may still be more beneficial for junior radiologists.

Clinical studies have shown that dapagliflozin can reduce cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM), but the exact mechanism is unclear. In this study, we used the molecular docking and network pharmacology methods to explore the potential mechanism of dapagliflozin on T2DM complicated with cardiovascular diseases (CVD). Dapagliflozin's potential targets were predicted via the Swiss Target Prediction platform. The pathogenic targets of T2DM and CVD were screened by the Online Mendelian Inheritance in Man (OMIM) and Gene Cards databases. The common targets of dapagliflozin, T2DM and CVD were used to establish a protein‐protein interaction (PPI) network; the potential protein functional modules in the PPI network were found out by MCODE. Metascape tool was used for Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A potential protein functional module with the best score was obtained from the PPI network and 9 targets in the protein functional module all showed good binding properties when docking with dapagliflozin. The results of KEGG pathway enrichment analysis showed that the underlying mechanism mainly involved AGE‐RAGE signalling pathway in diabetic complications, TNF signalling pathway and MAPK signalling pathway. Significantly, the MAPK signalling pathway was considered as the key pathway. In conclusion, we speculated that dapagliflozin played a therapeutic role in T2DM complicated with CVD mainly through MAPK signalling pathway. This study preliminarily reveals the possible mechanism of dapagliflozin in the treatment of T2DM complicated with CVD and provides a theoretical basis for future clinical research.

Objectives An increase in the incidence of congenital hypothyroidism (CH) with eutopic gland has been reported worldwide due to neonatal screening programs. In this study, we aimed to determine the prevalence of transient CH (TCH) and to investigate predictive factors that could distinguish between permanent and transient CH in patients with eutopic thyroid glands. Methods We retrospectively reviewed 508 children treated for CH with eutopic thyroid glands between June 1998 and June 2020 in Jiangxi Newborn Screening Center. All patients were treated with levothyroxine and underwent Diagnostic re-evaluation after 2–3 years of age. Patients were classified as having TCH or permanent CH (PCH) during follow-up. Results Of the 508 patients initially treated for CH with a normally located gland, 335 patients (65.9%) were classified in the TCH group and 173 (34.1%) in the PCH group based on the defined criteria. Multivariate analysis revealed that TCH was associated with a lower levothyroxine dose at 24 months of age (p Conclusions TCH presents a significant portion of patients with CH. The levothyroxine dose requirement at 24 months of age has a predictive role in differentiating TCH from PCH in CH patients with eutopic thyroid glands.

Passive daytime radiative cooling (PDRC) involves cooling down an object by simultaneously reflecting sunlight and thermally radiating heat to the cold outer space through the Earth's atmospheric window. However, for practical applications, current PDRC materials are facing unprecedented challenges such as complicated and expensive fabrication approaches and performance degradation arising from surface contamination. Herein, we develop scalable cellulose-fiber-based composites with excellent self-cleaning and self-cooling capabilities, through air-spraying ethanolic poly(tetrafluoroethylene) (PTFE) microparticle suspensions embedded partially within the microsized pores of the cellulose fiber to form a dual-layered structure with PTFE particles atop the paper. The formed superhydrophobic PTFE coating not only protects the cellulose-fiber-based paper from water wetting and dust contamination for real-life applications but also reinforces its solar reflectivity by sunlight backscattering. It results in a subambient cooling performance of 5 °C under a solar irradiance of 834 W/m2 and a radiative cooling power of 104 W/m2 under a solar intensity of 671 W/m2. The self-cleaning surface of composites maintains their good cooling performance for outdoor applications, and the recyclability of the composites extends their life span after one life cycle. Additionally, dyed cellulose-fiber-based paper can absorb appropriate visible wavelengths to display specific colors and effectively reflect near-infrared lights to reduce solar heating, which synchronously achieves effective radiative cooling and esthetic varieties.

To make preliminary exploration into the Golgi apparatus targeting of chondroitin sulfate-modified micelles (CSmicelles) co-loaded with pirarubicin (THP) and vinorelbine (VRL) in tumor cells, as well as theirThe cellular uptake efficiency and internalization mechanism of CSmicelles in 4T1 mouse breast cancer cell line were investigated by flow cytometry. Preliminary study of the Golgi apparatus targeting CSmicelles in tumor cells was conducted by co-localization experiment. Then, the effect of CSmicelles co-loaded with THP and VRL (THP+VTL-CSmicelles) on the structure of Golgi apparatus was investigated by GM130 immunofluorescence experiment. Finally, theIt was found that CSmicelles could significantly increase cellular uptake of drugs. CSmicelles were internalized into cells through clathrin-mediated and caveolin-mediated endocytosis, which was energy-dependent active transport and exhibited substantial ability of targeting Golgi apparatus in tumor cells. THP+VTL-CSmicelles could break down the structure of Golgi apparatus and significantly inhibit the migration and invasion of tumor cells.THP+VTL-CSmicelles demonstrate high affinity towards Golgi apparatus in tumor cells, exert targeted effects and inhibit tumor cell metastasis, which provides a novel idea and method for the treatment of cancer metastasis.

Objective To improve the understanding and diagnostic accuracy of pulmonary mucoepidermoid carcinoma(PMEC) by analyzing the imaging and clinical characteristics.Methods The clinical and CT data of 27 cases of PMEC confirmed by histopathology in the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020 were retrospectively analyzed,including the location,size,margin,density,enhancement characteristics,accompanying signs,and pathological grade.Results The 27 cases included 6(6/27,22.2%) of large airway type,14(14/27,51.9%) of hilar type,and 7(7/27,26.9%) of peripheral type.The CT manifestations of 20 cases of large airway and hilar PMEC were soft-tissue nodules or mass with clear boundary in the lumen of the trachea and main bronchi,including 6 cases of mild enhancement,4 cases of moderate enhancement,5 cases of marked enhancement,and 5 cases of uneven enhancement.Three of the 20 cases showed calcification.The 7 cases of peripheral PMEC showed soft-tissue nodules or masses in the lungs,including 3 cases of mild enhancement,1 case of moderate enhancement,and 3 cases of marked enhancement. Obstructive pneumonia or atelectasis and bronchiectasis with mucus plug formation occurred in 16(16/27,59.3%) cases,lymph node metastasis in 9(9/27,33.3%) cases,and multiple organ metastasis in 8(8/27,29.6%) cases.Age(

A 100 kW solid target was successfully developed for the CSNS phase one. Tungsten was selected as the CSNS target material and a layer of tantalum with a thickness of only 0.3mm as a protective layer. Eleven target blocks were fixed in parallel in a stainless steel target container with 1.2mm gap between each block. Using a specially designed spreader, the target plug can be easily replaced. The parameters of the target were stable and normal in the course of more than a year of operation, the temperature rise of the target cooling water inlet and outlet increased as the proton beam power increased.

AIM: To evaluate the driving performance in young and middle-aged Chinese glaucoma patients with mild to severe visual field loss compared to those without glaucoma by using a driving simulation test. METHODS: Twenty-nine participants were included in this study: nine patients with glaucoma but pass the binocular Esterman visual field test, ten patients with glaucoma and fail the binocular Esterman visual field test, and ten age-matched healthy controls. A driving simulation test was designed as a frequency-based analysis of a lane-keeping task. The total performance error, the control-response amplitude and delay were calculated. RESULTS: Esterman visual field test fail group showed the longest delay of control-response among three groups (P=0.02). And the delay in lane-keeping task was significantly associated with inferior field of better-eye (r=0.51, P=0.004) and integrated visual field (r=0.55, P=0.002). CONCLUSION: Young and middle-aged glaucoma patients with binocular visual field loss suffered from a longer delay of response in driving simulation test, while inferior visual field having more impact than superior visual field.

Herein, a highly active Mott–Schottky nanocatalyst with tunable Schottky barrier was constructed by embedding Co nanoparticles (NPs) into phosphorus-doped graphitic carbon nitrides (PxCN) for the enhanced dehydrogenation of ammonia-borane (AB). Analyses show that P doping can efficiently decrease the work function of g-C3N4 and elevate the conduction band edge potential; thus, P doping offers a simple approach to tune the Schottky barrier of Co/PxCN by varying the doping amount of P atoms. Upon rationally tuning the Schottky barrier from 0.60 to 0.78 eV, the obtained photocatalyst with the molar composition Co/P3.59CN showed a remarkable TOF (total turnover frequency) value of 67.09 mol H2 per mol metal per min for the dehydrogenation of AB under visible light at 298 K, which, to the best of our knowledge, is one of the highest values reported to date for non-noble metal-based monometallic catalysts and is even comparable to those of some noble metal catalysts. This study opens a new prospect for the rational design and preparation of metal/g-C3N4 nanocatalysts with tunable Schottky barriers and provides a simple way to elevate the catalytic activity of these nanocatalysts.

BACKGROUND The variability of metabolic biomarkers has been determined to provide incremental prognosis information, but the implications of electrolyte variability remained unclear. METHODS We investigate the relationships between electrolyte fluctuation and outcomes in survivors of acute myocardial infarction (n = 4386). Ion variability was calculated as the coefficient of variation, standard deviation, variability independent of the mean (VIM) and range. Hazard ratios (HR) were estimated using the multivariable-adjusted Cox proportional regression method. RESULTS During a median follow-up of 12 months, 161 (3.7%) patients died, and heart failure occurred in 550 (12.5%) participants after discharge, respectively. Compared with the bottom quartile, the highest quartile potassium VIM was associated with increased risks of all-cause mortality (HR = 2.35, 95% CI: 1.36–4.06) and heart failure (HR = 1.32, 95% CI: 1.01–1.72) independent of cardiac troponin I (cTnI), N terminal pro B type natriuretic peptide (NT-proBNP), infarction site, mean potassium and other traditional factors, while those associations across sodium VIM quartiles were insignificant. Similar trend remains across the strata of variability by other three indices. These associations were consistent after excluding patients with any extreme electrolyte value and diuretic use. CONCLUSIONS Higher potassium variability but not sodium variability was associated with adverse outcomes post-infarction. Our findings highlight that potassium variability remains a robust risk factor for mortality regardless of clinical dysnatraemia and dyskalaemia.

Parylene C (PC) films have been widely used in many fields, such as metal anti-corrosion, electronic packaging, etc. However, the relatively poor mechanical properties and the deteriorated water barrier performance due to the easy fracture under external stress have restricted their application. It is a relatively simple and good method to maintain the water vapor barrier and enhance the mechanical properties of PC film by covering a flexible coating on its surface. In this work, a new polyurethane acrylate (PUA) coating was prepared and coated on the PC film by ultraviolet curing technology to form the PC/PUA composite film. The results showed that the PUA coatings could improve the water vapor barrier and mechanical properties of the PC film simultaneously. The water vapor transmittance rate was reduced from 1.1791 g·(m−2·day−1) of the original PC film to 0.5636 g·(m−2·day−1) of the PC/PUA composite film. The elongation at break and the impact energy were increased to 48.36% and 41.67%, respectively, which would widen the application of PC films in the fields of flexible electronics or smart wear.

An efficient synthetic method has been developed for the synthesis of 2'-deoxyguanosine from the more commercially available 2'-deoxyadenosine

Background and Purpose: Atrial metabolic remodeling plays a critical role in the pathogenesis of atrial fibrillation (AF). Sirtuin3 (Sirt3) plays an important role in energy homeostasis. However, the effect of Sirt3 agonist Honokiol (HL) on AF is unclear. Therefore, the aim of this study is to determine the effect of HL on atrial metabolic remodeling in AF and to explore possible mechanisms.Experimental Approach: irt3 and glycogen deposition in left atria of AF patients were examined. Twenty-one rabbits were divided into sham, P (pacing for 3 weeks), P + H treatment (honokiol injected with pacing for 3 weeks). The HL-1 cells were subjected to rapid pacing at 5 Hz for 24 h, in the presence or absence of HL and overexpression or siRNA of Sirt3 by transfection. Metabolic factors, circulating metabolites, atrial electrophysiology, ATP level, and glycogens deposition were detected. Acetylated protein and activity of its enzymes were detected.Key Results: Sirt3 was significantly down-regulated in AF patients and rabbit/HL-1cell model, resulting in the abnormal expression of its downstream metabolic key factors, which were significantly restored by HL. Meanwhile, AF induced an increase of the acetylation level in long-chain acyl-CoA dehydrogenase (LCAD), AceCS2 and GDH, following decreasing of activity of it enzymes, resulting in abnormal alterations of metabolites and reducing of ATP, which was inhibited by HL. The Sirt3 could regulate acetylated modification of key metabolic enzymes, and the increase of Sirt3 rescued AF induced atrial metabolic remodeling.Conclusion and Implications: HL inhibited atrial metabolic remodeling in AF via the Sirt3 pathway. The present study may provide a novel therapeutical strategy for AF.

BackgroundWhether women have a higher risk of adverse events compared with men following coronary angiography (CAG) and percutaneous coronary intervention (PCI) remains controversial. We aimed to investigate the sex differences in characteristics, treatments and outcomes among patients undergoing CAG and PCI in a large Chinese cohort.MethodsWe analyzed patients undergoing CAG and/or PCI in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Clinical characteristics, treatment (discharge medication and PCI) and in-hospital outcomes (mortality and major bleeding) were compared between women and men.ResultsTotally 141,459 patients underwent CAG (44,362 [31.4%] women), of which 69,345 patients underwent PCI (15,376 [22.2%] women). Women were older (64.4 vs. 60.8 years), had more chronic comorbidities and lower PCI rate for stable coronary artery disease (CAD) than men (52.8 vs. 64.2%). Women received less CAG and PCI procedures. Among women undergoing PCI they received similar discharge medication treatment. In addition, women undergoing PCI had mildly lower rate of major bleeding (0.2 vs. 0.3%, P = 0.033) but higher in-hospital mortality (1.2 vs. 0.8%, P < 0.001). After adjustment, women had a higher risk in the major bleeding (adjusted odds ratio, 2.04 [95% CI: 1.07 to 3.62]), and the in-hospital mortality (adjusted odds ratio, 1.87 [95% CI: 1.36 to 2.56]).ConclusionAmong our Chinese cohort, women are older with more chronic comorbidities, receiving less PCI procedure and similar discharge medication treatment. Women have nearly 90% higher risk of in-hospital mortality and over 1-fold increased risk of major bleeding after PCI compared with men.

Esophageal squamous cell carcinoma (ESCC) is one of the world’s leading causes of death, and its primary clinical therapy relies on surgical resection, chemotherapy, radiotherapy, and chemoradiotherapy. Although the genomic features and clinical significance of ESCC have been identified, the outcomes of targeted therapies are still unsatisfactory. Here, we demonstrate that mitogen-activated protein kinase (MAPK) signaling is highly activated and associated with poor prognosis in patients with ESCC. Mitogen-activated protein kinase kinase (MEK) inhibitors efficiently blocked the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in ESCC, while signal transducer and activator of transcription 3 (STAT3) signaling was rapidly activated. Combined STAT3 inhibition prevented the emergence of resistance and enhanced MEK inhibitor-induced cell cycle arrest and senescence in vitro and in vivo. Mechanistic studies revealed that the suppressor of cytokine signaling 3 (SOCS3) was downregulated, resulting in an increase in STAT3 phosphorylation in MEK-inhibited cells. Furthermore, chromatin immunoprecipitation showed that ELK1, which was activated by MEK/ERK signaling, induced SOCS3 transcription. These data suggest that the development of combined MEK and STAT3 inhibition could be a useful strategy in ESCC targeted therapy.

Acute liver failure (ALF) is a fatal liver disease characterized by severe hepatocyte destruction. MicroRNAs (miRNAs/miRs) have been reported to serve a key role in a number of liver diseases. Therefore, the aim of the present study was to investigate the role and underlying mechanism of miR‑214 in ALF. ALF murine and hepatocyte models were established using D‑galactosamine (D‑GalN) and lipopolysaccharide (LPS) or D‑GalN + tumor necrosis factor (TNF)‑α, respectively. The expression levels of miR‑214 and Bax were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and/or western blotting. Furthermore, an automatic biochemical analyzer was used to measure the levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT). The levels of TNF‑α and interleukin (IL)‑6 were detected by ELISA and RT‑qPCR. In addition, TUNEL staining and flow cytometry were used to analyze cell apoptosis, and the protein expression of caspase‑3 was determined by western blotting. It was identified that the levels of AST and ALT were increased and that hepatocyte apoptosis was enhanced in the D‑GalN/LPS‑stimulated group compared with the control. Furthermore, higher expression of caspase‑3 was observed in the D‑GalN/LPS‑stimulated group. In addition, it was demonstrated that miR‑214 was downregulated, while Bax was upregulated in D‑GalN/LPS‑stimulated mice and D‑GalN/TNF‑α‑stimulated BNLCL2 cells. Moreover, in D‑GalN/TNF‑α‑stimulated BNLCL2 cells, miR‑214 overexpression suppressed apoptosis and decreased TNF‑α and IL‑6 levels, and these effects were reversed by the Bax plasmid. It was also identified that overexpression of miR‑214 significantly decreased Bax mRNA and protein expression levels in vitro. Collectively, the present results suggested that miR‑214 inhibited hepatocyte apoptosis during ALF development via targeting Bax, thus indicating that miR‑214 may be a potential target for ALF treatment.

The role of androgen receptor (AR) in breast cancer has been unveiled in succession for the past few years. In this study, we conducted a comprehensive analysis based on four online public databases of data from many previous studies. We found that the expression of AR is significantly related to age, histological grade, and subtype but not to lymph node status. The low expression level of AR is strongly associated with poor recurrence-free survival, especially with poor distance metastasis-free survival in luminal A patients, but inverse in HER2 (human epidermal growth factor receptor-2) enriched patients. AR might be a biomarker of chemosensitivity in the basal subtype. Besides, the expression of melanophilin (MLPH) is distinctly in accordance with that of AR. AR could play diverse roles in different subtypes of breast cancer.

Background. Shear stress is an effective modulator of endothelial progenitor cells (EPCs) and has been suggested to play an important role in angiogenesis. The phosphatase and tensin homolog (PTEN)/Akt and guanosine triphosphate cyclohydrolase (GTPCH)/tetrahydrobiopterin (BH4) pathways regulate the function of early EPCs. However, the role of these pathways in the shear stress-induced angiogenesis of late EPCs remains poorly understood. Therefore, we aim to investigate whether shear stress could upregulate the angiogenesis capacity of late EPCs and to further explore the possible underlying mechanisms. Methods. Late EPCs were subjected to laminar shear stress (LSS), and their in vitro migration, proliferation, and tube formation capacity were determined. In addition, the in vivo angiogenesis capacity was explored, along with the expression of molecules involved in the PTEN/Akt and GTPCH/BH4 pathways. Results. LSS elevated the in vitro activities of late EPCs, which were accompanied by downregulated PTEN expression, accelerated Akt phosphorylation, and GTPCH/BH4 pathway activation (all P<0.05). Following Akt inhibition, LSS-induced upregulated GTPCH expression, BH4, and NO level of EPCs were suppressed. LSS significantly improved the migration, proliferation, and tube formation ability (15 dyn/cm2 LSS vs. stationary: 72.2±5.5 vs. 47.3±7.3, 0.517±0.05 vs. 0.367±0.038, and 1.664±0.315 vs. 1±0, respectively; all P<0.05) along with the in vivo angiogenesis capacity of late EPCs, contributing to the recovery of limb ischemia. These effects were also blocked by Akt inhibition or GTPCH knockdown (P<0.05, respectively). Conclusions. This study provides the first evidence that shear stress triggers angiogenesis in late EPCs via the PTEN/Akt/GTPCH/BH4 pathway, providing a potential nonpharmacologic therapeutic strategy for promoting angiogenesis in ischemia-related diseases.

Background/Aims. Sexual differences exist in endothelial progenitor cells (EPCs), and various cardiovascular risk factors are associated with the preservation of endothelial function in premenopausal women. However, it is unclear whether differences in endothelial function and circulating EPCs exist between overweight premenopausal women and age-matched men. Methods. We compared EPC counting and functions in normal-weight and overweight premenopausal women and men, evaluated endothelial function in each group, and detected the expression of the guanosine triphosphate cyclohydrolase I (GTPCH I) pathway. Results. The number of EPCs was lower in the male group than in the female group, regardless of normal-weight or overweight status, and there was no significant difference between the different weight groups among females or males. Endothelial function and EPC migration and proliferation were preserved in overweight premenopausal women compared with overweight men as were nitric oxide (NO) levels in plasma and secreted by EPCs. Endothelial function, the circulating EPC population, and NO levels were not different between normal-weight and overweight premenopausal women. Flow-mediated dilatation was significantly correlated with EPC function, plasma NO levels, and EPC-secreted NO. Conclusions. This investigation provides the first evidence for sex-based differences in EPC activity and endothelial function in overweight middle-aged individuals; these differences are associated with alterations in NO production and may partly occur through downregulation of the GTPCH I pathway. The present results provide new insights into the mechanism underlying the preserved endothelial function in overweight premenopausal women and may uncover a potential therapeutic target for endothelial repair in overweight population.

The medicinal plant Rhodiola crenulata grows at high altitudes in the Arctic and mountainous regions and is commonly used in phytotherapy in Eastern European and Asian countries. In the present study, we investigated the anti-apoptotic effect of Rhodiola crenulata and its neuroprotective mechanism of action in a rat model of D-galactose-induced aging. Two groups of twelve-week-old male Wistar rats received a daily injection of D-galactose (150[Formula: see text]mg/kg/day, i.p.) and orally administered Rhodiola crenulata (0, 248[Formula: see text]mg/kg/day) for eight weeks, while a control group received a saline injection (1[Formula: see text]ml/kg/day, i.p.). We examined apoptosis in the cortex and hippocampus of three groups of rats based on a terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) positive assay. The expression levels of apoptotic and anti-apoptotic proteins in excised brains were analyzed by Western blotting. Our findings indicated that D-galactose caused marked neuronal apoptosis via activation of both extrinsic-dependent and mitochondrial-dependent apoptotic pathways. When compared to the control group, the protein levels of Fas receptor, Fas ligand, Fas-associated death domain (FADD), and activated caspase-8 (Fas-dependent apoptotic pathways), as well as those of t-Bid, Bax, cytochrome [Formula: see text], activated caspase-9, and activated caspase-3 (mitochondrial-dependent apoptotic pathways), were significantly increased in the D-galactose treated group. In addition, D-galactose impaired the phosphorylation of PI3K/Akt, an important survival signaling event in neurons. Rhodiola crenulata, however, protected against all these neurotoxicities in aging brains. The present study suggests that neuronal survival promoted by Rhodiola crenulata may be a potentially effective method to enhance the resistance of neurons to age-related disorders.