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Abstract Objectives The study aimed to investigate the interaction of intraoperative stress hyperglycemia with monocyte functions and their impact on major adverse events (MAEs) in acute aortic dissection (AAD) patients who underwent open repair surgery. Methods A total of 321 adults who underwent open surgery for AAD at two tertiary medical centers in China were enrolled in the study. The primary endpoint was defined as the incidence and characteristics of perioperative stress hyperglycemia. The secondary endpoints included the incidence of postoperative MAEs, postoperative monocyte counts and inflammatory cytokine expression. Multi-logistic, linear regression and receiver operating characteristic (ROC) curve analyses were used to establish relationships between intraoperative time-weighted average glucose (TWAG), day-one postoperative monocyte counts, serum inflammatory cytokines and postoperative outcomes. In addition, in vitro experiments were conducted to evaluate changes in the inflammatory features of monocytes under high glucose conditions. Results Intraoperative hyperglycemia, as indicated by a TWAG level over 142 mg/dL, was associated with elevated postoperative monocyte counts and inflammatory cytokines, which correlated with extended intensive care unit (ICU) stays and worsened outcomes. In vitro, high glucose treatment induced mitochondrial impairment in monocytes, increased the release of inflammatory cytokines and the proportion of classical monocytes from AAD patients. Conclusions Intraoperative stress hyperglycemia, in combination with day-one postoperative monocyte counts, were clinically significant for predicting adverse outcomes in AAD patients undergoing open repair surgery. Elevated glucose concentrations shaped the inflammatory features of monocytes in AAD by impairing mitochondrial functions. Graphical abstract High glucose-driven mitochondrial functional impairment mediates a more pronounced monocytic inflammatory state in Stanford type-A AAD.

BackgroundAnoikis is intricately associated with the malignant progression of cancer. Thyroid cancer (THCA) is the most common endocrine tumor, metastasis is closely related to treatment response and prognosis of THCA. Hence, it is imperative to comprehensively identify predictive prognostic genes and novel molecular targets for effective THCA therapy.MethodsDifferential expression analysis and weighted gene co-expression network analysis (WGCNA) were utilized to mine differentially expressed anoikis-related (DE-ARGs). Then, the prognostic genes were identified and a risk signature was constructed for THCA using univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) method. Furthermore, the associations between risk signature and immune infiltration, immunotherapy, as well as potential mechanisms of action were determined using multiple R packages and Wilcoxon test. Finally, Mendelian randomized (MR) analysis was conducted to investigate the causal relationship between the prognostic genes and THCA.ResultsIn total, six prognostic genes (LRRC75A, METTL7B, ADRA1B, TPD52L1, TNFRSF10C, and CXCL8) related to anoikis were identified, and the corresponding risk signature were constructed to assess the survival time of THCA patients. Immunocorrelation analysis demonstrated the anoikis-relevant risk signature could be used to evaluate immunotherapy effects in THCA patients, and the infiltration of immune cells was correlated with the degree of risk in THCA patients. According to two-sample MR analysis, there was the significant causal relationship between CXCL8 and THCA (odds ratio [OR] > 1 & p< 0.05), and the increase of its gene expression would lead to an increased risk of THCA. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) confirmed the upregulated expression patterns of these prognostic genes in THCA tissues.ConclusionIn conclusion, we constructed the risk signature related to anoikis for THCA, which might have important clinical significance for improving the quality of life and treatment effect of THCA patients.

ObjectiveIn this study, the impact of inhibiting the PI3K/AKT/NF-κB pathway on lung oxidative damage induced by Echinococcus granulosus cyst fluid was investigated.MethodsTwenty-four mice were randomly assigned to four groups. Three months after inoculation with hydatid cyst segments, mice in group A were treated with intraperitoneal and intratracheal saline injections; mice in group B were administered a caudal vein injection of a PI3K inhibitor, followed by cyst fluid sensitization; mice in group C received an AKT inhibitor via caudal vein, followed by cyst fluid sensitization; and mice in group D were subjected to cyst fluid sensitization without any inhibitor treatment. Cellular changes in lung tissues across all groups were evaluated, including pathological section analysis. Analysis of pulmonary tissue and serum from these mice included the assessment of PI3K/AKT/NF-κB pathway proteins, inflammatory factors, and related mRNA levels.ResultsMice in groups B and C exhibited a higher proportion of M2-type macrophages and significantly lower levels of PI3K/AKT/NF-κB pathway proteins, inflammatory factors (interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), and oxidative markers in lung tissues compared to mice in group D (P < 0.05).ConclusionOur results in this study indicate that activation of the PI3K/AKT/NF-κB pathway contributed to an increase in the M1 macrophage phenotype, leading to enhanced secretion of peroxidases and inflammatory factors. This mechanism plays a crucial role in the oxidative and inflammatory lung damage associated with allergic reactions to E. granulosus cyst fluid.

This research was a quasi-experiment that examined the effects of CLIL in an educational context in Taiwan’s higher education. Two groups of first-year undergraduate students were involved. One (65 students) was taught with CLIL; the other (59), the conventional approach. Their knowledge of the content and learning attitudes (self-efficacy and motivation) were quantitatively compared through achievement tests and a questionnaire. A qualitative semi-structured survey asked both groups for their perspectives on and perceptions of the treatments. The quantitative results show that both approaches were significantly effective for improving students’ knowledge of the content of the target subject (literary text), but the EG outperformed the CG. Likewise, both groups had positive learning attitudes to their treatments, but the EG also outweighed the CG. Furthermore, the qualitative accounts generated diverse results, reflecting the underlying difference between the approaches but showing that both approaches were welcomed. However, the conventional method was more favored than CLIL, mostly because of the participants’ learning preferences or because of the learning patterns which they had formed over years of studying in the specific cultural-education system (i.e., that of Taiwan) chosen for the study.

The kinetics of type I interferon (IFN) induction versus the virus replication compete, and the result of the competition determines the outcome of the infection. Chaperone proteins that involved in promoting the activation kinetics of PRRs rapidly trigger antiviral innate immunity. We have previously shown that prior to the interaction with MAVS to induce type I IFN, 14-3-3η facilitates the oligomerization and intracellular redistribution of activated MDA5. Here we report that the cleavage of 14-3-3η upon MDA5 activation, and we identified Caspase-3 activated by MDA5-dependent signaling was essential to produce sub-14-3-3η lacking the C-terminal helix (αI) and tail. The cleaved form of 14-3-3η (sub-14-3-3η) could strongly interact with MDA5 but could not support MDA5-dependent type I IFN induction, indicating the opposite functions between the full-length 14-3-3η and sub-14-3-3η. During human coronavirus or enterovirus infections, the accumulation of sub-14-3-3η was observed along with the activation of Caspase-3, suggesting that RNA viruses may antagonize 14-3-3η by promoting the formation of sub-14-3-3η to impair antiviral innate immunity. In conclusion, sub-14-3-3η, which could not promote MDA5 activation, may serve as a negative feedback to return to homeostasis to prevent excessive type I IFN production and unnecessary inflammation.

Abstract Covalent organic frameworks show great potential in gas adsorption/separation, biomedicine, device, sensing, and printing arenas. However, covalent organic frameworks are generally not dispersible in common solvents resulting in the poor processability, which severely obstruct their application in practice. In this study, we develop a convenient top-down process for fabricating solution-processable covalent organic frameworks by introducing intermolecular hydrogen bonding and π-π interactions from ionic liquids. The bulk powders of imine-linked, azine-linked, and β-ketoenamine linked covalent organic frameworks can be dispersed homogeneously in optimal ionic liquid 1-methyl-3-octylimidazolium bromide after heat treatment. The resulting high-concentration colloids are utilized to create the covalent organic framework inks that can be directly printed onto the surface. Molecular dynamics simulations and the quantum mechanical calculations suggest that C‒H···π and π-π interaction between ionic liquid cations and covalent organic frameworks may promote the formation of colloidal solution. These findings offer a roadmap for preparing solution-processable covalent organic frameworks, enabling their practical applications.

Key Clinical Message In a patient with metastatic breast cancer, an acquired BRCA mutation in the BRCA gene was detected, resulting in benefits from olaparib treatment. This underscores the importance of ongoing genetic phenotype testing after paclitaxel chemotherapy. Abstract Triple‐negative breast cancer (TNBC) is associated with a poor prognosis and elevated mortality risk. BRCA mutations are commonly regarded as prevalent mutations in TNBC patients, strongly associated with congenital familial heredity. Dynamic changes in mutation sites, however, are rarely reported. In this case report, we report a 59‐year‐old TNBC patient who developed pulmonary metastases post‐chemoradiotherapy. No BRCA mutations were detected through NGS. After 7.6 months of nab‐paclitaxel treatment, the patient experienced progression of lung metastases, and BRCA mutations were detected through NGS testing. Subsequent administration of olaparib resulted in a reduction in lung metastasis, demonstrating significant therapeutic efficacy. This case underscores the infrequent occurrence of treatment‐induced BRCA mutations and emphasizes the significance of dynamic NGS genetic testing for real‐time assessment of a patient's mutational status.

In recent years, smart fisheries, as an emerging model for fishery development, have become a research hotspot in the fishery and aquaculture industries of many countries. Smart fisheries can be thought of as a system that combines techniques for raising, catching, or selling aquatic products to improve production and sustainable development. Smart fisheries are crucial to improving fishery and aquaculture management. In this study, a comprehensive analysis was conducted using bibliometric analysis, the results of which are presented through visual mapping and data charts. This study collected data from the China National Knowledge Infrastructure (CNKI) database and compared it with the WoS database. A total of 949 articles were retrieved on topics related to smart fisheries, including 579 articles from WoS and 370 articles from CNKI. The results present the visualization and analysis of annual publications, author collaboration maps, research collaboration institutions, keywords, etc. The development of smart fisheries in China is obviously different from that in foreign countries. China attaches great importance to technology and production, while foreign countries focus on environmental issues. Therefore, this study helps us to understand the current research status, research hotspots, and future development directions of smart fisheries, providing certain references for future management.

Abstract Objective To investigate the changes in memory T cells and the related factors in mice by the establishment of a BALB/c mouse model of Echinococcus granulosus‐induced sensitization. Methods A sensitized BALB/c mouse model was established by intraperitoneal injection of E. granulosus. A control group (CTRL), a nonsensitized group infected with E. granulosus (CE), and a sensitized group infected with E. granulosus (ANPC) were set up. The pathological changes in lung tissue in mice, the change in memory T cells (CD4 Tm), and the change in peripheral blood nucleated interleukin‐23 (IL‐23) were detected using HE staining, flow cytometry, and liquid‐phase multiple protein quantification techniques, respectively. Results The individual percentage of mouse memory T cells was 9.14 ± 0.45, 25.23 ± 0.17, and 13.29 ± 0.32 in the CTRL, CE, and ANPC groups, respectively. The percentage of memory T cells in the ANPC group was higher than that in the CTRL group (t = 18.410, p

Summary: Background: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I–III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities—clinical, genomic, and histopathological—to improve the predictive accuracy for localised renal cell carcinoma recurrence. Methods: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI). Findings: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825–0·876 vs 0·608–0·793; p

In traditional textile manufacturing, downstream manufacturers use raw materials, such as Nylon and cotton yarns, to produce textile products. The manufacturing process involves warping, sizing, beaming, weaving, and inspection. Staff members typically use a trial-and-error approach to adjust the appropriate production parameters in the manufacturing process, which can be time consuming and a waste of resources. To enhance the efficiency and effectiveness of textile manufacturing economically, this study proposes a query-based learning method in regression analytics using existing manufacturing data. Query-based learning allows the model training to evolve its decision-making process through dynamic interactions with its solution space. In this study, predefined target parameters of quality factors were first used to validate the training results and create new training patterns. These new patterns were then imported into the solution space of the training model. In predicting product quality, the results show that the proposed query-based regression algorithm has a mean squared error of 0.0153, which is better than those of the original regression-related methods (Avg. mean squared error = 0.020). The trained model was deployed as an application programing interface (API) for cloud-based analytics and an extensive auto-notification service.

Abstract Background N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity. Methods Bladder cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan–Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated. Results Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan–Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib. Conclusions An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.

Abstract Plumbene, with a structure similar to graphene, is expected to possess a strong spin–orbit coupling and thus enhances its superconducting critical temperature (Tc). In this work, a buckled plumbene‐Au Kagome superstructure grown by depositing Au on Pb(111) is investigated. The superconducting gap monitored by temperature‐dependent scanning tunneling microscopy/spectroscopy shows that the buckled plumbene‐Au Kagome superstructure not only has an enhanced Tc with respect to that of a monolayer Pb but also possesses a higher value than what owned by a bulk Pb substrate. By combining angle‐resolved photoemission spectroscopy with density functional theory, the monolayer Au‐intercalated low‐buckled plumbene sandwiched between the top Au Kagome layer and the bottom Pb(111) substrate is confirmed and the electron–phonon coupling‐enhanced superconductivity is revealed. This work demonstrates that a buckled plumbene‐Au Kagome superstructure can enhance superconducting Tc and Rashba effect, effectively triggering the novel properties of a plumbene.

Abstract Background The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment. Methods Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients’ ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment. Results Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits. Conclusions TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy.

Abstract Background Immune reconstitution inflammatory syndrome (IRIS) refers to the phenomenon of intense immune responses against pathogens in patients with AIDS undergoing antiretroviral therapy to reconstitute immune function, resulting in functional impairment of multiple organs. Non-AIDS immunosuppressed hosts may also develop similar manifestations to IRIS during immune recovery. Case presentation An 8-year-old girl presented with acute lymphoblastic leukaemia was admitted for scheduled chemotherapy treatment. During chemotherapy, she experienced pancytopenia and Pneumocystis jirovecii pneumonia, which was diagnosed based on the abnormal shadows observed on chest computed tomography, the elevation of serum β-D-glucan, and the positive mNGS results of Pneumocystis jirovecii in both sputum and blood. After treatment with Granulocyte Colony-Stimulating Factor, sulfamethoxazole, and caspofungin, aggravation of lung lesions was discovered and severe interstitial lung disease developed in a short period along with a rapidly increasing leukocyte count. Intravenous methylprednisolone pulse therapy was given, but lung function did not improve, and she finally died after the withdrawal of medical care. Conclusions For patients with acute lymphocytic leukaemia infected with Pneumocystis jirovecii, the rapid aggravation of pulmonary lesions in the process of blood recovery and immune reconstitution should raise vigilance against the possibility of IRIS-like reactions. The use of granulocyte stimulating factors may aggravate the inflammatory response in the lungs. The timing, dosage, and duration of treatment of glucocorticoids and the impact of high-dose methylprednisolone pulse therapy on the prognosis of patients should be explored in further research.

Tempeh is a traditional fermented soybean product widely consumed as part of the staple Indonesian diet. Besides its role as a protein source, the consumption of tempeh has been associated with health benefits, such as those from antioxidants. The fermentation of soybean by tempeh starter (Rhizopus oligosporus) determines the antioxidant capacities of tempeh. Updated studies reporting the fermentation conditions effect on tempeh are limited. Therefore, this research aimed to evaluate various fermentation conditions (lactic acid addition, fermentation time, fermentation temperature) on antioxidant capacities and physical characteristics of tempeh. In this study, soybean was soaked for 4 h, dehulled and boiled in water containing lactic acid with different concentrations (0.8%, 0.9% and 1.0%) for 30 mins. After cooling, the tempeh starter (106 CFU/g of Rhizopus oligosporus) was inoculated into the soybean. Afterward, the soybean was incubated at three different temperatures (25, 30 and 35 ℃) for 2, 3 and 4 days. For each fermentation condition, the physical characteristic (L*a*b* color value), antioxidant capacities and isoflavones contents of the tempeh powder were observed. The results showed that the tempeh fermented for more than 2 days was overripe, and higher incubation temperature could intensify the speed of fermentation, resulting in darker tempeh. A significant decrease in the L* value and increases in the a* and b* values were observed on tempeh stored at longer incubation time at various storage temperatures and various lactic acid concentrations (p < 0.05). Tempeh incubated at a higher temperature and longer incubation time exhibited lower EC­ 50 values of 2, 2'-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid (ABTS) scavenging and ferrous chelating ability, increase total phenolic contents and significantly increase aglycone isoflavones (p < 0.05). Therefore, the highest antioxidant capacity, the highest total phenolic content and the highest aglycone isoflavones were found in the tempeh incubated for 4 days at 35 ℃. The 1% lactic acid-tempeh had the highest antioxidant of chelating ability, highest total phenolic content and highest aglycone isoflavone increase.

BackgroundPublic health faces a significant challenge in reducing rural–urban disparities in diabetes. Since dietary control is part of the medical regimen for diabetes management, how diabetic patients perceive the impact of oral health on their quality of life is critical. The present study aimed to compare the Oral Health-related Quality of Life (OHRQoL) between rural and urban diabetic patients.MethodsThe study design was cross-sectional. The study sample included 831 self-reported diabetic patients, extracted from the first wave of the new-cohort Taiwan Longitudinal Study on Aging survey (NC_TLSA) that comprised a nationally representative sample of community-dwelling adults aged 50 and above in Taiwan. The composite score generated from the Oral Health Impact Profile-7 (OHIP-7), which has seven questions, was used to construct two OHRQoL measures, the severity of perceived poor OHRQoL and the prevalence of poor OHRQoL. These two OHRQoL measures were treated as dichotomous variables. Multivariate logistic regression models were applied for analysis.ResultsRural diabetic patients had a higher likelihood of experiencing the severity of perceived poor OHRQoL than those in urban areas (OR = 2.40, 95% CI: 1.30–4.40). Although rural diabetic patients also had a higher prevalence of poor OHRQoL than urban diabetic patients, the difference was not significant (OR = 1.47, 95% CI: 0.95–2.28). Social determinants, such as education, are essential factors attributed to both OHRQoL measures.ConclusionOverall, rural diabetes community-dwelling patients had a poorer OHRQoL than those in urban areas. Given a bidirectional relationship between oral health and diabetes, improving oral health in rural areas may be a critical avenue to improve the quality of diabetes care in rural areas.

BackgroundSome evidence suggests abnormalities in fatty acids in patients with atopic dermatitis (AD), and benefits of supplementation with these fatty acids have been reported. However, there is still substantial controversy on the correlation between fatty acids and AD. Therefore, the aim of this study was to determine whether fatty acid levels are causally related to AD using a Mendelian randomization approach.MethodsWe evaluated the data about the fatty acids levels and AD with various methods from Genome-Wide Association Study (GWAS). GWAS results were available both from European ancestry. Mendelian randomization methods were used to analysis the casual inference of fatty acids on AD. MR Egger and MR-PRESSO were used to determine pleiotropy and heterogeneity. Further analysis was conducted using instruments associated with the FADS genes to address mechanisms involved. We also used Multivariate MR (MVMR) to show the independent casual inference of omega-3 (n-3) fatty acids on AD.ResultsMendelian randomization (MR) analysis suggests that n-3 fatty acid levels are associated with a lower risk of AD (n-3 ORIVW: 0.92, 95% confidence interval [CI]: 0.87–0.98; p = 0.01). Moreover, docosahexaenoic acids (DHA) levels, which is a kind of long-chain, highly unsaturated omega-3 (n-3) fatty acid, and its higher level was associated with a lower risk of AD (DHA ORIVW: 0.91, 95% CI: 0.84–0.98; p = 0.02). We ran multivariable MR analysis while controlling for variables within the other types of fatty acids. The effect estimates agreed with the preliminary MR analysis indicating the effect of n-3 fatty acids levels on AD was robust. MR-egger suggest no significant pleiotropy and heterogeneity on genetic instrumental variants. Outliers-corrected MR analyses after controlling horizontal pleiotropy were still robust. The single-SNP analyses revealed that n-3 fatty acids are likely linked to a decreased risk of AD through FADS cluster, highlighting the significance of the FADS gene in the fatty acids synthesis pathway in the development of AD.ConclusionOur studies suggest that n-3 fatty acids may reduce the risk of AD. Risk prediction tools based on n-3 fatty acid levels may be valuable methods for improving AD screening and primary prevention. To reduce the risk of AD, individuals could enhance n-3 fatty acids intake through supplement or diet.

While protein palmitoylation has been studied for decades, our understanding of its clinical importance is minimal compared to other post translational modifications. As a result of the inherent challenges preventing the production of antibodies to palmitoylated epitopes we are unable to correlate levels of protein palmitoylation in biopsied tissues at a meaningful resolution. The most common method for detecting palmitoylated proteins without metabolic labelling is through chemical labeling of palmitoylated cysteines with the acyl-biotinyl exchange (ABE) assay. We have adapted the ABE assay to detect protein palmitoylation in formalin fixed paraffin embedded (FFPE) tissue sections. The assay is sufficient to detect subcellular regions of cells with increased labeling which indicates areas enriched in palmitoylated proteins. To visualize specific palmitoylated proteins in both cultured cells and in FFPE preserved tissue arrays we have integrated the ABE assay with a proximity ligation assay (ABE-PLA). Our findings demonstrate for the first time that FFPE preserved tissues can be labelled with unique chemical probes to detect either areas enriched in palmitoylated proteins or the localization of specific palmitoylated proteins using our ABE-PLA methodology.

Co-infection of RNA viruses may contribute to their recombination and cause severe clinical symptoms. However, the tracking and identification of SARS-CoV-2 co-infection persist as challenges. Due to the lack of methods for detecting co-infected samples in a large amount of deep sequencing data, the lineage composition, spatial–temporal distribution, and frequency of SARS-CoV-2 co-infection events in the population remains unclear. Here, we propose a hypergeometric distribution–based method named Cov2Coinfect with the ability to decode the lineage composition from 50,809 deep sequencing data. By resolving the mutational patterns in each sample, Cov2Coinfect can precisely determine the co-infected SARS-CoV-2 variants from deep sequencing data. Results from two independent and parallel projects in the United States achieved a similar co-infection rate of 0.3–0.5 % in SARS-CoV-2 positive samples. Notably, all co-infected variants were highly consistent with the co-circulating SARS-CoV-2 lineages in the regional epidemiology, demonstrating that the co-circulation of different variants is an essential prerequisite for co-infection. Overall, our study not only provides a robust method to identify the co-infected SARS-CoV-2 variants from sequencing samples, but also highlights the urgent need to pay more attention to co-infected patients for better disease prevention and control.

Abstract Background Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC. Methods circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization. Results The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression. Conclusions We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.

Abstract A biological research framework to define Alzheimer’ disease with dichotomized biomarker measurement was proposed by National Institute on Aging–Alzheimer’s Association (NIA–AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic 18F-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline 18F-AV-1451 tau PET (baseline age 73.9 ± 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, using linear mixed-effect models and Cox proportional hazard models. Significant cognitive decline was first observed in stage 1 when tau levels only increased in transentorhinal regions. Rates of cognitive decline and clinical progression accelerated from stage 2 to stage 3 and stage 4. Higher stages were also associated with greater CSF phosphorylated tau and total tau concentrations from stage 1. Abnormal tau accumulation did not appear with normal β-amyloid in neocortical regions but prompt cognitive decline by interacting with β-amyloid in temporal regions. Highly accumulated tau in temporal regions independently led to cognitive deterioration. Topographic PET staging scheme have potentials in early diagnosis, predicting disease progression, and studying disease mechanism. Characteristic tau spreading pattern in Alzheimer’s disease could be illustrated with biomarker measurement under NIA–AA framework. Clinical–neuroimaging–neuropathological studies in other cohorts are needed to validate these findings.

BackgroundReduced dopamine transporter (DAT) binding in the striatum has been reported in patients with progressive supranuclear palsy (PSP). However, the relationship between striatal dopaminergic lesions and the disease severity of PSP remains to be explored.ObjectiveTo investigate the contributions of striatal dopaminergic lesions to the disease severity of PSP.MethodsOne hundred patients with clinically diagnosed PSP were consecutively enrolled in this study. The disease severity was systemically assessed using the PSP rating scale (PSPrs), and the dopaminergic lesions were assessed using the 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane positron emission tomography (11C-CFT PET) imaging. To explore the correlations between striatal DAT bindings and the disease severity, both the region-wise and voxel-wise analysis were adopted. Partial correlations and multiple linear regressions were performed to investigate the contribution of striatal dopaminergic lesions to the disease severity in PSP.ResultsSixty-three patients of PSP with Richardson’s syndrome (PSP-RS) and 37 patients with PSP-non-RS were finally included. The disease severity in PSP-RS was much heavier than that in the PSP-non-RS. The DAT bindings in the caudate and anterior putamen correlated significantly with the PSPrs total scores, mainly in the domains of history, mentation, bulbar, and ocular motor symptoms. The striatal DAT bindings (caudate) contributed significantly to the disease severity of PSP, independent of the motor, cognition, emotion and behavioral dysfunctions.ConclusionOur study highlighted the independent contribution of striatal dopaminergic lesions to the disease severity in PSP.

This study explores the developmental course of training to become a content and language integrated learning (CLIL) practitioner in higher education. Thirteen in-service teachers (five Japanese, four Taiwanese, two Chinese, one Filipino, and one Thai) wholly new to the CLIL approach received an intensive fortnight’s training in CLIL. The training, following the CLIL model, started by introducing the theory, rationale and foundations of CLIL and concluded with a mini-CLIL teaching session from each teacher. Two quantitative surveys and a qualitative semi-structured survey yielded data on the trainees’ experiences as course members. The results show that the teachers generally approved of CLIL, endorsing its effectiveness more than its efficiency. The teachers’ self-confidence in English skills and their past teaching experiences seemingly affected their belief in CLIL’s practices. Finally, the teachers revealed some challenges in implementing CLIL in general, in higher education, and in their specific culture-education contexts. The study made important contributions in the field, with its findings serving as valuable references for higher education, teacher-training programs, and interested teachers.

Accurately predicting the survival prospects of patients suffering from pancreatic adenocarcinoma (PAAD) is challenging. In this study, we analyzed RNA matrices of 182 subjects with PAAD based on public datasets obtained from The Cancer Genome Atlas (TCGA) as training datasets and those of 63 subjects obtained from the Gene Expression Omnibus (GEO) database as the validation dataset. Genes regulating the metabolism of PAAD cells correlated with survival were identified. Furthermore, LASSO Cox regression analyses were conducted to identify six genes (XDH, MBOAT2, PTGES, AK4, PAICS, and CKB) to create a metabolic risk score. The proposed scoring framework attained the robust predictive performance, with 2-year survival areas under the curve (AUCs) of 0.61 in the training cohort and 0.66 in the validation cohort. Compared with the subjects in the low-risk cohort, subjects in the high-risk training cohort presented a worse survival outcome. The metabolic risk score increased the accuracy of survival prediction in patients suffering from PAAD.

Abstract Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB’s toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB’s active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.

The purpose of this paper is to use the principle of hydraulic amplification and design a piezoelectric drive-based hydraulically amplified flexible Braille contact device with good performance output. In this paper, the structure and working principle of the Braille contact device are described, and the theoretical analysis and parametric design of the hydraulic amplification unit are carried out. The influence relationship between the displacement amplification and diameter and height of the reservoir are obtained by using MATLAB simulation analysis, whereas the output displacement of the piezoelectric vibrator and the flexible film under different driving voltages is measured by using a laser micrometer. Subsequently, the experiments are consistent with the theoretical analysis, and the correctness of the theoretical analysis is verified. Finally, experimental tests of the system are implemented. The results suggest that the displacement amplification ratio is 4.16, and the contact displacement formed by the flexible film is 0.226 mm. Thus, the requirements of the touch sensitivity standard for the blind are satisfied when the reservoir diameter is 20 mm and the reservoir height is 3 mm. The filling water is 7.5 ml, and the resonance frequency is 317.5 Hz. This study proves that constructing a Braille bump device in this way is feasible as well as effective.

Background. Eosinophils were common inflammatory cells involved in the occurrence and development of various inflammatory diseases. Multiple recent studies have pointed to the increasingly important role of eosinophils in respiratory diseases. This article aims to compare the expression differences of blood eosinophil counts between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Methods. Patients with asthma, COPD, and ACO who were seen in the First Affiliated Hospital of Guangzhou Medical University from January 2012 to June 2019 were included. We collected information such as age, gender, diagnosis, the eosinophil counts from the medical records. Moreover, the levels of 10 cytokines in the plasma of each group were detected by using the Meso Scale Discovery method. Results. We included 9787 patients with asthma, 15806 patients with COPD, and 831 ACO patients. From our results, it can be first found that eosinophil levels were age-related in the three diseases (asthma and ACO: p

The epidermal growth factor receptor (EGFR) is an essential driver of oncogenic signalling, and EGFR inhibitors are some of the earliest examples of successful targeted therapies in multiple types of cancer. The tractability of EGFR as a therapeutic target is overshadowed by the inevitable drug resistance that develops. Overcoming resistance mechanisms requires a deeper understanding of EGFR regulation in cancer cells. In this review, we discuss our recent discovery that the palmitoyltransferase DHHC20 palmitoylates EGFR on the C-terminal domain and plays a critical role in signal regulation during oncogenesis. Inhibiting DHHC20 expression or mutating the palmitoylation site on EGFR alters the EGF-induced signalling kinetics from a transient signal to a sustained signal. The change in signalling is accompanied by a decrease in cell proliferation in multiple human cancer cell lines. Our in vivo studies demonstrate that ablating the gene Zdhhc20 by CRISPR/Cas9-mediated inhibition in a mouse model of oncogenic Kras-driven lung adenocarcinoma potently inhibits tumorigenesis. The negative effect on tumorigenesis is mediated by EGFR since the expression of a palmitoylation-resistant mutant form of EGFR also inhibits Kras-driven lung adenocarcinoma. Finally, reducing EGFR palmitoylation increases the sensitivity of multiple cancer cell lines to existing inhibitors of EGFR and downstream signalling effector pathways. We will discuss the implications of these effects and strategies for targeting these new vulnerabilities.

ABSTRACT Picornaviruses are a diverse and major cause of human disease, and their genomes replicate with intracellular membranes. The functionality of these replication organelles depends on the activities of both viral nonstructural proteins and co-opted host proteins. The mechanism by which viral-host interactions generate viral replication organelles and regulate viral RNA synthesis is unclear. To elucidate this mechanism, enterovirus A71 (EV-A71) was used here as a virus model to investigate how these replication organelles are formed and to identify the cellular components that are critical in this process. An immunoprecipitation assay was combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify 172 cellular proteins and four viral proteins associating with viral 3A protein. Secretory carrier membrane protein 3 (SCAMP3) was one of the host proteins we selected for further investigation. Here, we demonstrate by immunoprecipitation assay that SCAMP3 associates with 3A protein and colocalizes with 3A protein during virus infection. SCAMP3 knockdown or knockout in infected cells decreases synthesis of EV-A71 viral RNA, viral proteins, and viral growth. Furthermore, the viral 3A protein associates with SCAMP3 and phosphatidylinositol-4-kinase type III β (PI4KIIIβ) as shown by immunoprecipitation assay and colocalizes to the replication complex. Upon infection of cells with a SCAMP3 knockout construct, PI4KIIIβ and phosphatidylinositol-4-phosphate (PI4P) colocalization with EV-A71 3A protein decreases; viral RNA synthesis also decreases. SCAMP3 is also involved in the extracellular signal-regulated kinase (ERK) signaling pathway to regulate viral replication. The 3A and SCAMP3 interaction is also important for the replication of coxsackievirus B3 (CVB3). SCAMP3 also associates with 3A protein of CVB3 and enhances viral replication but does not regulate dengue virus 2 (DENV2) replication. Taken together, the results suggest that enterovirus 3A protein, SCAMP3, PI4KIIIβ, and PI4P form a replication complex and positively regulate enterovirus replication. IMPORTANCE Virus-host interaction plays an important role in viral replication. 3A protein of enterovirus A71 (EV-A71) recruits other viral and host factors to form a replication complex, which is important for viral replication. In this investigation, we utilized immunoprecipitation combined with proteomics approaches to identify 3A-interacting factors. Our results demonstrate that secretory carrier membrane protein 3 (SCAMP3) is a novel host factor that associates with enterovirus 3A protein, phosphatidylinositol-4-kinase type III β (PI4KIIIβ), and phosphatidylinositol-4-phosphate (PI4P) to form a replication complex and positively regulates viral replication. SCAMP3 is also involved in the extracellular signal-regulated kinase (ERK) signaling pathway to regulate viral replication.

Abstract. Background:. Studies have reported mitophagy activation in renal tubular epithelial cells (RTECs) in acute kidney injury (AKI). Phosphatase and tensin homolog-induced putative kinase 1 (PINK1) and E3 ubiquitin-protein ligase Parkin are involved in mitophagy regulation; however, little is known about the role of PINK1-Parkin mitophagy in septic AKI. Here we investigated whether the PINK1-Parkin mitophagy pathway is involved in septic AKI and its effects on cell apoptosis in vitro and on renal functions in vivo. Methods:. Mitophagy-related gene expression was determined using Western blot assay in human RTEC cell line HK-2 stimulated with bacterial lipopolysaccharide (LPS) and in RTECs from septic AKI rats induced by cecal ligation and perforation (CLP). Autophagy-related ultrastructural features in rat RTECs were observed using electron microscopy. Gain- and loss-of-function approaches were performed to investigate the role of the PINK1-Parkin pathway in HK-2 cell mitophagy. Autophagy activators and inhibitors were used to assess the effects of mitophagy modulation on cell apoptosis in vitro and on renal functions in vivo. Results:. LPS stimulation could significantly induce LC3-II and BECN-1 protein expression (LC3-II: 1.72 ± 0.05 vs. 1.00 ± 0.05, P

Purpose: To assess the predictive validity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive scores at 6 months of corrected age (CA) for cognitive outcomes at 24 months of CA in very-low-birth-weight (VLBW) infants and investigate the predictors of change in cognitive outcomes.Methods: We retrospectively evaluated VLBW children enrolled in the Taiwan Premature Infant Follow-up Network between 2010 and 2015 and completed the Bayley-III at CA of 6 and 24 months. The predictive validity of the cognitive performance at 6-month CA for the cognitive outcomes at 24-month CA was analyzed. The positive and negative predictive factors were also evaluated using logistic regression. Cut-off scores of

This study has the aim of improving the English speaking ability of Taiwanese college freshmen by a video featuring connected speech instruction. Forty-eight students from a private university in northern Taiwan participated in the study, which lasted for 7 weeks. Pre- and post-tests were used to assess their speaking performance in terms of connected speech before and after the experimental treatment. Entry and exit questionnaires were also used to investigate students’ learning attitudes. The results show that such instruction was significantly effective for improving the English language learners’ connected speech skills. Positive results were also observed in the outcomes of the questionnaires, showing significantly enhanced learning attitudes to English speaking. It is hoped that the study results may offer language teachers some insights into the practice of video-aided learning in English speech classes, particularly its efficacy for connected speech.

Objective: We aimed to characterize the cognitive profiles in multiple system atrophy (MSA) and explore the cerebral metabolism related to the cognitive decline in MSA using 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET).Methods: In this study, 105 MSA patients were included for cognitive assessment and 84 of them were enrolled for 18F-FDG PET analysis. The comprehensive neuropsychological tests covered five main domains including execution, attention, memory, language, and visuospatial function. The cognitive statuses were classified to MSA with normal cognition (MSA-NC) and MSA with cognitive impairment (MSA-CI), including dementia (MSA-D), and mild cognitive impairment (MSA-MCI). With 18F-FDG PET imaging, the cerebral metabolism differences among different cognitive statuses were analyzed using statistical parametric mapping and post-hoc analysis.Results: Among 84 MSA patients, 52 patients were found with MSA-CI, including 36 patients as MSA-MCI and 16 patients as MSA-D. In detail, the cognitive impairments were observed in all the five domains, primarily in attention, executive function and memory. In 18F-FDG PET imaging, MSA-D and MSA-MCI patients exhibited hypometabolism in left middle and superior frontal lobe compared with MSA-NC (p < 0.001). The normalized regional cerebral metabolic rate of glucose (rCMRglc) in left middle frontal lobe showed relative accuracy in discriminating MSA-CI and MSA-NC [areas under the curve (AUC) = 0.750; 95%CI = 0.6391–0.8609].Conclusions: Cognitive impairments were not rare in MSA, and the hypometabolism in frontal lobe may contribute to such impairments.

Abstract It is very desirable to develop advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications. Herein, biomass‐derived multilayer‐structured absorbable microparticles (MQxTy) composed of starches and plant polyphenols are readily constructed for the safe and effective treatment of bone defects with intractable bleeding by coating multiple layers of quaternized starch (Q+) and tannic acid onto microporous starch microparticles via facile layer‐by‐layer assembly. MQxTy microparticles exhibit efficient degradability, low cytotoxicity, and good blood compatibility. Among various MQxTy microparticles with distinct Q+/T− double layers, MQ2T2 with outmost polyphenol layer possess the unique properties of platelet adhesion/activation and red blood cell aggregation, resulting in the best hemostatic performance. In a mouse cancellous‐bone‐defect model, MQ2T2 exhibits the favorable hemostatic effect, low inflammation/immune responses, high biodegradability, and promoted bone repair. A proof‐of‐concept study of beagles further confirms the good performance of MQ2T2 in controlling intractable bleeding of bone defects. The present work demonstrates that such biomass‐based multilayer‐structured microparticles are very promising biomedical materials for clinical use.

Introduction Anterior cruciate ligament (ACL) injury is one of the most common injuries of the knee. ACL reconstruction (ACLR) has been widely performed as a safe and effective treatment for ACL injuries. As there is an increasing trend in the incidence of ACL injury, hospital readmission after ACLR has attracted renewed attention for the financial burden to both patients and the healthcare system. However, information about hospital readmission after ACLR remains fragmented. Therefore, we plan to systematically review the literature to investigate the rate of, causes and risk factors for hospital readmission after ACLR, and summarise interventions to reduce hospital readmission. This article is to provide the protocol for an upcoming systematic review and meta-analysis on this important issue.Methods and analysis Reporting of this protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. Electronic databases, including PubMed, Embase and the Cochrane Library, will be systematically searched from inception to June 2020. No language restrictions will be applied. Studies will be included if they reported hospital readmission or explored the associated potential causes and risk factors for hospital readmission after ACLR. The primary outcome will be the number and time frame of hospital readmission after ACLR. Secondary outcomes will be reasons for readmission, number and types of complications, risk factors for readmission and preventive measures for readmission after ACLR. Quality assessments will be performed by using the Newcastle-Ottawa Scale (NOS). If possible, study results will be summarised in a forest plot, and heterogeneity will be tested by using the Cochran’s Q and I2 statistics.Ethics and dissemination No ethical approval is required because our study is not related to patients or animals. The results will be published in a peer-reviewed journal.PROSPERO registration number CRD42020058624.

BackgroundObjective motor ratings and subjective motor complaints are both widely used in Parkinson’s disease (PD). However, the objective basis to the self-perceived mobility quality is still not well elucidated.PurposesWe aimed to figure out the relevancy between the UPDRS motor scores and PDQ39 mobility sub-scores, and further explore whether physician-assessed motor dysfunctions and patients-reported mobility deficits have some shared mechanisms.Methods49 patients with PD who completed the PDQ39 scale were retrospectively included. The relevancy between mobility quality and UPDRS scores was assessed, as well as the related presynaptic dopaminergic binding (11C-CFT) and glucose metabolism (18F-FDG) in this dual-tracer PET imaging study.ResultsModest correlation was found between UPDRS motor score and the PDQ39 mobility sub-score (r = 0.440, p = 0.002). No correlation was found between PDQ39 mobility SI and the dopaminergic lesions in putamen; however, the strict correlation was found with the UPDRS motor scores. In terms of global PD related pattern (PDRP) scores, the two motor scores both correlated strictly. In the further regional metabolism exploration, cerebellum correlated positively with PDQ39 mobility sub-scores, and the frontal and parietal regions mainly correlated negatively with the motor quality scores.ConclusionUPDRS motor scores and PDQ39 mobility scores were only modestly correlated. The mechanisms involved under mobility quality were beyond dopaminergic deficiency, including motor related cerebellum hyper-metabolism and non-motor related frontal hypo-metabolism. Conclusively, the self-reported mobility experience may have the neurophysiological basis related to both motor and non-motor manifestations in PD.

Objective This study assessed the efficacy of conbercept for patients with non-proliferative diabetic retinopathy (NPDR). Methods In this retrospective clinical study, 54 patients with NPDR (54 eyes) were treated with intravitreal injection of conbercept using a 3+ pro re nata regimen and followed up for 12 months. Best corrected visual acuity (BCVA), central foveal thickness (CFT), area of hard exudate (HE), and number of microaneurysms (MAs) were used as indicators of therapeutic effects. Systemic adverse reactions were recorded to assess safety. Results During the 12-month follow-up period, the mean number of injections was 6.12 ± 1.89 on demand. From baseline to the 12-month follow-up, the BCVA of patients with NPDR increased from 0.71 ± 0.20 logMAR to 0.43 ± 0.16 logMAR, CFT decreased from 424.26 ± 64.89 μm to 269.27 ± 44.79 μm, and the number of MAs declined from 79.53 ± 27.18 to 33.34 ± 16.53. Moreover, the area of HE was significantly reduced after 9 months of treatment. There were no serious systemic adverse events during the follow-up. Conclusions Intravitreal injection of conbercept has a stable and robust effect on patients with NPDR over a 12-month follow-up period. Thus, conbercept is an effective and feasible treatment for NPDR.

Bandpass impedance transformers (BPIMTs) with extremely high transforming ratios by adopting the proposed Π-tapped feeds are realized in this paper. Π-tapped feeds composed of two shunt stubs and one-section line performing the impedance transforming function are introduced. To validate the generality of the proposed approach, two different types of bandpass transformers, i.e., type-A and type-B adopting a short-ended parallel coupled-line and a via-inductive coupling as their interstage couplings, respectively, originating from two coupled-resonator filter topologies are designed. The synthesis procedures and design formulas of the two transformer types are provided, and the auxiliary graphs for different impedance transforming ratios are thoroughly investigated. The circuit-level simulated results of the proposed BPIMTs agree well with the theoretical results calculated from the coupling matrix, thus validating the design approach. Specifically, two type-A prototypes with the transforming ratios of 20 (200 Ω/10 Ω) and 95 (475 Ω/5 Ω), respectively, and one type-B prototype with a transforming ratio of 104 (520 Ω/5 Ω) were demonstrated. The proposed transformer is capable of satisfactorily matching the low and high impedances, and it also possesses the highest impedance transforming ratio ever reported in the literature.

As the demand for secure digital data continues to increase, image encryption and decryption have recently received tremendous attention. The rapid development of ultrathin metasurfaces has mainly been driven by the desire for the introduction of novel methods with which electromagnetic waves can be manipulated. As a promising application of metasurfaces, metalenses have shown great potential to replace bulky traditional optical devices. In this work, we present that the images produced by a commercially available projector are encrypted by using the color superposition principle, and the fabricated metalens is subsequently utilized to perform image decryption with an incidence made of white light-emitting diodes (LEDs). The correct positions for image decryption are carefully found by three distinct diode lasers as incident light sources. Recent investigations show that high-performance metalenses can be successfully developed once the suitable dielectric material is chosen. As a consequence, our metalens of high performance is composed of hexagon-resonated elements (HREs) made of gallium nitride (GaN) and is capable of resolving line width as small as 870 nm. The metalens with a smaller diameter of 8 μm is numerically simulated with a diffraction-limited focusing efficiency as high as 92%. This work once again shows that GaN metalenses, as future optics, have great prospects in expanding widespread applications in the near future.

INTRODUCTION: Treatment for osteoporosis commonly includes the use of bisphosphonates. Serious side effects of these drugs are caused by the inhibition of bone resorption as a result of osteoclast apoptosis. Treatment using calcitonin along with bisphosphonates overcomes these side-effects in some patients. Calcitonin is known to inhibit bone resorption without reducing the number of osteoclasts and is thought to prolong osteoclast survival through the inhibition of apoptosis. Further understanding of how calcitonin inhibits apoptosis could prove useful to the development of alternative treatment regimens for osteoporosis. This study aimed to analyze the mechanism by which calcitonin influences osteoclast apoptosis induced by a bisphosphate analog, sintered dicalcium pyrophosphate (SDCP), and to determine the effects of co-treatment with calcitonin and SDCP on apoptotic signaling in osteoclasts. METHODS: Isolated osteoclasts were treated with CT, SDCP or both for 48 h. Osteoclast apoptosis assays, pit formation assays, and tartrate-resistant acid phosphatase (TRAP) staining were performed. Using an osteoporosis rat model, ovariectomized (OVX) rats received calcitonin, SDCP, or calcitonin + SDCP. The microarchitecture of the fifth lumbar trabecular bone was investigated, and histomorphometric and biochemical analyses were performed. RESULTS: Calcitonin inhibited SDCP-induced apoptosis in primary osteoclast cultures, increased Bcl-2 and Erk activity, and decreased Mcl-1 activity. Calcitonin prevented decreased osteoclast survival but not resorption induced by SDCP. Histomorphometric analysis of the tibia revealed increased bone formation, and microcomputed tomography of the fifth lumbar vertebrate showed an additive effect of calcitonin and SDCP on bone volume. Finally, analysis of the serum bone markers CTX-I and P1NP suggests that the increased bone volume induced by co-treatment with calcitonin and SDCP may be due to decreased bone resorption and increased bone formation. CONCLUSIONS: Calcitonin reduces SDCP-induced osteoclast apoptosis and increases its efficacy in an in vivo model of osteoporosis.

In the title compound, C18H22N4O, the dihedral angle between the planes of the benzotriazol unit and the phenyl ring of the phenoxy group is 6.4 (2)°. There is an intramolecular O—H...N hydrogen bond between the phenol and benzotriazol groups.

Objectives: This study aimed to evaluate the efficacy of air purifier therapy for patients with allergic asthma., Methods: Thirty-eight subjects were categorized under two groups namely treatment group and control group. All subjects were under 18 years of age and they had been clinically diagnosed with allergic asthma. The treatment group used high efficiency particulate air (HEPA) purifiers for six consecutive months, and the control group did not use the air filters. Particulate matter (PM) data and dust samples (from bedding and a static point) were collected from the subjects' bedrooms before they started using the air purifiers and each month thereafter. Simultaneously, the subjects were asked to complete a questionnaire for the Asthma Control Test (ACT) or Childhood Asthma Control Test (C-ACT). Fractional exhaled nitric oxide (FENO) tests were performed at the start and end of the study. The concentrations of Der p1 and Der f1 were measured in the dust samples., Results: (1) After utilizing the air purifier, the concentrations of house dust mite (HDM) allergens (Der p1+ Der f1) in the dust samples decreased. In addition, the PM indoor/outdoor values significantly decreased. (2) The ACT and C-ACT scores in the treatment group maintained a steady significant upward trend. (3) At the end of the study, the FENO levels in both groups were lower, although the differences were not significant., Conclusions: It is witnessed that HEPA air purifiers can decrease indoor HDM allergen and PM levels and improve the quality of life for allergic asthma patients., Competing Interests: The authors declare no direct, indirect, or personal interest.

Background: With the rising prevalence of allergic rhinitis, the utility of indoor environmental management deserves increasing scrutiny. This research aims at evaluating the ability of air purifiers to be a therapy of allergic rhinitis., Methods: 32 subjects (25±13.5 years old) diagnosed with allergic rhinitis were selected and HEPA air purifiers placed in their bedrooms for 4 months. Before the intervention and each month, dust samples were collected with a vacuum cleaner and the dust collector assessed for allergen content. Additionally, static dust collectors were left in place all month to collect dust by sedimentation. Particulate matter (PM) was assessed in terms of PMindoor/outdoor ratios. The Rhinitis Quality of Life Questionnaire (RQLQ) was used to assess symptoms., Results: Der p 1 (78 (30,82) ng/g) was the dominant dust mite allergen in air samples of patients' bedroom as well as static collections. Der f1 (444 (345,667) ng/g) was the dominant allergen in bedding. Der f1 levels in both air and bed sampling significantly decreased after initiation of HEPA air purifiers (P<0.05). PM1.0indoor/outdoor, PM2.5indoor/outdoor, PM10indoor/outdoor all decreased (P<0.001) with the HEPA filtration intervention. According to RQLQ data, HEPA filtration was associated with improvements in activity limitation, non-nasal-eye symptoms, practical problems, and nasal symptoms (P<0.001)., Conclusion: HEPA air purifiers can effectively reduce PM and HDM allergen concentration in the indoor air, and thereby improve clinical manifestations of patients with AR.