[Site-specific PCR identification of animal species and formula particles of Scorpio].

Scorpio, a commonly used animal medicine in China, is derived from Buthus martensii as recorded in the Chinese Pharmacopoeia. China harbors rich species of Scorpionida and adulterants exist in the raw medicinal material and deep-processed products of Scorpio. The microscopic characteristics of the deep-processed products may be incomplete or lost during processing, which makes the identification difficult. In this study, the maximum likelihood(ML) tree was constructed based on the morphology and cytochrome C oxidase subunit I(COⅠ) to identify the species of Scorpio products. The results showed that the main adulterant of Scorpio was Lychas mucronatus. According to the specific SNP sites in the COⅠ sequence of B. martensii, the stable primers were designed for the identification of the medicinal material and formula granules of Scorpio. The polymerase chain reaction(PCR) at the annealing temperature of 61 ℃ and 30 cycles produced bright specific bands at about 150 bp for both B. martensii and its formula particles and no band for adulterants. The adaptability of the method was investigated, which showed that the bands at about 150 bp were produced for Scorpio medicinal material, lyophilized powder, and formula granules, and commercially available formula granules. The results showed that the established method could be used to identify the adulterants of Scorpio and its formula granules, which could help to improve the quality control system and ensure the safe clinical application of Scorpio formula granules.

Erythrocyte membrane n-3 PUFA are inversely associated with breast cancer risk among Chinese women.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case-control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

Serum levels of n-3 PUFA and colorectal cancer risk in Chinese population.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case­control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

Pharmacogenomics-a New Frontier for Individualized Treatment of Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease with a significant public health burden. It is characterized by the gradual degeneration of dopamine neurons in the central nervous system. Although symptomatic pharmacological management remains the primary therapeutic method for PD, clinical experience reveals significant inter-individual heterogeneity in treatment effectiveness and adverse medication responses. The mechanisms behind the observed interindividual variability may be elucidated by investigating the role of genetic variation in human-to-human variances in medication responses and adverse effects. OBJECTIVE: This review aims to explore the impact of gene polymorphism on the efficacy of antiparkinsonian drugs. The identification of factors associated with treatment effectiveness variability might assist the creation of a more tailored pharmacological therapy with higher efficacy, fewer side outcomes, and cheaper costs. METHODS: In this review, we conducted a thorough search in databases such as PubMed, Web of Science, and Google Scholar, and critically examined current discoveries on Parkinson's disease pharmacogenetics. The ethnicity of the individuals, research methodologies, and potential bias of these studies were thoroughly compared, with the primary focus on consistent conclusions. RESULTS: This review provides a summary of the existing data on PD pharmacogenetics, identifies its limitations, and offers insights that may be beneficial for future research. Previous studies have investigated the impact of gene polymorphism on the effectiveness and adverse effects of levodopa. The trendiest genes are the COMT gene, DAT gene, and DRD2 gene. However, limited study on other anti-Parkinson's drugs has been conducted. CONCLUSION: Therefore, In order to develop an individualized precision treatment for PD, it is an inevitable trend to carry out multi-center, prospective, randomized controlled clinical trials of PD pharmacogenomics covering common clinical anti-PD drugs in large, homogeneous cohorts.

Pharmaceutical and pharmacological studies of Shen Ma Yi Zhi granule for prevention of vascular dementia: A review.

Background: With dementia significantly increasing hospitalization and disability rates, worldwide aging of the population presents major challenges to public health. The majority of cases of cognitive dysfunction among the elderly, however, are characterized by an identifiable, preventable and treatable vascular component. As such, increased study of preventative methods in the context of dementia is warranted. Traditional Chinese medicine compounds have been reported to be neuroprotective and improve cognitive function via a variety of mechanisms. Shen Ma Yi Zhi granule (SMYZG) is one such collection of compounds that has been proven clinically effective. Pharmacological mechanisms of action, pharmacokinetics and clinical applications of SMYZG have been previously studied using a variety of vascular dementia animal models. SMYZG activates and regulates four main signaling pathways relevant to vascular dementia including the AMPK/PPARα/PGC-1α/UCP2, Nrf2/HO-1, HIF-1/VEGF/Notch, and VEGF/Flk-1/p8 MAPK pathways. Furthermore, SMYZG influences anti-inflammatory and anti-oxidant stress responses, reverses demyelination of brain white matter and vascular endothelium, regulates pericyte function and normalizes mitochondrial metabolism. Neuroprotective effects of SMYZG, as well as those promoting regeneration of vascular endothelium, have also been reported in studies of rat models of vascular dementia. Future research concerning SMYG is warranted for development of vascular dementia preventative management strategies.

How to manage isolated tension non-surgical pneumoperitonium during bronchoscopy? A case report.

BACKGROUND: Tension pneumoperitonium is a rare complication during bronchoscopy that can cause acute respiratory and hemodynamic failure, with fatal consequences. Isolated pneumoperitonium during bronchoscopy usually results from ruptures of the abdominal viscera that need surgical repair. Non-surgical pneumoperitoneum (NSP) refers to some pneumoperitoneum that could be relieved without surgery and only by conservative therapy. However, the clinical experience of managing tension pneumoperitonium during bronchoscopy is limited and controversial. CASE SUMMARY: A 51-year-old female was admitted to our hospital for cough with bloody sputum of seven days. On the 8th day of her admission, a bronchoscopy was arranged for bronchial-alveolar lavage to detect possible pathogens in the lower respiratory tract, as oxygen was delivered via a 12 F nasopharyngeal cannula, approximately 5-6 cm from the tip of the catheter, with a flow rate of 5-10 L/min. After four minutes of bronchoscopy, the patient suddenly vomited 20 mL of water, followed by severe abdominal pain, while physical examination revealed obvious abdominal distension, as well as hardness and tenderness of the whole abdomen, which was considered pneumoperitonium, and the bronchoscopy was terminated immediately. A computer tomography scan indicated isolated tension pneumoperitonium, and abdominal decompression was performed with a drainage tube, after which her symptoms were relieved. A multidisciplinary expert consultation discussed her situation and a laparotomy was suggested, but finally refused by her family. She had no signs of peritonitis and was finally discharged 5 d after bronchoscopy with a good recovery. CONCLUSION: The possibility of tension pneumoperitonium during bronchoscopy should be guarded against, and given its serious clinical consequences, cardiopulmonary instability should be treated immediately. Varied strategies could be adopted according to whether it is complicated with pneumothorax or pneumomediastinum, and the presence of peritonitis. When considering NSP, conservative therapy maybe a reasonable option with good recovery. An algorithm for the management of pneumoperitonium during bronchoscopy is proposed, based on the features of the case series reviewed and our case reported.

Comparisons of the energy efficiency and intraocular safety of two torsional phacoemulsification tips.

BACKGROUND: During cataract phacoemulsification surgery, an Intrepid® balanced (IB) tip can achieve a larger amplitude, which may lead to higher energy efficiency than a Kelman (K) tip when paired with a torsional phaco platform. In this retrospective cohort study, we compared their energy efficiency and damage to the cornea under a new energy setting. METHODS: The medical records of 104 eyes of 79 patients were reviewed, with 47 eyes belonging to the IB group and 57 eyes belonging to the K group. All surgeries were performed on an Alcon Centurion® platform with gravity infiltration. Surgical parameters, visual outcome, central corneal thickness (CCT) changes, and endothelial cell density (ECD) loss rate were recorded and calculated. RESULTS: No significant differences in postoperative best corrected visual acuity (BCVA), intraocular pressure (IOP), total ultrasound time, estimated fluid aspirated, CCT changes, or ECD loss rate were observed between the two groups. We divided the included eyes into soft nucleus and hard nucleus subgroups and found lower cumulative dissipated energy (CDE, 8.15 ± 8.02 vs 14.82 ± 14.16, P = 0.023), cumulative torsional energy (CTE, 8.06 ± 7.87 vs 14.13 ± 13.02, P = 0.027), and cumulative longitudinal energy (CLE, 0.09 ± 0.17 vs 0.69 ± 1.37, P = 0.017) in the IB group than in the K group, implying less energy used and higher energy efficiency of the IB tip. CONCLUSION: Lower CLE in the IB group indicates fewer phaco tip obstructions and a significantly higher capability to conquer hard nuclei with IB tips with statistical significance. With an ultra-perfusion cannula, the balanced tip does not cause more corneal damage.

[Analysis of clinical application characteristics of Xingnaojing Injection in treating cerebral hemorrhage in real world].

To explore the population characteristics and clinical application characteristics of patients with cerebral hemorrhage treated with Xingnaojing Injection in real world. The model was established by Apriori algorithm, and the general information and medication information of 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection were analyzed by using Clementine 12.0 in the databases of information systems of 33 class Ⅲ grade A hospitals in China. The results showed that among the 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection, the median age was 59 years old. And the male to female ratio was about 1.74∶1. Most of them did manual labor(31.26%), and were hospitalized in winter(27.46%), especially during the Cold Dew(5.1%). The majority of the patients were in a stable condition(50.94%), and preferred neurosurgery department(48.82%). 29.03% of patients were hospitalized for 15-28 days, and 42.47% of patients spent 10 000-50 000 Yuan of hospitalization expenses. The single dose of Xingnaojing Injection was 10-20 mL at most(46.03%). And the course of medication was mostly 3 days or less(68.60%). Lidocain was the most frequently used Western medicine in drug combination(5.05%), and Huayu Tongmai Ji was the most frequently used traditional Chinese medicine in drug combination(10.73%). The most frequently used one type of traditional Chinese medicine combined with one type of Western medicine was Huayu Tongmai Ji + Dexamethasone(8.08%). The most frequently used two Western medicines in drug combination were Omeprazole + Dexamethasone(5.07%). Prilosec + Dexamethasone + Lidocaine(3.35%) were three Western drugs with the most frequent combination. When the dosage was 10-20 mL and the number of days of treatment was > 15 days, the largest number of the patients was cured and improved(44.78%, 45.85%). The results showed that cerebral hemorrhage patients treated with Xingnaojing Injection were mostly middle-aged and elderly people, with more males than females. Brain hemorrhage often occurred in winter and spring. Xingnaojing Injectiont was often combined with glucocorticoids, proton pump inhibitors and cardiovascular drugs to prevent cerebral hemorrhage complications. The clinical medication met the guidelines for the treatment of cerebral hemorrhage. Some patients had over-treatment use, which can provide a reference for clinicians in treating cerebral hemorrhage.

KLF2 regulates neutrophil migration by modulating CXCR1 and CXCR2 in asthma.

Neutrophils are key inflammatory cells in the immunopathogenesis of asthma. Neutrophil migration can be initiated through activation of the CXCR1 and CXCR2 receptors by CXC chemokines, such as IL-8. Although transcription factor KLF2 has been found to maintain T cell migration patterns through repression of several chemokine receptors, whether KLF2 can regulate neutrophil migration via modulation of CXCR1 and CXCR2 is unknown. Here, we aimed to explore the functions of KLF2, CXCR1 and CXCR2 in neutrophil migration in asthma and to establish a regulatory role of KLF2 for CXCR1/2. We demonstrate that with asthma aggravation, the percentages and migration rates of peripheral blood neutrophils gradually increased in asthmatic patients and the guinea pig asthma model. Correspondingly, both the KLF2 mRNA and protein levels in neutrophils were gradually reduced. While CXCR1 and CXCR2 expression was negatively correlated with KLF2. In vitro knockdown of KLF2 dramatically increased the migration of HL-60-drived neutrophil-like cells, which was accompanied by an increase in the CXCR1 and CXCR2 mRNA and protein expression levels. Taken together, our results indicate that decreased KLF2 aggravates asthma progression by promoting neutrophil migration, which is associated with the transcriptional upregulation of CXCR1 and CXCR2. The KLF2 and/or CXCR1/2 expression levels may represent an indicator of asthma severity.

Characterization of network complexity by communicability sequence entropy and associated Jensen-Shannon divergence.

Characterizing the structural complexity of networks is a major challenging work in network science. However, a valid measure to quantify network complexity remains unexplored. Although the entropy of various network descriptors and algorithmic complexity have been selected in the previous studies to do it, most of these methods only contain local information of the network, so they cannot accurately reflect the global structural complexity of the network. In this paper, we propose a statistical measure to characterize network complexity from a global perspective, which is composed of the communicability sequence entropy of the network and the associated Jensen-Shannon divergence. We study the influences of the topology of the synthetic networks on the complexity measure. The results show that networks with strong heterogeneity, strong degree-degree correlation, and a certain number of communities have a relatively large complexity. Moreover, by studying some real networks and their corresponding randomized network models, we find that the complexity measure is a monotone increasing function of the order of the randomized network, and the ones of real networks are larger complexity-values compared to all corresponding randomized networks. These results indicate that the complexity measure is sensitive to the changes of the basic topology of the network and increases with the increase of the external constraints of the network, which further proves that the complexity measure presented in this paper can effectively represent the topological complexity of the network.

A Selective TRPC3 Inhibitor Pyr3 Attenuates Myocardial Ischemia/Reperfusion Injury in Mice.

An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery. Our previous study has identified transient receptor potential channel 3 (TRPC3) and TRPC6 as cation channels through which most of the damaging calcium enters, aggravates pathological changes in vivo and increases ischemia/reperfusion (I/R) injury in mice. This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice. C57BL/6J wild-type male mice (8 to 12 weeks old) were anesthetized with 3.3% chloral hydrate. A murine I (30 min)/R (24 h) injury model was established by temporary occlusion of the left anterior descending (LAD) coronary artery. Pyr3 was administered at concentrations of 0, 2.5, 5, or 10 mg/kg via the right jugular vein 5 min before reperfusion. We observed that the selective TRPC3 inhibitor, 10 mg/kg Pyr3, significantly decreased the infarct size of left ventricle, and reduced the myocardial cell apoptosis rate and inflammatory response in mice. In a conclusion, TRPC3 can function as a candidate target for I/R injury prevention, and Pyr3 may directly bind to TRPC3 channel protein, inhibit TRPC3 channel activity, and improve TRPC3-related myocardial I/R injury. Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.

The first case report of McLeod syndrome in an infant with a novel mutation (c.89C>A, p. Ser30X) in XK.

McLeod syndrome (MLS) is a rare multisystem disorder and X-linked recessive inheritance disorder caused by mutations of the X-linked Kx blood group (XK) gene. The manifestations progress slowly and mainly appear in middle age, which make it difficult to distinguish MLS from other neuromuscular disorders. Here, we present a case of a 10-month-old Chinese boy who was taken to hospital for herpes of the extremities and oral cavity along with febrile seizures in June 2017. The laboratory test revealed persistent elevated levels of serum creatine phosphokinase and abnormal liver function. The results of the electrocardiogram showed sinus tachycardia, and magnetic resonance imaging of the brain showed enlarged bilateral ventricles and third ventricle. Genetic analysis by next-generation sequencing revealed a novel nonsense mutation c.89C > A (p. Ser30X) in exon 1 of XK. To the best of our knowledge, this is the first case report of infants with MLS confirmed by genetic analysis.

[Application of next-generation sequencing in the molecular diagnosis of Duchenne muscular dystrophy].

The purpose of this study is to analyze the family's clinical data of 22 children who were given an intended clinical diagnosis of Duchenne muscular dystrophy (DMD), and to explore the clinical value of next-generation sequencing (NGS) in the molecular diagnosis of DMD. The probands were simultaneously tested by NGS for a gene panel associated with hereditary neuromuscular disease and multiplex ligation-dependent probe amplification (MLPA) for the Dystrophin gene. The exon deletion/repetition mutations of the Dystrophin gene determined by both methods were compared and the point mutations of the Dystrophin gene were verified by Sanger sequencing. Dystrophin gene mutations were found in all the 22 probands, including 14 exon deletion/repetition mutations and 8 point mutations/minor variations. The results of MLPA detection were consistent with those of NGS. The results of Sanger sequencing showed that the point mutations and minor variations determined by NGS were correct. One missense mutation (c.6290G>T), 1 nonsense mutation (c.3487C>T) and 4 minor deletion-induced frameshift mutations (c.1208delG, c.7497_7506delGGTGGGTGAC, c.9421_9422delAA and c.8910_8913delTCTC) had not been reported in the Human Gene Mutation Database, and thus were considered as novel mutations of the Dystrophin gene. The results of this study showed that NGS can detect variations in the Dystrophin gene, including exon deletion/repetition, point mutation, minor deletion and intron mutation. Therefore, NGS is of certain clinical value in the molecular diagnosis of DMD and is worthy of recommendation.

Complex network comparison based on communicability sequence entropy.

Identification and quantification of the structural dissimilarities between complex networks is a very important and challenging problem in network science. A simple and efficient way to quantify network differences remains unexplored. Although the methods for network comparison based on the probability distribution of a network descriptor have been shown to be effective for specific purposes, the information they provide is often limited or incomplete. In order to overcome the defect of the methods, here we use the communicability between two nodes to define the communicability sequence entropy of networks, and on the basis of this entropy measure, we propose a Jensen-Shannon divergence of two networks which can be used as natural distance measure between complex networks. By the extensive experiments, we find that the measure can accurately quantify the structural dissimilarities between synthetic networks. Most importantly, the measure can be able to identify the critical percolation probability of the random network in the evolution process, and it can also effectively guide us to choose a more suitable model to simulate real systems.

Vitamin D Enhances Efficacy of Oral Nifedipine in Treating Preeclampsia with Severe Features: A Double Blinded, Placebo-Controlled and Randomized Clinical Trial.

Vitamin D (VD) has exhibited immunomodulatory role in the pathogenesis of preeclampsia. We hypothesize VD potentiate nifedipine treatment for preeclampsia by shortened the time to control blood pressure and prolong time before subsequent hypertensive crisis. We conduct a randomized trial of 683 primigravid women with preeclampsia, who were assigned to different treatment groups, either nifedipine+placebo or nifedipine+VD orally, by random after screening. Primary endpoints include time to control hypertension and time before another hypertensive crisis. Maternal adverse effects including nausea, vomiting, chest pain, mild headache, dizziness, maternal tachycardia, hypotension or shortness of breath, and neonatal parameters including birth weight and Apgar scores, as well as the minimum number of dosages needed to control hypertension were defined as secondary endpoints. Serum levels of cytokines tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were also examined. There was a marked reduction of the time required to control hypertension and a significant lengthening (p = 0.013) of the time before a new hypertensive crisis in participants received nifedipine+VD treatments (41.8 ± 18.3 min), in comparison with the nifedipine+placebo controls (61.1 ± 15.9 min). In women treated with nifedipine+VD, the minimum number of dosages needed to control hypertension was also lower. With regard to adverse effects, no statistical difference was observed between the two treatment groups. Moreover, treatment with VD increased IL-10 and reduced TNF-α serum levels. VD possesses the potential of serving as a safe and effective adjuvant to oral nifedipine in treating women with preeclampsia against hypertension, possibly through the upregulation of IL-10 and the downregulation of TNF-α.

Plasma microRNA-16-5p, -17-5p and -20a-5p: Novel diagnostic biomarkers for gestational diabetes mellitus.

AIM: To explore whether plasma microRNA-16-5p, -17-5p and -20a-5p can be used as diagnostic biomarkers in gestational diabetes mellitus (GDM) and to investigate the relationship between those microRNAs and the risk factors of GDM (body mass index [BMI], insulin resistance [IR] and tumor necrosis factor-α (TNF-α)). METHODS: A total of 85 pregnant women with GDM and 72 pregnant women without GDM were enrolled in this study. The plasma concentration of microRNAs (microRNA-16-5p, -17-5p, -19a-3p, -19b-3p, -20a-5p) was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman's correlation analysis was used to evaluate the correlation between those microRNAs and the risk factors of GDM, and receiver operating characteristic curve analysis was used to evaluate diagnostic sensitivity and specificity. RESULTS: Compared with non-GDM women, the relative and absolute expression of plasma microRNA-16-5p, -17-5p, -20a-5p from GDM women were significantly upregulated, when those women were diagnosed as GDM. During pregnancy, the expression of those microRNAs from GDM women also were significantly upregulated. The expression of those microRNAs was also positively correlated with IR, a risk factor of GDM. Plasma microRNA-16-5p, -17-5p, -20a-5p reflected an obvious separation between GDM women and non-GDM women, with areas under the curve of 0.92 (95%CI: 0.871-0.984), 0.88 (95%CI: 0.798-0.962), and 0.74 (95%CI: 0.618-0.870), respectively, cut-offs >2554, 1820, 3886 copies/µL, respectively; sensitivity 41.6%, 21.4% and 17.8%, respectively; and specificity 95.8%, 95.4% and 95.4%, respectively. CONCLUSION: Plasma microRNA-16-5p, -17-5p and -20a-5p are potential diagnostic biomarkers in GDM.

Cloning of mating-type gene MAT1-1 from the caterpillar medicinal mushroom, Cordyceps militaris (Ascomycetes) using TAIL-PCR technology.

Cordyceps militaris and Ophiocordyceps sinensis (syn. Cordyceps sinensis), 2 well-known traditional Chinese medicines, contain the same bioactive components and share a similar developmental process. In this study, one C. militaris strain preserved in our laboratory was proven to be a MAT1 mating-type strain using a polymerase chain reaction-based mating-type assay. A 5000-bp nucleotide sequence of the mating-type MAT1-1 from C. militaris was amplified by thermal asymmetric interlaced polymerase chain reaction, but genes within the mating-type MAT1-2 remain undetectable. Sequence analysis shows that the mating-type gene MAT1-1 idiomorph contains 2 genes, MAT1-1-1 and MAT1-1-2. The MAT1-1-1 gene consists of 1480-bp nucleotides that encode 456 amino acids and contain the conserved a-box domain interrupted by 2 introns; the MAT1-1-2 gene consists of 1066 nucleotides that encode 377 amino acids interrupted by one intron. The intervening distance between MAT1-1-1 and MAT1-1-2 is 778 bp. The C. militaris MAT1-1 idiomorph organization is the same as that of Cordyceps takaomontana. The MAT1-1 mating-type idiomorph of both Cordyceps species lacks the MAT1-1-3 gene, which is typically present in Pyrenomycetes. These studies provide some insights for further study of the morphological development of C. militaris and will eventually benefit the domestication of O. sinensis.

PIAS1 negatively modulates virus triggered type I IFN signaling by blocking the DNA binding activity of IRF3.

During viral infection, production of proinflammatory cytokines including type I interferons (IFNs) is under stringent control to avoid detrimental overreaction. The protein inhibitor of activated STAT (PIAS) family proteins have been recognized as anti-inflammatory molecules by restraining type I IFN induced amplifying signaling. Here we identified PIAS1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of PIAS1 repressed virus-or RIG-I like receptor stimulated type I IFN transcription, whereas knockdown of PIAS1 expression augmented virus-induced production of type I IFNs. PIAS1 with a mutation in the SAP domain retained the inhibitory function in virus-induced IFN transcription, but abolished the inhibition in IFN-stimulated signaling. SUMO E3 ligase activity dead mutant PIAS1/C350S still had the comparable inhibitory function with WT PIAS1. Further study indicated that PIAS1 interacted with IRF3 and inhibited the DNA binding activity of IRF3. The C-terminal region of PIAS1 around a cluster of acidic amino acids is critical for the interaction with IRF3 and the inhibitory functions of PIAS1. Therefore, these results unveil PIAS1 functions both at the virus-induced early signaling stage and IFN stimulated amplifying stage with distinct mechanisms. PIAS1 is important in maintaining proper amounts of type I IFNs and restrains its magnitude when the antiviral response intensifies.

NDR1/STK38 potentiates NF-κB activation by its kinase activity.

Human NDR1/STK38 belongs to the nuclear-Dbf2-related (NDR) family of Ser/Thr kinases. It has been implicated to function in centrosome duplication, control of cell cycle and apoptosis. However, the mechanism of NDR1 signaling pathway remains largely elusive. Here, we report a novel role of NDR1 in NF-κB activation. By overexpression, NDR1 potentiates NF-κB activation induced by TNFα, whereas knockdown of NDR1 expression inhibits NF-κB activation induced by TNFα. Coimmunoprecipitation shows that NDR1 interacts with multiple signal components except p65 in NF-κB signaling pathway. Furthermore, both phosphorylation and kinase dead mutants of NDR1 lose their synergistic effects on TNFα-induced NF-κB activation. siRNA oligo against NDR1 and kinase dead mutant as well mainly block the NF-κB activation induced by TRAF2 but not RIP1. Furthermore, kinase dead mutant of NDR1 fails to interact with TRAF2. Taken together, our findings suggest an unknown function of NDR1, which may regulate NF-κB activation by its kinase activity.