Anti-hypertensive effect and potential mechanism of gastrodia-uncaria granules based on network pharmacology and experimental validation.

Hypertension has become a major contributor to the morbidity and mortality of cardiovascular diseases worldwide. Despite the evidence of the anti-hypertensive effect of gastrodia-uncaria granules (GUG) in hypertensive patients, little is known about its potential therapeutic targets as well as the underlying mechanism. GUG components were sourced from TCMSP and HERB, with bioactive ingredients screened. Hypertension-related targets were gathered from DisGeNET, OMIM, GeneCards, CTD, and GEO. The STRING database constructed a protein-protein interaction network, visualized by Cytoscape 3.7.1. Core targets were analyzed via GO and KEGG using R package ClusterProfiler. Molecular docking with AutodockVina 1.2.2 revealed favorable binding affinities. In vivo studies on hypertensive mice and rats validated network pharmacology findings. GUG yielded 228 active ingredients and 1190 targets, intersecting with 373 hypertension-related genes. PPI network analysis identified five core genes: AKT1, TNF-α, GAPDH, IL-6, and ALB. Top enriched GO terms and KEGG pathways associated with the anti-hypertensive properties of GUG were documented. Molecular docking indicated stable binding of core components to targets. In vivo study showed that GUG could improve vascular relaxation, alleviate vascular remodeling, and lower blood pressure in hypertensive animal models possibly through inhibiting inflammatory factors such as AKT1, mTOR, and CCND1. Integrated network pharmacology and in vivo experiment showed that GUG may exert anti-hypertensive effects by inhibiting inflammation response, which provides some clues for understanding the effect and mechanisms of GUG in the treatment of hypertension.

Multiplex LAMP assay for detecting the prevalent species of dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus in the domestic environment.

Dermatophagoides farina (D. farinae) and Dermatophagoides pteronyssinus (D. pteronyssinus) are the prevalent kinds of house dust mites (HDMs). HDMs are common inhalant allergens that cause a range of allergic diseases, such as rhinitis, atopic dermatitis, and asthma. The epidemiology of these diseases is associated with exposure to mites. Therefore, in the present study, a method named multiplex loop-mediated isothermal amplification (LAMP) was developed to detect environmental dust mites. The multiplex LAMP assay allows amplification within a single tube and has an ITS plasmid detection limit as low as 40 fg/µL for both single dust mites and mixed dust mites (D. pteronyssinus and D. farinae), which is up to ten times more sensitive than classical PCR techniques. Furthermore, the multiplex LAMP method was applied to samples of single dust mites and clinical dust to confirm its validity. The multiplex LAMP assay exhibited higher sensitivity, simpler instrumentation, and visualization of test results, indicating that this method could be used as an alternative to traditional techniques for the detection of HDMs.

Microstructured Polyelectrolyte Elastomer-Based Ionotronic Sensors with High Sensitivities and Excellent Stability for Artificial Skins.

High-performance flexible pressure sensors are highly demanded for artificial tactile sensing. Using ionic conductors as the dielectric layer has enabled ionotronic pressure sensors with high sensitivities owing to giant capacitance of the electric double layer (EDL) formed at the ionic conductor/electronic conductor interface. However, conventional ionotronic sensors suffer from leakage, which greatly hinders long-term stability and practical applications. Herein, a leakage-free polyelectrolyte elastomer as the dielectric layer for ionotronic sensors is synthesized. The mechanical and electrical properties of the polyelectrolyte elastomer are optimized, a micropyramid array is constructed, and it is used as the dielectric layer for an ionotronic pressure sensor with marked performances. The obtained sensor exhibits a sensitivity of 69.6 kPa-1 , a high upper detecting limit on the order of 1 MPa, a fast response/recovery speed of ≈6 ms, and excellent stability under both static and dynamic loads. Notably, the sensor retains a high sensitivity of 4.96 kPa-1 at 500 kPa, and its broad sensing range within high-pressure realm enables a brand-new coding strategy. The applications of the sensor as a wearable keyboard and a quasicontinuous controller for a robotic arm are demonstrated. Durable and highly sensitive ionotronic sensors potentialize high-performance artificial skins for soft robots, human-machine interfaces, and beyond.

Acaricidal activities of paeonol from Moutan Cortex, dried bark of Paeonia × suffruticosa, against the grain pest mite Aleuroglyphus ovatus (Acari: Acaridae).

Aleuroglyphus ovatus (Acari: Acaridae) is a major pest mite of stored grains that is distributed worldwide. Paeonol, a phenolic component of the essential oil extracted from the Chinese herb Paeonia moutan, possesses a range of biological activities, including antiviral, antifungal and acaricidal activity. This study investigated the bioactivity of paeonol against A. ovatus and its effect on the activity of detoxification enzymes. The bioactivity of paeonol against A. ovatus was determined by contact, fumigation and repellency bioassays, and the mechanism was preliminarily explored via morphological observation of the color changes of mite epidermis and determination of the changing trend of some important enzymes associated with acaricidal efficacy in the mites. The results showed that the median lethal concentration (LC50) in the contact and fumigation bioassays was 9.832 µg/cm2 and 14.827 µg/cm3, respectively, and the acaricidal activity of paeonol was higher under direct contact than under fumigation. Dynamic symptomatology studies registered typical neurotoxicity symptoms including excitation, convulsion and paralysis in A. ovatus treated with paeonol. The enzyme activity of catalase (CAT), nitric oxide synthase (NOS) and glutathione-S-transferase (GST) was higher, whereas the activity of superoxide dismutase (SOD) and acetylcholinesterase (AChE) was lower, compared to the control group. CAT, NOS and GST were activated, whereas SOD and AChE activities were inhibited after paeonol intervention. Our findings suggest paeonol has potent acaricidal activity against A. ovatus and thus may be used as an agent to control the stored-product mite A. ovatus.

Rapid and visual detection of Toxoplasma gondii oocyst in cat feces using loop-mediated isothermal amplification (LAMP) assay.

Toxoplasma gondii is an obligate parasitic protozoon that transmits to animals and humans via ingested food. Cats that act as T. gondii's final hosts play a critical role in T. gondii transmission by shedding millions of oocysts. Timely diagnosis of infected cats is essential for preventing toxoplasmosis because oocysts are a putative T. gondii source in epidemiology. We developed a new visual LAMP assay targeting the B1 gene to analyze single oocysts in cat feces in this study. The amplification result could be visually estimated based on the color change. LAMP assay analytical sensitivity was 101 copies/µL for the B1 gene plasmid, which was tenfold better than the PCR reaction. There were no cross-reactions with other parasites. The LAMP assay can detect a single T. gondii oocyst in 200 mg of cat feces. The LAMP assay detected a single oocyst in 200 mg cat feces at a higher rate than the PCR assay (83.3% vs. 50.0%).

The complete mitochondrial genome of the chicken roundworm Ascaridia galli (Nematoda: Ascaridiidae).

Ascaridia galli (Nematoda: Ascaridiidae), infecting mainly the small intestine of chickens, is one of the most common nematodes in poultry worldwide. The complete mitochondrial genome sequence of A. galli was 13,981 bp in total length with 36 coding genes, namely, 12 protein-coding genes (PCGs), two ribosomal RNAs, and 22 transfer RNAs. All PCGs were transcribed in one direction. Phylogenetic analysis of the mitogenome of A. galli would further contribute to resolving its phylogenetic position and offer novel perspectives on phylogenetic studies of A. galli.

Rapid visual detection of the allergen Dermatophagoides farinae in house dust by loop-mediated isothermal amplification.

Dermatophagoides farinae is considered to be an important factor causing some allergic diseases, such as urticaria, allergic rhinitis, asthma, and other interrelated diseases. Avoiding exposure to allergens is the most effective way to reduce allergic reactions. In this study, we successfully established a loop-mediated isothermal amplification (LAMP) method for the detection of D. farinae DNA target internal transcribed spacer (ITS) and D. farinae 1 allergen (Der f 1) genes. The turbidity-monitoring system and visual fluorescent reagents were used to verify the test results of LAMP assay. Following optimization of the primers and reaction temperatures, the amplification sensitivity, specificity, and efficiency of the method for detecting D. farinae were assessed. There was no cross-reaction with other arthropod species that are commonly found in indoor environmental dust, such as Dermatophagoides pteronyssinus, Alophagoides ovatus, Periplaneta americana, Anopheles sinensis, and Musca domestica. Furthermore, the sensitivity of LAMP assay for detecting D. farinae DNA was 10 times greater than that of conventional PCR. The positive detection rate by the LAMP method was greater than the conventional PCR for both single D. farinae mites and D. farinae mites in indoor dust. A new type of LAMP method for D. farinae based on the Der f 1 and ITS genes was, therefore, successfully established. This study is the first time to detect the D. farinae allergen using LAMP assay. This assay could be useful as a model for the rapid detection of allergens produced by other house dust mites in the future.

Therapeutic Hypothermia Inhibits Hypoxia-Induced Cardiomyocyte Apoptosis Via the MiR-483-3p/Cdk9 Axis.

Background Therapeutic hypothermia has a beneficial effect on cardiac function after acute myocardial infarction, but the exact mechanism is still unclear. Recent research has suggested that microRNAs participate in acute myocardial infarction to regulate cardiomyocyte survival. This study aimed to explore the ability of hypothermia-regulated microRNA-483-3p (miR-483-3p) to inhibit hypoxia-induced myocardial infarction. Methods and Results Primary cardiomyocytes were cultured under hypoxia at 32 °C to mimic therapeutic hypothermia, and the differentially expressed microRNAs were determined by RNA sequencing. Therapeutic hypothermia recovered hypoxia-induced increases in apoptosis, decreases in ATP levels, and decreases in miR-483-3p expression. Overexpression of miR-483-3p exhibited effects similar to those of therapeutic hypothermia on hypoxia in the treatment of cardiomyocytes to associate with maintaining the mitochondrial membrane potential, and cyclin-dependent kinase 9 (Cdk9) was identified as a target gene with downregulated expression by miR-483-3p. Knockdown of Cdk9 also promoted cardiac survival, ATP production, and mitochondrial membrane potential stability under hypoxia. In vivo, the expression of miR-483-3p and Cdk9 was tested in the cardiac tissue of the mice with acute myocardial infarction, and the expression of miR-483-3p decreased and Cdk9 increased in the region of myocardial infarction. However, miR-483-3p was overexpressed with lentivirus, which suppressed apoptosis, infarct size (miR-483-3p, 22.00±4.04% versus negative control, 28.57±5.44%, P<0.05), and Cdk9 expression to improve cardiac contractility. Conclusions MiR-483-3p antagonizes hypoxia, leading to cardiomyocyte injury by targeting Cdk9, which is a new mechanism of therapeutic hypothermia.

A systematic review and meta-analysis of the association between sarcopenia and myocardial infarction.

BACKGROUND: Systematic review and meta-analysis of the association between sarcopenia and the development of myocardial infarction. METHODS: PubMed, Cochrane Library, and Embase were searched for studies on the association between sarcopenia and myocardial infarction from their inception until November 26, 2022. The fixed-effects model was used to calculate the combined risk ratio (RR) of sarcopenia in patients with myocardial infarction. Sensitivity analysis was used to test the robust of the combined result, and funnel plot were used to test publication bias. RESULTS: Five studies were included finally. There was no significant association between sarcopenia and risk of developing myocardial infarction [RR = 1.01; 95% CI = 0.94, 1.08; P = 0.317]. The sensitivity analysis showed robust of the combined result. The funnel plot showed no significant publication bias. CONCLUSION: Limited evidence suggests no definitive association between sarcopenia and risk of myocardial infarction.

Detection and assessment of dust mite allergens in an indoor environment in Anhui, China.

Dust in the home environment is thought to be a potential trigger for increasing allergic diseases, such as allergic rash, rhinitis, asthma, and other conditions, associated with dust mites. To verify the status of dust mite prevalence in indoor surroundings, we collected 189 dust samples from the air conditioner filters (n = 75) and floors (n = 114) of households, schools, and hotels in the Anhui area, China. All samples were measured for dust mite breeding rate and breeding density under light microscopy and analyzed for dust mite species Dermatophagoides farinae 1 (Der f 1) and Dermatophagoides pteronyssinus 1 (Der p 1) allergen using enzyme-linked immunosorbent assay (ELISA). The dust mite breeding rates were 34.67% (26/75) and 20.18% (23/114), respectively, in the dust samples from the floor and air conditioning filters. The breeding density was the highest in households (10/g), followed by schools (9/g) and hotels (4/g). ELISA indicated that the allergen threshold (2.0 µg/g dust) of Der f 1 was exceeded in only two samples and Der p 1 in one sample. Additionally, a questionnaire was used to investigate the health knowledge on allergic diseases involved in indoor facilities, finding that most allergy sufferers were aware that indoor dust might be responsible for their conditions. The findings suggest that regular maintenance of indoor hygiene and cleaning of air-conditioning filters should reduce the risks of exposure to indoor allergens.

Rapid and convenient detection of SARS-CoV-2 using a colorimetric triple-target reverse transcription loop-mediated isothermal amplification method.

Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 poses a significant threat to global public health. Early detection with reliable, fast, and simple assays is crucial to contain the spread of SARS-CoV-2. The real-time reverse transcription-polymerase chain reaction (RT-PCR) assay is currently the gold standard for SARS-CoV-2 detection; however, the reverse transcription loop-mediated isothermal amplification method (RT-LAMP) assay may allow for faster, simpler and cheaper screening of SARS-CoV-2. In this study, the triple-target RT-LAMP assay was first established to simultaneously detect three different target regions (ORF1ab, N and E genes) of SARS-CoV-2. The results revealed that the developed triplex RT-LAMP assay was able to detect down to 11 copies of SARS-CoV-2 RNA per 25 µL reaction, with greater sensitivity than singleplex or duplex RT-LAMP assays. Moreover, two different indicators, hydroxy naphthol blue (HNB) and cresol red, were studied in the colorimetric RT-LAMP assay; our results suggest that both indicators are suitable for RT-LAMP reactions with an obvious color change. In conclusion, our developed triplex colorimetric RT-LAMP assay may be useful for the screening of COVID-19 cases in limited-resource areas.

Rapid and Visual Detection of Toxoplasma gondii in Blood Samples from Pet Cats and Dogs by Loop-Mediated Isothermal Amplification.

Background: Toxoplasma gondii is an obligate intracellular parasite that invades nearly all nucleated cells of a broad spectrum of vertebrate hosts, and which may cause serious disease in immunocompromised patients, as well as in the immunologically incompetent fetus. This study aimed to establish a loop-mediated isothermal amplification (LAMP) technique to rapidly detect T. gondii in the blood infection by targeting the 529 bp repeat element of T. gondii. Materials and Methods: A turbidity monitoring system, together with visual reagent, was used to test the amplification result of the LAMP assay. In addition, the specificity and sensitivity of the LAMP assay were measured. Results: The results suggest that the successfully established LAMP assay profile can detect the DNA of T. gondii at 67°C within 40 min. The limit of detection of the LAMP assay was 101 copies/µL. No cross reaction occurred with Plasmodium vivax, Toxocara cati, Clonorchis sinensi, Spirometra mansoni or Cryptosporidium parvum. We validated the developed LAMP assay by detecting T. gondii in DNA extracted from 353 blood samples collected from domestic cats and dogs. The percentages of positive results in detecting these blood samples by LAMP and conventional PCR were 5.38% and 2.83%, respectively. Conclusions: Our findings show that the developed LAMP assay offers higher analytical sensitivity than conventional PCR and good analytical specificity, minimizes aerosol contamination, and can be applied to on-site rapid detection of T. gondii.

Strong Interfaces Enable Efficient Load Transfer for Strong, Tough, and Impact-Resistant Hydrogel Composites.

Many biological hydrogels are mechanically robust to bear quasi-static and impact loads. In contrast, the mechanical properties of synthetic hydrogels against impact loads remain substantially unexplored, albeit their mechanical robustness under quasi-static loads has been extensively developed. Here, we report on the design and synthesis of strong, tough, and impact-resistant hydrogel composites by reinforcing Ca-alginate/polyacrylamide hydrogels with glass fabrics and conferring strong interfaces between the hydrogel matrix and the fibers. The fabric enables high elastic modulus, the hydrogel matrix enables large dissipation, and the strong interfaces enable efficient load transfer for synergistic strengthening and toughening, which is manifested by digital image correlation analyses. Under quasi-static loads, the hydrogel composite exhibits an elastic modulus of 35 MPa and a toughness of 206.7 kJ/m2. Under impact loads, a piece of 7.7 g sample bears the impact of energy of 7.4 J and resists more than 100 cycles of consecutive impact of 600 mJ. As a proof-of-concept, a hydrogel composite as a safeguard to protect fragile glasses from impact is demonstrated. Because impact phenomena are universal, it is expected that the study on the impact of hydrogels will draw increasing attention.

A novel rapid visual detection assay for Toxoplasma gondii combining recombinase-aided amplification and lateral flow dipstick coupled with CRISPR-Cas13a fluorescence (RAA-Cas13a-LFD).

Toxoplasmosis, a parasitic disease resulting from Toxoplasma gondii infection, remains prevalent worldwide, and causes great harm to immunodepressed patients, pregnant women and newborns. Although various molecular approaches to detect T. gondii infection are available, they are either costly or technically complex. This study aimed at developing a rapid visual detection assay using recombinase-aided amplification (RAA) and lateral flow dipstick (LFD) coupled with CRISPR-Cas13a fluorescence (RAA-Cas13a-LFD) to detect T. gondii. The RAA-Cas13a-LFD assay was performed in an incubator block at 37 °C within 2 h, and the amplification results were visualized and determined through LFD by the naked eye. The detection limit was 1 × 10-6 ng/µL by our developed RAA-Cas13a-LFD protocol, 100-fold higher than that by qPCR assay (1 × 10-8 ng/µL). No cross-reaction occurred either with the DNA of human blood or Ascaris lumbricoides, Digramma interrupta, Entamoeba coli, Fasciola gigantica, Plasmodium vivax, Schistosoma japonicum, Taenia solium, and Trichinella spiralis, and the positive rate by RAA-Cas13a-LFD assay was identical to that by qPCR assay (1.50% vs. 1.50%) in detecting T. gondii infection in the unknown blood samples obtained from clinical settings. Our findings demonstrate that this RAA-Cas13a-LFD assay is not only rapid, sensitive, and specific and allows direct visualization by the naked eye, but also eliminates sophisticated and costly equipment. More importantly, this technique can be applied to on-site surveillance of T. gondii.

Title: Un nouveau test de détection visuelle rapide pour Toxoplasma gondii combinant une amplification assistée par polymérase recombinase et une bandelette réactive à flux latéral couplée à la fluorescence CRISPR-Cas13a (RAA-Cas13a-LFD). Abstract: La toxoplasmose, une maladie parasitaire résultant d'une infection à Toxoplasma gondii, reste répandue dans le monde et cause de graves dommages aux patients immunodéprimés, aux femmes enceintes et aux nouveau-nés. Bien que diverses approches moléculaires pour détecter l'infection à T. gondii soient disponibles, elles sont coûteuses ou techniquement complexes. Cette étude visait à développer un test de détection visuelle rapide utilisant une amplification assistée par recombinase et une bandelette réactive à flux latéral couplée à la fluorescence CRISPR-Cas13a (RAA-Cas13a-LFD) pour détecter T. gondii. Le test RAA-Cas13a-LFD a été effectué dans un bloc incubateur à 37 °C en 2 h, et les résultats d'amplification ont été visualisés et déterminés par LFD à l'œil nu. La limite de détection était de 1 × 10−6 ng/µL par notre protocole développé RAA-Cas13a-LFD, 100 fois plus élevée que celle du test qPCR (1 × 10−8 ng/µL). Aucune réaction croisée ne s'est produite ni avec l'ADN du sang humain ni avec Ascaris lumbricoides, Digramma interrupta, Entamoeba coli, Fasciola gigantica, Plasmodium vivax, Schistosoma japonicum, Taenia solium et Trichinella spiralis, et le taux de positivité par le test RAA-Cas13a-LFD était identique à celui par test qPCR (1,50 % contre 1,50 %) pour détecter l'infection à T. gondii dans les échantillons de sang inconnus obtenus en milieu clinique. Nos résultats démontrent que ce test RAA-Cas13a-LFD est non seulement rapide, sensible, spécifique et permet une visualisation directe à l'œil nu, mais élimine également les équipements sophistiqués et coûteux. Plus important encore, cette technique peut être appliquée à la surveillance sur place de T. gondii.

Sarcopenia predicts adverse outcomes in an elderly population with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: The development of sarcopenia is attributed to normal aging and factors like type 2 diabetes, obesity, inactivity, reduced testosterone levels, and malnutrition, which are factors of poor prognosis in patients with coronary artery disease (CAD). This study aimed to perform a meta-analysis to assess whether preoperative sarcopenia can be used to predict the outcomes after cardiac surgery in elderly patients with CAD. METHODS: PubMed, Embase, the Cochrane library, and Web of Science were searched for available papers published up to December 2020. The primary outcome was major adverse cardiovascular outcomes (MACE). The secondary outcomes were mortality and heart failure (HF)-related hospitalization. The random-effects model was used. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. RESULTS: Ten studies were included, with 3707 patients followed for 6 months to 4.5 ± 2.3 years. The sarcopenia population had a higher rate of MACE compared to the non-sarcopenia population (HR = 2.27, 95%CI: 1.58-3.27, P < 0.001; I2 = 60.0%, Pheterogeneity = 0.02). The association between sarcopenia and MACE was significant when using the psoas muscle area index (PMI) to define sarcopenia (HR = 2.86, 95%CI: 1.84-4.46, P < 0.001; I2 = 0%, Pheterogeneity = 0.604). Sarcopenia was not associated with higher late mortality (HR = 2.15, 95%CI: 0.89-5.22, P = 0.090; I2 = 91.0%, Pheterogeneity < 0.001), all-cause mortality (HR = 1.35, 95%CI: 0.14-12.84, P = 0.792; I2 = 90.5%, Pheterogeneity = 0.001), and death, HF-related hospitalization (HR = 1.37, 95%CI: 0.59-3.16, P = 0.459; I2 = 62.0%, Pheterogeneity = 0.105). The sensitivity analysis revealed no outlying study in the analysis of the association between sarcopenia and MACE after coronary intervention. CONCLUSION: Sarcopenia is associated with poor MACE outcomes in patients with CAD. The results could help determine subpopulations of patients needing special monitoring after CAD surgery. The present study included several kinds of participants; although non-heterogeneity was found, interpretation should be cautious.

Toll-Like Receptor 4 Mediated Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation in Vascular Smooth Muscle Cells via Src and Sirt1/3 Pathway.

Oxidized low-density lipoprotein (oxLDL) induced a foam-cell-like phenotype of the vascular smooth muscle cells (VSMCs), leading to the inflammatory responses incorporating Toll-like receptor- (Tlr-) mediated cellular alterations. However, the role of Tlr4 in foam cell formation and underlying molecular pathways has not been comprehensively elucidated. To further investigate the mechanism, VSMCs were incubated with different doses of oxLDL, and then, the lipid, reactive oxygen species (ROS) accumulation, Tlr family genes, and the foam cell phenotype were explored. We observed that oxLDL induced foam cell-like phenotype in VSMCs and led to lipid and ROS accumulation in a dose-dependent manner. Furthermore, in the Tlr family, Tlr4 demonstrated the strongest upregulation under oxLDL stimulation. Simultaneously, oxLDL induced activation of Src, higher expression of Nox2, and lower expression of Mnsod, Sirt1, and Sirt3. By interfering the TLR4 expression, the phenotype alteration, lipid accumulation in VSMCs, and Src kinase activation induced by oxLDL were abolished. After interfering Src activation, the oxLDL-induced lipid accumulation and foam cell phenotype in VSMCs were also alleviated. Furthermore, the ROS accumulation, upregulated Nox2 expression, downregulated Sirt1, Sirt3, and Mnsod expression in VSMCs under oxLDL stimulation were also relieved after the knockdown of Tlr4. Additionally, overexpression of Sirt1 and Sirt3 ameliorated the ROS accumulation and foam cell-like marker expression in VSMCs. These results demonstrated that beyond its familiar role in regulating inflammation response, Tlr4 is a critical regulator in oxLDL-induced foam cell formation in VSMCs via regulating Src kinase activation as well as Sirt1 and Sirt3 expression.

Direct observation of chemical short-range order in a medium-entropy alloy.

Complex concentrated solutions of multiple principal elements are being widely investigated as high- or medium-entropy alloys (HEAs or MEAs)1-11, often assuming that these materials have the high configurational entropy of an ideal solution. However, enthalpic interactions among constituent elements are also expected at normal temperatures, resulting in various degrees of local chemical order12-22. Of the local chemical orders that can develop, chemical short-range order (CSRO) is arguably the most difficult to decipher and firm evidence of CSRO in these materials has been missing thus far16,22. Here we discover that, using an appropriate zone axis, micro/nanobeam diffraction, together with atomic-resolution imaging and chemical mapping via transmission electron microscopy, can explicitly reveal CSRO in a face-centred-cubic VCoNi concentrated solution. Our complementary suite of tools provides concrete information about the degree/extent of CSRO, atomic packing configuration and preferential occupancy of neighbouring lattice planes/sites by chemical species. Modelling of the CSRO order parameters and pair correlations over the nearest atomic shells indicates that the CSRO originates from the nearest-neighbour preference towards unlike (V-Co and V-Ni) pairs and avoidance of V-V pairs. Our findings offer a way of identifying CSRO in concentrated solution alloys. We also use atomic strain mapping to demonstrate the dislocation interactions enhanced by the CSROs, clarifying the effects of these CSROs on plasticity mechanisms and mechanical properties upon deformation.

Clinical Relevance of Plasma Endogenous Tissue-Plasminogen Activator and Aortic Valve Sclerosis: Performance as a Diagnostic Biomarker.

Background: Aortic valve sclerosis (AVSc), a common precursor to calcific aortic valve disease, may progress into advanced aortic stenosis with hemodynamic instability. However, plasma biomarkers of such a subclinical condition remain lacking. Since impaired fibrinolysis featuring dysregulated tissue plasminogen activator (t-PA) is involved in several cardiovascular diseases, we investigated whether endogenous t-PA was also associated with AVSc. Methods: Plasma t-PA levels were measured in 295 consecutive patients undergoing standard echocardiography and Doppler flow imaging. Multiple logistic regression analyses were used to assess the association between t-PA and AVSc. Receiver operating characteristic curve analysis was performed for determining the diagnostic value of t-PA for AVSc. The performance of adding t-PA to clinical signatures of AVSc was evaluated. Concentration of t-PA was assessed in human sclerotic and non-sclerotic aortic valves by histology and immunohistochemistry analysis. Results: Plasma t-PA was higher in patients with AVSc than in non-AVSc counterparts (median, 2063.10 vs. 1403.17 pg/mL, p < 0.01). C-statistics of plasma t-PA for discriminating AVSc was 0.698 (95%CI: 0.639-0.758). The performance of t-PA for identifying AVSc was better among male and non-hypertensive patients [C-statistics (95%CI): 0.712 (0.634-0.790) and 0.805 (0.693-0.916), respectively]. Combination of t-PA and clinical factors improved classification of the patients (category-free NRI: 0.452, p < 0.001; IDI: 0.020, p = 0.012). The concentration of t-PA was three times higher in sclerotic compared to non-sclerotic aortic valves. Conclusion: Elevated circulating t-PA level confers an increased risk for AVSc. Further prospective studies with larger sample size are needed to examine if t-PA could serve as a diagnostic clinical marker for AVSc.

Value of plasma homocysteine to predict stroke, cardiovascular diseases, and new-onset hypertension: A retrospective cohort study.

The influences of hyperhomocysteinemia on cardiovascular diseases (CVDs), stroke and new-onset hypertension are unclear. The aim of the study is to explore the associations of homocysteine levels with stroke, CVDs, and new-onset hypertension in Chinese individuals.This retrospective cohort study included outpatients and inpatients from the Department of Geriatrics at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine from January to December 2000. They were divided based on their homocysteine (Hcy) levels in 2000: Q1 (<10 µmol/L), Q2 (10-15 µmol/L), and Q3 (>15 µmol/L) and according to whether they had hypertension at baseline. Information about stroke, mortality and major adverse cardiac events, and newly onset hypertension was gathered in December each year until 2017. The effects of Hcy levels on the risk for stroke and CVDs among all patients, and new-onset hypertension among patients without hypertension at baseline were evaluated.After adjustment for confounders, compared with the Q1 group (Hcy <10 µmol/L), when the Hcy increased to 10 to 15 µmol/L, the risks for stroke, CVDs, and new-onset hypertension significantly increased, and the hazard ratio and 95% confidence interval were 2.02 (1.35-3.05, P = .001), 2.22 (1.32-3.76, P = .003), and 7.20 (4.52-11.48, P < .001), respectively. Hcy improved the predictive capability of traditional risk factors for stroke. The optimal cut-off value of Hcy for predicting stroke was 13.4 µmol/L (sensitivity: 70.9%, specificity: 62.2%).Hcy 10 to 15 µmol/L is significantly associated with the risks for stroke, mortality and major adverse cardiac events, and hypertension. The best cut-off point of Hcy for predicting stroke is 13.4 µmol/L.

Density-Dependent Demography and Mass-Rearing of Carposina sasakii (Lepidoptera: Carposinidae) Incorporating Life Table Variability.

Carposina sasakii Matsumura is one of the most destructive fruit-boring pests of pome and stone fruit trees in eastern Asia. Because larvae complete their development inside a single fruit, larval density per fruit is a critical factor in their survival, development, and fecundity. The effect of larval density was examined to determine the ideal density for devising an economic and sustainable mass-rearing system for harvesting of C. sasakii. Mass production of insects of the same age of a specific stage is not only important in biological control, but also in pheromone extraction, culturing of entomopathogenic nematodes and fungi, etc. Life history data for six larval densities (1-5, 6-10, 11-15, 16-20, 21-30, and 31-40 larvae/apple) were collected at 25.5 ± 0.5°C, 75.0 ± 5.0% RH, and a photoperiod of 15:9 (L: D) h. Data were analyzed using the age-stage, two-sex life table. The results showed that the highest preadult survival rate (42.00%), fecundity (104.70 eggs), and population parameters (intrinsic rate of increase r = 0.0718 d-1, net reproductive rate R0 = 23.03 eggs, and finite rate of increase λ = 1.0744 d-1) were observed at a density of 1-5 larvae/apple. However, when the rearing costs and production rate were considered, the density of 16-20 larvae/apple was the most economical for mass-rearing C. sasakii in order to achieve a daily harvest rate of 1,000 pupae (from 273 apples per day). To ensure the sustainability of the mass-rearing system, we included the life table variability in the harvesting strategy.