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Brain tumor accounts for about 1.6% of incidence and 2.5% of mortality of all tumors, and the median survival for brain tumor patients is only about 20 months. The treatment for brain tumor still faces many challenges, such as the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), the overexpressed efflux pumps, the infiltration, invasion, high heterogeneity of tumor cells, drug resistance and immune escape caused by tumor microenvironment (TME) and cancer stem cells (CSC). This review attempts to clarify the challenges for multi-functional nano drug delivery systems (NDDS) to cross the BBB and target the cancer cells or organelles, and also provides a brief description of the different types of targeted multi-functional NDDS that have shown potential for success in delivering drugs to the brain. Further, this review also summarizes the research progress of multi-functional NDDS in the combination therapy of brain tumors from the following sections, the combination of chemotherapy drugs, chemotherapy-chemodynamic combination therapy, chemotherapy-immunization combination therapy, and chemotherapy-gene combination therapy. We also provide an insight into the recent advances in designing multi-functional NDDS for combination therapy. [ABSTRACT FROM AUTHOR]

In this study, based on the effect of compounds on the activation of NF-κB and NO release, compound 51 was discovered as the best one with NO release inhibition IC50 value was 3.1 ± 1.1 μM and NF-κB activity inhibition IC50 value was 172.2 ± 11.4 nM. Compound 51 could inhibit the activation of NF-κB through suppressing phosphorylation and nuclear translocation of NF-κB, and suppress LPS-induced inflammatory response in RAW264.7 cells, such as the over-expression of TNF-α and IL-6, which were target genes of NF-κB. This compound also showed preferable anti-inflammatory activity in vivo, including alleviating significantly gastric distention and splenomegaly caused by LPS stimulation, reducing the level of oxidative stress induced by LPS, and inhibiting the expression of IL-6 and TNF-α in serum. Thus, it's reasonable to consider that this compound is a promising small molecule with anti-inflammatory effect for inhibiting the NF-κB signalling pathway. [ABSTRACT FROM AUTHOR]

To assess serum 25-hydroxyvitamin D3 (25(OH)D3), fibroblast growth factor 23 (FGF23), and C1q/tumor necrosis factor-related protein-3 (CTRP3) levels in nondialysis chronic kidney disease (CKD) patients and their relationship with coronary artery calcification (CAC). One hundred and twenty-eight patients diagnosed with CKD were selected and all underwent cardiac computed tomography. CAC was assessed using the Agatston score, and coronary artery calcification score (CACs) >10 was identified as CAC. The differences in serum 25(OH)D3, FGF23, and CTRP3 levels between the CAC and non-CAC groups were analyzed. Their correlation with CACs was assessed by Spearman's analysis, and logistic regression analysis was used to find risk factors for CAC. Compared to the non-CAC group, the CAC group was older (64.21 ± 9.68 years), with a higher percentage of hypertension (93.10%) and diabetes (63.80%) and higher levels of serum CTRP3 [1079.20 (644.4–1567.2) ng/mL]. However, there was no significant difference in serum 25(OH)D3 and FGF23 between these two groups. The high level CTRP3 group had a higher prevalence of CAC (61.5%). Logistic regression results showed that age, diabetes, decreased 25(OH)D3 (odds ratio (OR) = 0.95, p =.030) and high levels of CTRP3 (OR = 3.19, p =.022) were risk factors for CAC in nondialysis CKD patients. Serum CTRP3 levels progressively increased with the progression of kidney disease, while 25(OH)D3 levels progressively decreased. Decreased 25(OH)D3 and high levels of CTRP3 are associated with CAC in patients with nondialysis CKD. [ABSTRACT FROM AUTHOR]

Studies have shown the inhibitory effect of microRNA-34a on proliferation, migration, and invasion of oral squamous cell carcinoma. However, the lack of a safe and effective delivery system limits the clinical application of microRNA-34a in oral cancer treatment. An exosome is a small extracellular vesicle that mediates intercellular communication by delivering proteins, nucleic acids, and other contents, and functions as a natural drug delivery carrier. Here, we aimed to explore whether exosomes could be used to load microRNA-34a via co-incubation and further used to treat OSCC. Ultracentrifugation was used to obtain exosomes derived from HEK293T cells and the extracted exosomes were analyzed via transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Subsequently, we loaded cholesterol-modified microRNA-34a into HEK293T cell exosomes by co-incubation. Then, PKH67 and Cy3 co-labeled exo-microRNA-34a were co-incubated with HN6 cells and exosome entry into the HN6 cells was observed using a confocal laser scanning microscope. The cell proliferation, migration, and invasion were assessed by CCK-8 and Transwell assay analysis. SATB2 expression in HN6 cells was analyzed via western blotting. In this study, cholesterol-modified microRNA-34a was loaded into exosomes of HEK293T cells by co-incubation. The microRNA-34a-loaded exosomes were secreted from HEK293T cells and were absorbed by HN6 oral squamous carcinoma cells. Further, microRNA-34a-loaded exosomes led to a significant inhibition of HN6 cell proliferation, migration, and invasion by down regulating SATB2 expression. These results report a new delivery method for microRNA-34a, providing a new approach for the treatment of oral cancer. [ABSTRACT FROM AUTHOR]

To evaluate the feasibility of using an intrarectal Foley catheter during ultrasound-guided high-intensity focused ultrasound (US-HIFU) in patients with benign uterine diseases of the posterior wall beyond the HIFU therapeutic range. Patients were treated with US-HIFU and lesion changes were monitored using contrast-enhanced MRI from June 2020 to September 2021. A Foley catheter was inserted into the rectum to facilitate a successful US-HIFU ablation. Complications and lesion responses were recorded during the treatment and follow-up. Thirteen patients with 14 lesions beyond the device's treatable area were enrolled. The average placement time and insertion depth of the intrarectal Foley catheter was 7.6 ± 2.7 min and 23.2 ± 7.6 cm, respectively. A median of 50 mL degassed water was injected into the Foley catheter balloon. All 14 lesions were successfully pushed into a treatable area and subjected to HIFU. The average treatment time, irradiation time, and total therapeutic energy of HIFU were 44.2 ± 17.3 min, 394.4 ± 295.7 s, and 73.3 ± 46.6 kJ, respectively. The mean non-perfusion volume (NPV) in all treated lesions was 23.2 ± 19.2 cm3, and the mean NPV ratio was 57.8 ± 16.9%. Major complications were not observed. Intrarectal Foley catheter-assisted US-HIFU is effective and safe. Its clinical application could benefit patients with benign uterine diseases outside the HIFU therapeutic range. [ABSTRACT FROM AUTHOR]

In this paper, the aerodynamic noise of a centrifugal fan with an eccentric impeller is investigated and analyzed by adopting a hybrid method combining detached-eddy simulation and the acoustic finite element method (FEM). The impeller-eccentric effect of high-speed centrifugal fans, frequently ignored in theoretical studies, is objective in practical engineering applications owing to machining and installation errors, which have a significant influence on flow characteristics and subsequently noise characteristics. An impeller-whirling model combined with the sliding mesh method is introduced to obtain the actual flow with an eccentric impeller. First, the internal flow field handled with different eccentricities is investigated. The total pressure and internal efficiency decline, and the flow field near the leading edge shows intense unsteadiness, inducing a rise in the pressure fluctuation amplitude at the rotating frequency (RF) in both impeller flow passage and volute domain. Second, the variational formulation of Lighthill's analogy is implemented by acoustic FEM to better account for the interaction between the solid surface and aerodynamic sound, capturing a contribution by turbulence noise at the second RF. Under eccentric conditions, the sound source intensity shows a circumferential non-uniform distribution in a similar region to the flow field. The calculated sound pressure level captures the variation in the experimental result, which shows an obvious rise at RF induced by the impeller-eccentric effect. The characteristics of the noise spectrum and sound directivity change significantly, and the overall sound pressure level rises with the increase in eccentricity. This study provides an effective simulation strategy for predicting the aerodynamic noise of centrifugal fans under realistic conditions. [ABSTRACT FROM AUTHOR]

This paper investigates the hydrodynamic characteristic of a single-stage centrifugal pump with inlet inducer and outlet Radial Guided Vanes (RGVs) influenced by the clocking effect for the first time. Different from general ones, the outlet RGVs in this paper have specificities. The hydraulic performance and dynamic characteristics of the centrifugal pump are numerically studied and validated by experiments. The results indicate that there is an optimum position of RGVs that can not only increase the pump head and efficiency but also reduce the pressure fluctuation intensity. A non-dimensional parameter describing the velocity non-uniformity of the impeller outlet is first proposed, which is negatively related to the pump's hydraulic performance. The clocking position of the RGVs will affect the velocity homogeneity at the impeller outlet, and further influence the hydraulic characteristics of the pump. Besides, the clocking effect of outlet RGVs mainly affects the amplitudes of BPF for both the pressure fluctuation and radial force, and the most obvious frequency of pressure pulsation and radial force is 3 BPF correlating with the inlet inducer. It is recommended to install the volute-tongue tip near the middle of two vanes. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most aggressive tumors associated with a poor clinical prognosis, weakly effective therapeutic options. Therefore, there is a strong impetus to discover new therapeutic targets in pancreatic cancer. In the present study, we first demonstrated that TSPAN1 is upregulated in pancreatic cancer and that TSPAN1 depletion decreases pancreatic cancer cell proliferation in vitro and in vivo. TSPAN1 expression was correlated with poor overall survival of pancreatic cancer patients. Moreover, we demonstrated that TSPAN1 is a novel positive regulator of macroautophagy/autophagy characterized by decreased LC3-II and SQSTM1/p62 expressions, inhibited puncta formation of GFP-LC3 and autophagic vacuoles. We also demonstrated that tspan1 mutation impaired autophagy in the zebrafish model. Furthermore, we showed that TSPAN1 promoted autophagy maturation via direct binding to LC3 by two conserved LIR motifs. Mutations in the LIR motifs of TSPAN1 resulted in a loss of the ability to induce autophagy and promote pancreatic cancer proliferation. Second, we discovered two conservative TCF/LEF binding elements present in the promoter region of the TSPAN1 gene, which was further verified through luciferase activity and ChIP assays. Furthermore, TSPAN1 was upregulated by FAM83A through the canonical WNT-CTNNB1 signaling pathway. We further demonstrated that both TSPAN1 and FAM83A are both direct targets of MIR454 (microRNA 454). Additionally, we revealed the role of MIR454-FAM83A-TSPAN1 in the proliferation of pancreatic cancer cells in vitro and in vivo. Our findings suggest that components of the MIR454-FAM83A-TSPAN1 axis may be valuable prognosis markers or therapeutic targets for pancreatic cancer. Abbreviations: AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; APC: APC regulator of WNT signaling pathway; ATG: autophagy related; AXIN2: axin 2; BECN1: beclin 1; CCND1: cyclin D1; CSNK1A1/CK1α: casein kinase 1 alpha 1; CTNNB1/β-catenin: catenin beta 1; DAPI: 4ʹ6-diamino-2-phenylindole; EBSS: Earle's balanced salt solution; EdU: 5-ethynyl-20-deoxyuridine; FAM83A: family with sequence similarity 83 member A; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GSEA: gene set enrichment analysis; GSK3B: glycogen synthase kinase 3 beta; IHC: immunohistochemical; LAMP1: lysosomal associated membrane protein 1; LIR: LC3-interacting region; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MIR454: microRNA 454; miRNA: microRNA; MKI67: antigen identified by monoclonal antibody Ki 67; MTOR: mechanistic target of rapamycin kinase; MTT: 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; MYC: MYC proto-oncogene, bHLH transcription factor; OS: overall survival; PDAC: pancreatic ductal adenocarcinoma; RAB7A: RAB7A, member RAS oncogene family; shRNA: short hairpin RNA; SQSTM1: sequestosome 1; TBE: TCF/LEF binding element; TCGA: The Cancer Genome Atlas; TCF/LEF: transcription factor/lymphoid enhancer binding factor; TCF4: transcription factor 4; TSPAN1: tetraspanin 1; TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick end labeling; UTR: untranslated region; WT: wild type. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy plays key roles in development, oncogenesis, and cardiovascular and metabolic diseases. Autophagy-specific class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1) is essential for autophagosome formation. However, the regulation of this complex formation requires further investigation. Here, we discovered that STYK1 (serine/threonine/tyrosine kinase 1), a member of the receptor tyrosine kinases (RTKs) family, is a new upstream regulator of autophagy. We discovered that STYK1 facilitated autophagosome formation in human cells and zebrafish, which was characterized by elevated LC3-II and lowered SQSTM1/p62 levels and increased puncta formation by several marker proteins, such as ATG14, WIPI1, and ZFYVE1. Moreover, we observed that STYK1 directly binds to the PtdIns3K-C1 complex as a homodimer. The binding with this complex was promoted by Tyr191 phosphorylation, by means of which the kinase activity of STYK1 was elevated. We also demonstrated that STYK1 elevated the serine phosphorylation of BECN1, thereby decreasing the interaction between BECN1 and BCL2. Furthermore, we found that STYK1 preferentially facilitated the assembly of the PtdIns3K-C1 complex and was required for PtdIns3K-C1 complex kinase activity. Taken together, our findings provide new insights into autophagy induction and reveal evidence of novel crosstalk between the components of RTK signaling and autophagy. Abbreviations: AICAR: 5-aminoimidazole-4-carboxamide ribonucleotide; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; Bre A: brefeldin A; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; DAPI: 4′,6-diamidino-2-phenylindole; EBSS: Earle's balanced salt solution; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GSEA: gene set enrichment analysis; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MAPK8/JNK1: mitogen-activated protein kinase 8; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; MTT: 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; qRT-PCR: quantitative reverse transcription PCR; RACK1: receptor for activated C kinase 1; RUBCN: rubicon autophagy regulator; siRNA: small interfering RNA; SQSTM1: sequestosome 1; STYK1/NOK: serine/threonine/tyrosine kinase 1; TCGA: The Cancer Genome Atlas; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; UVRAG: UV radiation resistance associated; WIPI1: WD repeat domain, phosphoinositide interacting 1; ZFYVE1: zinc finger FYVE-type containing 1 [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of cooking and in vitro digestion on antioxidant activity of peptides in duck meat after 7 days postmortem aging. The 1, 1-diphenyl-2- picrylhydrazyl (DPPH) free radical scavenging activity and reducing power of the obtained peptides were evaluated. Results showed that the cooked sample possessed higher antioxidant activity than the raw sample and upon cooking at different temperatures, sample aged for 7 days had significantly higher antioxidant activity than that of unaged (day 0). The samples which showed higher antioxidant activity after cooking (65°C–30 min, 100°C–20 min, 121°C–10 min) were selected for in vitro digestion, and it is found that their DPPH radical scavenging activity decreased significantly but the reducing power increased significantly after gastrointestinal digestion. These results show the potential of aged duck meat as a good source of antioxidant peptides with high bioactivity after cooking and gastrointestinal digestion. [ABSTRACT FROM AUTHOR]

Based on our previous docking model, in order to carry out more rational drug design, totally 82 vinyl sulfonyl fluorides, including some 2-(hetero)arylethenesulfonyl fluorides and 1,3-dienylsulfonyl fluorides derivatives as potential human telomerase inhibitors were designed and synthesised. The in vitro anticancer activity assay showed that compound 57 (1E,3E)-4-(4-((E)-2-(fluorosulfonyl)vinyl)phenyl)buta-1,3-diene-1-sulfonyl fluoride exhibited high activity against A375 and MDA-MB-231 cell lines with IC50 1.58 and 3.22 µM, but it manifested obvious un-toxic effect against GES-1 and L-02 with IC50 with IC50 values less than 2.00 mM. By the modified TRAP assay, some compounds including 57 exhibited potent inhibitory activities against telomerase with IC50 values of 0.71-0.97 µM. [ABSTRACT FROM AUTHOR]

To ensure the safety of bridges, the comfort of pedestrians and vehicles on bridges, the vortex-induced forces on flat-steel-box girders need to be investigated. The total vortex-induced forces integrated on the surfaces of girders have been studied extensively. This study will be mainly focused on the characteristics of surface distributed vortex-induced force, which can be beneficial to the vortex-induced vibration (VIV) reduction with local aerodynamic optimization. Computational Fluid Dynamics (CFD) method is employed for the simulation of the VIVof a flat-steel-box girder. The simulation results are verified through the comparison with the results of corresponding wind tunnel test. A self-adaptive nonlinear fitting method is proposed to determine the vortex-induced force model. A vortex-induced force contribution factor is defined to account the contribution of the components and the surface location. Based on the surface distributed vortex-induced force analysis, several conclusions are made. The vortex-induced force presents a fairly strong multiple-frequency characteristic, and the high-order terms should be carefully considered. Most energy of the VIV comes from the linear and third-order aerodynamic damping terms. In terms of location, the roof takes most of the aerodynamic damping and the total vortex-induced force. The flow separation around the underside upstream corner, the underside downstream corner and the middle downstream comer lead to large third-order aerodynamic damping term. The flow separation around the underside upstream corner has great contribution to the linear aerodynamic stiffness term. [ABSTRACT FROM AUTHOR]

A series of new trimethoxyphenyl-4H-chromen derivatives as telomerase inhibitors through regulation dyskerin were designed and synthesised. The anticancer activity assay in vitro showed that compound 5i 3-(4-(4-isonicotinoylpiperazin-1-yl)butoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one exhibited high activity against Hela, SMMC-7721, SGC-7901, U87 and HepG2 cell lines. Compound 5i also showed potent inhibitory activity against telomerase. The further results confirmed this title compound could significantly improve pathological changes induced rat hepatic tumor in vivo. Preliminary mechanisms showed that compound 5i inhibited telomerase activity through decrease expression of dyskerin. [ABSTRACT FROM AUTHOR]

Aberrant methylation of tumour suppressor genes is associated with the progression to a blast crisis in chronic myeloid leukaemia (CML). Methyl-CpG-binding domain protein 2 (MBD2) has been studied as a “reader” of DNA methylation in many cancers, but its role in CML is unclear. We constructed cell models of a homozygous deletion mutation of MBD2 using gene-editing technology in K562 cells and BV173 cells. Here, we demonstrated that the deletion of MBD2 inhibited cell proliferation capacity in vitro. MBD2 deletion also significantly inhibited K562 cell proliferation in a xenograft tumour model in vivo. Additionally, the JAK2/STAT3 signalling pathway, which is abnormally active in CML, was inhibited by MBD2 deletion, and MBD2 deletion could up-regulate the expression of SHP1. In conclusion, our findings suggest that MBD2 is a candidate therapeutic strategy for the CML blast phase. [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested that bidirectional regulation of cell proliferation is one important effect of TGF-β1 in wound healing. Increased c-Ski expression plays a role in promoting fibroblast proliferation at low TGF-β1 concentrations, but the mechanism by which low TGF-β1 concentrations regulate c-Ski levels remains unclear. In this study, the proliferation of rat primary fibroblasts was assessed with an ELISA BrdU kit. The mRNA and protein expression and phosphorylation levels of corresponding factors were measured by RT-qPCR, immunohistochemistry or Western blotting. We first found that low TGF-β1 concentrations not only promoted c-ski mRNA and protein expression in rat primary fibroblasts but also increased the phosphorylation levels of Extracellular Signal-Regulated Kinases (ERK) and cAMP response element binding (CREB) protein. An ERK kinase (mitogen-activated protein kinase kinase, MEK) inhibitor significantly inhibited ERK1/2 phosphorylation levels, markedly reducing c-Ski expression and CREB phosphorylation levels and abrogating the growth-promoting effect of low TGF-β1 concentrations. At the same time, Smad2/3 phosphorylation levels were not significantly changed. Taken together, these results suggest that the increased cell proliferation induced by low TGF-β1 concentrations mediates c-Ski expression potentially through the ERK/CREB pathway rather than through the classic TGF-β1/Smad pathway. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between miR-122-5p and DUSP4 and their effects on gastric cancer (GC) cell mobility and invasiveness. Methods: Abnormally expressed miRNAs and mRNAs were analyzed using microarrays. The miR-122-5p and DUSP4 mRNA expression levels in GC tissues and cells were determined by RT-qPCR. The target relationship between miR-122-5p and DUSP4 was validated by dual luciferase reporter assay. GC cell mobility and invasiveness were respectively observed by wound healing assay and transwell invasion assay. Western blot and immunohistochemistry were used for detection of the expressions of DUSP4 protein and MMP2 and MMP9 proteins related to cell invasion and migration. The migration and invasion abilities of gastric cancer cells in vivo were evaluated according to the number of lung metastatic nodules in mice. Results: The expression of miR-122-5p in GC tissues and cells was significantly down-regulated, whereas DUSP4 expression was up-regulated. Bioinformatics prediction strategies and dual luciferase reporter assay verified the binding sites of miR-122-5p on 3′UTR of DUSP4 and the target relationship between miR-122-5p and DUSP4. Overexpression of miR-122-5p and knockdown of DUSP4 in BGC-823 cells observantly suppressed GC cell mobility and invasiveness, whereas downregulation of miR-122-5p expression promoted cell metastasis. MiR-122-5p inhibited GC cell mobility and invasiveness and pulmonary tumor metastasis via downregulation of DUSP4. Conclusion: MiR-122-5p restrained migration and invasion abilities of GC cells by repressing DUSP4. [ABSTRACT FROM AUTHOR]

Reservoir impoundment and water fluctuations have endangered the stability of the reservoir bank slopes, which have experienced several small-scale shallow slides/collapses and few large-scale slopes with failures/deformations. Field investigations, unmanned aerial vehicle technology and site displacement monitoring dates are used to study the spatiotemporal distribution and mechanisms of the reservoir landslides within the Dagangshan reservoir. The reservoir landslides can be divided into two main types: shallow small-scale slides and unstable deformation slopes, which are clearly associated with reservoir impoundment and fluctuations of the water level. Small-scale slides/collapses are continually distributed along the river banks nearest to the water level, but deep-seated landslides have usually experienced a long history, and some obvious precursor phenomena may exist in the slopes. According to the recognition of deformational and failure evolutionary processes of large-scale slopes, and based on hydrology and geomechanics, two types of potential failure models (creep-shear-tension failure and toppling-tensile-shear model) are proposed to interpret the mechanisms of the deformation slopes in the Dagangshan reservoir. Furthermore, some preliminary discussion is presented concerning the non-significant development of landslides in the Dagangshan reservoir that are also associated with smaller water fluctuations due to the daily regulation type of the reservoir. [ABSTRACT FROM AUTHOR]

Elaiophylin is a natural compound and a novel and potent inhibitor of late stage autophagy with outstanding antitumor activity in human ovarian cancer cells. However, the possible biologic effects and functional linkage between elaiophylin and multiple myeloma (MM) have not been explored. This study aimed to assess the effect of elaiophylin on MM cells with mutant TP53 and the possible molecular mechanism. The results suggested that elaiophylin exerted anti-myeloma activity by inducing apoptosis and proliferation arrest. As expected, elaiophylin blocked autophagy flux in MM cells. Subsequently, persistent activation of endoplasmic reticulum (ER) stress was induced. Moreover, the apoptotic effect was to some extent attenuated by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Further studies indicated that elaiophylin effectively suppressed MM cell growth without obvious side effects in zebrafish embryo and mouse xenograft models. Taken together, our data are the first to demonstrate that exposure of human MM cells with mutant TP53 to elaiophylin blocked autophagy flux and thus induced cell death, which partially involved ER stress-associated apoptosis. Targeted disruption of the cellular protein handling system by elaiophylin is therefore a promising therapeutic strategy for overcoming incurable MM, even when TP53 mutations are present. [ABSTRACT FROM PUBLISHER]

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It is clear that heat shock protein 70 (HSP70) is responsible for stressful conditions. However, the expression level and profile of HSP70 during cold stress are still unknown. In this study, the expression profile of HSP70 in the heart, liver, muscle and spleen of Huainan partridge chicken exposed to low temperature was investigated. HSP70 expression was showed tissue-dependent with highest expression in muscle, followed by liver and heart; conversely, there was no evidence of changes in spleen, where there were two expression peaks during cold stress, before 3 and after 72 h, respectively. The plasma creatine kinase (CK) activity exhibited a significant increase (P<0.01) after 1 h of cold stress exposure, and then decreased till to the lowest level after 72 h of cold stress exposure. On the other hand, nitric oxide content arose and reached the peak level (P<0.01) after 3 h of cold stress exposure, and then suddenly decreased to the original level with the duration of exposure time. In conclusion, mRNA expression of HSP70 turned out to be tissueand time-dependent in muscle, liver and heart in broilers under cold stress exposure. The distinct expression of HSP70 suggested that highenergy supply and balance of CK activity might be responsible for the HSP70 high expression. poultry. Little neglect would cause body and/or uniformity not to meet the professional standards, and then affect the production performances (Yahav, 2000). The extent of the deleterious effects of cold stress is determined not only by its magnitude but also by the status of cellular defense systems, particularly the cellular anti-oxidation. Both biotic and abiotic stress can induce nitric oxide (NO) synthesis and in turn mediate the reaction of hydrogen peroxide and accelerate oxidation. Such oxidation will increase the number of reactive oxygen metabolites (ROM) that can attack and irreparably damage membrane composition and permeability (Omar and Pappolla, 1993). Chickens have high metabolic rate but no sweat glands, so they are more sensitive to ambient temperatures. Stress responses and damage of liver and heart occurred in broilers, which were suddenly exposed to low temperatures (Lin et al., 2006). A common event observed in chicken during thermo-resistance was the high expression of heat shock protein (HSP) genes (Mahmoud et al., 2003; Hagiwara et al., 2007). Many studies have shown the importance of HSPs for the survival of cells under stress conditions. As universal cytoprotective proteins, HSPs expression may enhance stress tolerance and thereby increase the survival rate of stressed cells (Latchman, 2001). However, studies on the expression of heat shock protein 70 (HSP70) during cold stress were highly diverse. Some suggested that HSP70 only expressed after rewarming (Liu et al., 1995; Laios et al., 1997; Gabriel et al., 2003), and others implied a tissue-dependent expression (Givisiez et al., 2001). The expression profile of HSP70 in chicken tissue during cold stress is still unknown. In the present study, the mRNA expression level of HSP70 in the heart, liver, muscle and spleen of Huainan partridge chicken - a Chinese indigenous breed that was subjected to cold stress - was investigated. Plasma NO and creatine kinase (CK) were also measured for monitoring of oxidative stress and cell membrane damage. [ABSTRACT FROM AUTHOR]

Indigenous chickens from various part of China, due to different feather characters, always performed differently when countered with cold stress. In this study, the effects of long term hypothermia on serum hormones (triiodothyronine, thyroxine and insulin) and activity of plasma enzymes (Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, creatine kinase and lactic dehydrogenase) were studied in two indigenous broiler breeds, Huainan partridge (H) and Wenchang (W) chickens. Chickens in 20°C±2°C were compared with those subjected to moderate (15°C±2°C) and severe low temperature (10°C±2°C) for one week. Long-term hypothermia elevated plasma insulin and reduced T4 in W, deceleratedinsulin and increased T4 in H, while T3 did not change in the two breeds. Plasma enzymes AST, LDH and CK decreased in the two breeds and ALT only decreased in We exposed to cold stress. A significantly decreased body weight gain of H and no variations in W at low temperature were observed. However, a trend of decreased weight gain in W was observed when bred under low temperature condition. Follicle density and diameter were compared in the two breeds with back density in H significantly higher than W and diameter from back of H significantly smaller than W, while much larger than the latter at latero-abdominal part. We investigated the pattern of serum biological change, follicle diameter and density under cold stress condition in two indigenous broiler breeds from different areas of China to provide informative guidance for broiler production and indications in breeding of cold resistant breed. [ABSTRACT FROM AUTHOR]

The feasibility of non-destructive measurement of internal quality indices of intact pear fruit using visible and near-infrared (Vis/N1R) spectrometric techniques was studied. In the wavelength region from 350 to 1800 nm, calibration models relating Vis/NIR spectra to soluble solids content (SSC) and firmness were developed based on multilinear regression (MLR), principal component regression (PCR) and partial least squares regression (PLSR) with respect to the logarithms of the reflectance reciprocal log (1/R), its first derivative D1 log (1/R) and its second derivative D2 log (1/R). The best combination, based on the reliable and robust models obtained, was the PLS models with respect to log (1/R) at an equatorial position of the fruit. Prediction with the PLS model with respect to log (1/R) resulted in correlation coefficients (rp) of 0.9121 and 0.8541, and root mean standard error of prediction (RMSEP) of 0.6619 and 1.2324 for SSC and firmness, respectively. The experimental results indicate that the Vis/NIR spectrometric technique could provide an accurate, reliable and non-destructive method for assessing internal quality indices of pear fruit, especially for SSC. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genomes of two Sri Lankan junglefowl (Gallus lafayetti: CJF) individuals were sequenced by using next-generation sequencing technique. Samples were collected from Rathnapura and Pelmadulla areas in Sri Lanka. The complete mitochondrial DNA is 16,839 bp in length, with a typical mitogenome structure composed of a non-coding control region, 22 tRNA, two rRNA, and 13 protein-coding genes. Overall base composition is 30% A, 23.9% T, 32.3% C, and 13.6% G indicating high content of 54.0% A + T for both individuals. Phylogenetic analysis reveals that CJF samples cluster with the clade of the green junglefowl (Gallus varius) and red junglefowl (Gallus gallus) than to grey junglefowl (Gallus sonerattii: GyJF). This result can be subsequently used to provide essential information for junglefowl evolution. [ABSTRACT FROM AUTHOR]