First identification of Cytauxzoon manul in Eurasian lynx (Lynx lynx) in northwestern China.

BACKGROUND: Multiple species of the genera Cytauxzoon and Hepatozoon can infect wild felines, but the diversity of these and other apicomplexan parasites in Eurasian lynx is scarcely known. The aim of this study was to detect Cytauxzoon and Hepatozoon species with molecular methods in Eurasian lynxes and their ticks in northwestern China. METHODS: DNA was extracted from the heart, liver, spleen, lung, and kidney samples of three Eurasian lynxes as well as from their five ixodid ticks. These DNA samples were screened with polymerase chain reactions (PCRs) for Cytauxzoon with the partial cytochrome b gene (CytB), cytochrome c oxidase subunit I gene (COI), and small subunit ribosomal RNA gene (18S rRNA), and Hepatozoon with three different fragments of small subunit ribosomal RNA gene (18S rRNA). PCR products were sequenced, aligned, and phylogenetically analyzed. RESULTS: One adult female of Eurasian lynx (#1, adult female) was co-infected with Cytauxzoon manul and Hepatozoon felis genotype I, while an adult male lynx (#2) was infected with C. manul. Interestingly, H. felis genotype I was both detected in a male cub (#3) and two out of five infesting Hyalomma asiaticum ticks. CONCLUSIONS: For the first time, Cytauxzoon manul is reported here from Eurasian lynx. In addition, H. felis has not been known to occur in this host species in China and Central Asia. Thus, the findings of this study extend our knowledge on the geographical distribution and host range of these haemoprotozoan parasites. Moreover, this is also the first evidence of C. manul and H. felis co-infection in Eurasian lynx.

Superhydrophilic PANI/Ag/TA@PVDF Composite Membrane with Antifouling Property for Oil-Water Separation.

The current membrane materials used for oil-water separation suffer from low separation efficiency and poor durability, and membrane contamination is also a key issue that must be addressed urgently. In this paper, a superhydrophilic PANI/Ag/TA@PVDF composite membrane with PANI-Ag NPs heterojunction structure was prepared via chelation and reduction of Ag+ by tannic acid (TA) and in situ growth of hydrochloric acid-doped polyaniline (PANI). TA endows the prepared composite membrane with excellent superhydrophilicity and underwater oleophobicity, remarkable oil-water separation capacity (the separation efficiency of more than 97% for soybean oil), and extraordinary antifouling properties. Notably, the range of photodegradation is expanded from UV to visible light by the construction of a Schottky heterostructure between PANI and Ag NPs, the photocatalytic degradation ability of composite membrane for organic pollutants has been improved obviously, and the degradation efficiency for crystal violet (CV) is 97.9%. Considering these merits, the PANI/Ag/TA@PVDF composite membrane provides an effective strategy to overcome the shortcomings of existing membrane materials, presenting enormous potential in the treatment and purification of oily wastewater.

Depletion of mTOR ameliorates CD4+ T cell pyroptosis by promoting autophagy activity in septic mice.

A reduction in the number of CD4+ T cells is a central part of the immunosuppression phase of sepsis and leads to impaired immune defense ability and increased mortality. Pyroptosis, a newly discovered programmed cell death, was confirmed to be an important mechanism of lymphocytopenia in a lot of human diseases and is under the regulation of autophagy. The mammalian target of rapamycin (mTOR) pathway is closely related to CD4+ T-cell survival. Whether the mTOR pathway influences CD4+ T cell pyroptosis by regulating autophagy remains unknown. In this study, a septic mouse model was developed using cecal ligation and puncture (CLP) to explore the degree of pyroptosis and autophagy of CD4+ T cells. T-cell-specific mTOR/TSC1-knockout mice were used to investigate the role of mTOR pathway in the regulation of CD4+ T cell pyroptosis. Bafilomycin, a specific autophagy inhibitor, was used to verify the regulatory effect of autophagy on pyroptosis in septic mice. We observed aggravated pyroptosis in CD4+ T cells in CLP mice accompanied by impaired autophagy activity and an overactivated mTOR signaling pathway. Depletion of mTOR relieved autophagy deficiency and reduced the proportion of pyroptotic CD4+ T cells. In T-cell-specific mTOR-knockout mice treated with bafilomycin, the protective effect of mTOR depletion vanished. This indicated that autophagy negatively regulates CD4+ T cell pyroptosis, which is under the control of the mTOR pathway. Taken together, our findings emphasize the importance of pyroptosis in sepsis-induced lymphopenia and reveal the regulatory effects of the mTOR pathway and the role of autophagy in this regulation.

mTOR in programmed cell death and its therapeutic implications.

Mechanistic target of rapamycin (mTOR), a highly conserved serine/threonine kinase, is involved in cellular metabolism, protein synthesis, and cell death. Programmed cell death (PCD) assists in eliminating aging, damaged, or neoplastic cells, and is indispensable for sustaining normal growth, fighting pathogenic microorganisms, and maintaining body homeostasis. mTOR has crucial functions in the intricate signaling pathway network of multiple forms of PCD. mTOR can inhibit autophagy, which is part of PCD regulation. Cell survival is affected by mTOR through autophagy to control reactive oxygen species production and the degradation of pertinent proteins. Additionally, mTOR can regulate PCD in an autophagy-independent manner by affecting the expression levels of related genes and phosphorylating proteins. Therefore, mTOR acts through both autophagy-dependent and -independent pathways to regulate PCD. It is conceivable that mTOR exerts bidirectional regulation of PCD, such as ferroptosis, according to the complexity of signaling pathway networks, but the underlying mechanisms have not been fully explained. This review summarizes the recent advances in understanding mTOR-mediated regulatory mechanisms in PCD. Rigorous investigations into PCD-related signaling pathways have provided prospective therapeutic targets that may be clinically beneficial for treating various diseases.

Advances in the regulatory mechanisms of mTOR in necroptosis.

The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis.

Development and Validation of a Risk Score for Predicting Invasive Candidiasis in Intensive Care Unit Patients by Incorporating Clinical Risk Factors and Lymphocyte Subtyping.

Objective: To develop and validate a rapid invasive candidiasis (IC)-predictive risk score in intensive care unit (ICU) patients by incorporating clinical risk factors and parameters of lymphocyte subtyping. Methods: A prospective cohort study of 1054 consecutive patients admitted to ICU was performed. We assessed the clinical characteristics and parameters of lymphocyte subtyping at the onset of clinical signs of infection and their potential influence on IC diagnosis. A risk score for early diagnosis of IC was developed and validated based on a logistic regression model. Results: Sixty-nine patients (6.5%) had IC. Patients in the cohort (N=1054) were randomly divided into a development (n=703) or validation (n=351) cohorts. Multivariate logistic regression identified that CD8+ T-cell count ≤143 cells/mm3, receipt of high-dose corticosteroids (dose ≥50 mg prednisolone equivalent), receipt of carbapenem/tigecycline, APACHE II score≥15, (1,3)-ß-D-glucan (BDG) positivity and emergency gastrointestinal/hepatobiliary (GIT/HPB) surgery were significantly related with IC. IC risk score was calculated using the following formula: CD8+ T-cell count ≤143 cells/mm3 + receipt of high-dose corticosteroids + receipt of carbapenem/tigecycline + APACHE II score ≥15 + BDG positivity + emergency GIT/HPB surgery ×2. The risk scoring system had good discrimination and calibration with area under the receiver operating characteristic (AUROC) curve of 0.820 and 0.807, and a non-significant Hosmer-Lemeshow test P=0.356 and P=0.531 in the development and validation cohorts, respectively. We categorized patients into three groups according to risk score: low risk (0-2 points), moderate risk (3-4 points) and high risk (5-7 points). IC risk was highly and positively associated with risk score (Pearson contingency coefficient=0.852, P for trend=0.007). Candida score had a moderate predicting efficacy for early IC diagnosis. The AUROC of the risk score was significantly larger than that of Candida score (0.820 versus 0.711, Z=2.013, P=0.044). Conclusions: The predictive scoring system, which used both clinical factors and CD8+ T cell count, served as a clinically useful predictive model for rapid IC diagnosis in this cohort of ICU patients. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR-ROC-17010750.

Integrated Management of Chive Gnats (Bradysia odoriphaga Yang & Zhang) in Chives Using Entomopathogenic Nematodes and Low-Toxicity Insecticides.

Bradysia odoriphaga is a major pest that causes damage to chive production, and which has developed resistance to highly toxic chemical insecticides. Entomopathogenic nematodes (EPN) show a high potential for B. odoriphaga control. This study aimed to develop an effective management method against B. odoriphaga larvae, using EPN with low-toxicity insecticides. Fourteen selected insecticides had no significant effects on the survival and infectivity of Steinernema feltiae SN and Heterorhabditis indica LN2. Synergistic interactions were observed for imidacloprid and osthole with S. feltiae SN against B. odoriphaga larvae. Steinernema feltiae SN was more effective than H. indica LN2 against B. odoriphaga at 15 and 20 °C, and the addition of imidacloprid at 1/10 recommended concentration (RC) significantly increased the efficacy of S. feltiae SN. The year-round occurrence of the B. odoriphaga larvae in chive fields treated by EPN and imidacloprid at 1/10 RC was studied. Results showed that the application of EPN with imidacloprid at 1/10 RC successfully suppressed larval populations of B. odoriphaga in chive fields, thus significantly increasing the yield of chive. The practical method of applying EPN-imidacloprid combinations provided a cost-effective and environmental safety strategy for controlling B. odoriphaga larvae in chive production, which can reduce the usage of toxic chemical insecticides.

lncRNA 430945 promotes the proliferation and migration of vascular smooth muscle cells via the ROR2/RhoA signaling pathway in atherosclerosis.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are major cellular events in hypertension­induced vascular remodeling, which is closely involved in the progression of atherosclerosis (AS). Although long non­coding RNAs (lncRNAs) are gaining recognition as novel regulators of VSMCs, their functioning and role in AS remain to be elucidated. In the present study, the role of lncRNA ENST00000430945 (lncRNA 430945) in AS was investigated. VSMCs transfected with a small interfering RNA (siRNA; si­430945) and a negative control (si­NC) were used. Cell Counting Kit­8, wound­healing and Transwell migration arrays were performed to determine whether lncRNA 430945 influenced VSMC proliferation and migration. Furthermore, the study examined whether a correlation exists between lncRNA 430945 and the receptor tyrosine kinase­like orphan receptor 2 (ROR2) signaling pathway. It was found that the expression of lncRNA 430945 was high in human AS tissues, which in turn promoted angiotensin II (AngII)­induced VSMC proliferation. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analyses showed that lncRNA 430945 mediated the AngII­induced upregulation of ROR2. In addition, the microarray and RT­qPCR results showed that the expression of lncRNA 430945 was increased considerably in AS tissues. The downregulation of lncRNA 430945 significantly suppressed AngII­induced VSMC proliferation and migration. In addition, ROR2 levels in VSMCs transfected with si­430945 were markedly lower than those cells transfected with si­NC. Additionally, western blotting showed that lncRNA 430945 activated the signaling pathways associated with ROR2 and Ras homolog gene family member A (RhoA). The upregulation of lncRNA 430945 in AS promoted the proliferation and migration of VSMCs via activation of the ROR2/RhoA signaling pathway. Therefore, targeting ROR2 or RhoA may be a promising technique in developing therapeutic strategies for treating AS.

Correlation Between Hyperhomocysteinemia and Outcomes of Patients With Acute Myocardial Infarction.

Overwhelming clinical and epidemiological studies have identified elevated plasma total homocysteine (Hcy) as new important risk factor for atherosclerotic vascular disease. But the relationship between outcome and hyperhomocysteinemia in patients with acute myocardial infarction (AMI) has been rarely reported. This study aimed to evaluate the association between hyperhomocysteinemia and short-term outcomes of patients with AMI. Eight hundred five patients were divided into high Hcy level group (group H: N = 457) and low Hcy level group (group L: N = 348) according to the plasma Hcy levels of 15 mmol/L. The comparisons were made between 2 groups in the following aspects: sex, hypertension, diabetes, hyperlipidemia, the time for symptom from onset to percutaneous coronary intervention, homoccyteine, creatine phosphokinase isoenzyme (creatine kinase myocardial band), and the incidence of 30-day adverse events. The incidences of heart failure, cardiac rupture, death, and the total adverse cardiovascular events were statistically significantly higher in group H than in group L. But the incidence of postoperative angina pectoris and reinfarction was similar between groups. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to the age and the level of Hcy. An elevated plasma total Hcy level in patients with AMI experienced pemutaneous coronary intervention may be related to the short-term outcomes. An elevated high plasma Hcy level also seems to be an independent predictor of 30-day cardiovascular events in patients with AMI.

Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.

Although statins are generally well-tolerated drugs, recent cases of drug-induced liver injury associated with their use have been reported. A 52-year-old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.

[Compliance of antihypertensive drug use in patients with hypertension].

UNLABELLED: > OBJECTIVE: To understand the compliance of antihypertensive drug use in patients with hypertension. METHODS: A retrospective analysis was conducted among 218 patients with hypertension to understand their drug use compliancy and influencing factors, including side effect of the drugs, drug type, educational level, economic status and drug use length. RESULTS: The factors including disease course, drug type, drug use length and drug side effects, the economy status, educational level, awareness of hypertension related knowledge and psychological reaction could significantly influence the compliance of antihypertensive drug use. Among the patients surveyed, 86.67% of them with poor drug use compliance had only an educational level less than senior high school, 77.33% had poor awareness of hypertension related knowledge. CONCLUSION: The antihypertensive drug use compliance in patients with hypertension is directly related to the outcome of the disease in clinical treatment. It is necessary to take effective measures to improve the treatment compliance and maintain normal blood pressure level of the patients.