Background and Purpose: Polyphenols of Polygoni Multiflori Caulis (PMC) have been widely consumed as food supplements for lowing lipid, while their anti-obesity effects were poorly understood. Experimental Approach: Several polyphenol-rich extracts including 75% ethanol (ETOH), chloroform (CHL), ethyl acetate (EA), n-butanol (n-Bu) and water (W) fractions, composed of emodin, physcion, apigenin or 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside at different ratios, were isolated from PMC. Their effects on lipase activity and 3T3-L1 preadipocytes differentiation were comparatively investigated. Their effects on obesity-related disorders were comparatively investigated using various models both in vitro and in vivo. Key Results: EA and n-Bu extracts with greater anti-obesity potential were screened for further studies to reveal the underlying mechanisms. EA and n-Bu extracts treatment significantly modulated the antioxidant response and lipid accumulation in Caenorhabditis elegans. High fat diet (HFD)-induced changes of weight gain, liver steatosis and epididymal adipose tissues hypertrophy in mice were also significantly reversed by EA and n-Bu extracts supplementation. Moreover, EA and n-Bu extracts intervention increased the microbial diversity, reshaped the microbiota structure and enhanced the relative abundance of Bifidobacterium. N-Bu extracts supplementation significantly decreased the ratio of Firmicutes/Bacteroidetes and the abundance of Lactobacillus, while EA extracts treatment markedly reversed HFD-induced increase of Erysipelotrichaceae abundance. Conclusions and Implications: Dietary supplementation of polyphenols from PMC exhibited promising anti-obesity effects and the chemical difference could partially explain their bioactivity discrepancy.

How to perform allergy assessment with mRNA COVID vaccine?To the Editor:Vaccines against coronavirus-2019 (SARS-CoV-2) are the solution to the current pandemic, However anaphylactic reaction occurs following administration of Pfizer-BioNTech COVID-19 Vaccine (1). Previous sensitization to Polyethylene glycol (PEG) may be a cause of anaphylaxis to the first dose of vaccine (2). However, the molecular weight (MW) of PEG seems play a part both in the process of sensitization and in HSR severity. Low MWs penetrate skin and mucosa to a greater degree, increasing the risk of sensitization (3).We report the case of a 53-year-old female who had a history of urticaria 30 minutes after administration of oral PEG 3350 for Bowel preparation for colonoscopy. Her usual treatment is perindopril and leflunimide, which contain PEG 8000, and is well-tolerated.We performed intradermal injection (IDR) with 0.02 ml of COVID-19 vaccine, diluted 10-1. After 20 min, the diameter of the wheal has increased by 2 folds and was accompanied by an erythema (picture 1).We also perfumed a skin prick test with PEG 3350 which was positive (wheal 6mm, erythema 8mm).Positive (Histamine 10 mg/ml) and negative tests were used as recommended.IDR testing was performed in two healthy volunteers to confirm the non-irritation of the used dose (or concentration). One the two volunteers has received the first dose of COVID-19 vaccine 9 days before testing, but not the other. Both of IDR were negative.We also performed a skin prick test with PEG 3350 which was positive (wheal 6mm, erythema 8mm).We speculated that this concentration for intradermal test is not irritated and can be used to performed allergy assessment for BNT162b2 Pfizer- BioNTech mRNA. In a case of positive reaction with skin testing we do not recommend vaccination and advise to wait for another formulation of vaccine.1. Castells MC, Phillips EJ. Maintaining Safety with SARS-CoV-2 Vaccines. N Engl J Med [Internet]. 20202. Garvey LH, Nasser S. Anaphylaxis to the first COVID-19 vaccine: is polyethylene glycol (PEG) the culprit? Br J Anaesth. 2020;3. Wenande E, Garvey LH. Immediate-type hypersensitivity to polyethylene glycols: a review. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2016;46(7):907‑22.Sébastien Lefèvre, MD, Regional Institute for allergic disease, Metz Regional Hospital, Metz, FranceLaurianne Moumane, MD, Regional Institute for allergic disease, Metz Regional Hospital, Metz, FrancePascale Monfort, MD, Pharmacy Department, Metz Regional Hospital, Metz, FranceValentin Philippe, MD, Pharmacy Department, Metz Regional Hospital, Metz, FranceNadia Ouamara, PhD, Clinical Research Unit, Metz Regional Hospital, Metz, FranceCamille Cano, MD, Regional Institute for allergic disease, Metz Regional Hospital, Metz, FranceEtienne Beaudouin, MD, Regional Institute for allergic disease, Metz Regional Hospital, Metz, France

An Aortic dissection results due to intimal tear, causing passage of blood into the media creating a false channel. This dissected channel can extend proximally or distally, causing any branch artery to compromise or rupture. Acute aortic dissection is a very fatal condition having high risk of mortality. Involvement of the coronary artery in acute aortic dissection is a very rare condition [1] but if involved, has fatal results for the patient. Since, it involves high mortality, coronary malperfusion should be actively looked in all proximally aortic dissection patients. Coronary angiogram, contrast enhanced CT and Transesophageal Echocardiography are the diagnostics used for aortic and coronary dissection. Surgical management gets very complicated if coronaries get involved in aortic dissection, since patients usually need to undergo an additional bypass grafting distal to dissecting coronary artery with closure of the main ostia. Here, we describe an uncommon surgical management of a very rare case in a patient with chronic aortic dissection involving type C right coronary ostial dissection that could not be shown by CECT and TEE, and was diagnosed on table with effective local repair. This Case Study was approved by our local ethics committee, and individual patient consent was taken. The authors have no conflicts of interest to declare. Funding: None

In this study, a novel kirkovirus (kirV) was detected in anal swabs of piglets with diarrhoea, the positive rate was 100% (149/149), but this virus was detected in one of 261 clinically healthy piglets, this result suggests a strong relationship between the kirV and the diarrhoeal disease. We obtained the whole-genome sequences of three kirVs (named Cj-D5, Cj-D32 and Cj-D43), with the length of 3750 nt, shared 86.6%–89.0% nt-identity with equine kirV Equ1 and kirV Cj-7-7. Furthermore, three viruses share32.1%–93.4%, and 22.2%–27.1% of the Rep protein sequence identity with available reference strains of the proposed family Kirkoviridae, and the family Circoviridae, respectively. Moreover, like kirV Equ1 and Cj-7-7, RCR domain and P-loop NTPase domains of Rep protein, and nonanucleotide motif (CAATATTAC), of three viruses, were similar to Circoviruses and Cycloviruses. Phylogenetic analysis showed that these viruses were grouped together with members in the proposed family Kirkoviridae. This is the first report that kirV circulates in piglets with diarrhoea, and next studies are needed to determine the pathogenesis of this virus.

COVID-19: A New Challenge to the Teaching Management at a Conservatory of Music in ChinaYuan Zhoua, Kai Zhangb,*College of Continuing Education, Tianjin Conservatory of Music, Tianjin, 300171, China.Department of Acupuncture and Moxibustion, Tianjin Gong An Hospital, Tianjin, 300042, China.*Correspondence to: Kai Zhang, MD*Correspondence author at: Department of Acupuncture and Moxibustion, Tianjin Gong An Hospital, Tianjin, China.No. 78 Nanjing Road, Heping District, Tianjin,300042, China. Tel:008613043295598.E-mail address: coolzhangkai@163.com.Kai Zhang ORCID 0000-0002-7248-1451Yuan Zhou, MDCollege of Continuing Education, Tianjin Conservatory of Music, Tianjin, China.No.57 Shiyijing Road, Hedong District, Tianjin, 300171, China.E-mail address: lark.zhou@126.com.Number of words: 816.The number of Figure:2.

Calcium (Ca) is an essential macronutrient for plant growth. Although it has been demonstrated that exogenous Ca application could increase plant resistance to abiotic stress, its potential to enhance tolerance to biotic stress remains unclear. Here, we investigated the development time, population size, feeding behavior of aphids feeding on plants grown from CaCl2- and water-pretreated seeds, and plant defenses against aphids. CaCl2 seed-pretreatment increased aphid development time and reduced aphid population size and feeding efficiency. Additionally, CaCl2 pretreatment increased the concentrations of Ca2+ in wheat leaves. Furthermore, TaCaM genes were upregulated in plants by CaCl2 pretreatment, and callose synthase genes (TaGSL2, TaGSL8, TaGSL10, TaGSL12, TaGSL19, TaGSL22, and TaGSL23) were activated. Callose concentrations in the leaves of plants grown from CaCl2-pretreated seeds increased significantly after aphid attack. Furthermore, callose deposition was observed mainly in the phloem. The results suggest that seed pretreatment with CaCl2 primed the plant responses against wheat aphid attack. The underlying mechanism comprises a comprehensive interaction among Ca2+, callose regulation, and the expression of callose synthesis-related genes, as well as phloem localization of callose in response to aphid attack.

Objectives: This systematic review summarized and synthesized the available evidence to examines the cost-effectiveness of the implementation of Automated Medical Systems. Method: PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Full-text Database (VIP), WanFang Database, China Biopharmaceutical Scientific Literature Database (CBM) were searched from inception to February 2020. The reference lists of eligible studies were hand searched. After two investigators independently screened the literature and extracted the data, the quality of the included articles was evaluated by using the Cochrane Intervention Risk of Bias Assessment Tool, the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality Scale. Revman5.3 software was used for meta-analysis. Results: Sixteen articles (9 interventional studies, 6 cohort studies, 1 cross-sectional study) were finally included, 92,576 patients were included in analysis. Meta-analysis showed that: 1) compared with the traditional method, the incidence of adverse events (such as potential adverse drug reactions, deep vein thrombosis, etc.) was reduced after the implementation of the Automated Medical System (OR = 0.43, 95% CI = [0.20, 0.93]; P = 0.03); 2) the average medical costs incurred during the use of the Automated Medical System were lower than those of the traditional method (OR = 1.13, 95% CI = [1.02, 1.24]; P = 0.02), which was cost-effective (OR = 2.03, 95% CI = [1.34, 3.07]; P = 0.0008); 3) the quality-adjusted life years obtained by patients observed during the implementation of the Automated Medical System were significantly higher than those of the conventional medical system (OR = 1.13, 95% CI = [1.02, 1.24]; P = 0.02). Conclusion: A multicenter, large-sample randomized controlled trial is needed to comprehensively explore the cost-effectiveness of Automated Medical Systems using a unified economic evaluation model and considering all costs associated with Automated Medical Syst

Intro: Long-term treatment with interferon-alfa (IFN) can reduce the disease burden of patients diagnosed with myeloproliferative neoplasms (MPN). Determining individual patient-responses to IFN-therapy may allow for efficient personalized treatment, reducing both drop out and disease burden. Methods: A mathematical model describing hematopoietic stem cells and the immune system is suggested. Considering the bone marrow and the blood allows for modelling disease dynamics both in the absence and presence of treatment. Through comprehensive modelling of the effects of IFN, the model was related to individualized patient-data consisting of longitudinal hematologic and molecular measurements. Treatment responses are modelled on a population-level, allowing for personalized predictions from a single pre-treatment data point. Results: Personalized fits were found to agree well with data. This allowed for a quantitative description of the treatment-response, yielding a mechanistic interpretation of differences between individual patients. Population-level treatment-responses were simulated. Based on pre-treatment data and the actual treatment scheduling, the population-level response was found to predict the treatment-response of particular patients accurately over a five-year period. Conclusion: Mechanism-based modelling of treatment effects demonstrates that hematologic and molecular observables can be predicted on the level of individual patients. Personalized patient-fits suggest that the effect of IFN-treatment can be quantified and interpreted through mathematical modelling, despite variation in hematologic and molecular response for different patients. Modelling suggests that both hematologic and molecular markers must be considered to avoid immediate relapse. Furthermore, personalized model-fits provides quantitative measures of the hematologic and molecular response, determining when treatment-cessation is appropriate. Proof-of-concept population-level modelling of treatment-responses from pre-treatment data successfully predicted clinical measures for a five-year period. This approach could have direct clinical relevance, offering expert guidance for clinical decisions about IFN-treatment of MPN-patients.

Bladder cancer is a common malignancy with over 80,000 estimated new cases and nearly 18,000 deaths per year in the United States alone. Therapeutic options for metastatic bladder cancer had not evolved much for nearly four decades, until recently, when five immune checkpoint inhibitors were approved by the FDA. Despite the activity of these drugs in some patients, the objective response rate for each is less than 25%. At the same time, fibroblast growth factor receptors (FGFRs) have been attractive drug targets for a variety of cancers, and in 2019 the FDA approved the first therapy targeted against FGFR3 for bladder cancer. Given the excitement around these new receptor tyrosine kinase and immune checkpoint targeted strategies, and the challenges they each may face on their own, emerging data suggest that combining these treatment options could lead to improved therapeutic outcomes. In this paper, we develop a mathematical model for FGFR3-mediated tumor growth and use it to investigate the impact of the combined administration of a small molecule inhibitor of FGFR3 and a monoclonal antibody against the PD-1/PD-L1 immune checkpoint. The model is carefully calibrated and validated with experimental data before survival benefits and dosing schedules are explored. Predictions of the model suggest that FGFR3 mutation reduces the effectiveness of anti-PD-L1 therapy, that there are regions of parameter space where each monotherapy can outperform the other, and that pretreatment with anti-PD-L1 therapy always results in greater tumor reduction even when anti-FGFR3 therapy is the more effective monotherapy.

MicroRNAs (miRNAs) are short (~22 nucleotides) non-coding RNAs that are often intricately integrated into the regulatory networks of various cellular processes and govern the cell fate decision making events associated with oncogenesis by regulating the gene expression through post-transcriptional modifications. miRNAs repress the target genes by either degrading the target mRNA or by inhibiting the process of translation. However, mathematical and computational modeling of miRNA-mediated target gene regulation in various cellular network motifs suggests that miRNAs play a much more complex role in cellular decision-making events. In this review, we give an overview of the quantitative insights obtained from such kind of mathematical modeling of miRNA mediated gene regulation by highlighting the various factors associated with miRNA regulation that are pivotal in diversifying the cell fate decisions related to oncogenesis. Intriguingly, recent experiments suggest that miRNAs can even upregulate the translation of the target protein under certain circumstances, which may lead to more complexities in miRNA-mediated gene regulations. We discussed possible avenues to explore such unusual biological observations related to miRNA’s that can be modeled to get a detailed understanding of the influence of miRNAs in the context of oncogenesis.

Once cancer is initiated, with normal cells mutated into malignant ones, a solid tumour grows, develops and spreads within its microenvironment invading the local tissue; the disease progresses and the cancer cells migrate around the body leading to metastasis, the formation of distant secondary tumours. Interactions between the tumour and its microenvironment drive this cascade of events which have devastating, if not fatal, consequences for the human host/patient. Among these interactions, biomechanical interactions are a vital component. In this paper, key biomechanical relationships are discussed through a review of modelling efforts by the mathematical and computational oncology community. The main focus is directed, naturally, towards lattice-free agent-based, force-based models of solid tumour growth and development. In such models interactions between pairs of cancer cells (as well as between cells and other structures of the tumour microenvironment) are governed by forces. These forces are ones of repulsion and adhesion, and are typically modelled via either an extended Hertz model of contact mechanics or using Johnson-Kendal-Roberts theory, both of which are discussed here. The role of the extracellular matrix in determining disease progression is outlined along with important cell-vessel interactions which combined together account for a great proportion of Hanahan and Weinberg’s “Hallmarks of Cancer”.

Introduction: The use of prostate-specific antigen (PSA) as a prognostic indicator for prostate cancer (PCa) patients is controversial, especially since it has been shown to correlate poorly with tumor burden. The poor quality of PSA as a biomarker could be explained by current guidelines not accounting for the mechanism by which it enters circulation. Given that mature blood vessels are relatively impermeable to it, we hypothesize that immature and leaky blood vessels, formed under angiogenic cues in a hypoxic tumor, facilitate PSA extravasation into circulation. Methods: To explore our hypotheses, we develop a nonlinear dynamical systems model describing the vascular growth of PCa, that explicitly links PSA leakage into circulation with changes in intra-tumoral oxygen tension and vessel permeability. The model is calibrated versus serum PSA and tumor burden time-courses from a mouse xenograft model of castration resistant PCa response to androgen deprivation. Results: The model recapitulates the experimentally observed – and counter-intuitive – phenomenon of increasing tumor burden despite decreasing serum PSA levels. The validated model is then extended to the human scale by incorporating patient-specific parameters and fitting individual PSA time-courses from patients with biochemically failing PCa. Our results highlight the limitations of using time to PSA failure as a clinical indicator of androgen deprivation efficacy. We propose an alternative indicator, namely a treatment efficacy index, for patients with castration resistant disease, to identify who would benefit most from enhanced androgen deprivation. Conclusions: A critical challenge in prostate cancer therapeutics is quantifying the relationship between serum PSA and tumor burden. Our results underscore the potential of mathematical modeling in understanding the limitations of serum PSA as a prognostic indicator. Finally, we provide a means of augmenting PSA time-courses in the diagnostic process, with changes in intra-tumoral vascularity and vascular architecture .

This study investigates the phylogenetic relationships, taxonomic status, and morphometric analysis of 21 naturally occurring taxa of the Acer genus in Turkey. A comparative analysis was conducted using 18 informative morphometric characters and DNA sequence data from the cpDNA ndhF, trnL-F, and nrDNA ITS gene regions. To date, there has been no comprehensive molecular and morphometric study conducted on the genus in Turkey. Factor Analysis of Mixed Data (FAMD) was performed on selected morphometric traits, revealing highly distinctive characteristics for the Acer genus at the series, sectional, species, and sub-species levels, including Dim1 traits such as leaf length, leaf width, petiole length, loculus length, loculus width, fruit wing length, and fruit length, as well as Dim2 traits such as pubescence of leaf beneath, margin, latex, and form of nutlets, along with inflorescence, bud, and shoot features. The nuclear ITS and chloroplast trnL-F gene regions also exhibited significant diversity and provided valuable information. Phylogenetically, Acer species in Turkey showed close relationships with species native to the Eurosiberian phytogeography. The results of the phylogenetic and morphometric analyses offered reliable taxonomic clarifications for the first time, specifically for the species Acer tauricolum, A. divergens (endemic to Turkey), A. orthocampestre, and A. cappadocicum subsp. cappadocicum. The chloroplast lineage of Acer species native to Turkey appears to have originated in the late Oligocene and experienced significant diversification during the Miocene. The majority of Acer phylogenetic positions in Turkey are likely influenced by the habitats created by the northern mountain ranges.

As a development-enhancing or a risk-promoting environment, coparenting may shape the association between maternal prenatal depressive symptoms and infant regulatory capacity. This study aimed to analyze the moderator role of positive and negative coparenting in the association between maternal prenatal depressive symptoms and infant regulatory capacity at 3 months. A sample of 103 primiparous couples (N = 206 parents) was recruited at the 1st trimester of pregnancy. Mothers reported on depressive symptoms at the 1st trimester of pregnancy, and both parents reported on depressive symptoms, coparenting, and infant regulatory capacity at 2 weeks and 3 months postpartum. Higher levels of maternal prenatal depressive symptoms and higher levels of maternal and paternal reports of negative coparenting at 2 weeks postpartum were associated with lower infant regulatory capacity at 3 months. Negative coparenting at 2 weeks postpartum accentuated the association between maternal prenatal depressive symptoms and infant regulatory capacity at 3 months. The results support a view of negative coparenting as a risk-promoting environment that can accentuate the association between maternal prenatal depressive symptoms and infant regulatory capacity. Infants in families with mothers with elevated prenatal depressive symptoms and with high levels of negative coparenting may be at high risk of low regulatory capacity.

This study addresses the assessment of metacognitive monitoring in Turkish preschool children, a critical aspect of their learning and development. A specialized paired-association task was designed to create an assessment tool targeting higher-order thinking skills in this demographic. Out of 190 participants aged 48 to 66 months, gathered from three preschools in Ankara, Turkey, the data analysis centered on 160 children, excluding those with missing or incomplete responses. The Metacognitive Thinking Test’s Judgment Part (Jp) underwent factor analysis, revealing a two-factor structure with 14 items demonstrating memory-confidence alignment. Notably, children tended to overestimate inaccurate recollections, aligning with the Dunning-Kruger effect. Despite limitations, the study offers valuable insights, shedding light on the intricate relationship between confidence and correctness in metacognitive development among young learners. This research lays the groundwork for future investigations in this domain.

Abstract Background Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn’s disease (CD) and ulcerative colitis (UC). Methods We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results. Results We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649-1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn’s disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis(OR 0.940; 95% CI 0.628-1.407; P = 0.762). In the other direction, IBD and it’s subtypes were not related to glucose and glycemic traits. Conclusions This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it’s subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion.

Background: In addition to the elimination diet, dietary composition may influence disease severity in patients with Eosinophilic Esophagitis (EoE) through modulation of the immune response. Aim: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. Methods: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (SET) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for six weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/High Power Field (PEC), both at baseline and after six weeks. Results: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate and milk products and PEC (p<0.05), while calcium (p=0.058) and full fat cheese/curd (p=0.056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice and white bread were significantly positively related to PEC (p<0.05) (unfavorable), while ultra-processed meals (p=0.059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p=0.058). Conclusion: Dietary composition may be related to inflammation in adult EoE patients. High quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE.

Perspective taking and cognitive flexibility are important abilities for navigating our everyday lives. In this longitudinal study with 108 children (61 girls, mostly White), we investigated the developmental relation between Level 1 perspective taking at 27 months of age and Level 2 perspective taking at 52 months of age as well as relations to cognitive flexibility at 52 months of age. We found that early perspective taking was significantly related to later, more complex perspective taking abilities as well as to cognitive flexibility. This highlights the importance of early perspective taking abilities for later perspective understanding and flexible cognition.

This systematic literature review scrutinizes the implementation and analysis of zk-SNARK, zk-STARK, and Bulletproof non-interactive zero-knowledge proof (NIZKP) protocols in privacy-preserving applications across diverse sectors. Examining 43 research works published from 2015 to April 2023, we categorized findings into financial, medical, business, general, and other domains. Our analysis highlights significant variations in real-world performance across implementations utilizing NIZKP protocols. However, divergent methodologies in security analyses hindered conclusive comparisons. Addressing research gaps, our future endeavors aim to establish a real-world benchmark for these protocols.

The Additively-Manufactured, System-Integrated Tip (AMSIT) project is leveraging the flexibility of 3D printing to integrate several technologies in a wind turbine blade tip, while reducing the levelized cost of electricity (LCOE) produced. The design integration is demonstrated for a 200 kilowatt-scale turbine with 13-meter blades, with the outer 15% of the blade replaced with a 3D-printed design. Aerodynamic performance is enhanced through inclusion of a winglet and surface texturing, both challenging for traditional manufacturing. Longevity and durability is improved through integrated lightning and leading edge erosion protection. Increased power, reduced repair frequency, and ease of repair through blade modularity all contribute to reduced LCOE. Cost models are are extended to modern megawatt-scale designs to estimate the impact of the technology at scale, demonstrating the potential to reduce LCOE very significantly for modern onshore turbines, with even higher potential savings offshore.

In nature, fishes have evolved functional skins with effective hydrodynamic performance to reduce water resistance, anti-fouling, facilitating predation and escaping from predators. Although a large number of fish scale-inspired structured surfaces have been explored, the incorporation of mucus on the structured surfaces has been largely ignored. Inspired by the skins of Osteichthyes fishes, a Janus hydrogel coating (JHC) is successfully prepared by a two-step UV light irradiation at room temperature. The bottom side of JHC (STH) achieves a shear adhesive strength of 103.3 ± 17.5 kPa and can strongly adhere to a large variety of surfaces, including metals, ceramic and polymers. The top surface of JHC (SLH) replicates the structure of cycloid scales, while the nature of hydrogel mimics the mucus on fish skin. SLH possesses prominent mechanical, anti-swelling, anti-fouling and drag reduction properties. The design strategy for JHC has potential applications in numerous fields, like, pipeline transportation, bioengineering, and shipping industry.

Although an increasing number of studies suggest that ferroptosis is involved in the development of rheumatoid arthritis, the specific mechanisms by which this phenomenon occurs remain elusive. The aim of this study was to investigate the genes associated with ferroptosis in RA and their mechanisms of action. We downloaded four gene expression profiles from the Gene Expression Omnibus (GEO) database. After identifying differentially expressed genes (DEGs) between rheumatoid arthritis (RA) synovial tissues and control synovial tissues, basic bioinformatics analyses were performed, including functional annotation, protein-protein interaction (PPI) network, hub gene screening, pharmacogenetic prediction and TF-mRNA-miRNA regulatory network construction. In addition, we analyzed RA immune infiltration according to the CIBERSORT algorithm to assess the relevance of infiltrating immune cells in RA patients. Finally, we identified four hub genes, including CDKN1A, epidermal growth factor receptor, ATF3, and JUN genes, and a total of 92 miRNAs and 14 transcription factors were predicted to form a regulatory network with the hub genes, and 8 drug candidates were screened. These findings may help us to better understand RA pathophysiological changes in basic research, as well as provide new evidence for clinical transformation. We believe that the drug candidates obtained in this study might be helpful for effective therapeutic in RA.

The photocatalytic oxidative coupling of thiols is one of the most popular methods to synthesis the disulfides. Triphenylamine and its derivatives (TPAs) are promising for the above reaction, but suffer from the easy polymerization and difficult separation. To overcome these obstacles while controlling the photogenerated electrons transfer directly to target substrates, herein, we constructed one TPA-based metal-organic framework (MOF), (Me2NH2)[Sr(TCPBA)]·2DMA·3H2O (1), by direct self-assembly of tris(4′-carboxybiphenyl)amine (H3TCPBA) and photoredox inert strontium ion (Sr2+). DFT calculations revealed that the valence band maximum (VBM) and the conduction band minimum (CBM) are mainly located on TCBPA3-, successfully inhibiting the undesirable electron migration to metal nodes. Experimental results indicated that 1 displays superior performance than homogeneous H3TCPBA, which may result from the abundant π···π and C-H···π interactions between the well-arranged TCBPA3- and the build-in electric field between the anionic framework and the Me2NH2+. This work highlights that immobilizing TPAs into MOFs is one promising approach to design heterogeneous photocatalysts for the synthesis of disulfides by oxidative coupling of thiols.

3-Idolenone is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemi-stry. A new method for the synthesis of trifluoromethylated 3-indolenones by carbonylation reaction catalyzed by Pd (0) is de-scribed. In the absence of an additive, 1-chloro-3,3,3-trifluoro-propylene (a cheap ozone-friendly CF3 structural unit) reacts with indole and carbon monoxide to synthesize trifluoromethylatedindolenone, good yield, Regioselectivity and Chemoselectivity, and strong resistance to basal functional groups such as alkynes, aldehydes and esters. It is worth mentioning that not only indole compounds can be well transformed into the corresponding products, pyrrole, hetero-indole also can be well completed the cor-responding chemical transformation. This late construction of trifluoromethylated indole/pyrrole 3-ketene provides a scientific method.