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Turfgrass lawns provide many environmental benefits, including temperature moderation, soil stabilization in urban centers, and surface water runoff reduction in the rapidly urbanizing societies. Recently, more sustainable management of urban vegetation have arisen to encourage Florida homeowners to shift from high-input (e.g., fertilizer, water) to low-input landscapes through initiatives such as the Florida Friendly Landscapes and Florida Water Star Programs. To support the water conservation programs in Florida, and better understand homeowners' lawn choices, the objective of this study is to identify and evaluate homeowners' preferred turfgrass features for lawn choices and understand the context of promoting sustainable landscaping practices in the state of Florida. Approximately 1000 Florida homeowners were surveyed online and ranked their most preferred turfgrass features out of a set of 12 alternatives. A rank-ordered logit model was utilized to evaluate Florida homeowners’ preferences for different turfgrass features and determine if they influence turfgrass selection for Florida homeowners. The results showed that the top features were drought tolerance, color, frequency of mowing, disease resistance, and pest tolerance. Identification and communication of water proficient, low fertilizer input turfgrass cultivars that are tolerant to environmental stresses (e.g., drought, traffic, shade) are needed in Florida. Policymakers should promote strategies to combat drought tolerant cultivars. Extension agents should educate homeowners on grass dormancy and drought tolerance (affecting color change) as well as promote disease resistance and pest tolerant species through the Florida Friendly Landscape and WaterStar Programs.

Background Growing evidence indicates a significant correlation between polycystic ovary syndrome (PCOS) and endometrial carcinoma (EC); nevertheless, the fundamental molecular mechanisms involved continue to be unclear. Methods Initially, differential analysis, the least absolute shrinkage and selection operator (LASSO) regression, and support vector machine-recursive feature elimination (SVM-RFE) algorithms were employed to identify candidate genes associated with ferroptosis in PCOS. Subsequently, the TCGA-UCEC data were utilized to pinpoint the core gene. Then, the expression of ENPP2 in granulosa cells and endometrium of PCOS was validated using real-time PCR (RT-qPCR). Additionally, we investigated the role of ENPP2 in the progression from PCOS to EC through western blotting (WB), colony formation assay, cell scratch assay, transwell assay, and immunofluorescence (IF). Subsequently, ENPP2 gene set enrichment analysis (GSEA) analyses were conducted to identify common pathways involved in PCOS and EC, which were then verified by RT-qPCR. Finally, immune infiltration and the tumor microenvironment (TME) were explored to examine the involvement of ENPP2 in EC progression. Results The datasets TCGA-UCEC (pertaining to EC), GSE34526, GSE137684, and GSE6798 (related to PCOS) were procured and subjected to analysis. The gene ENPP2 has been recognized as the shared element connecting PCOS and EC. Next, we observed a significant downregulation of ENPP2 expression in the granulosa cells in PCOS compared to the normal patients, while an upregulation of ENPP2 expression was observed in the endometrium of hyperandrogenic PCOS patients relative to the normal. In vitro, the WB revealed that 5-dihydrotestosterone (DHT) upregulated ENPP2 expression in Ishikawa and HEC-1-A cells. Additionally, we found that ENPP2 promoted the proliferation, migration, and invasion of Ishikawa and HEC-1-A cells. Subsequently, we discovered that overexpressed ENPP2 may lead to an increase in CYP19A1 (aromatase) and AR mRNA level. IF demonstrated that ENPP2 increased the expression of AR, suggesting a regulatory role for ENPP2 in hormonal response within PCOS and EC. Our findings indicated a significant correlation between ENPP2 expression and the modulation of immune responses.

Abstract Objectives Examine US consumer pet‐related and veterinary service expenditures and factors influencing US households’ use of veterinary services. Methods Descriptive analysis on pet‐related and veterinary service expenditures and regression analysis on pet owners’ use of veterinary services, using data from the US Bureau of Labor Statistics Consumer Expenditure from 2006 to 2018, with the sample size of 257,836 households, of which 73,593 had pet expenses. Results From 1980 to 2018, the proportion of households with pet‐related and veterinary service expenditures increased. Since 2010, the percentage of pet‐owning households using veterinary services has increased substantially. Household characteristics were examined and significantly affected the probability of both pet and veterinary expenditures. Non‐White and Hispanic groups had increased pet ownership, but the likelihood of veterinary service use has not surpassed White and non‐Hispanic pet owners. Conclusions Understanding the effects of household sociodemographics, particularly race and ethnicity, on using veterinary services provides insights for optimizing strategic planning for the pet industry and veterinarians. Reviewing the implications helps adjust and fine‐tune strategies and influence the sustainability of the veterinary service sector by attracting different racial and ethnic groups. Future research might focus on other social and cultural factors influencing the utilization of veterinary care. The veterinary service sector can then effectively address pet care disparities, bridge existing gaps and improve economic viability.

Abstract Aspirin, also named acetylsalicylate, can directly acetylate the side‐chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic‐labeling aspirin‐d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+‐dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity. Interestingly, the lysine 408 of SIRT1 can be acetylated by CBP acetyltransferase in cells without aspirin supplement. Aspirin can inhibit SIRT1 to increase the levels of acetylated p53 and promote p53‐dependent apoptosis. Moreover, the knock‐in mice of the acetylation‐mimic mutant of SIRT1 show the decreased production of pro‐inflammatory cytokines and maintain intestinal immune homeostasis. The study indicates the importance of the acetylated internal functional site of SIRT1 in maintaining intestinal immune homeostasis.

Abstract Meiotic recombination requires the specific RecA homolog DMC1 recombinase to stabilize strand exchange intermediates in most eukaryotes. Normal DMC1 levels are crucial for its function, yet the regulatory mechanisms of DMC1 stability are unknown in any organism. Here, we show that the degradation of Arabidopsis DMC1 by the 26S proteasome depends on F-box proteins RMF1/2-mediated ubiquitination. Furthermore, RMF1/2 interact with the Skp1 ortholog ASK1 to form the ubiquitin ligase complex SCFRMF1/2. Genetic analyses demonstrate that RMF1/2, ASK1 and DMC1 act in the same pathway downstream of SPO11-1 dependent meiotic DNA double strand break formation and that the proper removal of DMC1 is crucial for meiotic crossover formation. Moreover, six DMC1 lysine residues were identified as important for its ubiquitination but not its interaction with RMF1/2. Our results reveal mechanistic insights into how the stability of a key meiotic recombinase that is broadly conserved in eukaryotes is regulated.

Environmental factors, including temperature, can modulate an animal’s lifespan. However, their underlying mechanisms remain largely undefined. We observed a profound effect of temperature on the aging of Caenorhabditis elegans (C. elegans) by performing proteomic analysis at different time points (young adult, middle age, and old age) and temperature conditions (20 °C and 25 °C). Importantly, although at the higher temperature, animals had short life spans, the shift from 20 °C to 25 °C for one day during early adulthood was beneficial for protein homeostasis since; it decreased protein synthesis and increased degradation. Consistent with our findings, animals who lived longer in the 25 °C shift were also more resistant to high temperatures along with oxidative and UV stresses. Furthermore, the lifespan extension by the 25 °C shift was mediated by three important transcription factors, namely FOXO/DAF-16, HSF-1, and HIF-1. We revealed an unexpected and complicated mechanism underlying the effects of temperature on aging, which could potentially aid in developing strategies to treat age-related diseases. Our data are available in ProteomeXchange with the identifier PXD024916.

Maintaining and caring for residential landscapes is a crucial aspect of homeownership in the United States. For homeowners in the United States, residential lawns represent a significant economic investment, signal their social commitments, and reflect their personal characters. To investigate the differences in Florida homeowners’ priorities regarding residential landscape features, an online survey of 1220 homeowners was conducted. Four different groups of homeowners were identified based on their perceived importance of the four landscape features, namely, environmental, financial, aesthetic, and psychological benefits. Factors such as environmental and financial attitudes and social norms influencing homeowners’ decision-making were examined. The findings revealed that homeowners’ knowledge of landscaping practices and environmental attitudes impact their prioritization regarding landscape features.

IntroductionThe overdiagnosing of papillary thyroid carcinoma (PTC) in China necessitates the development of an evidence-based diagnosis and prognosis strategy in line with precision medicine. A landscape of PTC in Chinese cohorts is needed to provide comprehensiveness.Methods6 paired PTC samples were employed for whole-exome sequencing, RNA sequencing, and data-dependent acquisition mass spectrum analysis. Weighted gene co-expression network analysis and protein-protein interactions networks were used to screen for hub genes. Moreover, we verified the hub genes' diagnostic and prognostic potential using online databases. Logistic regression was employed to construct a diagnostic model, and we evaluated its efficacy and specificity based on TCGA-THCA and GEO datasets.ResultsThe basic multiomics landscape of PTC among local patients were drawn. The similarities and differences were compared between the Chinese cohort and TCGA-THCA cohorts, including the identification of PNPLA5 as a driver gene in addition to BRAF mutation. Besides, we found 572 differentially expressed genes and 79 differentially expressed proteins. Through integrative analysis, we identified 17 hub genes for prognosis and diagnosis of PTC. Four of these genes, ABR, AHNAK2, GPX1, and TPO, were used to construct a diagnostic model with high accuracy, explicitly targeting PTC (AUC=0.969/0.959 in training/test sets).DiscussionMultiomics analysis of the Chinese cohort demonstrated significant distinctions compared to TCGA-THCA cohorts, highlighting the unique genetic characteristics of Chinese individuals with PTC. The novel biomarkers, holding potential for diagnosis and prognosis of PTC, were identified. Furthermore, these biomarkers provide a valuable tool for precise medicine, especially for immunotherapeutic or nanomedicine based cancer therapy.

As a role of TOX4, one of the regulatory proteins of PP1 phosphatases, in transcriptional regulation, authors here show that TOX4 restricts pause release and early productive elongation, and promotes Pol II recycling and transcriptional reinitiation.

State and local governments have implemented voluntary and mandatory programs to conserve and protect natural resources in and around urban developments. Even though the long-term environmental benefits are apparent, convincing homeowners to adopt sustainable landscapes with less water and chemical use is challenging. An important consideration from the successful policy implementation point of view is that homeowners have different environmental attitudes, which can be the determining factor that influences their adoption intentions of sustainable landscaping practices. This study assesses whether homeowners’ environmental attitude is a statistically significant predictor of sustainable landscape adoption intention. Moreover, homeowners’ perception of the effectiveness of the voluntary environmental programs may be influenced by their environmental attitudes and impose mediating effects on sustainable landscape adoption intentions. We also examine whether homeowners’ perceived effectiveness of voluntary environmental programs has a mediating effect on the adoption decision. The Value-Belief-Norm hierarchical model framework is utilized to examine both effects. The results revealed that homeowners’ pro-environmental attitudes influence their perceived effectiveness of voluntary programs and their sustainable landscape adoption intentions. The combined influence accounts for 13.6% of homeowners’ adoption intention. Homeowners’ personal norms also affect their perceived effectiveness of voluntary programs (9% variance explained), and the mediating effect of the perceived effectiveness of voluntary programs has an amplifying effect and positively influences the adoption intention. The implications for policymakers in the realm of landscape conservation programs are discussed.

Abstract Musk, the dried secretion from the musk sac gland which is located between the navel and genitals of mature male musk deer, is utilized as oriental medicine in east Asia. It has been utilized to treat conditions such as stroke, coma, neurasthenia, convulsions, and heart diseases in China since ancient times. This paper aims to provide a comprehensive overview of musk in zoology, chemical composition, pharmacology, clinical applications, and quality control according to the up-to-date literature. Studies found that musk mainly contains macrocyclic ketones, pyridine, steroids, fatty acids, amino acids, peptides, and proteins, whilst the main active ingredient is muscone. Modern pharmacological studies have proven that musk possesses potent anti-inflammatory effects, neuroprotective effects, anti-cancer effects, antioxidant effects, etc. Moreover, muscone, the main active ingredient, possesses anti-inflammatory, neuroprotective, antioxidant, and other pharmacological effects. In the quality control of musk, muscone is usually the main detection indicator, and the common analytical method is GC, and researchers have established novel and convenient methods such as HPLC-RI, RP-UPLC-ELSD, and Single-Sweep Polarography. In addition, quality evaluation methods based on steroids and the bioactivity of musk have been established. As for the identification of musk, due to various objective factors such as the availability of synthetic Muscone, it is not sufficient to rely on muscone alone as an identification index. To date, some novel technologies have also been introduced into the identification of musk, such as the electronic nose and DNA barcoding technology. In future research, more in vivo experiments and clinical studies are encouraged to fully explain the pharmacological effects and toxicity of musk, and more comprehensive methods are needed to evaluate and control the quality of musk.

This report is the third in a series from the Sustainable Residential Landscape Project. This report summarizes Floridian homeowners’ interest in and response to economic incentives to encourage the installation of more sustainable alternative residential landscapes based on a survey. Written by Hayk Khachatryan, Alicia Rihn, Xumin Zhang, and Michael Dukes, and published by the UF/IFAS Food and Resource Economics Department, July 2022.

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To understand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot, real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phosphoproteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloroplasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of photosystem (PS) II, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.

Live streaming commerce (LSC) effectively combines the traditional real economy and e-commerce. Based on more than half a million unique GIS data values on LSC activities sourced via Taobao (Alibaba), we traced the spatial distribution of different players along the supply chain and further highlighted the intermediary role of streamers in developing the inter-regional industry. This study guides industrial planning in a diversified regional context, especially in economically peripheral regions. Our results show the following outcomes: (1) in contrast to dispersed suppliers, streamers and consumers are highly clustered. This trend proves that streamers are rooted in a specific urban context while playing the role of an intermediary in inter-regional supply chains, effectively extending geographic interactivity between suppliers and (potential) customers. (2) LSC primarily promotes regional light industry, especially in economically peripheral and rural areas, and provides opportunities for rapid development in cities with skilled handicraft providers. (3) China’s LSC streams have a pyramid structure, and the top group is highly clustered in metropolitan regions, such as the Yangtze River Delta (YRD) and the Pearl River Delta (PRD). This clustering makes it easier for streamers to work with large, well-known brands. The bottom group is mainly in charge of expanding the supply chain within the region and relies more on the local industrial base. It is diversified due to the different types of businesses or products. Ultimately, we draw attention to adaptive spatial planning and resource allocation in the context of the economic and geographic reforms brought by this growing industry, and discuss the policy implications based on the relationships between the supply of and demand for live streamers from a broader regional perspective.

Introgression is an important driver of new genetic variation that increases species and genetic diversity. However, the relationship between introgression and geographic distribution of upland cotton is still unclear. Herein, we explored geographically comprehensive genomic data based on 890 upland cotton accessions to decipher the degree of introgression between different geographic distributions and its effect on selection and fiber quality. We found introgression intervals to exist across different geographic distributions. Introgression is affected by the similarity of the environment in which they live, and those with similar ecological environments tend to share the same introgression area. Introgression is affected by artificial selection. A genome-wide association study (GWAS) meta-analysis was performed with 6 fiber traits and identified 261 quantitative trait loci (QTLs). We found that 67 QTLs had introgression signals, and the genome interval size was 118.81 Mb, while 123 QTLs had selection signals, and the genomic interval was 28.38 Mb. These results provide insights into the population-scaled introgression landscape, suggesting that introgression contributed to the cotton genetic improvement, which provides a useful reference for studying intraspecific introgressions from different geographical distributions in other species.

The American landscape is well defined by the presence of turfgrass. To maintain the lush, green carpet, irrigation, fertilizer, and other necessary inputs are required. When these inputs are excessively applied, which is not uncommon, they are harmful to the natural environment. To mitigate potential adverse impacts, local and state governments are interested in policies that incentivize homeowners to maintain their lawns sustainably. But are there homeowners who are environmentally conscious and are willing to minimize their use of fertilizers or water? In this study, we evaluate the Floridian homeowners’ preferences for high- and low-level inputs of irrigation water and fertilizer using latent class logit (LCL) regression models based on data collected from an online choice experiment survey. Results indicated that there are heterogeneous preferences for the level of irrigation water and fertilizer application by Floridian homeowners, including high-input users (33% of the sample), irrigation-conscious users (27%), fertilizer-conscious users (23%), and moderate-input users (17%). The policy and marketing implications for relevant stakeholders are discussed.

Aramid nanofibers (ANFs) were successfully produced by deprotonation of Kevlar fiber followed by grafting epichlorohydrin in dimethyl sulfoxide solution. The ANFs were then incorporated into carboxylated acrylonitrile butadiene rubber (XNBR) by means of latex blending, followed by vulcanization. The interaction between ANFs and XNBR, and the effects of ANFs on the mechanical strength, dielectric properties, and thermal stability of ANF/XNBR nanocomposites were investigated. The results revealed that hydrogen bonding and covalent bonding interactions existed between ANFs and the XNBR matrix and played a critical role in the reinforcement of ANFs to XNBR nanocomposites. After adding 5 phr (parts per hundred rubber) of ANFs, the XNBR nanocomposite exhibited a significant improvement in mechanical properties, namely a 182% increase in tensile strength and a 101% increase in tear strength. In addition, the dielectric constant and thermal properties of ANF/XNBR also increased dramatically. ANFs may thus make an ideal candidate for high-performance rubber materials.

Post-translational protein modifications can affect lifespan and aging but age-dependent ubiquitylation changes have not yet been systematically characterized. Here, the authors analyze age-related proteome and ubiquitylome dynamics in Drosophila and identify increasing H2A ubiquitylation as a conserved aging marker.

Objective: The probability of late recurrent atrial fibrillation (AF) after radiofrequency ablation (RFA) has not yet been fully clarified. This study aims to study the association of left atrial appendage (LAA) morphology with AF recurrence after RFA.Methods: We retrospectively enrolled 84 patients (24 patients had persistent AF, 60 patients had paroxysmal AF) who underwent RFA in Shanghai East Hospital from June 2014 to May 2018. The mean follow-up of these patients was 618.6 days. According to preoperative transesophageal echocardiography (TEE), the morphology feature of LAA was classified and evaluated by two classification methods. The first method was divided into chicken-wing, windsock, cactus, and cauliflower, and the second method was divided into one lobe, two lobes, and multiple lobes. The correlation between morphological feature of LAA and the recurrence rate of AF after RFA was analyzed.Results: During follow-up, 12 patients (50%) and 10 patients (16.7%) had AF recurrence in persistent and paroxysmal AF, respectively. The LAA morphology was associated with the recurrence of AF after RFA with the chicken-wing highest recurrence risk (68.2%). The structure type of LAA was also related to the AF recurrence rate (p < 0.01). Compared with one lobe and multiple lobes, two lobes (recurrence, 47.6%) were more likely associated with the recurrence of AF (p < 0.02). Logistic regression analysis showed that the chicken-wing group had a higher risk of recurrence after RFA (OR = 8.13, p = 0.004), and the windsock group had a lower risk of recurrence (OR = 0.17, p = 0.002).Conclusion: The morphological feature of LAA is related to the recurrence risk of AF after RFA. LAA morphology assessment can predict the risk of AF recurrence.

This report summarizes Floridian homeowners’ perceptions of Florida-Friendly Landscapes, which aim to reduce inputs and costs while improving environmental health. Written by Hayk Khachatryan, Alicia Rihn, Xumin Zhang, and Michael Dukes, and published by the UF/IFAS Food and Resource Economics Department, May 2021.

This 5-page fact sheet written by Hayk Khachatryan, Alicia Rihn, Xumin Zhang, and Michael Dukes and published by the UF/IFAS Food and Resource Economics Department is the first in a series from the Sustainable Residential Landscape Project, a study conducted in 2016 to address perceptions of landscapes in Florida, different factors that could influence the adoption of more sustainable landscape options, and ways to promote sustainable landscaping options. The Sustainable Residential Landscape Project was funded by the UF/IFAS Center for Landscape Conservation and Ecology (CLCE).

Cercariae invasion of the human skin is the first step in schistosome infection. Proteases play key roles in this process. However, little is known about the related hydrolytic enzymes in Schistosoma japonicum. Here, we investigated the biochemical features, tissue distribution and biological roles of a cathepsin B cysteine protease, SjCB2, in the invasion process of S. japonicum cercariae. Enzyme activity analysis revealed that recombinant SjCB2 is a typical cysteine protease with optimum temperature and pH for activity at 37°C and 4.0, respectively, and can be totally inhibited by the cysteine protease inhibitor E-64. Immunoblotting showed that both the zymogen (50 kDa) and mature enzyme (30.5 kDa) forms of SjCB2 are expressed in the cercariae. It was observed that SjCB2 localized predominantly in the acetabular glands and their ducts of cercariae, suggesting that the protease could be released during the invasion process. The protease degraded collagen, elastin, keratin, fibronectin, immunoglobulin (A, G and M) and complement C3, protein components of the dermis and immune system. In addition, proteomic analysis demonstrated that SjCB2 can degrade the human epidermis. Furthermore, it was showed that anti-rSjCB2 IgG significantly reduced (22.94%) the ability of the cercariae to invade the skin. The cysteine protease, SjCB2, located in the acetabular glands and their ducts of S. japonicum cercariae. We propose that SjCB2 facilitates skin invasion by degrading the major proteins of the epidermis and dermis. However, this cysteine protease may play additional roles in host-parasite interaction by degrading immunoglobins and complement protein.

Synaptic positions underlie precise circuit connectivity. Synaptic positions can be established during embryogenesis and sustained during growth. The mechanisms that sustain synaptic specificity during allometric growth are largely unknown. We performed forward genetic screens in C. elegans for regulators of this process and identified mig-17, a conserved ADAMTS metalloprotease. Proteomic mass spectrometry, cell biological and genetic studies demonstrate that MIG-17 is secreted from cells like muscles to regulate basement membrane proteins. In the nematode brain, the basement membrane does not directly contact synapses. Instead, muscle-derived basement membrane coats one side of the glia, while glia contact synapses on their other side. MIG-17 modifies the muscle-derived basement membrane to modulate epidermal-glial crosstalk and sustain glia location and morphology during growth. Glia position in turn sustains the synaptic pattern established during embryogenesis. Our findings uncover a muscle-epidermis-glia signaling axis that sustains synaptic specificity during the organism’s allometric growth.

Abstract Background In a previous study, we found that titrating clopidogrel maintenance doses (MDs) according to vasodilator-stimulated phosphoprotein (VASP) monitoring minimised the rate of major adverse cardiovascular and cerebral events (MACCE) after percutaneous coronary intervention (PCI) without increasing bleeding in patients with high on-treatment platelet reaction to clopidogrel. This study aimed to investigate whether VASP-guided clopidogrel MD could reduce thromboembolism and bleeding in atrial fibrillation (AF) patients requiring anticoagulation and scheduled for PCI. Methods AF patients scheduled for PCI were recruited between July 2014 and July 2016. These patients were allocated into VASP-guided (n = 250) and control (n = 253) groups depending on the clopidogrel MD profile. In the VASP-guided group, clopidogrel MD was titrated by the platelet reactivity index (PRI), whereas in the control group, clopidogrel MD was fixed at 75 mg per day. The primary endpoint was MACCE and secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding 1 year after PCI. Results Five hundred and three patients were included in the present study, with 1-year data available for 95.6% patients. The average CHA2DS2-VASc score of the whole population was 3.7 ± 0.7 and the average HAS-BLED score was 3.2 ± 0.4. MACCE was less in the VASP-guided group than in the control group (2.5% vs. 5.0%, P = 0.02). The incidence of major bleeding was comparable between both groups (3.0% vs. 2.8%, P = 0.72) and minor bleeding was higher in the VASP-guided group than in the control group (15.3% vs. 9.7%, P = 0.03). Kaplan-Meier analysis indicated that there was no difference in survival between both groups (log-rank test, P = 0.68). Conclusions In AF patients requiring anticoagulation and scheduled for PCI, VASP-guided antiplatelet therapy reduced major cardiovascular and cerebral adverse events, accompanied by increased minor bleeding events. Trial registration The present study was retrospectively registered in the Chinese Clinical Trial Registry, A Primary Registry of the International Clinical Trial Registry Platform, World Health Organisation (Registration no: ChiCTR-IOR-17013854). The registered date was December 11, 2117.

CD4+ T-cells play crucial roles in the injured heart. However, the way in which different CD4+ T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4+ subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4+ T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1β, MCP-3, and GRO-α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1β, MCP-3, and GRO-α increased in both injured heart tissues and serum, while IFN-γ, IL-12P70, IL-2, IL-1β, IL-18, TNF-α, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1α, RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN-γ, IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN-γ, IL-12P70, IL-2, IL-18, TNF-α, IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO-α were reduced, while IL-1β and MIP-2 were elevated at day 14. IL-13 and MIP-1β showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1β, MCP-3, and GRO-α mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4+ T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.

Multiple sclerosis (MS), a common neurodegenerative disease of the CNS, is characterized by the loss of oligodendrocytes and demyelination. Tumor necrosis factor α (TNF-α), a proinflammatory cytokine implicated in MS, can activate necroptosis, a necrotic cell death pathway regulated by RIPK1 and RIPK3 under caspase-8-deficient conditions. Here, we demonstrate defective caspase-8 activation, as well as activation of RIPK1, RIPK3, and MLKL, the hallmark mediators of necroptosis, in the cortical lesions of human MS pathological samples. Furthermore, we show that MS pathological samples are characterized by an increased insoluble proteome in common with other neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). Finally, we show that necroptosis mediates oligodendrocyte degeneration induced by TNF-α and that inhibition of RIPK1 protects against oligodendrocyte cell death in two animal models of MS and in culture. Our findings demonstrate that necroptosis is involved in MS and suggest that targeting RIPK1 may represent a therapeutic strategy for MS.

Schistosomiasis is a devastating parasitic disease caused by tremotodes of the genus Schistosoma. Eggs produced by sexually mature schistosomes are the causative agents of for pathogenesis and transmission. Elucidating the molecular mechanism of schistosome development and sexual maturation would facilitate the prevention and control of schistosomiasis. Acetylation of lysine is a dynamic and reversible post-translational modification playing keys role in many biological processes including development in both eukaryotes and prokaryotes. To investigate the impacts of lysine acetylation on Schistosoma japonicum (S. japonicum) development and sexual maturation, we used immunoaffinity-based acetyllysine peptide enrichment combined with mass spectrometry (MS), to perform the first comparative analysis of proteome-wide lysine acetylation in both female and male, juvenile (18 days post infection, 18 dpi) and adult (28 dpi) schistosome samples. In total, we identified 874 unique acetylated sites in 494 acetylated proteins. The four samples shared 47 acetylated sites and 46 proteins. More acetylated sites and proteins shared by both females and males were identified in 28 dpi adults (189 and 143, respectively) than in 18 dpi schistosomula (76 and 59, respectively). More stage-unique acetylated sites and proteins were also identified in 28 dpi adults (494 and 210, respectively) than in 18 dpi schistosomula (73 and 44, respectively). Functional annotation showed that in different developmental stages and genders, a number of proteins involving in muscle movement, glycometabolism, lipid metabolism, energy metabolism, environmental stress resistance, antioxidation, etc., displayed distinct acetylation profiles, which was in accordance with the changes of their biological functions during schistosome development, suggesting that lysine acetylation modification exerted important regulatory roles in schistosome development. Taken together, our data provided the first comparative global survey of lysine acetylation in juvenile and adult S. japonicum, which would deepen our understanding of the molecular mechanism of schistosome development and sexual maturation, and provide clues for the development of new anti-schistosome strategies.

The amount and form of dietary casein have been shown to affect energy metabolism and lipid accumulation in mice, but the underlying mechanisms are not fully understood. We investigated 48 hrs urinary metabolome, hepatic lipid composition and gene expression in male C57BL/6J mice fed Western diets with 16 or 32 energy% protein in the form of extensively hydrolyzed or intact casein. LC-MS based metabolomics revealed a very strong impact of casein form on the urinary metabolome. Evaluation of the discriminatory metabolites using tandem mass spectrometry indicated that intake of extensively hydrolyzed casein modulated Phase II metabolism associated with an elevated urinary excretion of glucuronic acid- and sulphate conjugated molecules, whereas glycine conjugated molecules were more abundant in urine from mice fed the intact casein diets. Despite the differences in the urinary metabolome, we observed no differences in hepatic expression of genes involved in Phase II metabolism, but it was observed that expression of Abcc3 encoding ATP binding cassette c3 (transporter of glucuronic acid conjugates) was increased in livers of mice fed hydrolyzed casein. As glucuronic acid is derived from glucose and sulphate is derived from cysteine, our metabolomic data provided evidence for changes in carbohydrate and amino acid metabolism and we propose that this modulation of metabolism was associated with the reduced glucose and lipid levels observed in mice fed the extensively hydrolyzed casein diets.

Background: This study was designed to investigate the effect of clopidogrel-related gene polymorphisms on platelet reactivity and clinical outcome in Chinese Han patients. Materials and Methods: Three hundred and thirty-six percutaneous coronary intervention - treated patients were recruited and followed for 1 year. Blood samples were collected from all patients for DNA genotyping. The platelet reactivity unit was measured by the VerifyNow technique. The CYP2C19*2, CYP2C19*3, CYP2C19*17, ATP-binding cassette subfamily B member 1, ITGB3, CYP2C9*3, CYP2B6*9, and P2Y12 alleles were assessed. Results: The clinical endpoints were related to previous heart disease history (11.90% vs. 28.57%, P = 0.017), stroke (12.24% vs. 16.67%, P = 0.039), and diabetes (27.55% vs. 52.38%, P = 0.047). High on-treatment platelet reactivity (HTPR) was frequent in advanced age (P = 0.019), male gender (P = 0.016), hypertension (P = 0.033), and chronic renal failure (P = 0.040). There were more endpoints in the CYP2C19*2 and P2Y12 mutant carriers (76.19% vs. 43.20%, P< 0.001; 50.00% vs. 35.71%, P = 0.001, respectively), whereas fewer in the CYP2C19*17 mutant carriers (11.90% vs. 56.46%, P = 0.001). CYP2C19*2 and P2Y12 polymorphism manifested HTPR (194.25 ± 45.91 vs. 151.38 ± 58.14, P< 0.001; 180.33 ± 67.25 vs. 161.89 ± 56.49, P = 0.008, respectively), whereas CYP2C19*17 mutant improved platelet reactivity (97.17 ± 45.38 vs. 169.08 ± 57.15, P = 0.003). However, there were no further cardiovascular deaths in endpoint patients. Conclusion: In Han Chinese people of mainland China, clopidogrel-related gene polymorphisms are related to variable platelet reactivity after clopidogrel maintenance dosing, which influences major adverse cardiovascular events, without an effect on cardiac death.