Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin.

The emergence of multidrug-resistant (MDR) bacteria presents a significant challenge to public health, increasing the risk of infections that are resistant to current antibiotic treatment. Antimicrobial peptides (AMPs) offer a promising alternative to conventional antibiotics in the prevention of MDR bacterial infections. In the present study, we identified a novel cathelicidin AMP from Gekko japonicus, which exhibited broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with minimal inhibitory concentrations ranging from 2.34 to 4.69 µg/mL. To improve its potential therapeutic application, a series of peptides was synthesized based on the active region of the gecko-derived cathelicidin. The lead peptide (RH-16) showed an antimicrobial activity comparable to that of the parent peptide. Structural characterization revealed that RH-16 adopted an amphipathic α-helical conformation. Furthermore, RH-16 demonstrated neither hemolytic nor cytotoxic activity but effectively killed a wide range of clinically isolated, drug-resistant bacteria. The antimicrobial activity of RH-16 was attributed to the nonspecific targeting of bacterial membranes, leading to rapid bacterial membrane permeabilization and rupture. RH-16 also retained its antibacterial activity in plasma and exhibited mild toxicity in vivo. Notably, RH-16 offered robust protection against skin infection in a murine model. Therefore, this newly identified cathelicidin AMP may be a strong candidate for future pharmacological development targeting multidrug resistance. The use of a rational design approach for isolating the minimal antimicrobial unit may accelerate the transition of natural AMPs to clinically applicable antibacterial agents.

Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18.

Background: Management of low-density lipoprotein cholesterol (LDL-C) in Asia remains suboptimal, with ∼50% of patients who are treated with lipid-lowering therapies (LLTs) unable to achieve their guideline-recommended LDL-C goals. Asian-representative studies of the use of inclisiran are needed. Objectives: The authors sought to evaluate the efficacy and safety of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or high risk of ASCVD, as an adjunct to diet and maximally tolerated statin dose, with or without additional LLTs. Methods: The ORION-18 was a phase 3 double-blind trial in which patients were randomized 1:1 to receive either 300 mg inclisiran sodium or matching placebo on days 1, 90, and 270. Percentage change in LDL-C from baseline to day 330 was the primary endpoint. Results: A total of 345 patients (mean age 59.5 years, mean baseline LDL-C 109 mg/dL, 74.7% male) were randomized to inclisiran or placebo. Baseline characteristics were similar in both groups. The percentage decrease in LDL-C from baseline to day 330 was 57.2% (P < 0.001); proprotein convertase subtilisin/kexin type 9 was reduced by 78.3% (P < 0.001). Time-adjusted percentage reduction in LDL-C from baseline after day 90 and up to day 360 was 56.3%. At day 330, 71.7% of participants with inclisiran achieved ≥50% reduction in LDL-C compared with 1.5% with placebo. Over the study period, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol (HDL-C) levels were decreased significantly, and HDL-C levels increased. The incidence of adverse events with inclisiran was similar to that with placebo. Conclusions: In Asian patients with ASCVD or high risk of ASCVD, inclisiran was effective and safe. (Study of Efficacy and Safety of Inclisiran in Asian Participants With Atherosclerotic Cardiovascular Disease [ASCVD] or ASCVD High Risk and Elevated Low-Density Lipoprotein Cholesterol [LDL-C] [ORION-18]; NCT04765657).

Epidemiological characteristics of seven notifiable respiratory infectious diseases in the mainland of China: an analysis of national surveillance data from 2017 to 2021.

BACKGROUND: Respiratory infectious diseases (RIDs) remain a pressing public health concern, posing a significant threat to the well-being and lives of individuals. This study delves into the incidence of seven primary RIDs during the period 2017-2021, aiming to gain deeper insights into their epidemiological characteristics for the purpose of enhancing control and prevention strategies. METHODS: Data pertaining to seven notifiable RIDs, namely, seasonal influenza, pulmonary tuberculosis (PTB), mumps, scarlet fever, pertussis, rubella and measles, in the mainland of China between 2017 and 2021 were obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression software was utilized to analyze temporal trends, while SaTScan software with a Poisson probability model was used to assess seasonal and spatial patterns. RESULTS: A total of 11,963,886 cases of the seven RIDs were reported during 2017-2021, and yielding a five-year average incidence rate of 170.73 per 100,000 individuals. Among these RIDs, seasonal influenza exhibited the highest average incidence rate (94.14 per 100,000), followed by PTB (55.52 per 100,000), mumps (15.16 per 100,000), scarlet fever (4.02 per 100,000), pertussis (1.10 per 100,000), rubella (0.59 per 100,000), and measles (0.21 per 100,000). Males experienced higher incidence rates across all seven RIDs. PTB incidence was notably elevated among farmers and individuals aged over 65, whereas the other RIDs primarily affected children and students under 15 years of age. The incidences of PTB and measles exhibited a declining trend from 2017 to 2021 (APC = -7.53%, P = 0.009; APC = -40.87%, P = 0.02), while the other five RIDs peaked in 2019. Concerning seasonal and spatial distribution, the seven RIDs displayed distinct characteristics, with variations observed for the same RIDs across different regions. The proportion of laboratory-confirmed cases fluctuated among the seven RIDs from 2017 to 2021, with measles and rubella exhibiting higher proportions and mumps and scarlet fever showing lower proportions. CONCLUSIONS: The incidence of PTB and measles demonstrated a decrease in the mainland of China between 2017 and 2021, while the remaining five RIDs reached a peak in 2019. Overall, RIDs continue to pose a significant public health challenge. Urgent action is required to bolster capacity-building efforts and enhance control and prevention strategies for RIDs, taking into account regional disparities and epidemiological nuances. With the rapid advancement of high-tech solutions, the development and effective implementation of a digital/intelligent RIDs control and prevention system are imperative to facilitate precise surveillance, early warnings, and swift responses.

[Main Infection Control Measures for Respiratory Infectious Diseases in Medical Institutions and Public Places in China].

Respiratory infectious diseases (RID) are the major public health problems threatening the people's lives and health.Infection control (IC) is one of the effective tools to contain the occurrence and spread of RID.We collected the articles and data on IC published since January 1,2018 and summarized the achievements,problems,and challenges of IC from administrative control,management control,environment and engineering control,and personal protection in the medical institutions and public places in China.The efforts for IC vary in different regions and medical institutions of different levels.There are still links to be improved for IC from administrative control,management control,environment and engineering control,and personal protection,especially in community-level medical institutions and public areas.It is urgent to strengthen the implementation of IC policies and conduct IC precisely according to local situations.We proposed the following suggestions.First,the existing IC products and tools should be applied to precisely implement the IC measures;second,modern high technology should be employed to develop efficient and convenient IC products and tools;finally,a digital or intelligent IC platform should be built for monitoring infections,so as to contain the occurrence and spread of RID.

Epidemiological Characteristics of Notifiable Respiratory Infectious Diseases in Mainland China from 2010 to 2018.

Respiratory infectious diseases (RIDs) pose threats to people's health, some of which are serious public health problems. The aim of our study was to explore epidemic situations regarding notifiable RIDs and the epidemiological characteristics of the six most common RIDs in mainland China. We first collected the surveillance data of all 12 statutory notifiable RIDs for 31 provinces in mainland China that reported between 2010 and 2018, and then the six most prevalent RIDs were selected to analyze their temporal, seasonal, spatiotemporal and population distribution characteristics. From 2010 to 2018, there were 13,985,040 notifiable cases and 25,548 deaths from RIDs in mainland China. The incidence rate of RIDs increased from 109.85/100,000 in 2010 to 140.85/100,000 in 2018. The mortality from RIDs ranged from 0.18/100,000 to 0.24/100,000. The most common RIDs in class B were pulmonary tuberculosis (PTB), pertussis, and measles, while those in class C were seasonal influenza, mumps and rubella. From 2010 to 2018, the incidence rate of PTB and rubella decreased; however, pertussis and seasonal influenza increased, with irregular changes in measles and mumps. The mortality from PTB increased from 2015 to 2018, and the mortality from seasonal influenza changed irregularly. PTB was mainly prevalent among people over 15 years old, while the other five common RIDs mostly occurred among people younger than 15 years old. The incidence of the six common RIDs mostly occurred in winter and spring, and they were spatiotemporally clustered in different areas and periods. In conclusion, PTB, seasonal influenza and mumps remain as public health problems in China, suggesting that continuous government input, more precise interventions, and a high-tech digital/intelligent surveillance and warning system are required to rapidly identify emerging events and timely response.

Efficacy and Safety of Evolocumab in Chinese Patients with Primary Hypercholesterolemia and Mixed Dyslipidemia: 12-Week Primary Results of the HUA TUO Randomized Clinical Trial.

INTRODUCTION: Evolocumab, a fully human proprotein convertase/subtilisin kexin type 9 inhibitor antibody, significantly lowers low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes mellitus and hyperlipidemia and mixed dyslipidemia. This 12-week study evaluated the efficacy and safety of evolocumab in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia at different levels of cardiovascular disease risk. METHODS: HUA TUO was a 12-week randomized, double-blind, placebo-controlled study. Chinese patients aged 18 years or older on stable optimized statin therapy were randomized 2:2:1:1 to receive evolocumab 140 mg every 2 weeks (Q2W), evolocumab 420 mg monthly (QM), or a matching placebo. The coprimary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12 and at week 12. RESULTS: Overall, 241 randomized patients (mean [standard deviation] age, 60.2 [10.3] years) received evolocumab 140 mg Q2W (n = 79), evolocumab 420 mg QM (n = 80), placebo Q2W (n = 41), or placebo QM (n = 41). At weeks 10 and 12, the placebo-adjusted least-squares mean percent change from baseline in LDL-C for the evolocumab 140 mg Q2W group was - 70.7% (95% CI - 78.0% to - 63.5%); - 69.7% (95% CI - 76.5% to - 63.0%) for the evolocumab 420 mg QM group. Significant improvements in all other lipid parameters were observed with evolocumab. The patient incidence of treatment-emergent adverse events was similar between the treatment groups and across dosing regimens. CONCLUSION: In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, 12-week treatment with evolocumab significantly lowered LDL-C and other lipids, and was safe and well tolerated (NCT03433755).

Multi-UAV Path Planning Algorithm Based on BINN-HHO.

Multi-UAV (multiple unmanned aerial vehicles) flying in three-dimensional (3D) mountain environments suffer from low stability, long-planned path, and low dynamic obstacle avoidance efficiency. Spurred by these constraints, this paper proposes a multi-UAV path planning algorithm that consists of a bioinspired neural network and improved Harris hawks optimization with a periodic energy decline regulation mechanism (BINN-HHO) to solve the multi-UAV path planning problem in a 3D space. Specifically, in the procession of global path planning, an energy cycle decline mechanism is introduced into HHO and embed it into the energy function, which balances the algorithm's multi-round dynamic iteration between global exploration and local search. Additionally, when the onboard sensors detect a dynamic obstacle during the flight, the improved BINN algorithm conducts a local path replanning for dynamic obstacle avoidance. Once the dynamic obstacles in the sensor detection area disappear, the local path planning is completed, and the UAV returns to the trajectory determined by the global planning. The simulation results show that the proposed Harris hawks algorithm has apparent superiorities in path planning and dynamic obstacle avoidance efficiency compared with the basic Harris hawks optimization, particle swarm optimization (PSO), and the sparrow search algorithm (SSA).

Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma.

Although immune checkpoint inhibitors have improved the overall survival rate of skin cutaneous melanoma (SKCM) patients, there is a wide variation and low response rate to these treatments in clinical immunotherapy for melanoma patients. These problems can be addressed through the induction of immunogenic cell death (ICD).We constructed an ICD-based prognostic model to predict the prognosis of SKCM patients and the efficacy of immunotherapy. Information on melanoma and normal samples obtained by TCGA and GTEx was stratified by ICD-related genes. The samples were divided into two subtypes according to high and low expression of ICD using an unsupervised clustering method (K-means). Patients with ICD-high subtype showed longer overall survival. We found that the ICD-related differential genes were associated with several cell death and immune-related pathways through GO, KEGG and GSEA. Immunoscore and tumor purity of ICD-associated genes was calculated using ESTIMATE, and ICD-high subtypes had higher immunoscore and lower tumor purity than ICD-low subtypes. Seven ICD-associated genes were obtained by one-way Cox regression and Lasso regression of ICD genes. Risk models were constructed to classify melanoma patients into high- risk and low-risk groups. The expression of ICD-related pivotal genes was lower in the high-risk group than in the low-risk group, and the survival time was significantly higher in the low-risk group than in the high-risk group. We then found that ICD risk characteristics had predictive value for the clinical efficacy of immunotherapy, with higher ICD risk scores in the immunotherapy non-responsive group. Combined with clinicopathological factors, a nomogram was established. the ROC and calibration curves assessed the ability of the nomogram to predict prognosis. We developed a new classification system for SKCM based on the characteristics of ICDs. This stratification has important clinical implications for estimating the prognosis and immunotherapy of SKCM patients.

Novel contact-kinin inhibitor sylvestin targets thromboinflammation and ameliorates ischemic stroke.

Ischemic stroke is a leading cause of death and disability worldwide. Increasing evidence indicates that ischemic stroke is a thromboinflammatory disease in which the contact-kinin pathway has a central role by activating pro-coagulant and pro-inflammatory processes. The blocking of distinct members of the contact-kinin pathway is a promising strategy to control ischemic stroke. Here, a plasma kallikrein and active FXII (FXIIa) inhibitor (sylvestin, contained 43 amino acids, with a molecular weight of 4790.4 Da) was first identified from forest leeches (Haemadipsa sylvestris). Testing revealed that sylvestin prolonged activated partial thromboplastin time without affecting prothrombin time. Thromboelastography and clot retraction assays further showed that it extended clotting time in whole blood and inhibited clot retraction in platelet-rich plasma. In addition, sylvestin prevented thrombosis in vivo in FeCl3-induced arterial and carrageenan-induced tail thrombosis models. The potential role of sylvestin in ischemic stroke was evaluated by transient and permanent middle cerebral artery occlusion models. Sylvestin administration profoundly protected mice from ischemic stroke by counteracting intracerebral thrombosis and inflammation. Importantly, sylvestin showed no signs of bleeding tendency. The present study identifies sylvestin is a promising contact-kinin pathway inhibitor that can proffer profound protection from ischemic stroke without increased risk of bleeding.

Epidemiological characteristics of imported respiratory infectious diseases in China, 2014‒2018.

BACKGROUND: With the progress of globalization, international mobility increases, greatly facilitating cross-border transmission of respiratory infectious diseases (RIDs). This study aimed to analyze the epidemiological characteristics and factors influencing imported RIDs, with the goal of providing evidence to support adoption of high-tech, intelligent methods to early find imported RIDs and prevent their spread in China. METHODS: We obtained data of imported RIDs cases from 2014 to 2018 from the Inbound Sentinel Network of Customs and the National Notifiable Diseases Reporting System in China. We analyzed spatial, temporal, and population distribution characteristics of the imported RIDs. We developed an index to describe seasonality. Pearson correlation coefficients were used to examine associations between independent variables and imported cases. Data analyses and visualizations were conducted with R software. RESULTS: From a total of 1 409 265 253 inbound travelers, 31 732 (2.25/100 000) imported RIDs cases were reported. RIDs cases were imported from 142 countries and five continents. The incidence of imported RIDs was nearly 5 times higher in 2018 (2.81/100 000) than in 2014 (0.58/100 000). Among foreigners, incidence rates were higher among males (5.32/100 000), 0-14-year-olds (15.15/100 000), and cases originating in Oceania (11.10/100 000). The vast majority (90.3%) of imported RIDs were influenza, with seasonality consistent with annual seasonality of influenza. The spatial distribution of imported RIDs was different between Chinese citizens and foreigners. Increases in inbound travel volume and the number of influenza cases in source countries were associated with the number of imported RIDs. CONCLUSIONS: Our study documented importation of RIDs into China from 142 countries. Inbound travel poses a significant risks bringing important RIDs to China. It is urgent to strengthen surveillance at customs of inbound travelers and establish an intelligent surveillance and early warning system to prevent importation of RIDs to China for preventing further spread within China.

Chemical modifications to increase the therapeutic potential of antimicrobial peptides.

The continued use of antibiotics has been accompanied by the rapid emergence and spread of antibiotic-resistant strains of bacteria. Antimicrobial peptides (AMPs), also known as host defense peptides, show multiple features as an ideal antimicrobial agent, including potent, rapid, and broad-spectrum antimicrobial activity, low promotion of antimicrobial resistance, potent anti-biofilm activity, and lethality against metabolically inactive microorganisms. However, several crucial drawbacks constrain the use of AMPs as clinical drugs, e.g., liability in vivo, toxicity when used systemically, and high production costs. Based on recent findings and our own experiences, here we summarize some chemical modifications and key design strategies to increase the therapeutic potential of AMPs, including 1) enhancing antimicrobial activities, 2) improving in vivo effectiveness, and 3) reduction in toxicity, which may facilitate the design and optimization of AMPs for the development of drug candidates. We also discuss the present challenges in the optimization of AMPs and future concerns about the resistance and cross-resistance to AMPs in the development of AMPs as therapeutic drugs.

Iron-Deficiency and Estrogen Are Associated With Ischemic Stroke by Up-Regulating Transferrin to Induce Hypercoagulability.

RATIONALE: Epidemiological studies have identified an associate between iron deficiency (ID) and the use of oral contraceptives (CC) and ischemic stroke (IS). To date, however, the underlying mechanism remains poorly understood. Both ID and CC have been demonstrated to upregulate the level and iron-binding ability of Tf (transferrin), with our recent study showing that this upregulation can induce hypercoagulability by potentiating FXIIa/thrombin and blocking antithrombin-coagulation proteases interactions. OBJECTIVE: To investigate whether Tf mediates IS associated with ID or CC and the underlying mechanisms. METHODS AND RESULTS: Tf levels were assayed in the plasma of IS patients with a history of ID anemia, ID anemia patients, venous thromboembolism patients using CC, and ID mice, and in the cerebrospinal fluid of some IS patients. Effects of ID and estrogen administration on Tf expression and coagulability and the underlying mechanisms were studied in vivo and in vitro. High levels of Tf and Tf-thrombin/FXIIa complexes were found in patients and ID mice. Both ID and estrogen upregulated Tf through hypoxia and estrogen response elements located in the Tf gene enhancer and promoter regions, respectively. In addition, ID, administration of exogenous Tf or estrogen, and Tf overexpression promoted platelet-based thrombin generation and hypercoagulability and thus aggravated IS. In contrast, anti-Tf antibodies, Tf knockdown, and peptide inhibitors of Tf-thrombin/FXIIa interaction exerted anti-IS effects in vivo. CONCLUSIONS: Our findings revealed that certain factors (ie, ID and CC) upregulating Tf are risk factors of thromboembolic diseases decipher a previously unrecognized mechanistic association among ID, CC, and IS and provide a novel strategy for the development of anti-IS medicine by interfering with Tf-thrombin/FXIIa interactions.

Transferrin plays a central role in coagulation balance by interacting with clotting factors.

Coagulation balance is maintained through fine-tuned interactions among clotting factors, whose physiological concentrations vary substantially. In particular, the concentrations of coagulation proteases (pM to nM) are much lower than their natural inactivator antithrombin (AT, ~ 3 µM), suggesting the existence of other coordinators. In the current study, we found that transferrin (normal plasma concentration ~40 µM) interacts with fibrinogen, thrombin, factor XIIa (FXIIa), and AT with different affinity to maintain coagulation balance. Normally, transferrin is sequestered by binding with fibrinogen (normal plasma concentration ~10 µM) at a molar ratio of 4:1. In atherosclerosis, abnormally up-regulated transferrin interacts with and potentiates thrombin/FXIIa and blocks AT's inactivation effect on coagulation proteases by binding to AT, thus inducing hypercoagulability. In the mouse model, transferrin overexpression aggravated atherosclerosis, whereas transferrin inhibition via shRNA knockdown or treatment with anti-transferrin antibody or designed peptides interfering with transferrin-thrombin/FXIIa interactions alleviated atherosclerosis. Collectively, these findings identify that transferrin is an important clotting regulator and an adjuster in the maintenance of coagulation balance and modifies the coagulation cascade.

Acute Massive Gastrointestinal Bleeding in the Elderly.

An 82-year patient presented with nausea, coffee-ground emesis, melena and hematochezia on July 10, 2011. The patient received blood transfusion on July 11, and continued to bleed from July 12 to 17. The patient underwent upper gastrointestinal endoscopy on July 16. There were no abnormalities in the esophagus, stomach and duodenum. Then the patient presented with shortness of breath, extreme fear, fatigue, hypotension, sweating, and cold limbs. Dopamine, as well as pressurised infusion of packed red blood cells and fresh frozen plasma were given to the patient to maintain blood pressure. CT angiography (CTA) revealed no aortic fistula, and enteroscopy revealed active bleeding in the vicinity of the ligament of Treitz. The retrograde exploration of gastroscopy revealed a 5×4 cm diverticulum on the posterior wall of the duodenum under the ligament of Treitz. Active bleeding of the small artery in the diverticulum was observed via incision of the duodenal wall, and the diverticulum was isolated. Hemostasis was achieved after ligation of blood vessels, and diverticulectomy was performed. Enteroscopy is important for the diagnosis of duodenal and upper small intestinal diseases. Repeated endoscopic exploration of multiple sites in the small intestine revealed the cause of the bleeding. The multidisciplinary team finally found the cause of the bleeding and its proper management.

Antimicrobial peptide LL-37 forms complex with bacterial DNA to facilitate blood translocation of bacterial DNA and aggravate ulcerative colitis.

Bacterial DNA (bacDNA) is frequently found in serum of patient with ulcerative colitis (UC) and Crohn's disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated into blood remain unclear. Here, we showed that bacDNA avoids elimination and disables bacteria-killing function of antimicrobial peptide LL-37 (Cramp in mice) by forming complex with LL-37, which is inducible after culture with bacteria or bacterial products. Elevated LL-37-bacDNA complex was found in plasma and lesions of patients with UC. LL-37-bacDNA promoted inflammation by inducing Th1, Th2 and Th17 differentiation and activating toll-like receptor-9 (TLR9). The complex also increased paracellular permeability, which possibly combines its inflammatory effects to promote local damage and bacDNA translocation into blood. Cramp-bacDNA aggravated mouse colitis severity while interference with the complex ameliorated the disease. The study identifies that inflammatogenic bacDNA utilizes LL-37 as a vehicle for blood translocation and to evade immune elimination. Additionally, bacteria may make a milieu by releasing bacDNA to utilize and resist host antimicrobial peptides as a 'trojan horse'.

Application and Revision of Montreal Cognitive Assessment in China's Military Retirees with Mild Cognitive Impairment.

OBJECTIVE: In an effort to accommodate MOCA to better fit for the Chinese context, this study was designed to employ the MOCA criteria to screen mild cognitive impairment (MCI) and analyze associated risk factors in military retirees. METHODS: Three hundred and four retired military cadres were recruited using a random cluster sampling technique with information collected including personal, prevalence, MOCA scale, and related neuropsychiatry scale. Thirty retirees were randomly chosen to be further analyzed one month later using the revised MOCA scale. RESULTS: ①Our data indicated an incidence rate of 64.8% for mild cognitive impairment in retired military cadres. The incidence rate for MCI was significantly higher in those aged 80 or above compared with those 80 years of age or younger (P<0.05). The incidence rate of MCI was significantly higher in those with fewer than 6 years of education compared with those with over 7 years of education (P<0.05). The MCI incidence was higher for those with little exercise than those taking regular exercise (P<0.01). Moreover, the MCI incidence was higher in stroke patients than those who never had a stroke episode (P<0.05). ②There was a significant correlation between MOCA and MMSE scale scores (r = 0.81). MOCA scale scores were negatively correlated with ADL and CES-D scores (although not PSQI scores). ③ MOCA recension Cronbach's alpha value was 0.862. The related coefficient of MOCA and MOCA recension was 0.878(P<0.01). When the Score of cut-off -point of the MOCA recension was 28, the area in ROC curve analyses was 0.859, as well as the largest area. CONCLUSION: Retired cadres exhibited a greater incidence of MCI (than general population), which was closely associated with age, level of education and physical exercise and cerebral apoplexy. Revised MOCA scale displays a better validity and reaction degree of reliability and is more suitable for screening and diagnosis of MCI in the elderly in China.

Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition.

Atherosclerosis is a chronic inflammatory disease of arterial wall. Mitochondrial DNA (mtDNA) and human antimicrobial peptide LL-37 (Cramp in mice) are involved in atherosclerosis. Recently, mtDNA has been found to escape from autophagy and cause inflammation. Normally, mtDNA as an inflammatogenic factor cannot escape from autophagy and degradation by DNase II. In this study, we found elevated amounts of LL37-mtDNA complex in atherosclerotic plasma and plaques. The complex was resistant to DNase II degradation and escaped from autophagic recognition, leading to activation of Toll-like receptor 9 (TLR9)-mediated inflammatory responses. Mouse model studies indicated that Cramp-mtDNA complex aggravated atherosclerotic lesion formation in apolipoprotein E-deficient mice and antibody treatment against the complex alleviated the lesion. These findings suggest that the LL-37-mtDNA complex acts as a key mediator of atherosclerosis formation, and thus represents a promising therapeutic target.

Theoretical and experimental studies on the atmospheric degradation of 2-bromo-3,3,3-trifluoropropene.

As a new kind of Halon replacement, 2-bromo-3,3,3-trifluoropropene (2-BTP) is finding application as a fire extinguishing agent in confined spaces. For assessing its environmental impact, it is necessary to perform kinetic and product studies of its degradation in the atmospheric environment. In this sense, five possible reaction pathways between 2-BTP and OH radicals are found by Gaussian 03. Detailed analysis shows that the main product is the CF3CBrCH2OH radical, which may produce a series of compounds by further reaction with O2, NO, etc. In order to further prove the validity of the theoretical calculations and investigate the atmospheric transformation process of 2-BTP, atmospheric degradation of 2-BTP is then studied experimentally under controlled radiation conditions. Based on the theoretical analyses and experimental results, the atmospheric degradation mechanism of 2-BTP is finally proposed and detailed information on the atmospheric chemistry of 2-BTP is provided.

YY-39, a tick anti-thrombosis peptide containing RGD domain.

Ticks are obligatory blood feeding ectoparasites, which continuously attach to their hosts for 1-2 weeks. There are many biologically active compounds in tick salivary glands interfering host haemostatic system and to successfully obtain blood meal. Several platelet aggregation inhibitors have been identified from ticks. A family of conserved peptides, which were identified from transcriptome analysis of many tick salivary glands, were found to contain unique primary structure including predicted mature peptides of 39-47 amino acid residues in length and a Pro/Glu(P/E)-Pro/His(P/H)-Lys-Gly-Asp(RGD) domain. Given their unique structure and RGD domain, they are considered a novel family of disintegrins that inhibit platelet aggregation. One of them (YY-39) was tested for its effects on platelets and thrombosis in vivo. YY-39 was found effectively to inhibit platelet aggregation induced by adenosine diphosphate (ADP), thrombin and thromboxane A2 (TXA2). Furthermore, YY-39 blocked platelet adhesion to soluble collagen and bound to purified GPIIb/IIIa in a dose-dependent manner. In in vivo experiments, YY-39 reduced thrombus weight effectively in a rat arteriovenous shunt model and inhibited thrombosis in a carrageenan-induced mouse tail thrombosis model. Combined with their prevalence in ticks and platelet inhibitory functions, this family of peptides might be conserved tick anti-haemostatic molecules.