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High expression of truncated O‐glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N‐acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues. The current study aimed to determine the role of GALNT6 in ccRCC, and whether GALNT6‐mediated O‐glycosylation aggravates malignant behaviors. Gain‐ and loss‐of‐function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC‐derived xenograft tumor growth and lung metastasis. In line with this, silencing of GALNT6 yielded the opposite results. Mechanically, high expression of GALNT6 led to the accumulation of Tn antigen in ccRCC cells. By undertaking immunoprecipitation coupled with liquid chromatography/mass spectrometry, vicia villosa agglutinin blot, and site‐directed mutagenesis assays, we found that O‐glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6‐induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium‐derived growth factor (LEDGF) as a key regulator of GALNT6 transcriptional induction in ccRCC growth and an upstream contributor to ccRCC aggressive behavior. Collectively, our findings indicate that GALNT6‐mediated abnormal O‐glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development. [ABSTRACT FROM AUTHOR]

Background: Retinoids, defined as synthetic or natural derivatives of vitamin A, have been extensively studied as anti‐aging molecules that are widely applied in cosmetics. However, due to their physicochemical property, retinoids are highly unstable and extremely sensitive to light, oxygen, and temperature. Moreover, topical application of retinoids often leads to cutaneous irritation. These instabilities and irritant properties of retinoids limit their application in cosmetic and pharmaceutical products. Aim: Our study aimed to provide a systematic review to summarize the mechanisms underlying the instability and irritant properties of retinoids, as well as recent developments in addressing these challenges. Methods: A comprehensive PubMed search was conducted using the following keywords: retinoids, chemical instability, skin irritation, retinoid derivatives, nano lipid‐based carriers, liposomes, penetration‐enhancer vesicles, ethosomes, niosomes, nanoemulsions, solid lipid nanoparticles, vitamins, soothing and hydrating agents, antioxidants and metal chelator and retinol combinations. Relevant researches published between 1968 and 2023 and studies related to these reports were reviewed. Results: The development of new retinoid derivatives, the utilization of new delivery systems like nano lipid‐based carriers and the combination with other compounds like vitamins, soothing agents, antioxidants and metal chelator have been explored to improve the stability, bioavailability, and toxicity of the retinoid family. Conclusions: Through advancements in formulation techniques, structure modification of retinoid derivatives and development of novel nano lipid‐based carriers, the chemical instability and skin irritation of retinoids has been mitigated, ensuring their efficacy and potency over extended periods. [ABSTRACT FROM AUTHOR]

Summary: Kiwifruit ripening is a complex and highly coordinated process that occurs in conjunction with the formation of fruit edible quality. The significance of epigenetic changes, particularly the impact of N6‐methyladenosine (m6A) RNA modification on fruit ripening and quality formation, has been largely overlooked.We monitored m6A levels and gene expression changes in kiwifruit at four different stages using LC‐MS/MS, MeRIP, RNA‐seq, and validated the function of AcALKBH10 through heterologous transgenic expression in tomato.Notable m6A modifications occurred predominantly at the stop codons and the 3′ UTRs and exhibited a gradual reduction in m6A levels during the fruit ripening process. Moreover, these m6A modifications in the aforementioned sites demonstrated a discernible inverse relationship with the levels of mRNA abundance throughout the ripening process, suggesting a repression effect of m6A modification in the modulation of kiwifruit ripening.We further demonstrated that AcALKBH10 rather than AcECT9 predominantly regulates m6A levels in ripening‐related genes, thereby exerting the regulatory control over the ripening process and the accumulation of soluble sugars and organic acids, ultimately influencing fruit ripening and quality formation. In conclusion, our findings illuminate the epi‐regulatory mechanism involving m6A in kiwifruit ripening, offering a fresh perspective for cultivating high‐quality kiwifruit with enhanced nutritional attributes. [ABSTRACT FROM AUTHOR]

We describe small heterojunction polymer dots (Pdots) with deep‐red light catalyzed H2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo‐Pdots nanoreactors, which selectively scavenge ⋅OH radicals in live cells and tissues under 650 nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10 times higher than that of the single‐component Pdots described previously. Under a total light dose of 360 J/cm2, the Lipo‐Pdots nanoreactors effectively scavenged ⋅OH radicals and suppressed the expression of pro‐inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

This study delves into the potential therapeutic benefits of Fufang Sanling Granules for kidney cancer, focusing on their active components and the underlying mechanisms of their interaction with cancer‐related targets. By constructing a drug‐active component‐target network based on eight herbs, key active compounds such as kaempferol, quercetin, and linolenic acid were identified, suggesting their pivotal roles in modulating immune responses and cellular signaling pathways relevant to cancer progression. The research further identified 51 central drug‐disease genes through comprehensive bioinformatics analyses, implicating their involvement in crucial biological processes and pathways. A novel risk score model, encompassing six genes with significant prognostic value for renal cancer, was established and validated, showcasing its effectiveness in predicting patient outcomes through mutation analysis and survival studies. The model's predictive power was further confirmed by its ability to stratify patients into distinct risk groups with significant survival differences, highlighting its potential as a prognostic tool. Additionally, the study explored the relationship between gene expression within the identified black module and the risk score, uncovering significant associations with the extracellular matrix and immune infiltration patterns. This reveals the complex interplay between the tumor microenvironment and cancer progression. The integration of the risk score with clinical parameters through a nomogram significantly improved the model's predictive accuracy, offering a more comprehensive tool for predicting kidney cancer prognosis. In summary, by combining detailed molecular analyses with clinical insights, this study presents a robust framework for understanding the therapeutic potential of Fufang Sanling Granules in kidney cancer. It not only sheds light on the active components and their interactions with cancer‐related genes but also introduces a reliable risk score model, paving the way for personalized treatment strategies and improved patient management in the future. [ABSTRACT FROM AUTHOR]

Over the past decades, increasing evidences have demonstrated that five retinoids, including retinol (ROL), retinol acetate (RAc), retinol propionate (RP), retinol palmitate (RPalm), and hydroxypinacolone retinoate (HPR), can be potential therapeutic agents for skin photoaging. However, therapeutic efficacies and biosafety have never been compared to these compounds. This study aimed to determine the optimal retinoid type(s) for anti‐photoaging therapy both in vitro and in vivo. Our data demonstrated that four retinoids (RPalm, RP, HPR and ROL) but not RAc were effective for anti‐photoaging treatment at 5 μg/mL in vitro, with action mechanisms associated with antioxidative, anti‐inflammatory and anti‐skin ECM degradation activities. Notably, both RPalm and RP appeared superior to HPR and ROL for those activities. Importantly, both RPalm and RP were shown to be optimal for anti‐photoaging therapy when topically applied at 5 mg/kg in a UVB‐induced mice model of photoaging, which is consistent with their high anti‐photoaging activities in vitro. Additionally, topical application of these five retinoids showed satisfactory biosafety without causing significant apoptosis in animal organs, although RP application led to a slight decline in animal body weights. Collectively, these data have laid a good foundation for the next development of the clinical application of these retinoids for skin healthcare. [ABSTRACT FROM AUTHOR]

Summary: The plant hormone ethylene plays a critical role in fruit defense against Botrytis cinerea attack, but the underlying mechanisms remain poorly understood. Here, we showed that ethylene response factor SlERF.C1 acts as a key regulator to trigger the ethylene‐mediated defense against B. cinerea in tomato fruits without compromising ripening.Knockout of SlERF.C1 increased fruit susceptibility to B. cinerea with no effect on ripening process, while overexpression enhanced resistance. RNA‐Seq, transactivation assays, EMSA and ChIP‐qPCR results indicated that SlERF.C1 activated the transcription of PR genes by binding to their promoters.Moreover, SlERF.C1 interacted with the mitogen‐activated protein kinase SlMPK8 which allowed SlMPK8 to phosphorylate SlERF.C1 at the Ser174 residue and increases its transcriptional activity. Knocking out of SlMPK8 increased fruit susceptibility to B. cinerea, whereas overexpression enhanced resistance without affecting ripening. Furthermore, genetic crosses between SlMPK8‐KO and SlERF.C1‐OE lines reduced the resistance to B. cinerea attack in SlERF.C1‐OE fruits. In addition, B. cinerea infection induced ethylene production which in turn triggered SlMPK8 transcription and enhanced the phosphorylation of SlERF.C1.Overall, our findings reveal the regulatory mechanism of the 'Ethylene‐MPK8‐ERF.C1‐PR' module in resistance against B. cinerea and provide new insight into the manipulation of gray mold disease in fruits. [ABSTRACT FROM AUTHOR]

Modulation of the ligands and coordination environment of metal–organic frameworks (MOFs) has been an effective and relatively unexplored avenue for improving the anode performance of lithium‐ion batteries (LIBs). In this study, three MOFs are synthesized, namely, M4(o‐TTFOB)(bpm)2(H2O)2 (where M is Mn, Zn, and Cd; o‐H8TTFOB is ortho‐tetrathiafulvalene octabenzoate; and bpm is 2,2′‐bipyrimidine), based on a new ligand o‐H8TTFOB with two adjacent carboxylates on one phenyl, which allows us to establish the impact of metal coordination on the performance of these MOFs as anode materials in LIBs. Mn‐o‐TTFOB and Zn‐o‐TTFOB, with two more uncoordinated oxygen atoms from o‐TTFOB8−, show higher reversible specific capacities of 1249 mAh g−1 and 1288 mAh g−1 under 200 mA g−1 after full activation. In contrast, Cd‐o‐TTFOB shows a reversible capacity of 448 mAh g−1 under the same condition due to the lack of uncoordinated oxygen atoms. Crystal structure analysis, cyclic voltammetry measurements of the half‐cell configurations, and density functional theory calculations have been performed to explain the lithium storage mechanism, diffusion kinetics, and structure‐function relationship. This study demonstrates the advantages of MOFs with high designability in the fabrication of LIBs. [ABSTRACT FROM AUTHOR]

Summary: Kiwifruit (Actinidia chinensis) is one of the popular fruits world‐wide, and its quality is mainly determined by key metabolites (sugars, flavonoids, and vitamins). Previous works on kiwifruit are mostly done via a single omics approach or involve only limited metabolites. Consequently, the dynamic metabolomes during kiwifruit development and ripening and the underlying regulatory mechanisms are poorly understood.In this study, using high‐resolution metabolomic and transcriptomic analyses, we investigated kiwifruit metabolic landscapes at 11 different developmental and ripening stages and revealed a parallel classification of 515 metabolites and their co‐expressed genes into 10 distinct metabolic vs gene modules (MM vs GM). Through integrative bioinformatics coupled with functional genomic assays, we constructed a global map and uncovered essential transcriptomic and transcriptional regulatory networks for all major metabolic changes that occurred throughout the kiwifruit growth cycle.Apart from known MM vs GM for metabolites such as soluble sugars, we identified novel transcription factors that regulate the accumulation of procyanidins, vitamin C, and other important metabolites.Our findings thus shed light on the kiwifruit metabolic regulatory network and provide a valuable resource for the designed improvement of kiwifruit quality. [ABSTRACT FROM AUTHOR]

Summary: Soluble sugars, organic acids and volatiles are important components that determine unique fruit flavor and consumer preferences. However, the metabolic dynamics and underlying regulatory networks that modulate overall flavor formation during fruit development and ripening remain largely unknown for most fruit species.In this study, by integrating flavor‐associated metabolism and transcriptome data from 12 fruit developmental and ripening stages of Actinidia chinensis cv Hongyang, we generated a global map of changes in the flavor‐related metabolites throughout development and ripening of kiwifruit.Using this dataset, we constructed complex regulatory networks allowing to identify key structural genes and transcription factors that regulate the metabolism of soluble sugars, organic acids and important volatiles in kiwifruit. Moreover, our study revealed the regulatory mechanism involving key transcription factors regulating flavor metabolism. The modulation of flavor metabolism by the identified key transcription factors was confirmed in different kiwifruit species providing the proof of concept that our dataset provides a suitable tool for clarification of the regulatory factors controlling flavor biosynthetic pathways that have not been previously illuminated.Overall, in addition to providing new insight into the metabolic regulation of flavor during fruit development and ripening, the outcome of our study establishes a foundation for flavor improvement in kiwifruit. See also the Commentary on this article by Fernie & Alseekh, 233: 8–10. [ABSTRACT FROM AUTHOR]

Flexible electronic skins (e‐skins) play a very important role in the development of human–machine interaction and wearable devices. To fully mimic the functions of human skin, e‐skins should be able to perceive multiple external stimuli (such as temperature, touch, and friction) and be resistant to injury. However, both objectives are highly challenging. The fabrication of multifunctional e‐skins is difficult because of the complex lamination scheme and the integration of different sensors. The design of skin‐like materials is hindered by the trade‐off problem between flexibility, toughness, and self‐healing ability. Herein, flexible sodium methallyl sulfonate functionalized poly(thioctic acid) polymer chains are combined with rigid conductive polyaniline rods through ionic bonds to obtain a solvent‐free polymer conductive gel. The conductive gel has a modulus similar to that of skin, and shows good flexibility, puncture‐resistance, notch‐insensitivity, and fast self‐healing ability. Moreover, this conductive gel can convert changes in temperature and strain into electrical signal changes, thus leading to multifunctional sensing performance. Based on these superior properties, a flexible e‐skin sensor is prepared, demonstrating its great potential in the wearable field and physiological signal detection. [ABSTRACT FROM AUTHOR]

MiR‐148 is a negative regulator of autophagy 16‐like 1 (ATG16L1), a gene implicated in the pathogenesis of ventilator‐associated pneumonia (VAP). Therefore, the role of miR‐148 polymorphism in the pathogenesis of VAP was studied here. The expression of miR‐148, ATG16L1, Beclin‐I, LC3‐II, TNF‐α and IL‐6 in serum and peripheral blood mononuclear cells (PBMCs) of VAP patients was detected to study their relationship in the pathogenesis of VAP. Chronic obstructive pulmonary disease patients carrying the AA/AG genotypes of miR‐148 rs4719839 single nucleotide polymorphism (SNP) were more prone to VAP due to the higher expression of miR‐148, TNF‐α and IL‐6 along with suppressed expression of ATG16L1, Beclin‐I and LC3‐II in their serum and PBMCs. Transfection of miR‐148 mimics to primary PBMCs genotyped as GG and AA decreased the expression of ATG16L1, Beclin‐I and LC3‐II. Finally, cells carrying the AA genotype of rs4719839 SNP were more sensitive to the role of LPS stimulation in suppressing ATG16L1, Beclin‐I and LC3‐II expression while activating TNF‐α and IL‐6 expression. Our work presented detailed evidence, suggesting that the rs4719839 polymorphism can affect the risk of VAP. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL‐17A in lung injury, while its contribution to PM2.5‐induced lung injury remains largely unknown. Here, we probed into the possible role of IL‐17A in mouse models of PM2.5‐induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate γδT and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway‐, autophagy‐ and PI3K/Akt/mTOR signalling pathway‐related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL‐17A by γδT/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up‐regulating IL‐17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL‐17A impaired the energy metabolism of airway epithelial cells in the PM2.5‐induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL‐17A in γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway. [ABSTRACT FROM AUTHOR]

Summary: Polycomb group (PcG) proteins play vital roles in plant development via epigenetically repressing the transcription of target genes. However, to date, their function in fruit ripening is largely unknown.Combining reverse genetic approaches, physiological methods, yeast two‐hybrid, co‐immunoprecipitation, and chromatin immunoprecipitation assays, we show that Like Heterochromatin Protein 1b (SlLHP1b), a tomato Polycomb Repressive Complex 1 (PRC1)‐like protein with a ripening‐related expression pattern, represses fruit ripening via colocalization with epigenetic mark H3K27me3.RNA interference (RNAi)‐mediated downregulation of SlLHP1b advanced ripening initiation, climacteric ethylene production, and fruit softening, whereas SlLHP1b overexpression delayed these events. Ripening‐related genes were significantly upregulated in SlLHP1b RNAi fruits and downregulated in overexpressing fruits compared with wild‐type. Furthermore, SlLHP1b protein interacts with ripening regulator MSI1, a subunit of the PRC2 complex. Moreover, SlLHP1b also binds the epigenetic histone mark H3K27me3 in vivo and chromatin immunoprecipitation–quantitative PCR results showed binding occurs preferentially to regions of ripening‐associated chromatin marked by histone H3K27me3. Furthermore, the H3K27me3 levels in chromatin of ripening‐related genes is negatively correlated with accumulation of their transcripts in SlLHP1b down or upregulated fruits during ripening.Our findings reveal a novel regulatory function of SlLHP1b in fruit and provide new insights into the PcG‐mediated epigenetic regulation of climacteric fruit ripening. [ABSTRACT FROM AUTHOR]

Hiptage lushuiensis, a new species from the Hengduan Mountains, northwestern Yunnan Province, China, is described and illustrated here. This species was found growing at the margin of an open forest in the Nujiang Gorge of Lushui City. Hiptage lushuiensis is distinctive for its pink petals, 2 or more calyx glands, and large and pink samara with white hairs. This species is isolated in the deep gorge (25°51′N, 98°51′E, altitude 917 m), at the northern edge distribution range of the genus. These distinctive morphological differences and the geographic isolation suggest a history of long‐distance dispersal and allopatric speciation. Hiptage lushuiensis has a shorter filament but larger herkogamy than related species, suggesting that H. lushuiensis may have adapted to other pollinators with short but fat body such as Amegilla or Bombus spp. [ABSTRACT FROM AUTHOR]

In this report, we gave the first case of successful treatment for laryngeal NMC, which is exceedingly rare with dismal prognosis. intensity‐modulated radiation therapy accompanied by traditional Chinese medicine was administrated for the young woman, instead of radical resection, and she got continuous remission for more than 2 years, with no recurrence detected. [ABSTRACT FROM AUTHOR]

HLA‐C*07:1029 differs from HLA‐C*07:02:01:01 by one nucleotide in exon 5. [ABSTRACT FROM AUTHOR]

This study quantifies the characteristics of different satellite sampling errors in the time series of total precipitable water (TPW) derived from Constellation System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation, Special Sensor Microwave Imager Sounder (SSMIS), and High‐resolution Infrared Radiation Sounder (HIRS) during the overlapping time period of January 2007 to December 2013. Gap‐free data from ERA5 reanalysis of the European Centre for Medium Range Weather Forecasts are used as reference values. All TPW data are first compared with microwave radiometer measurements from Atmospheric Radiation Measurement Program. In general, they are consistent, with all their regression coefficients being greater than 0.77. Discrepancies in global TPW time series can be mainly attributed to the inherent sampling errors of these three different satellite remote sensing systems. COSMIC has small sampling errors in higher latitudes. But it has scarce samples in tropical regions, which leads to a large sampling error of 3.00 mm in the estimation of global TPW. Sampling in SSMIS is more uniform with mean errors less than 0.5 mm. But the sampling is only over the ocean. Sampling errors in HIRS are larger in tropics and north subtropical areas due to clear sky biased sampling. Moreover, it is significantly correlated with the variability of TPW, whereas the sampling error in COSMIC is less influenced by TPW. Sampling errors will be reduced and more consistent global TPW time series will be derived by simply combining the multisensor samplings together. Key Points: Sampling differences in COSMIC, SSMIS, and HIRS observations largely explain observed differences between associated TPW time seriesSampling in COSMIC, SSMIS, and HIRS has different characteristics; sampling errors in HIRS are significantly correlated with TPW variabilitySampling errors can be reduced by averaging multisensor sampling; more factors should be considered when merging real satellite data [ABSTRACT FROM AUTHOR]

Abstract: Typically, healthcare financing for an ageing population requires projections on healthcare demand and cost. However, projecting healthcare demand based on projected elderly does not consider changes in population health state over time. This paper proposes a new approach to forecast health variables using a stochastic health state function and the well‐established Lee–Carter stochastic mortality model. With the estimated health state at each age over time, we project the hospitalization rate, healthcare demand, and financing cost for Singapore using historical life tables and hospital admission data. Our findings show that while hospital insurance claims increase owing to an aging population, improving health state could save costs from hospital insurance claims. This has policy implications: more attention should be given to preventive healthcare such as health screening to improve the overall health state of the population. [ABSTRACT FROM AUTHOR]

Tree peony ( Paeonia suffruticosais) plants with yellowing symptoms suggestive of a phytoplasma disease were observed in Shandong Peninsula, China. Typical phytoplasma bodies were detected in the phloem tissue using transmission electron microscopy. The association of a phytoplasma with the disease was confirmed by polymerase chain reaction ( PCR) using phytoplasma universal primer pair R16m F2/ R16m R1 followed by R16 F2n/ R16 R2 as nested PCR primer pair. The sequence analysis indicated that the phytoplasma associated with tree peony yellows ( TPY) was an isolate of ' Ca. Phytoplasma solani' belonging to the stolbur (16 Sr XII) group. This is the first report of a phytoplasma associated with tree peony. [ABSTRACT FROM AUTHOR]

Doxorubicin is an anthracycline antibiotic agent used in the treatment of a variety of solid and haematopoietic tumours, but its use is limited by formation of metabolites that induce acute and chronic cardiac toxicities. Angelica sinensis has been widely used to treat cardiovascular and cerebrovascular diseases in China. In the present study, we used an in vivo mouse model to explore whether A. sinensis could protect against doxorubicin-induced chronic cardiotoxicity. Male ICR mice were treated with distilled water or water extraction of A. sinensis (15 g/kg, orally) daily for 4 weeks, followed by saline or doxorubicin (15 mg/kg, intravenously) treatments weekly. Cardiotoxicity was assessed by electrocardiograph, antioxidant activity in cardiac tissues, serum levels of creatine kinase, aspartate aminotransferase (AST) and histopathological change in cardiac tissues. A cumulative dose of doxorubicin (60 mg/kg) caused animal death and myocardial injury characterized by increased QT interval and decreased heart rate in electrocardiograph, decrease of heart antioxidant activity, increase of serum AST, as well as myocardial lesions. Pre-treatment with A. sinensis significantly reduced mortality and improved heart performance of the doxorubicin-treated mice as evidenced from normalization of antioxidative activity and serum AST, preventing loss of myofibrils as well as improving arrhythmias and conduction abnormalities. Furthermore, the in vitro cytotoxic study showed that A. sinensis did not compromise the antitumour activity of doxorubicin. These results suggested that A. sinensis elicited a typical cardioprotective effect on doxorubicin-related oxidative stress, and could be a novel adjunct in the combination with doxorubicin chemotherapy. [ABSTRACT FROM AUTHOR]

Hyperphosphorylation of cytoskeletal proteins seen in Alzheimer's disease is most probably the result of an imbalanced regulation in protein kinases and protein phosphatases (PP) in the affected neurons. Previous studies have revealed that PP-2A and PP-1 play important roles in the pathogenesis. Employing human neuroblastoma cells, we found that 10 n m calyculin A (CA), a selective inhibitor of PP-2A and PP-1, significantly increased phosphorylation and accumulation of neurofilament (NF) in the cells. Levels of NF-M (middle chain) and NF-L (light chain) mRNA decreased after CA treatment. Additionally, CA led to a decreased cell viability determined by MTT and crystal violet assay. Melatonin efficiently protects the cell from CA-induced alterations in NF hyperphosphorylation and accumulation, suppressed NF gene expression as well as decreased cell viability. It is concluded that inhibition of PP-2A/PP-1 by CA induces abnormalities in NF metabolism and cell survival, and melatonin efficiently arrests the lesions. [ABSTRACT FROM AUTHOR]

Summary: Multitiered storage systems, which are made up of heterogeneous devices, are widely used in distributed environments to accelerate the I/O performance of upper big data applications. It raises new challenges in efficient data migration through smart caching mechanisms among heterogeneous storage levels, such as MEM‐SSD‐HDD. To optimize the cache policy scheduling mechanism on the distributed tiered storage architecture, we proposed a general framework with five layers, including a tiered storage system layer, a cache migration policy layer, a cache policy adaptive scheduling layer, a data access pattern layer, and a big data application layer. The framework prototype has been designed and implemented on the widely used distributed hybrid storage system named Alluxio. To meet the demands of the big data application layer, on the one hand, we designed a couple of cache eviction policies and promotion policies covering various access patterns on the cache migration policy layer (several proposed eviction policies have been adopted by the Alluxio open‐source community). On the other hand, two adaptive cache policy scheduling algorithms for selecting appropriate policies in various scenarios are designed and implemented on the cache policy adaptive scheduling layer. The scheduling algorithms are designed based on the hit ratio statistics and data access pattern model prediction, respectively. Experimental results show that the proposed cache policies are very effective for various big data applications, such as Spark SQL. The proposed cache policy scheduling algorithms with various eviction policies can improve around 20% hit ratio than that with a single eviction policy. [ABSTRACT FROM AUTHOR]

To investigate drag reduction by a surfactant in a zero‐pressure gradient flat‐plate turbulent boundary layer flow, the velocities were measured by a two‐component laser Doppler velocimeter, and the buildup as well as relaxation of micelle shear‐induced structures in a simple shear flow was then analyzed by a strain‐controlled rheometer through applying and releasing a given constant shear strain rate. The surfactant was cetyltrimethyl ammonium bromide mixed with sodium salicylate as a counterion in a molar ratio of 1:2 at 60 and 100 ppm by weight. It has been found that the drag reduction rate first increases and then decreases with decreasing wall shear stress in the streamwise direction for the two concentrations of solutions, which is totally different with that in a pipe flow. In addition, the drag reduction in a lower concentration solution boundary layer flow reaches the maximum earlier. Moreover, a shorter buildup time for the micelle shear‐induced structures makes the maximal drag reduction reach earlier in surfactant solution boundary layer flows. [ABSTRACT FROM AUTHOR]