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Background The current worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, and the mortality rate of critical ill patients remains high. The purpose of this study was to identify factors that early predict the progression of COVID-19 from severe to critical illness. Methods This retrospective cohort study included adult patients with severe or critical ill COVID-19 who were consecutively admitted to the Zhongfaxincheng campus of Tongji Hospital (Wuhan, China) from February 8 to 18, 2020. Baseline variables, data at hospital admission and during hospital stay, as well as clinical outcomes were collected from electronic medical records system. The primary endpoint was the development of critical illness. A multivariable logistic regression model was used to identify independent factors that were associated with the progression from severe to critical illness. Results A total of 138 patients were included in the analysis; of them 119 were diagnosed as severe cases and 16 as critical ill cases at hospital admission. During hospital stay, 19 more severe cases progressed to critical illness. For all enrolled patients, longer duration from diagnosis to admission (odds ratio [OR] 1.108, 95% CI 1.022–1.202; P = 0.013), pulse oxygen saturation at admission Conclusions Higher neutrophil count and lower lymphocyte count at admission were early independent predictors of progression to critical illness in severe COVID-19 patients.

Background Patients after total knee arthroplasty (TKA) often develop moderate to severe pain. This study compared the analgesic effect of low-dose epidural morphine vs. a comparable saline injection in patients following TKA surgery. Methods This randomized, double-blinded, and placebo-controlled trial was conducted in a tertiary hospital in Beijing between July 1, 2017 and May 30, 2018. One hundred and ten patients following TKA under combined spinal-epidural anesthesia were randomized to receive either epidural morphine (2 mg diluted to 5 ml normal saline, the epidural morphine group) or placebo (5 ml normal saline, the placebo group). For all patients, single-injection femoral nerve block was performed, and a supplementary patient-controlled intravenous analgesia pump was provided. The severity of pain was assessed with the numerical rating scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) at 6, 12, 24, 36, and 48 hours after surgery. The primary endpoint was moderate to severe pain (NRS pain score ≥4) within 48 hours after surgery. Results The percentage with moderate to severe pain within 48 hours was lower in the epidural morphine group than in the placebo group (58.2% [32/55] with epidural morphine vs. 76.4% [42/55] with placebo; OR 0.43, 95% CI 0.19–0.98; p = 0.042). Furthermore, the cumulative morphine consumption within 48 hours was lower (18.4±6.1 mg vs. 22.4±7.3 mg; p = 0.002) whereas the mental component summary score of 30-day quality of life was higher (63.8±2.9 vs. 61.9±4.2; p = 0.008) in the epidural morphine group than in the placebo group. Conclusions For patients following TKA, the addition of epidural morphine to single-injection femoral nerve block improves the quality of analgesia within 48 hours, without increasing adverse events. Trial registration ClinicalTrials.gov NCT03203967.

Background Current evidences show that regional anesthesia is associated with decreased risk of complications after major surgery. However, the effects of combined regional-general anesthesia remain controversial. The purpose of our study was to analyze the impact of anesthesia (combined epidural-general anesthesia vs. general anesthesia) on the risk of postoperative complications in patients undergoing open surgery for pheochromocytoma. Methods This was a retrospective cohort study. 146 patients who underwent open surgery for pheochromocytoma (100 received combined epidural-general anesthesia and 46 received general anesthesia) in Peking University First Hospital from January 1, 2002 to December 31, 2015 were enrolled. The primary outcome was the occurrence of postoperative complications during hospital stay after surgery. Multivariate Logistic regression models were used to analyze the association between the choice of anesthetic method and the risk of postoperative complications. Results 17 (11.6%) patients developed complications during postoperative hospital stay. The incidence of postoperative complications was lower in patients with combined epidural-general anesthesia than in those with general anesthesia (6% [6/100] vs. 23.9% [11/46], P = 0.006). Multivariate Logistic regression analysis showed that use of combined epidural-general anesthesia (OR 0.219, 95% CI 0.065–0.741; P = 0.015) was associated with lower risk, whereas male gender (OR 5.213, 95% CI 1.283–21.177; P = 0.021) and perioperative blood transfusion (OR 25.879; 95% CI 3.130–213.961; P = 0.003) were associated with higher risk of postoperative complications. Conclusions For patients undergoing open surgery for pheochromocytoma, use of combined epidural-general anesthesia may decrease the occurrence of postoperative complications.

Suicide is a major public health concern worldwide. This study aimed to predict the suicidal behavior of Chinese university students by studying psychological measures such as hopelessness, orientation to happiness, meaning in life, depression, anxiety, stress, and coping styles. In November 2016, a stratified-clustered-random sampling approach was utilized to select subjects from two large public medical-related universities in Shandong province, China. This sample consisted of 2,074 undergraduate students (706 males, 1,368 females; mean age = 19.79±1.39 years). The students' major risk factors for suicide were depression, anxiety, stress, and hopelessness, and the students' minor risk factors included orientation to happiness and coping styles (including self-distraction, self-blame and substance use). Notably, the presence of meaning in life had a positive effect on preventing suicide and acted as a protective factor, which suggests that it is important to identify risk factors as well as protective factors relevant to the target population group in order to increase the effectiveness of counseling and suicide prevention programs.

Arrhythmogenesis in acute myocardial infarction (MI) is associated with depolarization of resting membraine potential (RMP) and decrease of inward rectifier potassium current (IK1) in cardiomyocytes. However, clinical anti-arrhythmic agents that primarily act on RMP by enhancing the IK1 channel are not currently available. We hypothesized that zacopride, a selective and moderate agonist of the IK1/Kir2.1 channels, prevents and cures acute ischemic arrhythmias. To test this viewpoint, adult Sprague-Dawley (SD) rats were subjected to MI by ligating the left main coronary artery. The antiarrhythmic effects of zacopride (i.v. infusion) were observed in the settings of pre-treatment (zacopride given 3 min prior to coronary occlusion), post-treatment (zacopride given 3 min after coronary occlusion) and therapeutic treatment (zacopride given 30 s after the onset of the first sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) post MI). In all the three treatment modes, zacopride (15 μg/kg) inhibited MI-induced ventricular tachyarrhythmias, as shown by significant decreases in the premature ventricular contraction (PVC) and the duration and incidence of VT or VF. In Langendorff perfused rat hearts, the antiarrhythmic effect of 1 μmol/L zacopride were reversed by 1 μmol/L BaCl2, a blocker of IK1 channel. Patch clamp results in freshly isolated rat ventricular myocytes indicated that zacopride activated the IK1 channel and thereby reversed hypoxia-induced RMP depolarization and action potential duration (APD) prolongation. In addition, zacopride (1 μmol/L) suppressed hypoxia- or isoproterenol- induced delayed afterdepolarizations (DADs). In Kir2.x transfected Chinese hamster ovary (CHO) cells, zacopride activated the Kir2.1 homomeric channel but not the Kir2.2 or Kir2.3 channels. These results support our hypothesis that moderately enhancing IK1/Kir2.1 currents as by zacopride rescues ischemia- and hypoxia- induced RMP depolarization, and thereby prevents and cures acute ischemic arrhythmias. This study brings a new viewpoint to antiarrhythmic theories and provides a promising target for the treatment of acute ischemic arrhythmias.

Background Dexmedetomidine in combination with opioids has been used for postoperative analgesia. The purpose of this study was to investigate the impacts of dexmedetomidine supplemented intravenous analgesia on morphine consumption and subjective sleep quality in elderly patients after open abdominal surgery. Methods This was a pilot randomized controlled trial. 58 elderly patients (age ≥ 60 years) who underwent open abdominal surgery were randomized to receive either dexmedetomidine supplemented morphine analgesia (0.5 mg/ml morphine plus 2 μg/ml dexmedetomidine in 100 ml normal saline, DEX group) or morphine analgesia (0.5 mg/ml morphine in 100 ml normal saline, CTRL group) for 72 hours after surgery. Patient-controlled analgesia pump was programmed to deliver a 2ml bolus with a lockout interval of 8 minutes and a background infusion at a rate of 1 ml/h. The primary endpoint was 72-hour morphine consumption. Secondary endpoints included pain intensity, subjective sleep quality, and 30-day complications and mortality after surgery. Results The 72-hour morphine consumption was lower in the DEX group than in the CTRL group (median 39.0 mg [interquartile range 37.3, 41.0] in the DEX group vs. 49.0 mg [45.5, 50.0] in the CTRL group; median difference -9.0 mg [95% CI -10.0, -6.0], P < 0.001). The intensity of pain within 48 hours was lower (P

The rice white tip nematode, Aphelenchoides besseyi, is widely distributed in rice planting areas worldwide and causes serious economic losses. Cathepsin genes have been demonstrated to have importance in studying the reproduction, development, pathogenicity, and control methods of plant nematodes. In this paper, a novel cathepsin B gene, Ab-cb-1, was found and cloned. The Ab-cb-1 gene was 1347 bp in length and encodes 369 amino acids. The Ab-CB-1 protein contains characteristic occluding loops but no signal peptide. A homology analysis showed that Ab-CB-1 had the highest identity value (64%) to the known amino acid sequence of cathepsin B-like cysteine protease 6 from Toxocara canis. When Ab-cb-1 was expressed in a prokaryotic system, the protein massed approximately 45 kDa and could decompose carrot callus. Ab-cb-1 mRNA was localized in the nematode intestine. The relative expression level of Ab-cb-1 in the A. besseyi Ab-S24 population, which had high reproductivity, was approximately 6.9 times that in the Ab-N10 population, which had low reproductivity, and the difference was significant (p

The chrysanthemum foliar nematode (CFN), Aphelenchoides ritzemabosi, is a plant parasitic nematode that attacks many plants. In this study, a transcriptomes of mixed-stage population of CFN was sequenced on the Illumina HiSeq 2000 platform. 68.10 million Illumina high quality paired end reads were obtained which generated 26,817 transcripts with a mean length of 1,032 bp and an N50 of 1,672 bp, of which 16,467 transcripts were annotated against six databases. In total, 20,311 coding region sequences (CDS), 495 simple sequence repeats (SSRs) and 8,353 single-nucleotide polymorphisms (SNPs) were predicted, respectively. The CFN with the most shared sequences was B. xylophilus with 16,846 (62.82%) common transcripts and 10,543 (39.31%) CFN transcripts matched sequences of all of four plant parasitic nematodes compared. A total of 111 CFN transcripts were predicted as homologues of 7 types of carbohydrate-active enzymes (CAZymes) with plant/fungal cell wall-degrading activities, fewer transcripts were predicted as homologues of plant cell wall-degrading enzymes than fungal cell wall-degrading enzymes. The phylogenetic analysis of GH5, GH16, GH43 and GH45 proteins between CFN and other organisms showed CFN and other nematodes have a closer phylogenetic relationship. In the CFN transcriptome, sixteen types of genes orthologues with seven classes of protein families involved in the RNAi pathway in C. elegans were predicted. This research provides comprehensive gene expression information at the transcriptional level, which will facilitate the elucidation of the molecular mechanisms of CFN and the distribution of gene functions at the macro level, potentially revealing improved methods for controlling CFN.

Background There may be significant difference between measurement of end-tidal carbon dioxide partial pressure (PetCO2) and arterial carbon dioxide partial pressure (PaCO2) during one-lung ventilation with low tidal volume for thoracic surgeries. Transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring can be used continuously to evaluate PaCO2 in a noninvasive fashion. In this study, we compared the accuracy between PetCO2 and PtcCO2 in predicting PaCO2 during prolonged one-lung ventilation with low tidal volume for thoracic surgeries. Methods Eighteen adult patients who underwent thoracic surgeries with one-lung ventilation longer than two hours were included in this study. Their PetCO2, PtcCO2, and PaCO2 values were collected at five time points before and during one-lung ventilation. Agreement among measures was evaluated by Bland-Altman analysis. Results Ninety sample sets were obtained. The bias and precision when PtcCO2 and PaCO2 were compared were 4.1 ± 6.5 mmHg during two-lung ventilation and 2.9 ± 6.1 mmHg during one-lung ventilation. Those when PetCO2 and PaCO2 were compared were -11.8 ± 6.4 mmHg during two-lung ventilation and -11.8 ± 4.9 mmHg during one-lung ventilation. The differences between PtcCO2 and PaCO2 were significantly lower than those between PetCO2 and PaCO2 at all five time-points (p < 0.05). Conclusions PtcCO2 monitoring was more accurate for predicting PaCO2 levels during prolonged one-lung ventilation with low tidal volume for patients undergoing thoracic surgeries.

E74-like factor 5 (Elf5) has been associated with tumor suppression in breast cancer. However, its role in urothelial cancer (UC) is completely unknown. Immunohistochemistry (IHC) and methylation specific PCR (MSP) were done to detect Elf5 expression level and its promoter methylation. Results revealed that low expression of Elf5 on protein and mRNA levels were associated with tumor progression, early relapse and poor survival. In vitro, down-regulation of Elf5 can increase epithelial-mesenchymal transition (EMT). Aberrant Elf5 methylation was identified as major mechanism for Elf5 gene silence. Accordingly, restoration of Elf5 by infection or demethylating treatment effectively reversed EMT processes. In conclusion, we identified Elf5 as a novel biomarker of UC on several biological levels and established a causative link between Elf5 and EMT in UC.

Background Delirium is a frequent complication after cardiac surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the impact of perioperative dexmedetomidine administration on the incidence of delirium in elderly patients after cardiac surgery. Methods This randomized, double-blinded, and placebo-controlled trial was conducted in two tertiary hospitals in Beijing between December 1, 2014 and July 19, 2015. Eligible patients were randomized into two groups. Dexmedetomidine (DEX) was administered during anesthesia and early postoperative period for patients in the DEX group, whereas normal saline was administered in the same rate for the same duration for patients in the control (CTRL) group. The primary endpoint was the incidence of delirium during the first five days after surgery. Secondary endpoints included the cognitive function assessed on postoperative days 6 and 30, the overall incidence of non-delirium complications within 30 days after surgery, and the all-cause 30-day mortality. Results Two hundred eighty-five patients were enrolled and randomized. Dexmedetomidine did not decrease the incidence of delirium (4.9% [7/142] in the DEX group vs 7.7% [11/143] in the CTRL group; OR 0.62, 95% CI 0.23 to 1.65, p = 0.341). Secondary endpoints were similar between the two groups; however, the incidence of pulmonary complications was slightly decreased (OR 0.51, 95% CI 0.26 to 1.00, p = 0.050) and the percentage of early extubation was significantly increased (OR 3.32, 95% CI 1.36 to 8.08, p = 0.008) in the DEX group. Dexmedetomidine decreased the required treatment for intraoperative tachycardia (21.1% [30/142] in the DEX group vs 33.6% [48/143] in the CTRL group, p = 0.019), but increased the required treatment for postoperative hypotension (84.5% [120/142] in the DEX group vs 69.9% [100/143] in the CTRL group, p = 0.003). Conclusions Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of postoperative delirium in elderly patients undergoing elective cardiac surgery. However, considering the low delirium incidence, the trial might have been underpowered. Trial Registration ClinicalTrials.gov NCT02267538

Fatty acid- and retinoid-binding protein (FAR) is a nematode-specific protein expressed in the nematode hypodermis. It is involved in nematode development, reproduction, and infection and can disrupt the plant defense reaction. In this study, we obtained the full-length sequence of the far gene from Radopholus similis (Rs-far-1), which is 828 bp long and includes a 558 bp ORF encoding 186 amino acids. A protein homology analysis revealed that Rs-FAR-1 is 75% similar to Mj-FAR-1 from Meloidogyne javanica. A neighbor-joining phylogenetic tree was inferred and showed that Rs-FAR-1 is most similar to Pv-FAR-1 from Pratylenchus vulnus. A fluorescence-based ligand-binding analysis confirmed that Rs-FAR-1 can combine with fatty acids and retinol. qPCR was used to assess Rs-far-1 expression levels at different developmental stages in different R. similis populations, and its expression was 2.5 times greater in the highly pathogenic Rs-C population than in the less pathogenic Rs-P population. The highest expression was found in females, followed by eggs, juveniles and males. When R. similis was treated with Rs-far-1 dsRNA for 36 h, the reproduction and pathogenicity decreased significantly. In situ hybridization revealed Rs-far-1 transcripts in the R. similis hypodermis. Additionally, R. similis treated with Rs-far-1 dsRNA or water were inoculated into Arabidopsis thaliana. Allene oxide synthase (AOS) expression in A. thaliana was upregulated during early infection in both treatments and then returned to the expression levels of the control plant. Compared with the control plant, AOS expression significantly decreased in A. thaliana inoculated with water-treated R. similis but significantly increased in A. thaliana inoculated with Rs-far-1 dsRNA-treated R. similis. This finding indicates that Rs-far-1 regulates AOS expression in A. thaliana. Rs-FAR-1 plays a critical role in R. similis development, reproduction, and infection and can disturb the plant defense reaction. Therefore, Rs-far-1 is an important target gene to control R. similis.

Ganoderma has been considered a very difficult genus among the polypores to classify and is currently in a state of taxonomic chaos. In a study of Ganoderma collections including numerous type specimens, we found that six species namely G. cupreum, G. densizonatum, G. limushanense, G. mastoporum, G. orbiforme, G. subtornatum, and records of G. fornicatum from Mainland China and Taiwan are very similar to one another in basidiocarp texture, pilear cuticle structure, context color, pore color and basidiospore characteristics. Further, we sequenced the nrDNA ITS region (ITS1 and ITS2) and partial mtDNA SSU region of the studied materials, and performed phylogenetic analyses based on these sequence data. The nrDNA ITS sequence analysis results show that the eight nrDNA ITS sequences derived from this study have single-nucleotide polymorphisms in ITS1 and/or ITS2 at inter- and intra-individual levels. In the nrDNA ITS phylogenetic trees, all the sequences from this study are grouped together with those of G. cupreum and G. mastoporum retrieved from GenBank to form a distinct clade. The mtDNA SSU sequence analysis results reveal that the five mtDNA SSU sequences derived from this study are clustered together with those of G. cupreum retrieved from GenBank and also form a distinct clade in the mtDNA SSU phylogenetic trees. Based on morphological and molecular data, we conclude that the studied taxa are conspecific. Among the names assigned to this species, G. fornicatum given to Asian collections has nomenclatural priority over the others. However, the type of G. fornicatum from Brazil is probably lost and a modern description based on the type lacks. The identification of the Asian collections to G. fornicatum therefore cannot be confirmed. To the best of our knowledge, G. orbiforme is the earliest valid name for use.

Flowering at the appropriate time is crucial for reproductive success and is strongly influenced by various pathways such as photoperiod, circadian clock, FRIGIDA and vernalization. Although each separate pathway has been extensively studied, much less is known about the interactions between them. In this study we have investigated the relationship between the photoperiod/circadian clock gene and FRIGIDA/FLC by characterizing the function of the B-box STO gene family. STO has two B-box Zn-finger domains but lacks the CCT domain. Its expression is controlled by circadian rhythm and is affected by environmental factors and phytohormones. Loss and gain of function mutants show diversiform phenotypes from seed germination to flowering. The sto-1 mutant flowers later than the wild type (WT) under short day growth conditions, while over-expression of STO causes early flowering both in long and short days. STO over-expression not only reduces FLC expression level but it also activates FT and SOC1 expression. It also does not rely on the other B-box gene CO or change the circadian clock system to activate FT and SOC1. Furthermore, the STO activation of FT and SOC1 expression is independent of the repression of FLC; rather STO and FLC compete with each other to regulate downstream genes. Our results indicate that photoperiod and the circadian clock pathway gene STO can affect the key flowering time genes FLC and FT/SOC1 separately, and reveals a novel perspective to the mechanism of flowering regulation.

Objective To determine the prevalence and distribution of human enteroviruses (HEVs) among healthy children in Shenzhen, China. Method Clinical specimens were obtained from 320 healthy children under 5 years old in Shenzhen, China from 2010 to 2011. The specimens were evaluated using real-time PCR and cell cultures. The positive specimens were further tested using reverse transcription-seminested PCR (RT-snPCR). Molecular typing and phylogenetic analysis were based on the sequence determined. Results Among the 320 samples, 34 were tested positive for HEVs (10.6%) and 22 different serotypes were identified using RT-snPCR. PV1 and PV2 were also detected. The predominant serotype observed was EV71 (17.6%), followed by CV-B4 (14.7%). HEV-B was detected most frequently, with an overall prevalence of 47.1%. HEV-A and HEV-C were found in 32.3% and 20.6% of the samples, respectively. No HEV-D was identified. Molecular phylogeny indicated that all EV71 strains were of C4 genotype. Conclusion Although a variety of HEVs was detected in healthy children, HEV-B was relatively more prevalent than other HEV species. Considering HEV-A is more prevalent than HEV-B among patients with hand-foot-mouth disease, additional long-term surveillance of HEV is warranted in both asymptomatic and symptomatic populations.

Context Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction. Objective To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery. Design Prospective cohort study. Setting Two teaching hospitals. Patients One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009. Intervention None. Main Outcome Measures Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction. Results Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016). Conclusions High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery.

The purpose of this cross-sectional study was to investigate the joint associations of physical activity level (PAL) and dietary patterns in relation to cardiovascular disease (CVD) risk factors among Chinese men. The study population consisted of 13 511 Chinese males aged 18-59 years from the 2002 China National Nutrition and Health Survey. Based on dietary data collected by a food frequency questionnaire, four dietary patterns were identified and labeled as "Green Water'' (high consumption of rice, vegetables, seafood, pork, and poultry), "Yellow Earth'' (high consumption of wheat flour products and starchy tubers), "New Affluent'' (high consumption of animal sourced foods and soybean products), and "Western Adopter'' (high consumption of animal sourced foods, cakes, and soft drinks). From the information collected by a 1-year physical activity questionnaire, PAL was calculated and classified into 4 categories: sedentary, low active, active, and very active. As compared with their counterparts from the New Affluent pattern, participants who followed the Green Water pattern had a lower likelihood of abdominal obesity (AO; 50.2%), hypertension (HT; 37.9%), hyperglycemia (HG; 41.5%), elevated triglyceride (ETG; 14.5%), low HDL (LHDL; 39.8%), and metabolic syndrome (MS; 51.9%). When compared to sedentary participants, the odds ratio of participants with very active PAL was 0.62 for AO, 0.85 for HT, 0.71 for HG, 0.76 for ETG, 0.74 for LHDL, and 0.58 for MS. Individuals who followed both very active PAL and the Green Water pattern had a lower likelihood of CVD risk factors (AO: 65.8%, HT: 39.1%, HG: 57.4%, ETG: 35.4%, LHDL: 56.1%, and MS: 75.0%), compared to their counterparts who followed both sedentary PAL and the New Affluent pattern. In addition, adherence to both healthy dietary pattern and very active PAL presented a remarkable potential for CVD risk factor prevention.

Aspergillus flavus is second only to A. fumigatus in causing invasive aspergillosis and it is the major agent responsible for fungal sinusitis, keratitis and endophthalmitis in many countries in the Middle East, Africa and Southeast Asia. Despite the growing challenge due to A. flavus, data on the molecular epidemiology of this fungus remain scarce. The objective of the present study was to develop a new typing method based on the detection of VNTR (Variable number tandem repeat) markers. Eight VNTR markers located on 6 different chromosomes (1, 2, 3, 5, 7 and 8) of A. flavus were selected, combined by pairs for multiplex amplifications and tested on 30 unrelated isolates and six reference strains. The Simpson index for individual markers ranged from 0.398 to 0.818. A combined loci index calculated with all the markers yielded an index of 0.998. The MLVA (Multiple Locus VNTR Analysis) technique proved to be specific and reproducible. In a second time, a total of 55 isolates from Chinese avian farms and from a Tunisian hospital have been evaluated. One major cluster of genotypes could be defined by using the graphing algorithm termed Minimum Spanning Tree. This cluster comprised most of the isolates collected in an avian farm in southern China. The MLVA technique should be considered as an excellent and cost-effective typing method that could be used in many laboratories without the need for sophisticated equipment.

Dopamine neurons in the ventral tegmental area (VTA) have been traditionally studied for their roles in reward-related motivation or drug addiction. Here we study how the VTA dopamine neuron population may process fearful and negative experiences as well as reward information in freely behaving mice. Using multi-tetrode recording, we find that up to 89% of the putative dopamine neurons in the VTA exhibit significant activation in response to the conditioned tone that predict food reward, while the same dopamine neuron population also respond to the fearful experiences such as free fall and shake events. The majority of these VTA putative dopamine neurons exhibit suppression and offset-rebound excitation, whereas ∼25% of the recorded putative dopamine neurons show excitation by the fearful events. Importantly, VTA putative dopamine neurons exhibit parametric encoding properties: their firing change durations are proportional to the fearful event durations. In addition, we demonstrate that the contextual information is crucial for these neurons to respectively elicit positive or negative motivational responses by the same conditioned tone. Taken together, our findings suggest that VTA dopamine neurons may employ the convergent encoding strategy for processing both positive and negative experiences, intimately integrating with cues and environmental context.

Tau, an important microtubule associated protein, has been found to bind to DNA, and to be localized in the nuclei of both neurons and some non-neuronal cells. Here, using electrophoretic mobility shifting assay (EMSA) in the presence of DNA with different chain-lengths, we observed that tau protein favored binding to a 13 bp or a longer polynucleotide. The results from atomic force microscopy also showed that tau protein preferred a 13 bp polynucleotide to a 12 bp or shorter polynucleotide. In a competitive assay, a minor groove binder distamycin A was able to replace the bound tau from the DNA double helix, indicating that tau protein binds to the minor groove. Tau protein was able to protect the double-strand from digestion in the presence of DNase I that was bound to the minor groove. On the other hand, a major groove binder methyl green as a negative competitor exhibited little effect on the retardation of tau-DNA complex in EMSA. This further indicates the DNA minor groove as the binding site for tau protein. EMSA with truncated tau proteins showed that both the proline-rich domain (PRD) and the microtubule-binding domain (MTBD) contributed to the interaction with DNA; that is to say, both PRD and MTBD bound to the minor groove of DNA and bent the double-strand, as observed by electron microscopy. To investigate whether tau protein is able to prevent DNA from the impairment by hydroxyl free radical, the chemiluminescence emitted by the phen-Cu/H(2)O(2)/ascorbate was measured. The emission intensity of the luminescence was markedly decreased when tau protein was present, suggesting a significant protection of DNA from the damage in the presence of hydroxyl free radical.

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4% ± 3.9% and 94.6 ± 3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL.

Objectives This study aims to compare the protein composition of high-density lipoprotein (HDL) particles in coronary heart disease (CHD) patients and controls by proteomic methods. Background HDL has been reported to exert pro-atherogenic properties in CHD patients. Accumulating evidence indicates that HDL composition, rather than the HDL-C level, determines its functions. The changes in HDL composition involved in the conversion of anti-atherogenic to pro-atherogenic properties in CHD patients are currently unknown. Methods and Results iTRAQ combined with nanoLC-MS/MS was performed to obtain a differential expression profile of the HDL pooled samples of the male age-matched CHD patients and controls (n = 10/group). Of the 196 proteins identified in the examined HDL, 12 were differentially expressed between the CHD patients and the controls, including five up-regulated proteins and seven down-regulated proteins. Using GO analysis, we determined that the up-regulated proteins were mostly involved in inflammatory reactions, displaying a potential pro-atherogenic profile. In contrast, the down-regulated proteins were mostly involved in lipid metabolism processes, displaying anti-atherogenic properties. To confirm the proteomic results, serum amyloid A (SAA) and apoC-I were selected and quantified by ELISA, in the same population as the proteomic analysis, as well as another independent population (n = 120/group). Consistent with the proteomic results, the amount of SAA was significantly increased, and apoC-I was significantly decreased in the HDL particles of CHD patients compared with those of controls (P

Ling-zhi, a widely cultivated fungus in China, has a long history in traditional Chinese medicine. Although the name 'Ganoderma lucidum', a species originally described from England, has been applied to the fungus, their identities are not the same. This study aims to clarify the identity of this medicinally and economically important fungus. Specimens of Ling-zhi from China (field collections and cultivated basidiomata of the Chinese 'G. lucidum'), G. lucidum from UK and other related Ganoderma species, were examined both morphologically and molecularly. High variability of basidioma morphology was found in the cultivated specimens of the Chinese 'G. lucidum', while some microscopic characters were more or less consistent, i.e. short clavate cutis elements, Bovista-type ligative hyphae and strongly echinulate basidiospores. These characters were also found in the holotype of G. sichuanense, a species originally described from Sichuan, China, and in recent collections made in the type locality of the species, which matched the diagnostic characters in the prologue. For comparison, specimens of closely related species, G. lucidum, G. multipileum, G. resinaceum, G. tropicum and G. weberianum, were also examined. DNA sequences were obtained from field collections, cultivated basidiomata and living strains of the Chinese 'G. lucidum', specimens from the type locality of G. sichuanense, and specimens of the closely related species studied. Three-gene combined analyses (ITS+IGS+rpb2) were performed and the results indicated that the Chinese 'G. lucidum' shared almost identical sequences with G. sichuanense. Based on both morphological and molecular data, the identity of the Chinese 'G. lucidum' (Ling-zhi) is considered conspecific with G. sichuanense. Detailed morphological descriptions and illustrations are provided in addition to discussion of nomenclature implications.

The amygdala is a key area in the brain for detecting potential threats or dangers, and further mediating anxiety. However, the neuronal mechanisms of anxiety in the amygdala have not been well characterized. Here we report that in freely-behaving mice, a group of neurons in the basolateral amygdala (BLA) fires tonically under anxiety conditions in both open-field and elevated plus-maze tests. The firing patterns of these neurons displayed a characteristic slow onset and progressively increased firing rates. Specifically, these firing patterns were correlated to a gradual development of anxiety-like behaviors in the open-field test. Moreover, these neurons could be activated by any impoverished environment similar to an open-field; and introduction of both comfortable and uncomfortable stimuli temporarily suppressed the activity of these BLA neurons. Importantly, the excitability of these BLA neurons correlated well with levels of anxiety. These results demonstrate that this type of BLA neuron is likely to represent anxiety and/or emotional values of anxiety elicited by anxiogenic environmental stressors.