A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid ß accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.

CH/CH2 Group Clusters Doping Methane Hydrate Cages.

Methane hydrate is a crystalline compound with methane molecules as guest species trapped in host water cages. In this study, we detected methane hydrate with water cages doped by (Caromatic-H)5 clusters, (Caromatic-H)6 clusters, and (3Caliphatic-H2 + 2H2O) clusters using current spectroscopic techniques and differential scanning calorimetry (DSC). Methane molecules are trapped in the doped cages with type sI forming in nanoscale silica gel pores. The relative quantity ratio of host carbon to guest carbon in the doped hydrate sample reaches approximately 3.58. Methane hydrate doped by CH/CH2 group clusters greatly improves the ability of the hydrate unit cell to store methane and increases the stability of methane hydrate. Fast proton diffusion in the doped methane hydrate was confirmed. The results of this study will provide efficient and energy saving technical support for disruptive changes in hydrate storage and transportation of methane gas technology with a doped and dense solid phase.

Effect of Graphene Oxide on Properties of Alkali-Activated Slag.

Alkali-activated materials, a new kind of low-carbon cement, have received extensive attention. While in order to obtain excellent functions, the modification of alkali-activated materials by nano-materials has become one of the important research directions of alkali-activated materials. Therein, the hydration property, mechanical properties, and action mechanism of the alkali-activated slag with and without graphene oxide (GO) were analyzed and evaluated. Results showed the compressive strength of mortar decreased at 3 days and 28 days by adding GO. While the flexural strength of mortar cured for different ages increased with increasing GO content, and the flexural strength increasing rate reached up to 15.94% at 28 days, thus, the toughening effect of GO was significant. GO accelerated the hydration process of alkali-activated slag because the functional groups offered nucleation sites to induce the generation of more hydration products. Furthermore, the addition of GO increased the number of harmless pores and reduced the pore size, but also introduced a large number of harmful pores, resulting in the reduction of compressive strength.

Plant developmental stage drives the differentiation in ecological role of the maize microbiome.

BACKGROUND: Plants live with diverse microbial communities which profoundly affect multiple facets of host performance, but if and how host development impacts the assembly, functions and microbial interactions of crop microbiomes are poorly understood. Here we examined both bacterial and fungal communities across soils, epiphytic and endophytic niches of leaf and root, and plastic leaf of fake plant (representing environment-originating microbes) at three developmental stages of maize at two contrasting sites, and further explored the potential function of phylloplane microbiomes based on metagenomics. RESULTS: Our results suggested that plant developmental stage had a much stronger influence on the microbial diversity, composition and interkingdom networks in plant compartments than in soils, with the strongest effect in the phylloplane. Phylloplane microbiomes were co-shaped by both plant growth and seasonal environmental factors, with the air (represented by fake plants) as its important source. Further, we found that bacterial communities in plant compartments were more strongly driven by deterministic processes at the early stage but a similar pattern was for fungal communities at the late stage. Moreover, bacterial taxa played a more important role in microbial interkingdom network and crop yield prediction at the early stage, while fungal taxa did so at the late stage. Metagenomic analyses further indicated that phylloplane microbiomes possessed higher functional diversity at the early stage than the late stage, with functional genes related to nutrient provision enriched at the early stage and N assimilation and C degradation enriched at the late stage. Coincidently, more abundant beneficial bacterial taxa like Actinobacteria, Burkholderiaceae and Rhizobiaceae in plant microbiomes were observed at the early stage, but more saprophytic fungi at the late stage. CONCLUSIONS: Our results suggest that host developmental stage profoundly influences plant microbiome assembly and functions, and the bacterial and fungal microbiomes take a differentiated ecological role at different stages of plant development. This study provides empirical evidence for host exerting strong effect on plant microbiomes by deterministic selection during plant growth and development. These findings have implications for the development of future tools to manipulate microbiome for sustainable increase in primary productivity. Video Abstract.

Formation of a Low-Density Liquid Phase during the Dissociation of Gas Hydrates in Confined Environments.

The large amounts of natural gas in a dense solid phase stored in the confined environment of porous materials have become a new, potential method for storing and transporting natural gas. However, there is no experimental evidence to accurately determine the phase state of water during nanoscale gas hydrate dissociation. The results on the dissociation behavior of methane hydrates confined in a nanosilica gel and the contained water phase state during hydrate dissociation at temperatures below the ice point and under atmospheric pressure are presented. Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD) were used to trace the dissociation of confined methane hydrate synthesized from pore water confined inside the nanosilica gel. The characterization of the confined methane hydrate was also analyzed by PXRD. It was found that the confined methane hydrates dissociated into ultra viscous low-density liquid water (LDL) and methane gas. The results showed that the mechanism of confined methane hydrate dissociation at temperatures below the ice point depended on the phase state of water during hydrate dissociation.

Echinacoside inhibits breast cancer cells by suppressing the Wnt/ß-catenin signaling pathway.

Echinacoside, a small molecule derived from the natural herbs Cistanche and Echinacea, shows effective anticancer abilities, but the mechanism remains unclear. By using colony formation, scratch, and transwell assays in MDA-MB-231 breast cancer cells, we confirmed the anti-breast cancer ability of Echinacoside in vitro. In addition, we found that Echinacoside can dose-dependently reduce phosho-LRP6, total LRP6, phosho-Dvl2, active ß-catenin, and total ß-catenin protein expression level in MDA-MB-231 and MDA-MB-468 cells by western blot. We also detected well-known Wnt targets genes, including LEF1, CD44, and cyclin D1 by real-time PCR and western blot, and Echinacoside significantly shows inhibition effect in these two breast cancer cell lines. Furthermore, we investigated its anti-breast cancer ability in an MDA-MB-231 xenograft model in vivo. Echinacoside treatment significantly reduced tumor growth, which was accompanied by a reduction in Wnt/ß-catenin signaling. In summary, our results demonstrate that Echinacoside can effectively inhibit Wnt/ß-catenin signaling, and therefore, it may be a promising therapeutic target to treat breast cancer.

Whole Mitochondrial DNA Sequencing Analysis in 47 Han Populations in Southwest China.

BACKGROUND Mitochondrial DNA (mtDNA) sequencing has been used in many areas, including forensic genetics. Due to the rapid development of sequencing technology, whole mtDNA sequencing is now possible and may be used in epidemiological and forensic studies. This study aimed to use whole mtDNA sequencing to investigate 47 Chongqing Han populations in southwest China and the diversity in the mtGenome reference data. MATERIAL AND METHODS The mtDNA of 47 Chongqing Han populations was generated using the Ion Torrent Personal Genome Machine (PGM) system. The extent of the effects of the mtDNA on the subpopulations was investigated and compared with six other populations from published studies. Pairwise fixation index (FST), a measure of population differentiation due to genetic structure, were calculated. Analysis of molecular variance (AMOVA) was performed, and 1257 hypervariable region data sets were added to the principal component analysis (PCA). RESULTS The whole mtDNA sequencing data of 47 southwest Chinese Han populations were successfully recovered. Expanding the sequencing rage increased the discrimination power of mtDNA from three-times to 25-times based on different populations. The subpopulation effects showed 20 times the differences in match probability when compared with south China regions. CONCLUSIONS Whole mtDNA sequencing distinguished between individuals from 47 Chongqing Han populations in southwest China and has potential applications that include high-quality forensic identification.

Activation of IL-8 and its participation in cancer in schizophrenia patients: new evidence for the autoimmune hypothesis of schizophrenia.

To investigate the autoimmune mechanisms of schizophrenia, we explored the relationship between schizophrenia and cancer using gene expression data of peripheral blood mononuclear cells from GSE27383 datasets. Gene screening and enrichment analysis using Gene Set Enrichment Analysis were applied to identify possible connections between schizophrenia and cancer. Real-time PCR (quantitative PCR), Western blotting and immunohistochemistry were performed on the brain tissue from both schizophrenia patients and normal controls. The genes for IL-8, as well as PTGS2, TPR, JUN, CXCL1, CXCL3, CXCL5 and PARD3 were highly expressed in schizophrenia patients. Cancer and chemokine signaling pathways were enriched in the schizophrenic group, related to the high expression of IL-8. Increased expression of IL-8 was further confirmed by quantitative PCR, Western blotting and immunohistochemistry results. Our results suggest that IL-8 may participate specifically in the pathophysiological changes that occur in schizophrenia. Additionally, our findings provide novel evidence supporting the autoimmune hypothesis of schizophrenia.

Concordance of mitochondrial DNA sequencing methods on bloodstains using Ion PGM™.

In this study, the complete mitochondrial genome (mtGenome) of six samples from three forensic cases was sequenced using the Ion Torrent Personal Genome Machine (PGM). The analyzed samples from forensic cases included bloodstains from several materials, such as gauze, Flinder's Technology Associates (FTA) cards and swabs. The age of the samples ranged from two months to twelve years. The complete mtGenomes were amplified using the tiling sequencing strategy which divided the whole mtGenome into 162 amplicons. All amplicons were successfully recovered. A phylogenetic analysis was performed to determine the accuracy of the PGM data, and which were compared to partial Sanger-based sequencing data. The average coverage of the PGM data were above 4000× in all case samples, and 99.86% concordance was observed using both sequencing methods. In conclusion, we demonstrate the ability to recover the complete mtGenome from bloodstains with relatively poor DNA quality by PGM. Moreover, the results are concordant with Sanger sequencing data. This new method has potential use in forensic practice.

FasL incapacitation alleviates CD4+ T cells-induced brain injury through remodeling of microglia polarization in mouse ischemic stroke.

Inflammation responses involving the crosstalk between infiltrated T cells and microglia play crucial roles in ischemia stroke. Recent studies showed that Fas ligand (FasL) mutation could reduce post-stroke T cell invasion and microglia activation. In this study, we demonstrated that CD4+ T cells could induce M1 microglia polarization through NF-κB signaling pathway, whereas FasL mutant CD4+ T cells significantly reversed this effect. Besides, Th17/Treg cells balance was skewed into Treg cells after FasL mutation. In addition, conditioned medium from co-culture of FasL mutant CD4+ T cells and microglia could alleviate neuronal injury. Collectively, FasL incapacitation could alleviate CD4+ T cells-induced inflammation through remodeling microglia polarization, suggesting a therapeutic potential for control of inflammation responses after ischemic stroke.

New insights into decomposition characteristics of nanoscale methane hydrate below the ice point.

In this paper, molecular dynamics simulation was used to study the decomposition process of nanoscale methane hydrate at 1 atm and 227 K. The results predict that methane hydrate decomposes into supercooled water (SCW) and methane gas and the resulting SCW turns into very high density amorphous ice (VHDA). The density of the VHDA is as high as 1.2-1.4 g cm-3. The X-ray diffraction phase analysis showed that VHDA has a broad peak at 2θ of around 30°. The VHDA encapsulates the methane hydrate crystal so that the crystal can survive for a long time. The dissolved gas from the hydrate melt cannot escape out of the VHDA in a short time. The simulation results reveal new molecular insights into the decomposition behaviour of nanoscale methane hydrate below the ice point.

Developmental Times of Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) at Constant Temperatures and Applications in Forensic Entomology.

The characteristic life stages of infesting blowflies (Calliphoridae) such as Chrysomya megacephala (Fabricius) are powerful evidence for estimating the death time of a corpse, but an established reference of developmental times for local blowfly species is required. We determined the developmental rates of C. megacephala from southwest China at seven constant temperatures (16-34°C). Isomegalen and isomorphen diagrams were constructed based on the larval length and time for each developmental event (first ecdysis, second ecdysis, wandering, pupariation, and eclosion), at each temperature. A thermal summation model was constructed by estimating the developmental threshold temperature D0 and the thermal summation constant K. The thermal summation model indicated that, for complete development from egg hatching to eclosion, D0 = 9.07 ± 0.54°C and K = 3991.07 ± 187.26 h °C. This reference can increase the accuracy of estimations of postmortem intervals in China by predicting the growth of C. megacephala.

A checklist of beetles (Insecta, Coleoptera) on pig carcasses in the suburban area of southwestern China: A preliminary study and its forensic relevance.

Examining the succession pattern of carrion insects on vertebrate carcasses is widely accepted as an effective method to estimate the postmortem interval (PMI) of decayed bodies. Investigation of the community of sarcosaprophagous insects, especially flies and beetles, is the foundation of the succession pattern study. This study aimed to investigate the sarcosaprophagous beetles succession on animal carcasses in the suburban area of southwestern China and to establish a basic catalog for forensic application. The present study was conducted in 2013 in a mountain in Chongqing municipality with modified Schoenly traps. Carcasses of miniature pig were used to simulate human bodies. For most carcasses, five decomposition stages were observed. A total of 2108 adult coleopterans belonging to at least 61 species and 18 families were collected in the study, and most of the specimens occurred at the advanced decay stage. Omosita colon (Linnaeus, 1758), Necrodes nigricornis (Harold, 1875), Necrobia ruficollis (Fabricius, 1775) and Neosilusa ceylonica (Kraatz, 1857) were the dominant species.

Technical note: Development of Hemipyrellia ligurriens (Wiedemann) (Diptera: Calliphoridae) at constant temperatures: Applications in estimating postmortem interval.

Blowflies (Calliphoridae) are recognized as a powerful tool for estimating the minimum postmortem interval (PMImin). The times for blowflies to develop from oviposition to eclosion is mainly controlled by temperature, which can differ between even closely related species. Hemipyrellia ligurriens (Wiedemann) (Diptera: Calliphoridae) is a blowfly distributed throughout Asia and Australia. However, a systematic determination of the developmental times of H. ligurriens under constant temperature, necessary for estimating the PMImin, is lacking. Such an examination would broaden the forensic importance of the species. Thus, this study explored the growth curves of larval H. ligurriens at 7 constant temperatures (16, 19, 22, 25, 28, 31, and 34°C). Isomegalen and isomorphen diagrams were successfully constructed, depicting the time of larval length or developmental event, respectively, at different temperatures. A thermal summation model was also constructed via regression analysis, by estimating the developmental threshold temperature t and thermal summation constant K. The thermal summation model indicated that t at 8.3°C and K at 5747.5 degree-hours (°Ch) are required for complete development from oviposition to eclosion, and suggested an optimum temperature range of 16-28°C for the development of H. ligurriens. These data establish for the first time the temperature-dependent developmental time of H. ligurriens for forensic entomology application. The 3 developmental models are provided.

Survivin gene functions and relationships between expression and prognosis in patients with nasopharyngeal carcinoma.

This study aimed to investigate the relationship between prognosis and protein and mRNA expression of an apoptotic inhibitor gene, survivin, in patients with nasopharyngeal carcinoma. Furthermore, functions of the survivin gene in the CNE2 nasopharyngeal carcinoma cell line were assessed. Immunohistochemistry and in situ hybridization were used in detecting the survivin protein and mRNA in 44 nasopharyngeal carcinoma specimens, and 30 chronic nasopharyngitis samples as controls. Survivin gene expression in CNE2 cell line was suppressed with an shRNA (short hairpin RNA). The positive ratios of expression for survivin protein and mRNA in nasopharyngeal carcinoma were 79.5% and 75.0% respectively, obviously higher than in the control group (p<0.01), and there is very good consistency between the two methods. The mean survival time of patients with higher survivin protein or mRNA expression was shorter than in patients with lower levelsv(p<0.01). Proliferation of the CNE2 cell line was distinctly inhibited by the shRNA . The results indicate that overexpression of the survivin gene plays an important role in onset and development of nasopharyngeal carcinoma, and it may be helpful for prognostic appraisal.

High frequency variations of Earth Rotation Parameters from GPS and GLONASS observations.

The Earth's rotation undergoes changes with the influence of geophysical factors, such as Earth's surface fluid mass redistribution of the atmosphere, ocean and hydrology. However, variations of Earth Rotation Parameters (ERP) are still not well understood, particularly the short-period variations (e.g., diurnal and semi-diurnal variations) and their causes. In this paper, the hourly time series of Earth Rotation Parameters are estimated using Global Positioning System (GPS), Global Navigation Satellite System (GLONASS), and combining GPS and GLONASS data collected from nearly 80 sites from 1 November 2012 to 10 April 2014. These new observations with combining different satellite systems can help to decorrelate orbit biases and ERP, which improve estimation of ERP. The high frequency variations of ERP are analyzed using a de-trending method. The maximum of total diurnal and semidiurnal variations are within one milli-arcseconds (mas) in Polar Motion (PM) and 0.5 milli-seconds (ms) in UT1-UTC. The semidiurnal and diurnal variations are mainly related to the ocean tides. Furthermore, the impacts of satellite orbit and time interval used to determinate ERP on the amplitudes of tidal terms are analyzed. We obtain some small terms that are not described in the ocean tide model of the IERS Conventions 2010, which may be caused by the strategies and models we used or the signal noises as well as artifacts. In addition, there are also small differences on the amplitudes between our results and IERS convention. This might be a result of other geophysical excitations, such as the high-frequency variations in atmospheric angular momentum (AAM) and hydrological angular momentum (HAM), which needs more detailed analysis with more geophysical data in the future.

[Rapid Start-up of Simultaneous Nitrification and Denitrification Coupled Phosphorus Removal Process and Its Performing Characteristics].

In this study, simultaneous nitrification and denitrification (SND) coupled Phosphorus removal process through gradually decreasing DO concentration was investigated by treating wastewater with a low COD/TN ratio (C/N = 3 : 1-4: 1) in a sequencing batch reactor (SBR) inoculated with aerobic granular sludge (AGS). Successful SND coupled Phosphorus phenomenon occurred after 20d at the DO concentration of 0.50-1.0 mg x L(-1). In the following 40 days, the average removal rates of COD, NH4(+) -N, TN and TP were 84.84% , 93.51%, 77.06% and 85.69%, and the NO3(-) -N and NO2(-) -N average accumulations in the effluent were only 4.01 mg x L(-1) and 3.17 mg x L(-1), respectively. The AGS had complete forms and good settling performances, and the sludge volume index (SVI) was about 55.22 mL x g(-1) at the end of starting-up stage. The results of different nitrogen sources showed that the removal rate of TN was in the order of NH4(+) -N > NO2(-) -N > NO3(-) -N, and the removal rate of TP was in the order of NO3(-) -N > NO2(-) -N > NH4(+) -N. The nitrogen and phosphorus removal of wastewater were mainly realized by simultaneous nitrification and denitrification and denitrifying phosphorus removal, respectively.

The role of IGFBP-5 in mediating the anti-proliferation effect of tetrandrine in human colon cancer cells.

Colon cancer is one of the most common malignancies, causes considerable morbidity and mortality. The current treatment for colon cancer is more modest than had been hoped. There is an urgent clinical need to explore new agents or adjuvants for colon cancer treatment. Natural products and their derivates act as one of the major source for anticancer agent. In the present study, we investigated the anti-proliferation and chemoprevention effects of tetrandrine (Tet) on colon cancer cells to uncover the possible molecular basis of this effect. We found that Tet can inhibit proliferation and induce apoptosis in LoVo cells. With dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) induced colon cancer model, we found that Tet can prevent or inhibit DMH plus DSS induced aberrant crypt foci (ACF) and colon cancer formation, as well as suppress tumor growth in the xenograft colon cancer model. Tet can downregulate the expression of IGFBP-5 in LoVo cells. Exogenous expression of IGFBP-5 can attenuate the anti-cancer activity of Tet, while IGFBP-5 knockdown potentiates this effect of Tet on LoVo cells. Tet can inhibit Wnt/ß-catenin signaling transduction, which can be partly reversed by exogenous expression of IGFBP-5, but is enhanced by IGFBP-5 knockdown. Our results demonstrated that the anticancer activity of Tet in colon cancer cells may be mediated partly by downregulating the expression of IGFBP-5, thus inactivating Wnt/ß-catenin signaling transduction.

[The selection of 30 ancestry informative markers and its application in ancestry inference].

A panel of ancestry informative markers (AIMs) can be used to describe the genetic components of a population and infer the ancestral origin of a DNA sample. In this study, we selected 30 AIMs from 282 SNPs screened from 30 phenotype-related genes based on the genotyping data of 658 samples from nine populations in the HapMap database. Then,a multiplex assay was developed based on micro-sequencing general chip technologies, and a population allele frequency database was established. This system was utilized to ascertain the origin of subjects from East Asian, European, and African.First, 658 HapMap samples were analyzed using this panel of AIMs, and then 194 unrelated DNA samples from five populations were used for further validation of the system. Finally, population genetic components and individual genetic composition were generated using Structure software, and individual ancestry inferences were made. The 30-AIM assay was well balanced for Hardy-Weinberg equilibrium (P > 0.01), and there was no linkage disequilibrium (l < 0.1). Ancestry component analyses for the 658 HapMap samples and 194 recruited samples were consistent with their known origins. The established panel filtered and developed by the 30 AIMs can be applied to analyze the genetic components of Asian, European,and African populations, as well as individual genetic composition.

[Effect of diets with different fat levels on the body size and development of Lucilia sericata].

OBJECTIVE: To observe the effect of diets with different fat levels on the body size and development of Lucilia sericata. METHODS: Under the constant temperature of 28 degrees C, the larvae were reared on the diets containing 0% (G0), 10% (G1), 30% (G3), 50% (G5) and 80% (G8) fat tissues (fat/muscle ratio), respectively. Length and weight of larvae and pupae were measured at 12 h interval since 16 h after eclosion. Length of inter-medial cross vein (m-m) of adult left wing was measured. 10 samples were collected in each group. The developmental duration time, mortality and sex ratios of adults were recorded. RESULTS: The mean maximal larval length [(13.3 +/- 1.2), (12.0 +/- 1.1), (10.2 +/- 0.9) and (8.8 +/- 0.8) mm, respectively] and mean maximal larval weight [(72.8 +/- 6.1), (62.2 +/- 5.7), (47.2 +/- 4.3), and (34.9 +/- 5.7) mg] in G1, G3, G5 and G8 groups were significantly less than that of the G0 group [(14.8 +/- 1.3) mm and (80.4 +/- 8.1) mg](P < 0.01). The body size of pupae and adults was also significantly less than that of G0 group (P < 0.01). The total duration time of G5 and G8 groups [(293.3 +/- 22.2) and (285.2 +/- 24.6) h] were significantly shorter than that of G0 group [(312.8 +/- 20.1)h] (P < 0.01). The mortality of larvae [(32.6 +/- 5.6)% and (44.3 +/- 7.7)%] and pupae [(28.6 +/- 5.5)% and (43.5 +/- 6.2)%] of G5 and G8 group were also significantly higher than that of G0 group [(5.7 +/- 3.3)% and (4.5 +/- 1.9)%] (P < 0.01). There was no significant difference in sex ratio among the 5 groups (P > 0.05). CONCLUSION: The body size of larvae, pupae and adults of Lucilia sericata is smaller, the development time is shorter and mortality is higher when the food substrate contains more fat tissues.