Clinical Analysis of Microvascular Reconstruction Combined With Decompressive Craniectomy in Patients With Malignant Middle Cerebral Artery Infarctions.

PURPOSE: This study aimed to evaluate the safety and efficacy of microvascular reconstruction combined with decompressive craniectomy (DHC) in patients with malignant middle cerebral artery infarctions (MMCA). METHODS: We searched for patients with MMCA and aged＜60 years old, postoperative survival of more than 3 months, consistent with decompression of bone flap removal. Patients were divided into experimental group and control group according to whether they underwent emergency vascular revascularization within 5 days after onset of ischemic stroke. RESULTS: A total of sixpatients were included in the treatment group and 12 patients in the control group. The National Institutes of Health Stroke Scale (NIHSS) score of the treatment group was lower than that of the control group seven days after operation, but the difference was not statistically significant; 3 months after surgery, modified ranking scale (mRs) score in the treatment group was lower than that in the control group, the difference was statistically significant (P = 0.002); mRs scores of the treatment group 3 months after surgery were significantly different from those before surgery (P < 0.05), but no such difference was found in the control group. CONCLUSION: Compared with decompressive craniectomy, open surgical revascularization can improve early cerebral perfusion in MMCA patients, and neurological recovery is better at 3 months after operation. By ensuring that surgeons are properly trained and hospitals are equipped, open surgical revascularization can be a treatment option for patients with MMCA.

Deciphering signatures of natural selection via deep learning.

Identifying genomic regions influenced by natural selection provides fundamental insights into the genetic basis of local adaptation. However, it remains challenging to detect loci under complex spatially varying selection. We propose a deep learning-based framework, DeepGenomeScan, which can detect signatures of spatially varying selection. We demonstrate that DeepGenomeScan outperformed principal component analysis- and redundancy analysis-based genome scans in identifying loci underlying quantitative traits subject to complex spatial patterns of selection. Noticeably, DeepGenomeScan increases statistical power by up to 47.25% under nonlinear environmental selection patterns. We applied DeepGenomeScan to a European human genetic dataset and identified some well-known genes under selection and a substantial number of clinically important genes that were not identified by SPA, iHS, Fst and Bayenv when applied to the same dataset.

KLFDAPC: a supervised machine learning approach for spatial genetic structure analysis.

Geographic patterns of human genetic variation provide important insights into human evolution and disease. A commonly used tool to detect and describe them is principal component analysis (PCA) or the supervised linear discriminant analysis of principal components (DAPC). However, genetic features produced from both approaches could fail to correctly characterize population structure for complex scenarios involving admixture. In this study, we introduce Kernel Local Fisher Discriminant Analysis of Principal Components (KLFDAPC), a supervised non-linear approach for inferring individual geographic genetic structure that could rectify the limitations of these approaches by preserving the multimodal space of samples. We tested the power of KLFDAPC to infer population structure and to predict individual geographic origin using neural networks. Simulation results showed that KLFDAPC has higher discriminatory power than PCA and DAPC. The application of our method to empirical European and East Asian genome-wide genetic datasets indicated that the first two reduced features of KLFDAPC correctly recapitulated the geography of individuals and significantly improved the accuracy of predicting individual geographic origin when compared to PCA and DAPC. Therefore, KLFDAPC can be useful for geographic ancestry inference, design of genome scans and correction for spatial stratification in GWAS that link genes to adaptation or disease susceptibility.

Information-based summary statistics for spatial genetic structure inference.

The measurement of biodiversity at all levels of organization is an essential first step to understand the ecological and evolutionary processes that drive spatial patterns of biodiversity. Ecologists have explored the use of a large range of different summary statistics and have come to the view that information-based summary statistics, and in particular so-called Hill numbers, are a useful tool to measure biodiversity. Population geneticists, on the other hand, have focused largely on summary statistics based on heterozygosity and measures of allelic richness. However, recent studies proposed the adoption of information-based summary statistics in population genetics studies. Here, we performed a comprehensive assessment of the power of this family of summary statistics to inform regarding spatial patterns of genetic diversity and we compared it with that of traditional population genetics approaches, namely measures based on allelic richness and heterozygosity. To give an unbiased evaluation, we used three machine learning methods to test the performance of different sets of summary statistics to discriminate between spatial scenarios. We defined three distinct sets, (i) one based on allelic richness measures which included the Jaccard index, (ii) a set based on heterozygosity that included FST and (iii) a set based on Hill numbers derived from Shannon entropy, which included the recently proposed Shannon differentiation, ΔD. The results showed that the last of these performed as well or, under some specific spatial scenarios, even better than the traditional population genetics measures. Interestingly, we found that a rarely or never used genetic differentiation measure based on allelic richness, Jaccard dissimilarity (J), showed the highest discriminatory power to discriminate among spatial scenarios, followed by Shannon differentiation ΔD. We concluded, therefore, that information-based measures as well as Jaccard dissimilarity represent excellent additions to the population genetics toolkit.

Precopulatory oral sex contact plays an important role in copulatory success in a cryptic desert beetle.

Precopulatory courtship plays an essential role in the insemination process and influences postcopulatory behavior between males and females. Male precopulatory oral stimulation of female genitals is rare for invertebrates. Here, we describe an intriguing oral sexual courtship in a cryptic desert beetle Platyope mongolica Faldermann. The males repeatedly contact the female's genitals using their mouths to gain consent to mate. Furthermore, the rate at which males contact the female's genitals relates to the copulation success in a series of observations. However, interference in oral sexual contacts decreased the proportion of successful copulation. Further no-choice tests found homosexual behavior between males with antenna removed. We report the precopulatory oral sexual behavior and its important role for copulation success in P. mongolica for the first time. These findings highlight the significance of oral sexual courtship in sexual selection.

Salinity Influences Plant-Pest-Predator Tritrophic Interactions.

Climate change-induced salinity intrusion into agricultural soils is known to negatively impact crop production and food security. However, the effects of salinity increase on plant-herbivore-natural enemy systems and repercussions for pest suppression services are largely unknown. Here, we examine the effects of increased salinity on communities of rice (Oryza sativa), brown planthopper (BPH), Nilaparvata lugens, and green mirid bug (GMB), Cyrtorhinus lividipennis, under greenhouse conditions. We found that elevated salinity significantly suppressed the growth of two rice cultivars. Meanwhile, BPH population size also generally decreased due to poor host plant quality induced by elevated salinity. The highest BPH density occurred at 2.0 dS/m salinity and declined thereafter with increasing salinity, irrespective of rice cultivar. The highest population density of GMB also occurred under control conditions and decreased significantly with increasing salinity. Higher salinity directly affected the rice crop by reducing plant quality measured with reference to biomass production and plant height, whereas inducing population developmental asynchrony between BPH and GMB observed at 2 dS/m salinity and potentially uncoupling prey-predator dynamics. Our results suggest that increased salinity has harmful effects on plants, herbivores, natural enemies, as well as plant-pest-predator interactions. The effects measured here suggest that the bottom-up effects of predatory insects on rice pests will likely decline in rice produced in coastal areas where salinity intrusion is common. Our findings indicate that elevated salinity influences tritrophic interactions in rice production landscapes, and further research should address resilient rice insect pest management combining multipests and predators in a changing environment.

Farmer's behavior in pesticide use: Insights study from smallholder and intensive agricultural farms in Bangladesh.

Since independence and over the years, pesticides have become a dominant feature of Bangladesh agriculture. To protect farmers' health, environment and to improve sustainability of chemical pest control quantitative understanding of farmers' behavior in pesticide use is critical. However, study on the levels of knowledge and awareness of farmers and the practices of pesticide use are often limited. We conducted a broad analysis on the effects of knowledge and awareness of farmers as well as the influence of the different associated stakeholders such as pesticide retailers and the government, on farmers' behavior in pesticide use from a detailed survey of 917 agricultural households in different regions of Bangladesh. Within eight protective behaviors (PBs) or PPEs were largely influenced by the crops growers and regions. Never discarding empty pesticide containers in the field, never applying pesticides more than prescribed by DAE or the instruction manual, selecting new types of pesticides recommended by DAE and purchasing low toxicity pesticides were the most adopted practices. Most farmers from the South-East region were adopting the PB of wearing mask, gloves and long sleeved clothes when spraying and farmers from South trusted the recommendations of pesticides by village leaders and neighbors. Majority of vegetables growers were well informed that pesticides were very harmful to the quality of agricultural products, the environment, and human health but not rice or mixed crops growers. Generally, PBs were positively affected by the perception of the consequences of farmers' behavior and knowledge of pesticide use but negatively influenced by action of governments and trust of retailers. It is important to recognize the differences that exist among different crops growers and locations. Attempt needs to bridge the gap among crop growers, locations and different stakeholder such as government agencies and retailers to develop policy.

Plant composition changes in a small-scale community have a large effect on the performance of an economically important grassland pest.

BACKGROUND: The grasshopper Oedaleus asiaticus Bey-Bienko (Acrididae: Oedipodinae) is a dominant and economically important pest that is widely distributed across the Mongolian plateau. This herbivore pest causes major damage to the grassland of the Inner Mongolian steppe in China. The population dynamics of herbivore pests is affected by grassland management practices (e.g., mowing and heavy livestock grazing) that alter plant community structures and stoichiometric characteristics. For example, O. asiaticus outbreak is closely associated with plant preference changes caused by nitrogen loss from heavy livestock grazing. However, the manner by which small-scale variation in vegetation affects grasshopper performance and promotes outbreak is poorly characterized. To address this question, we investigated the relationship between small-scale (1 m2) vegetation variability and measures of O. asiaticus performance associated with plant stoichiometric characteristics. RESULTS: We found that food preferences of O. asiaticus varied significantly, but maintained a specific dietary structure for different plant compositions. Notably, small-scale changes in plant community composition significantly affected grasshopper food preference and body size. Partial least-square modeling indicated that plant proportion and biomass affected grasshopper body size and density. We found that this effect differed between sexes. Specifically, female body mass positively correlated with the proportion of Stipa krylovii grass, whereas male mass positively correlated with the proportion of Artemisia frigida grass. Further analyses indicated that grasshopper performance is closely associated with plant stoichiometric traits that might be responsible for the pest's plague. CONCLUSIONS: This study provides valuable information for managing grasshoppers using rational grassland management practices.

Effectiveness of Bacillus pumilus PDSLzg-1, an innovative Hydrocarbon-Degrading Bacterium conferring antifungal and plant growth-promoting function.

Genome of the hydrocarbon-degrading bacterium Bacillus pumilus PDSLzg-1 was analyzed. A group of gene clusters and pathways associated with nitrogen fixation, plant-bacterial interactions, plant growth-promoting hormone synthesis, antibiotics, secondary metabolite, and disease resistance were identified. In addition, 0.06 mg/L of 3-indoleacrylic acid (IAA) and 2 mg/L of gibberellin (GA) were, respectively, detected in PDSLzg-1 fermentation broth by high-performance liquid chromatography (HPLC). Up-regulated expression levels of 11 key genes related to GA and IAA biosynthesis pathways were detected after the induction of 0.2% n-hexadecane. Furthermore, bioassays showed that PDSLzg-1 fermentation could significantly promote the length and biomass of the stems and roots of Triticum aestivum L., while inhibited Colletotrichum truncatum colonization. Results indicated that B. pumilus PDSLzg-1 had plant growth-promoting and antifungal functions, besides its potential applications in phyto-microbial bioremediation combinations for oil-contaminated soil.

Molecular Ecological Basis of Grasshopper (Oedaleus asiaticus) Phenotypic Plasticity under Environmental Selection.

While ecological adaptation in insects can be reflected by plasticity of phenotype, determining the causes and molecular mechanisms for phenotypic plasticity (PP) remains a crucial and still difficult question in ecology, especially where control of insect pests is involved. Oedaleus asiaticus is one of the most dominant pests in the Inner Mongolia steppe and represents an excellent system to study phenotypic plasticity. To better understand ecological factors affecting grasshopper phenotypic plasticity and its molecular control, we conducted a full transcriptional screening of O. asiaticus grasshoppers reared in four different grassland patches in Inner Mongolia. Grasshoppers showed different degrees of PP associated with unique gene expressions and different habitat plant community compositions. Grasshopper performance variables were susceptible to habitat environment conditions and closely associated with plant architectures. Intriguingly, eco-transcriptome analysis revealed five potential candidate genes playing important roles in grasshopper performance, with gene expression closely relating to PP and plant community factors. By linking the grasshopper performances to gene profiles and ecological factors using canonical regression, we first demonstrated the eco-transcriptomic architecture (ETA) of grasshopper phenotypic traits (ETAGPTs). ETAGPTs revealed plant food type, plant density, coverage, and height were the main ecological factors influencing PP, while insect cuticle protein (ICP), negative elongation factor A (NELFA), and lactase-phlorizin hydrolase (LCT) were the key genes associated with PP. Our study gives a clear picture of gene-environment interaction in the formation and maintenance of PP and enriches our understanding of the transcriptional events underlying molecular control of rapid phenotypic plasticity associated with environmental variability. The findings of this study may also provide new targets for pest control and highlight the significance of ecological management practice on grassland conservation.

Large manipulative experiments revealed variations of insect abundance and trophic levels in response to the cumulative effects of sheep grazing.

Livestock grazing can affect insects by altering habitat quality; however, the effects of grazing years and intensities on insect abundance and trophic level during manipulative sheep grazing are not well understood. Therefore, we investigated these effects in a large manipulative experiment from 2014 to 2016 in the eastern Eurasian steppe, China. Insect abundance decreased as sheep grazing intensities increased, with a significant cumulative effect occurring during grazing years. The largest families, Acrididae and Cicadellidae, were susceptible to sheep grazing, but Formicidae was tolerant. Trophic primary and secondary consumer insects were negatively impacted by increased grazing intensities, while secondary consumers were limited by the decreased primary consumers. Poor vegetation conditions caused by heavy sheep grazing were detrimental to the existence of Acrididae, Cicadellidae, primary and secondary consumer insects, but were beneficial to Formicidae. This study revealed variations in insect abundance and trophic level in response to continuous sheep grazing in steppe grasslands. Overall, our results indicate that continuous years of heavy- and over- sheep grazing should be eliminated. Moreover, our findings highlight the importance of more flexible sheep grazing management and will be useful for developing guidelines to optimize livestock production while maintaining species diversity and ecosystem health.

Biology, physiology and gene expression of grasshopper Oedaleus asiaticus exposed to diet stress from plant secondary compounds.

We studied the role of plant primary and secondary metabolites in mediating plant-insect interactions by conducting a no-choice single-plant species field experiment to compare the suitability, enzyme activities, and gene expression of Oedaleus asiaticus grasshoppers feeding on four host and non-host plants with different chemical traits. O. asiaticus growth showed a positive relationship to food nutrition content and a negative relationship to secondary compounds content. Grasshopper amylase, chymotrypsin, and lipase activities were positively related to food starch, crude protein, and lipid content, respectively. Activity of cytochrome P450s, glutathione-S-transferase, and carboxylesterase were positively related to levels of secondary plant compounds. Gene expression of UDP-glucuronosyltransferase 2C1, cytochrome P450 6K1 were also positively related to secondary compounds content in the diet. Grasshoppers feeding on Artemisia frigida, a species with low nutrient content and a high level of secondary compounds, had reduced growth and digestive enzyme activity. They also had higher detoxification enzyme activity and gene expression compared to grasshoppers feeding on the grasses Cleistogenes squarrosa, Leymus chinensis, or Stipa krylovii. These results illustrated Oedaleus asiaticus adaptive responses to diet stress resulting from toxic chemicals, and support the hypothesis that nutritious food benefits insect growth, but plant secondary compounds are detrimental for insect growth.

Apolipoprotein E ε4: A Possible Risk Factor of Intracranial Pressure and White Matter Perfusion in Good-Grade Aneurysmal Subarachnoid Hemorrhage Patients at Early Stage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating and complicated disease with significant morbidity and mortality. Previous studies have shown that genetic susceptibility may play an important role in the outcome of a given individual with aSAH. This study evaluates the potential association in effects of the APOE allele on the early brain injury (EBI) in light of elevated intracranial pressure (ICP) and cerebral perfusion disorders in a consecutive series of non-comatose Chinese patients with aSAH. A total of 122 patients with aSAH (54 males and 68 females) were enrolled in this study. Demographic and clinical data were collected. We measured ICP before microsurgical clipping or endovascular coiling during the first 72 h after aneurysm rupture. Computed tomography perfusion (CTP) examination in patients was performed before treatment. The distributions of APOE genotypes and alleles matched Hardy-Weinberg law (p > 0.05). In this study, 68 patients (55.7%) had a normal ICP, whereas 54 (44.3%) had an elevated ICP. Fourteen of 21 patients with APOE ε4 had an elevated ICP, which was significantly different from those without APOE ε4 (p = 0.03). The patients with the ε4 allele had a higher incidence of elevated ICP [p = 0.009, 95% confidence interval (CI) = 1.481-15.432, odds ratio = 4.780] than those without this allele. For CTP measurements, a lower mean cerebral blood flow (difference, -4.74; 95% CI, 0.53-8.94 s, p = 0.03), longer mean transit time (difference, 0.47; 95% CI, -0.87 to -0.78, p = 0.02), and time-to-peak (difference, 2.29; 95% CI, -3.64 to -0.93 s, p = 0.02) were observed in patients with ε4 allele than in those without in the internal capsule regions. In conclusion, the APOE ε4 allele predisposes patients to elevated ICP and perfusion disorders in white matter regions during the first 72 h after aSAH. The presence of an APOE ε4 allele plays an important role in the EBI response to aSAH.

Gut Transcriptome Analysis Shows Different Food Utilization Efficiency by the Grasshopper Oedaleous asiaticus (Orthoptera: Acrididae).

Oedaleus asiaticus B. Bienko is a persistent pest occurring in north Asian grasslands. We found that O. asiaticus feeding on Stipa krylovii Roshev. had higher approximate digestibility (AD), efficiency of conversion of ingested food (ECI), and efficiency of conversion of digested food (ECD), compared with cohorts feeding on Leymus chinensis (Trin.) Tzvel, Artemisia frigida Willd., or Cleistogenes squarrosa (Trin.) Keng. Although this indicated high food utilization efficiency for S. krylovii, the physiological processes and molecular mechanisms underlying these biological observations are not well understood. Transcriptome analysis was used to examine how gene expression levels in O. asiaticus gut are altered by feeding on the four plant species. Nymphs (fifth-instar female) that fed on S. krylovii had the largest variation in gene expression profiles, with a total of 88 genes significantly upregulated compared with those feeding on the other three plants, mainly including nutrition digestive genes of protein, carbohydrate, and lipid digestion. GO and KEGG enrichment also showed that feeding S. krylovii could upregulate the nutrition digestion-related molecular function, biological process, and pathways. These changes in transcripts levels indicate that the physiological processes of activating nutrition digestive enzymes and metabolism pathways can well explain the high food utilization of S. krylovii by O. asiaticus.

High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage.

Subarachnoid haemorrhage (SAH) is a fatal neurovascular disease following cerebral aneurysm rupture with high morbidity and mortality rates. Long non-coding RNAs (lncRNAs) are a type of mammalian genome transcript, are abundantly expressed in the brain and are involved in many nervous system diseases. However, little is currently known regarding the influence of lncRNAs in early brain injury (EBI) after SAH. This study analysed the expression profiles of lncRNAs and mRNAs in SAH brain tissues of mice using high-throughput sequencing. The results showed a remarkable difference in lncRNA and mRNA transcripts between SAH and control brains. Approximately 617 lncRNA transcripts and 441 mRNA transcripts were aberrantly expressed at 24 hours after SAH. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the differentially expressed mRNAs were mostly involved in inflammation. Based on the lncRNA/mRNA co-expression network, knockdown of fantom3_F730004F19 reduced the mRNA and protein levels of CD14 and toll-like receptor 4 (TLR4) and attenuated inflammation in BV-2 microglia cells. These results indicate that lncRNA fantom3_F730004F19 may be associated with microglia induced inflammation via the TLR signaling pathway in EBI following SAH. LncRNA represent a potential therapeutic target for the prognosis, diagnosis, and treatment of SAH.

Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

Quantitative analysis of diet structure by real-time PCR, reveals different feeding patterns by two dominant grasshopper species.

Studies on grasshopper diets have historically employed a range of methodologies, each with certain advantages and disadvantages. For example, some methodologies are qualitative instead of quantitative. Others require long experimental periods or examine population-level effects, only. In this study, we used real-time PCR to examine diets of individual grasshoppers. The method has the advantage of being both fast and quantitative. Using two grasshopper species, Oedaleus asiaticus and Dasyhippus barbipes, we designed ITS primer sequences for their three main host plants, Stipa krylovii, Leymus chinensis and Cleistogenes squarrosa and used real-time PCR method to test diet structure both qualitatively and quantitatively. The lowest detection efficiency of the three grass species was ~80% with a strong correlation between actual and PCR-measured food intake. We found that Oedaleus asiaticus maintained an unchanged diet structure across grasslands with different grass communities. By comparison, Dasyhippus barbipes changed its diet structure. These results revealed why O. asiaticus distribution is mainly confined to Stipa-dominated grassland, and D. barbipes is more widely distributed across Inner Mongolia. Overall, real-time PCR was shown to be a useful tool for investigating grasshopper diets, which in turn offers some insight into grasshopper distributions and improved pest management.

Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity.

Apolipoprotein E (Apoe) genetic polymorphisms have been implicated in the long term outcome of subarachnoid haemorrhage (SAH), but little is known about the effect of Apoe on the early brain injury (EBI) after SAH. This study investigated the potential role of APOE in EBI post-SAH. Multiple techniques were used to determine the early BBB disruption in EBI post-SAH in a murine model using wild-type (WT) and Apoe-/- (KO) mice. Progressive BBB disruption (Evans blue extravasation and T2 hyperintensity in magnetic resonance imaging) was observed before the peak of endogenous APOE expression elevation at 48h after SAH. Moreover, Apoe-/- mice exhibited more severe BBB disruption charcteristics after SAH than WT mice, including higher levels of Evans blue and IgG extravasation, T2 hyperintensity in magnetic resonance imaging, tight junction proteins degradation and endothelial cells death. Mechanistically, we found that APOE restores the BBB integrity in the acute stage after SAH via the cyclophilin A (CypA)-NF-κB-proinflammatory cytokines-MMP-9 signalling pathway. Consequently, although early BBB disruption causes neurological dysfunctions after SAH, we capture a different aspect of the effects of APOE on EBI after SAH that previous studies had overlooked and open up the idea of BBB disruption as a target of APOE-based therapy for EBI amelioration research in the future.

A study of the synergistic effect of folate-decorated polymeric micelles incorporating Hydroxycamptothecin with radiotherapy on xenografted human cervical carcinoma.

In this study, Hydroxycamptothecin (HCPT)-loaded micelles were formed in water by the self-assembly of folate (FA)-decorated amphiphilic block copolymer, methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL), and achieved a hydrodynamic diameter about of 132 nm. HCPT release from the micelles exhibited no initial burst but showed a sustained release profile. The cytotoxicity and targeting ability of FA conjugated polymeric micelles was investigated by using methylthiazoletetrazolium (MTT) and fluorescence microscopy. We found that FA-conjugated micelles had superior cytotoxicity against HeLa cells compared to non-conjugated micelles, and that they exerted this effect by folate receptor (FR)-mediated endocytosis. In addition, HeLa cells were xenografted into nude mice and subjected to radiotherapy (RT) and/or HCPT-loaded micelle treatment. The antitumor efficacy was detected by analysis of tumor growth delay (TGD) and median survival time. Micro fluorine-18-deoxyglucose PET/computed tomography ((18)F-FDG PET/CT) was performed to assess early tumor response to HCPT-loaded micelles in combination with RT. Analysis of cell cycle redistribution, apoptosis and expression of histone H2AX phosphorylation (λ-H2AX) was used to evaluate the mechanism by which HCPT loaded micelles led to radiosensitization. Taken together, the results showed that HCPT-loaded FA decorated micelles efficiently sensitized xenografts in mice to RT, and induced G2/M phase arrest, apoptosis and expression of λ-H2AX.

Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury.

The degree of post-traumatic brain edema and dysfunction of the blood-brain barrier (BBB) influences the neurofunctional outcome after a traumatic brain injury (TBI). Previous studies have demonstrated that the administration of apolipoprotein E-mimetic peptide COG1410 reduces the brain water content after subarachnoid hemorrhage, intra-cerebral hemorrhage, and focal brain ischemia. However, the effects of COG1410 on vasogenic edema following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously after a controlled cortical impact (CCI) injury on BBB dysfunction and vasogenic edema at an acute stage in mice. The results demonstrated that treatment with COG1410 suppressed the activity of matrix metalloproteinase-9, reduced the disruption of the BBB and Evans Blue dye extravasation, reduced the TBI lesion volume and vasogenic edema, and decreased the functional deficits compared with mice treated with vehicle, at an acute stage after CCI. These findings suggest that COG1410 is a promising preclinical therapeutic agent for the treatment of traumatic brain injury.