Biological characteristics of Cordyceps militaris single mating-type strains.

Cordyceps militaris has been extensively cultivated as a model cordyceps species for commercial purposes. Nevertheless, the problems related to strain degeneration and breeding technologies remain unresolved. This study assessed the physiology and fertility traits of six C. militaris strains with distinct origins and characteristics, focusing on single mating-type strains. The results demonstrated that the three identified strains (CMDB01, CMSY01, and CMJB02) were single mating-type possessing only one mating-type gene (MAT1-1). In contrast, the other three strains (CMXF07, CMXF09, and CMMS05) were the dual mating type. The MAT1-1 strains sourced from CMDB01, CMSY01, and CMJB02 consistently produced sporocarps but failed to generate ascospores. However, when paired with MAT1-2 strains, the MAT1-1 strains with slender fruiting bodies and normal morphology were fertile. The hyphal growth rate of single mating-type strains (CMDB01, CMSY01, and CMJB02) typically surpassed that of dual mating-type strains (CMXF07, CMXF09, and CMMS05). The growth rates of MAT1-2 and MAT1-1 strains were proportional to their ratios, such that a single mating-type strain with a higher ratio exhibited an increased growth rate. As C. militaris matured, the adenosine content decreased. In summary, the C. militaris strains that consistently produce sporocarps and have a single mating type are highly promising for production and breeding.

Repeat dose and reproductive toxicity of thrombopoietin mimic peptide in Sprague-Dawley rats.

Thrombopoietin mimic peptide (TMP) is a novel thrombopoietin receptor agonist. In this report, we evaluated the potential toxicity of TMP in repeat-dose toxicity and reproductive/developmental toxicity studies (segment Ⅰ, Ⅱ, Ⅲ). TMP was administered subcutaneously to Sprague-Dawley (SD) rats at 5, 15 or 50 mcg/kg. In repeat-dose toxicity study, the rats were administrated three times a week for 26 week with a 4-week recovery. TMP could produce anti-drug antibodies and induce platelet counts increase, megakaryocyte proliferation. While platelet counts decreased gradually and returned to normal after 4 weeks in male rats. Other significant findings included myelofibrosis of bone marrow, hepatic extramedullary hematopoiesis, splenic lymphocytic depletion and bone hyperostosis. All treatment-related effects were reversed following recovery. The NOAEL of repeat-dose toxicity in female rats is 5 mcg/kg. In the reproductive/developmental toxicity (segment Ⅰ, Ⅲ), no deaths occurred, and no general toxicological effects or abnormal reproductive functions were observed. In embryo-fetal developmental toxicity study (segment Ⅱ), the number of resorbed fetuses in the 50 mcg/kg group was significantly increased. The NOAEL as related to reproductive/developmental toxicity in these rats was 15 mcg/kg.

[Effect of Using Hydrogen Peroxide for Periodic Disinfection Combined With Continuous Disinfection to Control Contamination in Dental Unit Waterline]. / è¿‡æ°§åŒ–æ°¢å®šæœŸæ¶ˆæ¯’ç»“åˆæŒç»­æ¶ˆæ¯’å¯¹å£è ”ç»¼åˆæ²»ç–—å°æ°´è·¯æ±¡æŸ“æŽ§åˆ¶çš„æœ‰æ•ˆæ€§è§‚å¯Ÿ.

Objective: To observe the effect of using hydrogen peroxide in periodic disinfection combining with continuous disinfection of dental unit waterlines and to provide references for the selection of waterway disinfection measures. Methods: A total of 4 dental units in a hospital of stomatology were selected through convenience sampling. The dental unit waterlines received periodic disinfection once every 4 weeks in addition to continuous disinfection (When the dental units were not used for more than 3 days, an additional periodic disinfection would be performed.). Periodic disinfection referred to filling up the waterlines with a disinfectant solution (1.4% hydrogen peroxide) by using the waterline disinfection device that came with the dental unit, immersing for 24 hours, and then emptying out the disinfectant solution. Continuous disinfection referred to using hydrogen peroxide at a concentration of 0.014% as dental treatment water and using it to flush the waterlines for 2 minutes before any dental treatment in the morning and to flush the waterlines for 30 seconds after each dental treatment. The study lasted for 25 weeks, with periodic disinfection being performed for 7 times and continuous disinfection carried out for the rest of the dental treatment time. During the 25 weeks, water samples were collected from air/water syringes and high-speed handpieces. Then, the water samples were incubated and the bacterial concentration and the qualification rates were calculated accordingly. When the bacterial concentration≤100 CFU/ mL, the water samples were considered to be qualified. Waterline tubes of 1 cm were collected before and after the 25 weeks of disinfection with hydrogen peroxide. Biofilms in the waterline tube were observed under scanning electron microscope. Results: A total of 352 water samples were collected. Eight water samples were collected before disinfection with hydrogen peroxide, with the median of bacterial concentration being 3140 CFU/mL. On the first day of disinfection with hydrogen peroxide, the median bacterial concentration in dental treatment water was 7.5 CFU/mL. There was a significant difference between the bacterial concentration of the water samples before the disinfection and that after the disinfection (P=0.012). A total of 344 water samples were collected after the disinfection, with the median bacterial concentrations for air/water syringes and high-speed handpieces being 11 CFU/mL and 11CFU/mL and the qualified rates being 83.7% and 82.0%, respectively. There was no significant difference in bacterial concentration or the qualification rates. During week 1 through week 9 of the disinfection, the qualification rates of the dental treatment water always exceeded 80% in 8 weeks, with week 3 being the exception. In the two four-week disinfection periods of week 14 through week 17 and week 18 through week 21, the qualification rate was maintained at above 80% for only the first two weeks and started to decrease from the third week. Biofilm morphology was observed under scanning electron microscope. Before the disinfection, the biofilm was found to be a dense structure and the mixture of a large number of bacteria. After 25 weeks of the disinfection, the biofilm structure appeared to be loose and did not show consistent characteristics of a large number of bacteria retained. Conclusion: Periodic disinfection combined with continuous disinfection using hydrogen peroxide can effectively control contamination in dental unit waterlines. But the cycles of periodic disinfection and the concentration of hydrogen peroxide for continuous disinfection should be further discussed according to the actual clinical situation.

Clustering-Evolved Frontier Orbital for Low-Temperature CO2 Dissociation.

In this study, single Ni2 clusters (two Ni atoms bridged by a lattice oxygen) are successfully synthesized on monolayered CuO. They exhibit a remarkable activity toward low-temperature CO2 thermal dissociation, in contrast to cationic Ni atoms that nondissociatively adsorb CO2 and metallic Ni ones that are chemically inert for CO2 adsorption. Density functional theory calculations reveal that the Ni2 clusters can significantly alter the spatial symmetry of their unoccupied frontier orbitals to match the occupied counterpart of the CO2 molecule and enable its low-temperature dissociation. This study may help advance single-cluster catalysis and exploit the unexcavated mechanism for low-temperature CO2 activation.

A Spear and Shield-Inspired Ar Plasma Safeguard Few-Layer Black Phosphore with Firefighting of Epoxy Resin.

Appearing as an innovative and efficient strategy, a facile strategy of a plasma ball mill is carried out to prepare few-layer black phosphorus nanosheets (BPNSs), for abating the fire risk of epoxy resin (EP). A spear and shield-inspired Ar plasma emergeed through a plasma ball mill to prevent Ar@BP nanosheets from oxidation compared with the preparation of BP nanosheets (MBPNSs) in a mechanical ball mill. The absorption coefficient in the synchrotron radiation spectrum is increased by 16.91%, indicating that BP is effectively protected by Ar proof. The Vienna ab initio simulation reveals that the combination of Ar@BP with oxygen cannot proceed spontaneously with the binding energy of 4.44 eV. With the introduction of 1.5 wt% Ar@BP, the total heat release (THR), total smoke release (TSR), total smoke production(TSP), CO, and CO2 yield, compared with that of EP, are descended by 30.40%, 24.41%, 24.10%, 33.23%, and 37.60%, respectively, indicating excellent flame retardancy property. It is attributed to the condensed and gas phase function. Meanwhile, the tensile strength and elongation at break increase by 27.92% and 56.04%, respectively, with the incorporation of 1.5 wt% Ar@BP.

Transcriptome and metabolome profiling unveils the mechanisms of naphthalene acetic acid in promoting cordycepin synthesis in Cordyceps militaris.

Cordycepin, an important active substance in Cordyceps militaris, possesses antiviral and other beneficial activities. In addition, it has been reported to effectively promote the comprehensive treatment of COVID-19 and thus has become a research hotspot. The addition of naphthalene acetic acid (NAA) is known to significantly improve the yield of cordycepin; however, its related molecular mechanism remains unclear. We conducted a preliminary study on C. militaris with different concentrations of NAA. We found that treatment with different concentrations of NAA inhibited the growth of C. militaris, and an increase in its concentration significantly improved the cordycepin content. In addition, we conducted a transcriptome and metabolomics association analysis on C. militaris treated with NAA to understand the relevant metabolic pathway of cordycepin synthesis under NAA treatment and elucidate the relevant regulatory network of cordycepin synthesis. Weighted gene co-expression network analysis (WGCNA), transcriptome, and metabolome association analysis revealed that genes and metabolites encoding cordycepin synthesis in the purine metabolic pathway varied significantly with the concentration of NAA. Finally, we proposed a metabolic pathway by analyzing the relationship between gene-gene and gene-metabolite regulatory networks, including the interaction of cordycepin synthesis key genes; key metabolites; purine metabolism; TCA cycle; pentose phosphate pathway; alanine, aspartate, and glutamate metabolism; and histidine metabolism. In addition, we found the ABC transporter pathway to be significantly enriched. The ABC transporters are known to transport numerous amino acids, such as L-glutamate, and participate in the amino acid metabolism that affects the synthesis of cordycepin. Altogether, multiple channels work together to double the cordycepin yield, thereby providing an important reference for the molecular network relationship between the transcription and metabolism of cordycepin synthesis.

Facial nerve function training in patients with peripheral facial paralysis: an expert consensus.

Facial nerve training can prevent facial expression muscle atrophy and promote the recovery of facial para-lysis in patients with peripheral facial paralysis. However, there is still a lack of specific and unified technical standards for facial nerve training, which results in a variety of clinical training methods and uneven levels. In order to standardize the application of facial nerve function training technology for nursing staff, the study convened relevant domestic experts, based on evidence-based combination with the disease characteristics of peripheral facial paralysis and expert clinical experience, conducted in-depth interviews with experts, expert correspondence and expert meetings, and finally formulated the expert consensus on facial nerve function training in patients with peripheral facial paralysis. Overall, suggestions for standardizing the timing, training methods, evaluation methods, health education and other aspects were provided for clinical reference.

Magnetic Resonance/Infrared Dual-Modal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy Nanoplatform Based on Cu1.96S-Gd@FA for Precision Cancer Theranostics.

Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM-1 s-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu1.96S nanoparticles. The Cu1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu1.96S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.

Assessment of microbiota diversity in dental unit waterline contamination.

BACKGROUND: Dental unit waterlines (DUWLs) provide water for handpieces, air/water syringes, and mouth-rinse water outlets. DUWL contamination can negatively affect the operating environment and public health. Therefore, it is important to elucidate the bacterial concentrations and microbial composition in the DUWLs from different dental specialties. METHODS: We collected 350 5-mL dental water samples (from high-speed handpieces, air/water syringes, and mouth-rinse water outlets) from 60 dental chair units (DCUs) at a dental hospital to determine the bacterial concentrations by culture methods. Meanwhile, to investigate the diversity and community structure of microbe in the DUWLs, 17 high-quality DNA from 60 250-mL air/water syringe water samples, which were collected from the same 60 DCUs, were analyzed using 16S rDNA high-throughput sequencing. RESULTS: The median bacterial concentration was 166 (31.5, 672.5) CFU/mL and the range was 0-3,816,000 CFU/mL. Only 42.6% of the water samples had bacterial concentrations below 100 CFU/mL. The Kruskal-Wallis H-test revealed that the water samples from three dental specialties had significantly different bacterial concentrations (H = 27.441, P < 0.01). High-throughput sequencing results showed significant differences in bacterial community structure between periodontics and the other two dental specialties. In the samples from three dental specialties, 508 OTUs were detected, with 160, 182 and 176 OTUs unique to the periodontics, endodontics and prosthodontics specialties, respectively. Linear discriminant analysis (LDA) effect size (LEfSe) suggested that Hydrocarboniphaga, Zoogloea, Aquabacterium, and Hydrogenophaga were enriched in the periodontics specialty; Acinetobacter, Geothrix, and Desulfovibrio were enriched in the prosthodontics specialty; and Alistipes, Clostridium XIVa, and Serratia were enriched in the endodontics specialty. Seven potentially human-pathogenic genera (Pseudomonas, Acinetobacter, Sphingomonas, Ochrobactrum, Rhizobium, Brevundimonas, and Methylobacterium) with relative abundance exceeding 1% were also detected in the DUWLs. CONCLUSIONS: The bacterial concentrations and microbial composition were influenced by different dental specialties, so a validated disinfection protocol should be used to control DUWL contamination in different dental specialties.

Application and prospect of antimonene: A new two-dimensional nanomaterial in cancer theranostics.

With the rise of two-dimensional nanomaterials in medicine, finding suitable materials has become our top priority. Since the first report of antimonene in 2015, due to its excellent physical and chemical properties, it has gradually attracted widespread attention, including its application prospects in cancer treatment. In this paper, the preparation, stability and infrared degradability of antimonene, as well as its experimental examples in tumor treatment in recent years are reviewed, the latest research results are listed and summarized, the advantages and existing problems are analyzed, and the future of antimonene in tumor therapy is prospected.

Oral Glutamine May Have No Clinical Benefits to Prevent Radiation-Induced Oral Mucositis in Adult Patients With Head and Neck Cancer: A Meta-Analysis of Randomized Controlled Trials.

Objectives: The role of oral glutamine for the management of oral mucositis (OM) has not yet been confirmed. The objective of the present study is to further investigate whether oral glutamine is effective in preventing and treating OM among patients with head and neck cancer (HNC) receiving radiotherapy alone or concurrent with chemotherapy. Methods: A systematic search was performed in PubMed, EMBASE, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) to capture all potential citations from the inception to June 2019. Then data extraction and assessment of risk of bias were carried out after selecting the eligible citations. RevMan 5.3 software was used to perform all statistical analyses. Results: Six randomized controlled trials (RCTs) including 441 patients were included in the final analysis. The meta-analysis showed that oral glutamine couldn't significantly decrease the incidence of OM (risk ratio [RR] = 0.98, 95% confidence interval [CI] = 0.94-1.02) and alleviate the development of moderate or severe grade of OM (Moderate-to-severe OM: RR = 0.81, 95% CI = 0.59-1.12; Severe OM: RR = 0.45, 95% CI = 0.13-1.52). But oral glutamine may have the potential to reduce the opioid use (RR = 0.84, 95% CI = 0.71-0.99). The role of oral glutamine in delaying the onset of OM remains uncertain due to conflicting results between quantitative (mean difference [MD] = 4.11 days, 95% CI = 3.49-4.73) and qualitative results. Conclusions: Oral glutamine may have no clinical benefits to prevent or reduce the incidence and severity of radiation-induced OM in patients with HNC receiving radiotherapy alone or concurrent with chemotherapy. It is also uncertain whether oral glutamine can delay the onset of OM. But it may have the potential to relieve the degree of oral pain. Nevertheless, we must cautiously interpret the results because the observed effect size for delay in mucositis start or reduction in opioid use is marginal. Moreover, further RCTs with more rigorous methodology and large-scale are required to enhance the quality of evidence.

Prophylaxis With Oral Zinc Sulfate Against Radiation Induced Oral Mucositis in Patients With Head and Neck Cancers: A Systematic Review and Meta-Analysis of Four Randomized Controlled Trials.

Background: Oral mucositis is an inevitable and distressing adverse event patients, who were treated with irradiation for head and neck cancer, face. Although several studies have investigated the potential of oral zinc sulfate in preventing radiation-induced oral mucositis in patients with head and neck cancers, conclusive results have not yet been found. Objective: The aim of the present study is to determine whether oral zinc sulfate is effective in preventing radiation-induced oral mucositis, in patients with head and neck cancers. Methods: We electronically searched all potential citations in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and EBSCO from their inception to December 2018. After the search and checked literatures, extracted data and appraised risk of bias, RevMan software version 5.3 was used to perform meta-analysis. Results: Four randomized controlled trials (RCTs) involving 162 patients were included. A meta-analysis showed that zinc sulfate did not decrease the incidence (RR [relative risk], 0.97; 95% CI [confidence interval], 0.74-1.28), and did not relieve the moderate and severe grade of radiation induced oral mucositis (moderate and severe oral mucositis: RR, 0.84; 95% CI, 0.14-4.87; severe oral mucositis: RR, 0.43; 95% CI, 0.00-38.98). A qualitative analysis suggested that zinc sulfate was associated with the onset of oral mucositis. Conclusions: Based on limited evidence, zinc sulfate may not have the benefit of prophylaxis against radiation-induced oral mucositis, in patients with head and neck cancers. However, further RCTs with larger sample sizes and more rigorous methodologies are needed to enhance the evidence of these results.

Prophylaxis with oral zinc sulfate against radiation-induced oropharyngeal mucositis in patients with head and neck cancer: Protocol for a meta-analysis of randomized controlled trials.

BACKGROUND: Oropharyngeal mucositis is considered to be an inevitable and the most troubling side effect of head and neck irradiation, which is caused by the direct toxic action of radiation on oral mucosa. Several randomized controlled trials (RCTs) have investigated the efficacy of zinc sulfate in prevention of radiation-induced oropharyngeal mucositis in patients with head and neck cancer. However, the definite conclusions have not been confirmed. The systematic review and meta-analysis will be performed to comprehensively evaluate whether zinc sulfate is effective in prevention of radiation-induced oropharyngeal mucositis in patients with head and neck cancer. METHODS: Relevant information will be identified by a comprehensive search of the following electronic databases: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and EBSCO from their inception to October 2018. Only RCTs which evaluated whether zinc sulfate is effective in prevention of radiation-induced oropharyngeal mucositis in patients with head and neck cancer will be eligible. Two independent investigators will be assigned to search literature, screen information, extract data, and appraise the risk of bias. The primary investigator will use Revman 5.3 software to perform all statistical analyses. We designed this systematic review and meta-analysis on June 5. 2018, and expect to complete the full-text on December 20, 2018. RESULTS: This protocol has been registered with a unique identifier of CRD42018108533. We will submit this systematic review and meta-analysis to a peer-reviewed journal. Meanwhile, we also will dissemination the whole findings in topic-related conferences. CONCLUSION: As the first systematic review and metaanalysis, the present study will elucidate current evidence of the role of oral zinc for the prevention and treatment of radiation-induced oropharyngeal mucositis in the head and neck cancer.

A gastroenteritis outbreak associated with drinking water in a college in northwest China.

An acute gastroenteritis outbreak occurred at a private college in June 2014 in northwest China. This outbreak involved two teachers and 629 students (range: 17-27 years, average 21.3 years). The main symptoms included non-bloody watery diarrhea, stomach ache, nausea, and vomiting, and the duration of illness ranged from 1 to 7 days. Eight of 18 water samples were disqualified. Thirty-four norovirus (NoV) RNA-positive samples were identified from 48 stool-related samples (genotyping results: 13 GII, 13 GI and 8 GI + GII mixture). Fourteen NoV samples were successfully characterized for genotype, including two GII.6, five GI.6, four GI.3, and three GI.1. Enteropathogenic Escherichia coli (EPEC) and enteroadherent Escherichia coli (EAEC) DNA was detected from patient stool specimens and water samples from well one; two EAEC strains and one EPEC strain were isolated from patient stool specimens. The risk ratios (RRs) associated with wells one and two were 1.66 and 1.49, respectively, and the RR associated with living in north dormitory building one was 2.59. The patients' epidemiological characteristics, symptoms, and duration of illness indicated that NoV-contaminated water might be the origin of this outbreak, and RR analysis suggested that the two wells were linked to the outbreak.

Salivary matrix metalloproteinase (MMP)-8 as a biomarker for periodontitis: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Salivary matrix metalloproteinase (MMP)-8 is currently considered to be one of the most promising biomarkers for early diagnosis of periodontitis, however, several recent studies showed conflicting results. OBJECTIVE: To determine the salivary matrix metalloproteinase (MMP)-8 levels between periodontitis patients and healthy individuals, and to assess its diagnostic value in periodontitis. METHODS: Literatures were searched on PubMed and Embase databases up to August 2017, for articles reporting salivary MMP-8 levels between periodontitis patients and health controls with the data of means ±â€Šstandard deviation (SD). Methodological quality was assessed by the Newcastle Ottawa scale (NOS). Standard mean differences (SMDs), heterogeneity, and publication bias were assessed by Stata 13.0 software. RESULTS: A total of 10 studies including 485 periodontitis patients and 379 healthy controls that met the preset inclusion criteria were included, the qualities of these studies were either good (n = 7) or moderate (n = 3). Eight studies showed salivary MMP-8 levels were higher in periodontitis patients compared with healthy controls (P < .05), while 2 studies showed opposite results (P > .05). The pooled SMD was 1.195 (95% CI: 0.720-1.670), with I of 89.3%, indicating high heterogeneity. Funnel plot showed publication bias existed. CONCLUSION: Our meta-analysis showed that salivary MMP-8 levels were significantly higher in periodontitis patients compared with healthy controls overall. Due to the heterogeneity and publication bias of included studies, further high quality studies are still needed to verify the conclusion.

Nurse-physician collaboration impacts job satisfaction and turnover among nurses: A hospital-based cross-sectional study in Beijing.

This study aims to explore the impact of physician-nurse collaboration on nurse job satisfaction and turnover in a dental hospital. Physician-nurse collaboration is important for the stability of the entire nursing team. Few studies have shown the impact on job satisfaction and turnover among nurses working in Chinese dental hospitals. This was a prospective, cross-sectional study and investigated nurses from a tertiary dental hospital in Beijing using convenience non-randomized sampling. A structured questionnaire was used to collect data, which included general information, the Index of Work Satisfaction, the Nurse-Physician Collaboration Scale and the Turnover Intention Scale. The scores of physician-nurse collaboration correlated positively with those for job satisfaction and negatively with the stated likelihood of turnover intention. Physician-nurse collaboration scores positively predicted job satisfaction and negatively predicted the likelihood of quitting the current job. In conclusion, improving the level of physician-nurse collaboration is helpful to enhance job satisfaction and reduce turnover among nurses in a dental hospital.

P-glycoprotein-evading anti-tumor activity of a novel tubulin and HSP90 dual inhibitor in a non-small-cell lung cancer model.

P-glycoprotein (P-gp)-induced drug resistance is a major road block for successful cancer chemotherapy. Through phenotypic screening, the compound 2-(2-chlorophenylimino)-5-(4-dimethylaminobenzylidene) thiazolidin-4-one (CDBT) was discovered to have potent anti-tumor activity in P-gp over-expressing drug-resistant non-small-cell lung cancer (NSCLC) H460TaxR cells. Here, we report mechanistic investigations of the P-gp-evading anti-tumor activity of CDBT. CDBT is evidently not a P-gp substrate and escapes the P-gp efflux pump. As a novel microtubule and heat shock protein 90 (HSP90) dual targeting inhibitor, CDBT causes the destabilization of microtubules and degradation of HSP90 client proteins CRAF-1 and ERBB2, resulting in cell cycle arrest at the G2/M phase and apoptosis. Furthermore, CDBT effectively inhibits tumor growth by 60.4% relative to the vehicle control after intraperitoneal administration at 30 mg/kg for 11 days and shows no toxicity in normal tissues in the NSCLC H460TaxR xenograft mouse model. Our data suggest a novel drug discovery strategy to combat P-gp over-expressing drug-resistant NSCLC cancer cells with a single therapeutic agent.

Effect of sodium valproate on the sleep structures of epileptic patients.

The aims of the present study were to investigate the effect of sodium valproate (VPA) on the sleep structures of epileptic patients and the correlation of these effects with patient weight gain. A total of 60 epileptic patients were divided into three groups: E-AED I (VPA administration for a duration of <3 months), E-AED II (VPA administration for a duration of >3 months) and ECO (without VPA) groups, for polysomnography monitoring. When the E-AED II group was compared with the E-AED I and ECO groups, non-rapid eye movement sleep phase 1 was significantly prolonged (92.10±48.24, 29.50±10.61 and 23.94±13.27 min, respectively; P<0.01), rapid eye movement sleep was significantly shortened (70.82±17.69, 116.99±12.90 and 126.19±35.01 min, respectively; P<0.01), sleep efficiency was significantly reduced (89.39±2.55, 91.98±2.53 and 91.96±3.14%, respectively; P<0.01), the number of times of that the patients awoke was significantly increased (7.25±2.86, 2.55±1.42 and 2.40±1.39, respectively; P<0.01) and the number of REM phases throughout the night was significantly reduced (P<0.01). There were no significant differences for the various sleep parameters between the E-AED I and ECO groups. Therefore, VPA is capable of inducing sleep structure disorders in epileptic patients. In addition, these disorders begin 3 months following the administration of VPA, which indicates that these disorders may be associated with VPA-induced weight gain.

Correlation between aortic/carotid atherosclerotic plaques and cerebral infarction.

The aim of this study was to investigate the correlation between aortic/carotid atherosclerotic plaques and cerebral infarction. We examined 116 cases of cerebral infarction using transcranial Doppler ultrasound in order to exclude cerebrovascular stenosis. Transesophageal echocardiography and color Doppler ultrasound were used to detect aortic atherosclerotic plaques (AAPs) and carotid atherosclerotic plaques (CAPs). AAPs were detected in a total of 70 of the 116 cases (60.3%), including 56 with moderate/severe atherosclerotic changes (48.3%). The difference in the incidence of various types of infarction between APP severity levels was significant (P<0.01). Of the 116 cases, 64 had CAPs (55.2%), including 46 with unstable plaque (39.7%). The difference in the incidence of various types of infarction between CAP stability levels was significant (P<0.01). The results indicate that moderate/severe AAP and unstable CAP are significant causes of embolic infarction without stenosis in the internal carotid arteries.

Antitumor activity of (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one, a novel microtubule-depolymerizing agent, in U87MG human glioblastoma cells and corresponding mouse xenograft model.

Glioblastoma is the most lethal brain cancer. In spite of intensive therapy, the prognosis of patients with glioblastoma is very poor. To discover novel therapeutic agents, we screened a combinatorial compound library containing 372 thiazolidinone compounds using U87MG human glioblastoma cells. (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one (HBPT) was identified as the most potent anti-glioblastoma compound. HBPT inhibits U87MG human glioblastoma cell proliferation with an IC50 of 20 µM, which is almost 5-fold more potent than temozolomide (a widely used drug for treating malignant glioma in the clinic). Mechanistic investigation demonstrated that HBPT is a novel microtubule-depolymerizing agent, which arrests cancer cells at the G2/M phase of the cell cycle and induces cell apoptosis. In the mouse U87MG xenograft model, HBPT elicits a robust tumor inhibitory effect. More importantly, no obvious toxicity was observed for HBPT therapy in animal experiments. These findings indicate that HBPT has the potential to be developed as a novel agent for the treatment of glioblastoma. [Supplementary Tables: available only at http://dx.doi.org/10.1254/jphs.13064FP].