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High night temperature stress is one of the main environmental factors affecting rice yield and quality. More and more evidence shows that microRNA (miRNA) plays an important role in various abiotic stresses. However, the molecular network of miRNA regulation on rice tolerance to high night temperatures remains unclear. Here, small RNA, transcriptome and degradome sequencing were integrated to identify differentially expressed miRNAs, genes, and key miRNA-target gene pairs in rice heat-sensitive and heat-tolerant lines at the filling stage suffering from high night temperature stress. It was discovered that there were notable differences in the relative expression of 102 miRNAs between the two rice lines under stress. Meanwhile, 5263 and 5405 mRNAs were differentially expressed in the heat-sensitive line and heat-tolerant line, and functional enrichment analysis revealed that these genes were involved in heatrelated processes and pathways. The miRNAs-mRNAs target relationship was further verified by degradome sequencing. Eventually, 49 miRNAs-222 mRNAs target pairs with reverse expression patterns showed significant relative expression changes between the heat-tolerant and the heat-sensitive line, being suggested to be responsible for the heat tolerance difference of these two rice lines. Functional analysis of these 222 mRNA transcripts showed that high night temperature-responsive miRNAs targeted these mRNAs involved in many heat-related biological processes, such as transcription regulation, chloroplast regulation, mitochondrion regulation, protein folding, hormone regulation and redox process. This study identified possible miRNA-mRNA regulation relationships in response to high night temperature stress in rice and potentially contributed to heat resistance breeding of rice in the future. [ABSTRACT FROM AUTHOR]

The observations of some samples are usually collected in an imprecise way. By employing uncertain variables to model these imprecise observations, this paper proposes uncertain statistical inferences for nonparametric regression model based on the least absolute deviations criterion. A numerical example and simulation comparison with least squares estimate are presented to illustrate the proposed method. [ABSTRACT FROM AUTHOR]

In this paper, an Internet of Things (IoT) remote acquisition and processing system for urediospores images based on microscope CCD digital photography technology is designed to implement the IoT remote acquisition and monitoring of urediospores in wheat stripe rust (Puccinia striiformis) properly. Firstly, based on the network cloud technology, the cloud server interface of the acquisition system is designed in the Linux environment to implement automatic photography by microcomputer. The HTTP protocol encapsulated based on the TCP protocol is used to connect the cloud server and implement the image upload function. Secondly, the Intel NUC5CPYH is used as the acquisition termination, and a hardware platform of the image acquisition system is established. Finally, the K-means clustering algorithm is used to perform segmentation of the background and urediospores in the urediospores images remotely collected at the receiving terminal, morphological processing of urediospores images, corner detection based on Harris, and other processing to implement counting of urediospores ultimately. The transmission success rate of the wireless acquisition system is 96.6%, and the average counting accuracy of the processing system is 97.1%, with a good effect. The acquisition and processing system can be used for real-time online monitoring of the over-summering urediospores in wheat stripe rust. [ABSTRACT FROM AUTHOR]

The compressive-equivalent source method near-field acoustic holography (C-ESM) is disturbed by reverberation in the enclosed space such as room and cabin, which leads to large reconstruction error and disturbs the judgment of sound source position. In order to solve this problem, an improved C-ESM algorithm based on room impulse response (RIR) is proposed to filter out reverberation interference in this paper. Different from the original equivalent source method, the improved algorithm constructs the transfer function through the room impulse response to establish the relationship between the equivalent source and the sound pressure on any plane in space, and the sparse signal reconstruction method of the compressive sensing technology is used to obtain the strength of the equivalent source. Then the transfer function to any plane of space is established according to the free field Green's function, to eliminate the interference of reverberation and improve the effect of sound source location. The accuracy and effectiveness of the improved method are verified by preliminary numerical simulation. And the results show that compared with the original algorithm, this method has obvious advantages in sound source localization in a reverberant field. [ABSTRACT FROM AUTHOR]

The stable configurations and electronic properties of [formula]-surfaces-derivated ZnS nanofilms (NFs) were investigated using first-principles calculations. The size-dependent stable configurations of these NFs are characterized by a graphiticlike structure-NF (G-NF), a film terminated by [formula] surfaces, and a new phase composed of quadrilateral-octagon network-NF (QO-NF), respectively. Their formation energies with respect to bulk crystal are proportional to the inverse of film thickness, except the G-NFs. The QO-NFs are more stable than the polar [formula] NFs when the film thickness is smaller than 66 Å. The [formula]-terminated NFs are metallic, while the others are direct-band-gap semiconductors. Surface reconstruction and possible stabilization mechanisms of the polar [formula] surfaces were also discussed. [ABSTRACT FROM AUTHOR]

Background: Pulmonary large-cell neuroendocrine carcinoma (pLCNEC) represents a rare malignancy characterized by its aggressive behavior and a notably high recurrence rate. Remarkably, there is currently no established standard treatment protocol for this condition. Case description: In this report, we present an intriguing case of pLCNEC diagnosed at clinical-stage IIB. This case involves a 64-year-old man with a smoking history spanning four decades. In our approach, we initiated a course of neoadjuvant chemotherapy in combination with pembrolizumab, administered for two cycles prior to surgical resection. This innovative treatment strategy resulted in a significant pathological response, culminating in a major pathological remission (MPR). As of the time of composing this report, the patient has been diligently monitored for 39 months post-surgery, exhibiting no indications of recurrence, and has demonstrated exceptional tolerance to the entire treatment regimen. Conclusions: We have first reported a clinically successful case of neoadjuvant combination chemotherapy with pembrolizumab in the treatment of pLCNEC. This case offers promising clinical insights and suggests that this therapeutic approach could be a viable option for managing pLCNEC. [ABSTRACT FROM AUTHOR]

Background: Polyploidy, or whole-genome duplication (WGD) promotes genetic diversification in plants. However, whether WGD is accompanied by epigenetic regulation especially DNA methylation remains yet elusive. Methylation of different region in genomic DNA play discrete role in gene regulation and developmental processes in plants. Results: In our study, we used an apomictic rice line (SARII-628) that produces twin seedlings of different ploidy for methylated DNA immunoprecipitation sequencing (MeDIP-seq). We compared the level of methylation and mRNA expression in three different (CG, CHG, and CHH) sequence contexts of promoter region among haploid (1X), diploid (2X), and triploid (3X) seedling. We used MeDIP-Seq analysis of 14 genes to investigate whole genome DNA methylation and found that relative level of DNA methylation across different ploidy was in following order e.g. diploid > triploid > haploid. GO functional classification of differentially methylated genes into 9 comparisons group of promoter, intergenic and intragenic region discovered, these genes were mostly enriched for cellular component, molecular function, and biological process. By the comparison of methylome data, digital gene expression (DGE), mRNA expression profile, and Q-PCR findings LOC_ Os07g31450 and LOC_ Os01g59320 were analyzed for BS-Seq (Bisulphite sequencing). Conclusions: We found that (1) The level of the promoter DNA methylation is negatively correlated with gene expression within each ploidy level. (2) Among all ploidy levels, CG sequence context had highest methylation frequency, and demonstrated that the high CG methylation did reduce gene expression change suggesting that DNA methylation exert repressive function and ensure genome stability during WGD. (3) Alteration in ploidy (from diploid to haploid, or diploid to triploid) reveals supreme changes in methylation frequency of CHH sequence context. Our finding will contribute an understanding towards lower stability of CHH sequence context and educate the effect of promoter region methylation during change in ploidy state in rice. [ABSTRACT FROM AUTHOR]

Background: In China, on more than 100 weekends or holidays, only on-duty cardiologists are available during admissions. This study aimed to analyze the impact of admission time on major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI). Methods: This prospective observational study enrolled patients with AMI between October 2018 and July 2019. The patients were assorted into off-hour (admitted on weekends or national holidays) and onhour groups. The outcome was MACEs at admission and 1 year after discharge. Results: A total of 485 patients with AMI were enrolled in this study. The occurrence of MACEs was significantly higher in the off-hour group compared with the on-hour group (P < .05). Multivariate regression analysis showed that age (HR = 1.047, 95% CI: 1.021-1.073), blood glucose level (HR = 1.029, 95% CI: 1.009-1.050), multivessel disease (HR = 1.904, 95% CI: 1.074-3.375), and off-hour hospital admission (HR = 1.849, 95% CI: 1.125-3.039) were all independent risk factors for in-hospital MACEs, while percutaneous coronary intervention (HR = 0.210, 95% CI: 0.147-0.300) and on-hour admission (HR = 0.723, 95% CI: 0.532-0.984) were protective factors for MACEs 1 year after discharge. Conclusion: The "off-hour effect" still existed in patients with AMI, and the risk of MACEs in the hospital and 1 year after discharge was higher for off-hour admission. [ABSTRACT FROM AUTHOR]

A conductive pattern is formed by a conductive material on the substrate having an electromagnetic function. Ink-jet printing using metal nanoparticles is an attractive method for the direct fabrication of a conductive pattern, with low-cost, low-waste, and simple process. The conductive pattern that is usually fabricated on complex surface substrates is widely used, but this method has several drawbacks like stacking of printing curves to the surface and complexity of the motion path; moreover, the conductive inks flow easily on the surface, resulting in low printing accuracy. In addition, each curve needs to be individually cured leading to a long interface, thus resulting into the decrease in conductivity. In this pursuit, the current work presents a reduced dimension patch printing method, which uses a series of patches to approach the surface. These patches were rotated to the horizontal plane through the five-axis motion system for printing and curing by turn, so that the surface printing gets converted to two-dimensional printing. To execute this method, we designed the print path planning algorithm as follows: initially, based on the topological relation of the triangles in the STL (stereolithography) model, the sub-region culling method was used to reduce the number of final patches and the length of the boundary, as well as to improve the conductivity. Subsequently, the patches were rotated to the horizontal plane for optimizing the print path, by turn according to the adjacent relation, thus achieving the ink-jet process in two-dimensional motion. This improved the efficiency and ensured that the conductive inks were always on the horizontal plane before curing, thus effectively avoiding its flow and improving the printing precision. Additionally, the patch was integrally cured to improve the overall connectivity. The results show that the algorithm could achieve the print path planning and significantly reduce the number of print patches and boundary length. [ABSTRACT FROM AUTHOR]

A novel and green approach for the coproduction of xylooligosaccharides (XOS), in terms of a series of oligosaccharide components from xylobiose to xylohexose, and fermentable sugars was developed using the prehydrolysis of acetic acid that was fully recyclable and environmentally friendly, followed by enzymatic hydrolysis. Compared to hydrochloric acid and sulfuric acid, acetic acid hydrolysis provided the highest XOS yield of 45.91% and the highest enzymatic hydrolysis yield. More than 91% conversion of cellulose was achieved in a batch-hydrolysis using only a cellulase loading of 20 FPU/g cellulose and even a high solid loading of 20% without any special strategies. The acetic acid pretreated corncob should be washed adequately before saccharification to achieve complete hydrolysis. Consequently, a mass balance analysis showed that 139.8 g XOS, 328.1 g glucose, 25.1 g cellobiose, and 147.8 g xylose were produced from 1000 g oven dried raw corncob. [ABSTRACT FROM AUTHOR]

Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. [ABSTRACT FROM AUTHOR]

Evidence is presented for the role of a mitochondrial ribosomal (mitoribosomal) L18 protein in cell division, differentiation, and seed development after the characterization of a recessive mutant, heart stopper (hes). The hes mutant produced uncellularized endosperm and embryos arrested at the late globular stage. The mutant embryos differentiated partially on rescue medium with some forming callus. HES (At1g08845) encodes a mitochondrially targeted member of a highly diverged L18 ribosomal protein family. The substitution of a conserved amino residue in the hes mutant potentially perturbs mitoribosomal function via altered binding of 5S rRNA and/or influences the stability of the 50S ribosomal subunit, affecting mRNA binding and translation. Consistent with this, marker genes for mitochondrial dysfunction were up-regulated in the mutant. The slow growth of the endosperm and embryo indicates a defect in cell cycle progression, which is evidenced by the down-regulation of cell cycle genes. The down-regulation of other genes such as EMBRYO DEFECTIVE genes links the mitochondria to the regulation of many aspects of seed development. HES expression is developmentally regulated, being preferentially expressed in tissues with active cell division and differentiation, including developing embryos and the root tips. The divergence of the L18 family, the tissue type restricted expression of HES, and the failure of other L18 members to complement the hes phenotype suggest that the L18 proteins are involved in modulating development. This is likely via heterogeneous mitoribosomes containing different L18 members, which may result in differential mitochondrial functions in response to different physiological situations during development. [ABSTRACT FROM AUTHOR]

Background Endoplasmic reticulum (ER) stress-induced apoptosis plays a major role in various diseases, including spinal cord injury (SCI). Nerve growth factor (NGF) show neuroprotective effect and improve the recovery of SCI, but the relations of ER stress-induced apoptosis and the NGF therapeutic effect in SCI still unclear. Methods Young adult female Sprague-Dawley rats's vertebral column was exposed and a laminectomy was done at T9 vertebrae and moderate contusion injuries were performed using a vascular clip. NGF stock solution was diluted with 0.9% NaCl and administered intravenously at a dose of 20 μg/kg/day after SCI and then once per day until they were executed. Subsequently, the rats were executed at 1d, 3 d, 7d and 14d. The locomotor activities of SCI model rats were tested by the 21-point Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test and footprint analysis. In addition, Western blot analysis was performed to identify the expression of ER-stress related proteins including CHOP, GRP78 and caspase-12 both in vivo and in vitro. The level of cell apoptosis was determined by TUNEL in vivo and Flow cytometry in vitro. Relative downstream signals Akt/GSK-3β and ERK1/2were also analyzed with or without inhibitors in vitro. Results Our results demonstrated that ER stress-induced apoptosis was involved in the injury of SCI model rats. NGF administration improved the motor function recovery and increased the neurons survival in the spinal cord lesions of the model rats. NGF decreases neuron apoptosis which measured by TUNEL and inhibits the activation of caspase-3 cascade. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 are inhibited by NGF treatment. Meanwhile, NGF administration also increased expression of growthassociated protein 43 (GAP43). The administration of NGF activated downstream signals Akt/GSK-3β and ERK1/2 in ER stress cell model in vitro. Conclusion The neuroprotective role of NGF in the recovery of SCI is related to the inhibition of ER stress-induced cell death via the activation of downstream signals, also suggested a new trend of NGF translational drug development in the central neural system injuries which involved in the regulation of chronic ER stress. [ABSTRACT FROM AUTHOR]

Background: The overconsumption of a high-fat diet (HFD) has been repeatedly blamed as being a possible contributor to the global prevalence of emotional problems in modern society. Our group recently demonstrated the deleterious effect of a chronic HFD throughout adulthood on both emotional behavior and neuroplasticity markers in mice. As a heightened preference for palatable HFDs from the time of the juvenile period (when the brain is particularly vulnerable to environmental insults) is universal among populations around the world, a comparison of the consequences of chronic HFDs starting from juveniles or adults will assist in obtaining better knowledge of the impact that chronic HFDs have on mental health, thus potentially leading to the discovery of more effective strategies for reducing the incidence of psychiatric disorders. Methods: In the present study, male C57BL/6J mice with an initial age of 4 weeks (IA-4 W) or 8 weeks (IA-8 W) were separately assigned to two subgroups and fed either a control diet (CD, 10 kJ% from fat) or HFD (60 kJ% from fat) for 9 months followed by an analysis focused on metabolic, emotional behavioral, and neuroplastic profiles. Results: The results illustrated that, in addition to abnormal glucolipid metabolism and insulin sensitivity, mice on a chronic HFD exhibited increased levels of anxiety and depression-like behaviors and aberrant hippocampal neuroplasticity. When compared with IA-8 W mice, several changes indicating systemic metabolic disturbance and neurobehavioral disorder after chronic HFD consumption were aggravated in IA-4 W mice, accompanied by exaggerated impairments in hippocampal insulin sensitivity and neurogenesis. Conclusions: These results not only provide in vivo evidence that the juvenile stage is a critical period of vulnerability to detrimental effects of HFD consumption on metabolic and neuronal function but also suggest dampened hippocampal insulin signaling as a potential link between prolonged HFD consumption and negative neurobehavioral outcomes. Considering the substantial burden posed by psychiatric disorders and the high prevalence of HFD among youth, these observations are meaningful for raising awareness of the harmful effects of excessive dietary fat intake and developing strategy for preventing mental disorders. [ABSTRACT FROM AUTHOR]

The charge carrier transporting ability in the polymorphism of tris(8-hydroxyquinolinato)aluminum(III) (Alq3) has been studied using density functional theory (DFT) and Marcus charge transport theory. α- and β-Alq3 composed of mer-Alq3 molecules have stronger electron-transporting property (n-type materials) compared with their hole-transporting ability. In contrast, γ- and δ-Alq3 formed by fac-Alq3 molecules possess stronger hole-transporting character than their electron-transporting ability. The detailed theoretical calculations indicate the reason lies in the differences of HOMO and LUMO distribution states of the two kinds of isomers, and the different molecular packing modes of charge-transporting pathways for different phases. [ABSTRACT FROM AUTHOR]

In order to avoid low absorption, incorporation, and undesirable side effects of inorganic oxovanadium compounds, the antidiabetic activities of organic oxovanadium (IV) compounds in alloxan-induced diabetic mice were investigated. Vanadyl carboxymethyl carrageenan (VOCCA) and vanadyl carboxymethyl chitosan (VOCCH) were synthesized and administrated through intragastric administration in different doses for 20 days in alloxan-induced diabetic mice. Glibenclamide was administrated as the positive control. Our results showed that low-dose group, middle-dose group, and high-dose group of VOCCA and VOCCH could significantly reduce the levels of blood glucose (P < 0.05) compared with untreated group, but not in normal mice. Besides, high-dose groups of VOCCA and VOCCH exhibited more significant hypoglycemic activities (P < 0.01). After treated with VOCCH, the oral glucose tolerance of high-dose group of VOCCH was improved compared with model control group (P < 0.05). [ABSTRACT FROM AUTHOR]

Cardiac diseases persistently increase the contractility demands of cardiac myocytes, which require activation of the sympathetic nervous system and subsequent increases in myocyte Ca2+ transients. Persistent exposure to sympathetic and/or Ca2+ stress is associated with myocyte death. This study examined the respective roles of persistent β-adrenergic receptor (13-AR) agonist exposure and high Ca2+ concentration in myocyte death. Ventricular myocytes (VMs) were isolated from transgenic (TO) mice with cardiac-specific and inducible expression of the 132+-subunit of the L-type Ca2+ channel (LTCC). VMs were cultured, and the rate of myocyte death was measured in the presence of isoproterenol (ISO), other modulators of Ca2+ handling and the β-adrenergic system, and inhibitors of caspases and reactive oxygen species generation. The rate of myocyte death was greater in TO vs. wild-type myocytes and accelerated by ISO in both groups, although ISO did not increase LTCC current (ICaL) in TO-VMs. Nifedipine, an LTCC antagonist, only partially prevented myocyte death. These results suggest both LTCC-dependent and -independent mechanisms in ISO induced myocyte death. ISO increased the contractility of wild type and TO-VMs by enhancing sarcoplasmic reticulum function and inhibiting sarco(endo)plasmic reticulum Ca2+-ATPase, Na/Ca2+ exchanger, and CaMKII partially protected myocyte from death induced by both Ca2+ and ISO. Caspase and reactive oxygen species inhibitors did not, but 32-AR activation did, reduce myocyte death induced by enhanced ∫Ca-L, and ISO stimulation. Our results suggest that catecholamines induce myocyte necrosis primarily through β1-AR-mediated increases in ∫Ca-L, but other mechanisms are also involved in rodents. [ABSTRACT FROM AUTHOR]

The article discusses a study of the quality evolution of two large-scale open source software systems, Eclipse and Gnome, with emphasis on the number of defects. A quality control chart called the c-chart is used in monitoring quality evolution of the two software applications. Based on the defect plots in c-charts, it was found that the evolution for constantly maintained and updated systems is complicated rather than monotonic. It describes several quality evolution patterns observed including downward, upward and impulse patterns.

Increased expression of the facilitative glucose transporter, GLUT1, leads to glomerulopathy that resembles diabetic nephropathy, whereas prevention of enhanced GLUT1 expression retards nephropathy. While many of the GLUT1-mediated effects are likely due to mesangial cell effects, we hypothesized that increased GLUT1 expression in podocytes also contributes to the progression of diabetic nephropathy. Therefore, we generated two podocyte-specific GLUT1 transgenic mouse lines (driven by a podocin promoter) on a db/m C57BLKS background. Progeny of the two thunders were used to generate diabetic db/db and control db/m littermate mice. Immunoblots of glomerular lysates showed that transgenic mice had a 3.5-fold (line 1) and 2.1-fold (line 2) increase in GLUT1 content compared with wild-type mice. Both lines showed similar increases in fasting blood glucose and body weights at 24 wk of age compared with wild-type mice. Mesangial index (percent PAS-positive material in the mesangial tuft) increased 88% (line 1) and 75% (line 2) in the wild-type diabetic mice but only 48% (line 1) and 39% (line 2) in the diabetic transgenic mice (P < 0.05, transgenic vs. wild-type mice). This reduction in mesangial expansion was accompanied by a reduction in fibronectin accumulation, and vascular endothelial growth factor (VEGF) levels increased only half as much in the transgenic diabetic mice as in wild-type diabetic mice. Levels of nephrin, neph1, CD2AP, podocin, and GLUT4 were not significantly different in transgenic compared with wild-type mice. Taken together, increased podocyte GLUT1 expression in diabetic mice does not contribute to early diabetic nephropathy; surprisingly, it protects against mesangial expansion and fibronectin accumulation possibly by blunting podocyte VEGF increases. [ABSTRACT FROM AUTHOR]

Upon the treatment of bis(arylcarbonyl)diphenylacetylenes with lithium naphthalenide, the carbonyl reduction dominantly occurs over the acetylene reduction. The produced bis(radical anion) intermediate undergoes a synchronous double-radical 5-endo-digcyclization. This simple reduction procedure produces two intriguing classes of ladder π-conjugated skeletons, i.e., emissive methylene-bridged stilbenes and dibenzo[a,e]pentalenes regarded as a cyclic 1,4-diphenylbutadiene. [ABSTRACT FROM AUTHOR]

Preclinical studies have shown that photodynamic therapy (PDT) enhances immune responses. To examine the role of the direct effects of PDT in liver cancer with regard to enhancement of the antitumor response, we injected PDT-generated H22 liver cancer cell lysate (as a tumor vaccine) intradermally into Kunming mice. In the control group, the cell lysate was substituted with normal saline solution. A liver tumor model was established by the injection of H22 cell suspension. We found that the PDT-generated vaccine significantly increased the percentages of CD4(+), CD8(+), and CD19(+) cells, inhibited tumor growth, and prolonged the survival time. Our findings suggest that PDT-generated vaccines can significantly enhance the antitumor immune response and may have the potential to be used as an adjuvant therapy clinically. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Glomerular mesangial expansion and podocyte loss are important early features of diabetic nephropathy, whereas tubulointerstitial injury and fibrosis are critical for progression of diabetic nephropathy to kidney failure. Therefore, we analyzed the expression of genes in glomeruli and tubulointerstitium in kidney biopsies from diabetic nephropathy patients to identify pathways that may be activated in humans but not in murine models of diabetic nephropathy that fall to progress to glomerulosclerosis, tubulointerstitial fibrosis, ,and kidney failure. RESEARCH DESIGN AND METHODS--Kidney biopsies were obtained from 74 patients (control subjects, early and progressive type 2 diabetic nephropathy). Glomerular and tubulointerstitial mRNAs were microarrayed, followed by bioinformatics analyses. Gene expression changes were confirmed by real-time RT-PCR and immunohistological staining. Samples from db/db C57BLKS and streptozotocin-induced DBA/2J mice, commonly studied murine models of diabetic nephropathy, were analyzed. RESULTS--In human glomeruli and tubulointerstitial samples, the Janus kinase (Jak)-signal transducer and activator of transcription (Stat) pathway was highly and significantly regulated. Jak-1, -2, and -3 as well as Stat-1 and -3 were expressed at higher levels in patients with diabetic nephropathy than in control subjects. The estimated glomerular filtration rate significantly correlated with tubulointerstitial Jak-1, -2, and -3 and Stat-1 expression (R² = 0.30-0.44). Immunohistochemistry found strong Jak-2 staining in glomerular and tubulointerstitial compartments in diabetic nephropathy compared with control subjects. In contrast, there was little or no increase in expression of Jak/Stat genes in the db/db C57BLKS or diabetic DBA/2J mice. CONCLUSIONS--These data suggest a direct relationship between tubulointerstitial Jak/Stat expression and progression of kidney failure in patients with type 2 diabetic nephropathy and distinguish progressive human diabetic nephropathy from non-progressive murine diabetic nephropathy. Diabetes 58:469-477, 2009 [ABSTRACT FROM AUTHOR]

Recent studies suggest that thiazolidinediones ameliorate diabetic nephropathy (DN) independently of their effect on hyperglycemia. In the current study, we confirm and extend these findings by showing that rosiglitazone treatment prevented the development of DN and reversed multiple markers of oxidative injury in DBA/2J mice made diabetic by low- dose streptozotocin. These diabetic mice developed a 14.2-fold increase in albuminuria and a 53% expansion of renal glomerular extracellular matrix after 12 wk of diabetes. These changes were largely abrogated by administration of rosiglitazone beginning 2 wk after the completion of streptozotocin injections. Rosiglitazone had no effect on glycemic control. Rosiglitazone had similar effects on insulin-treated diabetic mice after 24 wk of diabetes. Podocyte loss and glomerular fibronectin accumulation, other markers of early DN, were prevented by rosiglitazone in both 12- and 24-wk diabetic models. Surprisingly, glomerular GLUT1 levels did not increase and nephrin levels did not decrease in the diabetic animals; neither changed with rosiglitazone. Plasma and kidney markers of protein oxidation and lipid peroxidation were significantly elevated in the 24-wk diabetic animals despite insulin treatment and were reduced to near-normal levels by rosiglitazone. Finally, urinary metabolites were markedly altered by diabetes. Of 1,988 metabolite features identified by electrospray ionization time of flight mass spectrometry, levels of 56 were altered more than twofold in the urine of diabetic mice. Of these, 21 were returned to normal by rosiglitazone. Thus rosiglitazone has direct effects on the renal glomerulus to reduce reactive oxygen species accumulation to prevent type 1 diabetic mice from development of DN. [ABSTRACT FROM AUTHOR]

Facile photochemical exocyclic [2 + 2 + 2] cycloaddition produced a series of electron-donating 1,1′-bi(isobenzofuran)s having various aryl groups at the 3,3′ positions. The 1,1′-bi(isobenzofuran) skeleton with a highly coplanar structure is a useful building unit to construct the narrow bandgap π-conjugated systems with low oxidation potentials. [ABSTRACT FROM AUTHOR]

LRP1 [LDL (low-density lipoprotein) receptor-related protein 1]-null CHO cells (Chinese-hamster ovary cells) (13-5-1 cells) exhibited accelerated cell growth and severe tumour progression after they were xenografted into nude mice. Reconstitution of LRP1 expression in these cells, either with the full-length protein or with a minireceptor, reduced growth rate as well as suppressed tumour development. We tested the role of the tyrosine residue in the FXNPXY63 motif within the LRP1 cytoplasmic domain in signal transduction and cell growth inhibition by site-specific mutagenesis. The LRP1 minireceptors harbouring Tyr63 to alanine or Tyr63 to phenylalanine substitution had diametrically opposite effects on cell growth, cell morphology and tumour development in mice. The Y63F-expressing cells showed suppressed cell growth and tumour development, which were associated with decreased β-catenin and cadherin concentrations in the cells. On the other hand, the Y63A-expressing cells lacked inhibition on cell growth and tumour development, which were associated with hyperactivation of ERKs (extracellular-signal-regulated kinases), FAK (focal adhesion kinase) and cyclin D1 in the cells. The mutant Y63A minireceptor also exhibited reduced capacity in binding to the Dab2 (disabled 2) adaptor protein. In addition, the Y63A mutant showed increased caveolar localization, and cells expressing Y63A had altered caveolae architecture. However, tyrosine to alanine substitution at the other NPXY29 motif had no effect on cell growth or tumorigenesis. These results suggest that the FXNPXY63 motif of LRP1 not only governs cellular localization of the receptor but also exerts multiple functional effects on signalling pathways involved in cell growth regulation. [ABSTRACT FROM AUTHOR]

Syntheses of the four mixed phenol-pyridine derivatives 1,6-bis(2-hydroxyphenyl)pyridyl boron naphthalene (1), 1,6-bis(2-hydroxy-5-methylphenyl)pyridyl boron naphthalene (2), 1,6-bis(2-hydroxyphenyl)pyridyl boron 2-methoxyl- benzene (3), and 1,6-bis(2-hydroxy-5-methylphenyl)pyridyl boron 2-methoxylbenzene (4) are reported. The structures of the boron compounds 1 3, and 4 were determined by single-crystal X-ray diffraction. The molecular packing is characterized by intermolecular σ···σ and hydrogen-bonding interactions. DSC analysis demonstrates that 1 and 2 have good thermal stability with higher glass transition temperatures (Tg) and melting points (Tm) than 3 and 4. Boron complexes 1-4 display bright blue luminescence in solution and the solid state. White and blue electroluminescent (EL) devices were fabricated successfully using these boron compounds. [ABSTRACT FROM AUTHOR]

The insulin-induced translocation of low density lipoprotein receptor-related protein 1 (LRP1) from intracellular membranes to the cell surface in 3T3-L1 adipocytes was differentiation-dependent and did not occur in 3T3-L1 fibroblasts. Prompted by findings that the plasma membrane of 3T3-L1 adipocytes was rich in caveolae, we determined whether LRP1 became caveolae-associated upon insulin stimulation. The caveolae domain was isolated by the well characterized detergent solubilization and sucrose density ultracentrifugation methodology. Under basal conditions, only a trace amount of LRP1 was caveolae-associated despite the markedly elevated caveolin-1 and caveolae after adipocytic cell differentiation. Upon insulin treatment, the amount of LRP1 associated with caveolae was increased by 4-fold within 10 min, which was blocked completely by pretreatment with wortmannin prior to insulin. The caveolar localization of LRP1 in adipocytes was specific to insulin; treatment with platelet-derived growth factor-bb isoform did not promote but rather decreased caveolar localization of LRP1 below basal levels. The insulin-induced caveolar localization of LRP1 was also observed in 3T3-L1 fibroblasts where translocation of LRP1 from intracellular membranes to the cell surface was absent, suggesting that association of LRP1 with caveolae was achieved, at least in part, through lateral transmigration along the plane of plasma membranes. Immunocytochemistry studies revealed partial co-localization of LRP1 (either endogenous LRP1 or an epitopetagged minireceptor) with caveolin-1 in cells treated with insulin, which was confirmed by co-immunoprecipitation of LRP1 with caveolin-1 in cells treated with insulin but not platelet-derived growth factor-bb. These results suggest that the localization of LRP1 to caveolae responds selectively to extracellular signals. [ABSTRACT FROM AUTHOR]

Background: Astrocytoma is a common aggressive intracranial tumor and presents a formidable challenge in clinic. Association of the altered DNA methylation pattern of the promoter CpG islands with the expression profile of the cancer related genes has been found in many human tumors. Therefore, DNA methylation status as such may serve as the epigenetic biomarker for both diagnosis and prognosis of human tumors including astrocytoma. Methods: We used the methylation specific PCR in conjunction with sequencing verification to establish the methylation profile of the promoter CpG island of thirty four genes in astrocytoma tissues from fifty three patients (The WHO grading:. I: 14, II: 15, III: 12 and IV: 12 cases, respectively). In addition, the compatible tissues (normal tissues distant from lesion) from three non-astrocytoma patients were also included as the control. Results: Seventeen genes (ABL, APC, APAF1, BRCA1, CSPG2, DAPK1, hMLH1, LKB1, PTEN, p14ARF, p15INK4b, p27KIP1, p57KIP2, RASSF1C, RB1, SURVIVIN, and VHL) displayed a uniformly unmethylated pattern in all the astrocytoma and non-astrocytoma tissues examined. However, the MAGEA1 gene that was inactivated and hypermethylated in non-astrocytoma tissues, was partially demethylated in 24.5% of the astrocytoma tissues (co-existence of the hypermethylated and demethylated alleles). Of the astrocytoma associated hypermethylated genes, the methylation pattern of the CDH13, cyclin a1, DBCCR1, EPO, MYOD1, and p16INK4a genes changed in no more than 5.66% (3/53) of astrocytoma tissues compared to non-astrocytoma controls, while the RASSF1A, p73, AR, MGMT, CDH1, OCT6,, MT1A, WT1, and IRF7 genes were more frequently hypermethylated in 69.8%, 47.2%, 41.5%, 35.8%, 32%, 30.2%, 30.2%, 30.2% and 26.4% of astrocytoma tissues, respectively. Demethylation mediated inducible expression of the CDH13, MAGEA1, MGMT, p73 and RASSF1A genes was established in an astrocytoma cell line (U251), demonstrating that expression of these genes is likely regulated by DNA methylation. The AR hypermethylation was found exclusively in female patients (22/27, 81%, 0/26, 0%, P < 0.001), while the IRF7 hypermethylation occurred in the male counterparts (11/26, 42.3% to 3/27, 11%, P < 0.05). Applying the mathematic method "the Discovery of Association Rules", we have identified the groups consisting of up to three genes that more likely display the altered methylation patterns in concert in astrocytoma. Conclusions: Of the thirty four genes examined, sixteen genes exhibited astrocytoma associated changes in the methylation profile. In addition to the possible pathological significance, the established concordant methylation profiles of the subsets consisting of two to three target genes may provide useful clues to the development of the useful prognostic as well as diagnostic assays for astrocytoma. [ABSTRACT FROM AUTHOR]

During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease. [ABSTRACT FROM AUTHOR]

Establishes a formula to calculate two pKa values of perylenequinoid photosensitizer through thermodynamic methods. Details on the existence of intramolecular hydrogen bond and intramolecular proton transfer; Effects of the disassociation of phenolic hydrogen on photosensitive activity; Conclusions reached.

Presents an equation which relates to combinatorial properties of ineffable cardinals. Indepth look at the equation.

The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad-spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. Z-penicillamine-stabilized NPs with left-handed curved apexes display half-maximal inhibitory concentrations (IC50) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC50 values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while anti-bodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments. [ABSTRACT FROM AUTHOR]

The X-ray energy spectrum is crucial for image quality and dosage assessment in mammography, radiography, fluoroscopy, and CT which are frequently used for the diagnosis of many diseases including but not limited to patients with cardiovascular and cerebrovascular diseases. X-ray tubes have an electron filament (cathode), a tungsten/rubidium target (anode) oriented at an angle, and a metal filter (aluminum, beryllium, etc.) that may be placed in front of an exit window. When cathode electrons meet the anode, they generate X-rays with varied energies, creating a spectrum from zero to the electrons' greatest energy. In general, the energy spectrum of X-rays depends on the electron beam's energy (tube voltage), target angle, material, filter thickness, etc. Thus, each imaging system's X-ray energy spectrum is unique to its tubes. The primary goal of the current study is to develop a clever method for quickly estimating the X-ray energy spectrum for a variety of tube voltages, filter materials, and filter thickness using a small number of unique spectra. In this investigation, two distinct filters made of beryllium and aluminum with thicknesses of 0.4, 0.8, 1.2, 1.6, and 2 mm were employed to obtain certain limited X-ray spectra for tube voltages of 20, 30, 40, 50, 60, 80, 100, 130, and 150 kV. The three inputs of 150 Multilayer Perceptron (MLP) neural networks were tube voltage, filter type, and filter thickness to forecast the X-ray spectra point by point. After training, the MLP neural networks could predict the X-ray spectra for tubes with voltages between 20 and 150 kV and two distinct filters made of aluminum and beryllium with thicknesses between 0 and 2 mm. The presented methodology can be used as a suitable, fast, accurate and reliable alternative method for predicting X-ray spectrum in medical applications. Although a technique was put out in this work for a particular system that was the subject of Monte Carlo simulations, it may be applied to any genuine system. [ABSTRACT FROM AUTHOR]

Searching for two-dimensional (2D) organic Dirac materials, which have more adaptable practical applications compared with inorganic ones, is of great significance and has been ongoing. However, only two such materials with low Fermi velocity have been discovered so far. Herein, we report the design of an organic monolayer with C4N3H stoichiometry that possesses fascinating structure and good stability in its free-standing state. More importantly, we demonstrate that this monolayer is a semimetal with anisotropic Dirac cones and very high Fermi velocity. This Fermi velocity is roughly one order of magnitude larger than the largest velocity ever reported in 2D organic Dirac materials, and it is comparable to that in graphene. The Dirac states in this monolayer arise from the extended π-electron conjugation system formed by the overlapping 2pz orbitals of carbon and nitrogen atoms. Our finding paves the way to a search for more 2D organic Dirac materials with high Fermi velocity. [ABSTRACT FROM AUTHOR]

The mechanical noise in the cabin of the ship is so large that the leakage of high-pressure fluid is not easily noticed. In view of this situation, a near-field acoustic holography for high-frequency weak sound source under low signal-to-noise ratio is proposed. The method uses the empirical mode decomposition method to add weights to the time-domain sampling signals of each array element, and then uses the plane equivalent source near-field acoustic holography combined with compressive sensing to find the holographic surface acoustic pressure distribution. The simulation and experiment show that this method has certain feasibility under low signal-to-noise ratio, and the results are better than the method based on Fourier transform and the traditional boundary element method. It is of positive significance to apply it to engineering practice. [ABSTRACT FROM AUTHOR]

[Objectives] The use of natural enemies of living insects and their derivatives can effectively avoid the problems of pesticide residues, pest resistance, biodiversity decline, control effect weakening and so on. [Methods] Parasites inject various parasitic factors into hosts to inhibit the development of hosts, adjust the immunity of hosts, interfere with the growth and development of hosts, and reduce the nutrition metabolism of hosts, so as to ensure the growth and development of the offspring. Host pests can escape or conquer the parasitism of parasitic wasps through immune defense system in order to reproduce their own offspring. [Results] Under intense and strong selection pressure, in order to effectively ensure the success rate of parasitism, the adaptive diversity of parasitism strategies of parasitic wasps is finally caused. In the process of evolution and under the pressure of directional selection, the innate immunity and acquired immunity gradually evolve. [Conclusions] In-depth research on parasitic factors of parasitic wasps and their interaction with crop pests' immunity and development can not only improve theoretical understanding of insect immunity and development biology, pest biological control and other disciplines, but also be expected to enable the application of some components of parasitic factors to agriculture, medicine and pharmacy. Bactrocera dorsalis is a destructive fruit and vegetable pest. This paper summarized the venom protein of B. dorsalis parasitoids and the immune interaction with hosts, in order to provide theoretical basis for biological control of plant pests by using parasitic natural enemies. [ABSTRACT FROM AUTHOR]

A series of angucyclinone antibiotics have been isolated from marine Streptomyces sp. strain W007 and identified. Here, a draft genome sequence of Streptomyces sp. W007 is presented. The genome contains an intact biosynthetic gene cluster for angucyclinone antibiotics, which provides insight into the combinatorial biosynthesis of angucyclinone antibiotics produced by marine streptomycetes. [ABSTRACT FROM AUTHOR]

The Pareto principle is often used to describe how faults in large software systems are distributed over modules. A recent paper by Andersson and Runeson again confirmed the Pareto principle of fault distribution. In this paper, we show that the distribution of software faults can be more precisely described as the Weibull distribution. [ABSTRACT FROM AUTHOR]

In this correspondence, we point out a discrepancy in a recent paper, "Data Mining Static Code Attributes to Learn Defect Predictors," that was published in this journal Because of the small percentage of detective modules, using Probability of Detection (pd) and Probability of False Alarm (pf) as accuracy measures may lead to irnpractical prediction models. [ABSTRACT FROM AUTHOR]

[Display omitted] • The greater role of grain size than the type of grain boundaries in Ag-Au interconnection. • The explanation of the cause of local delamination at Ag-Au interface. • The molecular simulation on the performance of high angle grain boundaries in Ag-Au interdiffusion. As an environmentally friendly interconnection material in power electronics, silver paste is widely used in gold surface finish. To explain the delamination at the Ag-Au interface and clarify the mechanism of Ag-Au interconnection, the bonding properties of sintered silver joints on different gold-plated substrates are studied. It was concluded that the effect of grain size on Ag-Au diffusion is greater than that of grain boundary type. The gold-plating layer with larger grains provides fewer grain boundaries, which inhibits the rapid diffusion of Ag atoms due to high angle grain boundaries. In addition, to investigate the effects of Au grain boundary misorientation on Ag-Au interdiffusion, molecular dynamics simulation is carried out on the sintering process. It is not found that high angle grain boundary of Au layer promotes the diffusion of Ag atoms during pre-drying. However, in the sintering stage, the MSD (mean square displacement) of Ag atoms in the substitute-model with high angle grain boundaries is about 4 times that of with low angle grain boundaries. It is proved that owing to lots of high angle grain boundaries in the gold-plated substrate, the diffusion of Ag atoms is faster in the sintering stage. [ABSTRACT FROM AUTHOR]

Aims L-type Ca2+ channels (LTCCs) in adult cardiomyocytes are localized to t-tubules where they initiate excitation-contraction coupling. Our recent work has shown that a subpopulation of LTCCs found at the surface sarcolemma in caveolae of adult feline cardiomyocytes can also generate a Ca2+ microdomain that activates nuclear factor of activated T-cells signaling and cardiac hypertrophy, although the relevance of this paradigm to hypertrophy regulation in vivo has not been examined. Methods and results Here we generated heart-specific transgenic mice with a putative caveolae-targeted LTCC activator protein that was ineffective in initiating or enhancing cardiac hypertrophy in vivo. We also generated transgenic mice with cardiac-specific overexpression of a putative caveolae-targeted inhibitor of LTCCs, and while this protein inhibited caveolae-localized LTCCs without effects on global Ca2+ handling, it similarly had no effect on cardiac hypertrophy in vivo. Cardiac hypertrophy was elicited by pressure overload for 2 or 12 weeks or with neurohumoral agonist infusion. Caveolae-specific LTCC activator or inhibitor transgenic mice showed no greater change in nuclear factor of activated T-cells activity after 2 weeks of pressure overload stimulation compared with control mice. Conclusion Our results indicate that LTCCs in the caveolae microdomain do not affect cardiac function and are not necessary for the regulation of hypertrophic signaling in the adult mouse heart. [ABSTRACT FROM AUTHOR]

Extended grey numbers (EGNs), integrated with discrete and continuous grey numbers, have a powerful capability in expressing uncertainty. Considering the grey and randomness of multi-criteria decision-making (MCDM) problems and the limitation of human knowledge, a grey stochastic MCDM approach based on prospect theory and distance measures is proposed, in which the criteria values take the form of EGNs. Firstly, a new order relationship of EGNs is defined, and the generalized distance measures of EGNs as well as their properties are introduced. Then the value function of EGNs based on a plurality of reference points and the weight function are constructed. After calculation, the prospect value for each alternative concerning each criterion is obtained, which is in the form of EGNs. Furthermore, based on the distance measures of EGNs and TODIM, all the alternatives are ranked according to their global value. Finally, two illustrate examples show the feasibility and usability of the proposed approach, and comparison analysis with the existing method is made. [ABSTRACT FROM AUTHOR]

A growing number of studies have suggested that traditional Chinese medicine (TCM) plays an essential role in the development and occurrence of liver cancer. However, the function of Ruangan Lidan decoction (RLD) in liver cancer are not yet adequately identified and manifested, which attracted our attention. The key genes related to liver cancer and RLD and the upstream miRNAs of PDK4 were obtained based on bioinformatics analysis, followed by verification of the targeting relationship between miR-9-5p and PDK4. Next, Huh7 cells were treated with RLD to detect cell proliferation, colony formation, migration, invasion, and apoptosis by multiple assays with gain- and loss-of-function experiments. Moreover, subcutaneous transplanted tumor model and lung metastasis model of liver cancer in nude mice were established to further verify the functional role of RLD in liver cancer growth and metastasis via miR-9-5p/PDK4 axis. Bioinformatics analysis found that PDK4 and miR-9-5p were related to liver cancer, and PDK4 may be a downstream regulator of RLD. miR-9-5p could target and inhibit PDK4. In vitro cell experiments demonstrated that RLD suppressed liver cancer cell proliferation, invasion and migration, and promoted apoptosis by inhibiting miR-9-5p expression and promoting PDK4 expression. In vivo animal experiments further confirmed that RLD inhibited liver cancer growth and metastasis via upregulation of miR-9-5p-dependent PDK4. RLD downregulated miR-9-5p and upregulated PDK4 to inhibit the proliferation, migration, invasion, and induce apoptosis, thereby suppressing the growth and metastasis of liver cancer, highlighting a potential novel target for treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Phospholipase Cε (PLCε) is a phospholipase C isoform with a wide range of physiological functions. It has been implicated in aortic valve disorders, but its role in frequently associated aortic disease remains unclear. To determine the role of PLCε in thoracic aortic aneurysm and dissection (TAAD) we used PLCε-deficient mice, which develop aortic valve insufficiency and exhibit aortic dilation of the ascending thoracic aorta and arch without histopathological evidence of injury. Fourteen days of infusion of Plce1+/+ and Plce1−/− mice with angiotensin II (ANG II), which induces aortic dilation and dissection, led to sudden death secondary to ascending aortic dissection in 43% of Plce1−/− versus 5% of Plce1+/+ mice (P < 0.05). Medial degeneration and TAAD were detected in 80% of Plce1−/− compared with 10% of Plce1+/+ mice (P < 0.05) after 4 days of ANG II. Treatment with ANG II markedly increased PLCε expression within the ascending aortic adventitia. Total RNA sequencing demonstrated marked upregulation of inflammatory and fibrotic pathways mediated by interleukin-1β, interleukin-6, and tumor necrosis factor-α. In silico analysis of whole exome sequences of 258 patients with type A dissection identified 5 patients with nonsynonymous PLCE1 variants. Our data suggest that PLCε deficiency plays a role in the development of TAAD and aortic insufficiency. NEW & NOTEWORTHY We describe a novel phenotype by which PLCε deficiency predisposes to aortic valve insufficiency and ascending aortic aneurysm, dissection, and sudden death in the setting of ANG II-mediated hypertension. We demonstrate PLCE1 variants in patients with type A aortic dissection and aortic insufficiency, suggesting that PLCE1 may also play a role in human aortic disease. This finding is of very high significance because it has not been previously demonstrated that PLCε directly mediates aortic dissection. [ABSTRACT FROM AUTHOR]

Accumulation of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) is an oxidative stress response, which induced various defense mechanisms or programmed cell death (PCD). As one of the major types of PCD, autophagy has been observed in response to several anticancer drugs and demonstrated to be responsible for cell death. To date, however, the exact mechanism by which ROS regulates autophagy is still poorly understood. Thus, the purposes of this study were to elucidate how H2O2 exerts its cytotoxic effects on malignant glioma U251 cells and to uncover the molecular mechanism that might be involved. Here, we show that H2O2-induced autophagy and apoptosis in U251 cells are mediated through the Beclin 1 and Akt/mTOR pathways. Accumulation of ROS leads to changes in mitochondrial permeability with loss of mitochondrial membrane potential and disruption of mitochondrial dynamics at a transcriptional level of fission and fusion. Overexpression of cellular Bcl-2 partially inhibited autophagy through both the Beclin 1 and the Akt/mTOR pathways and led to recovery of mitochondrial dynamics. When autophagy was prevented at an early stage by 3-methyladenine, apoptosis significantly increased. Our data provide the first evidence that H2O2 induces autophagy through interference with the Beclin 1 and Akt/mTOR signaling pathways and is regulated by the anti-apoptotic gene Bcl-2 in glioma U251 cells. [ABSTRACT FROM AUTHOR]

The microstructure and mechanical behaviors of a hot-pressed Nb-23Ti-15Al (at.%) alloy have been investigated. The results indicate that with different hot-pressing temperatures, the alloy presents remarkably different microstructural morphologies: blocky microstructure or columnar microstructure. At lower hot-pressing temperature, the blocky d phase is formed by the reaction of the metastable s phase and the β phase; at higher hot-pressing temperature, the d phase directly precipitates from the supersaturated β phase with preferred orientation relationships of [212]d//[001]β and (02 View the MathML source1?)d//(110)β to form columnar microstructure. The columnar microstructure leads to higher microhardness and better toughness, for the reason that the columnar microstructure could resist deformation of the alloy effectively, and impede initiation and propagation of cracks. [ABSTRACT FROM AUTHOR]

Mantle plumes are thought to play key roles in Earth's geodynamics, including mantle convection, continental formation, and plate tectonics. The connection between plume activity and continental dispersion, as exemplified by the breakup of Gondwana and the generation of the Neo-Tethys Ocean, is a key question for the geosciences. Here, we present detailed investigations for the picrite-basalt sequence in the Baoshan-Gongshan Block of the northern Sibumasu terrane, southwest China. Field relations and petrological and geochemical data reveal that these volcanic rocks are continental flood picrites and basalts, consistent with a mantle plume origin. The estimated mantle potential temperatures range from 1527 ± 86 °C to 1546 ± 98 °C, and melting depths vary from the spinel to garnet stability fields (1.1-5.3 GPa), similar to Cenozoic Hawaiian picrites. Zircon geochronological data show that the mantle plume activity started at ca. 335 Ma and lasted to 280 Ma; this range is earlier than the breakup of the Gondwana continent and opening of the Neo-Tethys Ocean (270-260 Ma). We conclude that the long-lived mantle plume impacted the continental lithosphere but it did not drive continental breakup and the opening of Neo-Tethys Ocean, which took place because of the subduction-induced stress generated by initial subduction of the Paleo-Tethys Ocean. [ABSTRACT FROM AUTHOR]

Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared human--mouse cross-species glomerular transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db), and 162 (Human-BKS eNOS-/- db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetes complications, such as elements of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and vascular endothelial growth factor receptor (VEGFR) signaling pathways. In addition, novel pathways not previously associated with DN and cross-species gene nodes and pathways unique to each of the human--mouse networks were discovered. The human--mouse shared glomerular transcriptional networks will assist DN researchers in selecting mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans. [ABSTRACT FROM AUTHOR]

CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to mitochondria, endoplasmic reticulum (ER), nucleus and cytoplasm, and participates in the apoptotic response to stress. Apoptosis and autophagy, the main types of the programmed cell death, seem interconnected under certain stress conditions. However, the role of CLIC4 in autophagy regulation has yet to be determined. In this study, we demonstrate upregulation and nuclear translocation of the CLIC4 protein following starvation in U251 cells. CLIC4 siRNA transfection enhanced autophagy with increased LC3-II protein and puncta accumulation in U251 cells under starvation conditions. In that condition, the interaction of the 14-3-3 epsilon isoform with CLIC4 was abolished and resulted in Beclin 1 overactivation, which further activated autophagy. Moreover, inhibiting the expression of CLIC4 triggered both mitochondrial apoptosis involved in Bax/Bcl-2 and cytochrome c release under starvation and endoplasmic reticulum stress-induced apoptosis with CHOP and caspase-4 upregulation. These results demonstrate that CLIC4 nuclear translocation is an integral part of the cellular response to starvation. Inhibiting the expression of CLIC4 enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation. [ABSTRACT FROM AUTHOR]

Our goal was to identify the bacteria inhabiting the reproductive system of the female oriental fruit fly, Bactrocera dorsalis (Hendel), and evaluate the chemotaxis of B. dorsalis to the metabolites produced by the bacteria. Based on 16S rRNA-based polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), 18 operational taxonomic units (OTUs) were assigned to the five bacterial classes Betaproteobacteria, Alphaproteobacteria, Gammaproteobacteria, Bacilli and Actinobacteria. Nine OTUs were assigned to Gammaproteobacteria, which was the most highly represented class. Enterobacteriaceae constituted the dominant family, and within this family, three genera and five species were identified, including Enterobacter sakazakii, Klebsiella oxytoca, Klebsiella pneumoniae, Raoultella terrigena and Enterobacter amnigenus. In this set, the first two species were the dominant components, and the latter three species were the minor ones. Finally, we found that the metabolites produced by R. terrigena, K. oxytoca and K. pneumoniae were attractive to the B. dorsalis adults, and in field studies, B. dorsalis adults were most attracted to K. oxytoca. Collectively, our results suggest that the female reproductive system plays an important role in the transfer of enterobacteria from the gut to fruit. Our data may prompt the development of a female-targeted population control strategy for this fly. [ABSTRACT FROM AUTHOR]