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Metal chalcogenides, as a new class of semiconductor materials, have a broad range of applications in synthetic chemistry due to their rich structures and excellent properties. We have synthesized two selenoantimonates A4Zn2Sb2Se7 [A = Rb(1), Cs(2)] under solvothermal conditions in the visible region using a band gap optimization strategy with alkali metals as structure-directing agents. Compounds 1 and 2 have a two-dimensional layered structure consisting of charge-balanced Rb+(1) or Cs+ (2) cations and [Zn2Sb2Se7]4- anions with novel 20-membered rings (20-MR) [Zn6Sb4Se10] with an aperture of 5.6949 × 13.7741 Ų formed in the middle. Furthermore, we have investigated the crystal structure, band gap, photoelectronic properties, and energy band structure. [ABSTRACT FROM AUTHOR]

This research study presents a novel approach to enhance the efficiency and performance of Battery Energy Storage Systems (BESSs) within microgrids, focusing particularly on the integration of wind energy. The inherent inconsistency and unpredictability of Renewable Energy Resources (RERs) necessitate the development of effective integration solutions to accommodate them. Our article provides a customized iteration of the metaheuristic algorithm referred to as the Contracted fitness-dependent optimizer. The proposed methodology involves the adaptive adjustment of migration rates based on habitat suitability indices, while also considering variations in perturbations. The incorporation of Lévy flight and an elimination phase significantly enhances the algorithm’s efficacy in problem-solving. In order to establish the superiority of our strategy over alternative optimization approaches, we conduct simulations across diverse conditions and subsequently compare the outcomes. It was calculated that the daily scheduling cost was 235.2$ and the daily operational cost was USD 268$. In Scenario 3, the total operating expenses and arranging costs for 1 day, respectively, were determined to be 165$ and 115$. Further, the highest depth of discharge level was around 77%. Moreover, a −9.18 kW and 23.02 kW maximum charging and discharging power adjustment was made. The findings of our study emphasize the economic and operational benefits associated with appropriately sized BESSs within microgrid contexts. These advantages have the potential to enhance battery longevity and promote the development of more sustainable energy systems. [ABSTRACT FROM AUTHOR]

The Hessian fly (HF, Mayetiola destructor) is one of the destructive pests of wheat (Triticum aestivum L.) worldwide. Resistant cultivars can effectively minimize wheat damage due to this insect pest. To identify new quantitative trait loci (QTL) for HF resistance, a population of recombinant inbred lines (RILs) was developed from a cross between the HF-resistant wheat cultivar 'Chokwang' and susceptible wheat 'Ning 7840', and phenotyped for responses to HF attack. A linkage map was constructed using 1147 single nucleotide polymorphism (SNP) markers generated from genotyping-by-sequencing (GBS). One major QTL, QHf.hwwg-6BS, for HF-resistance was identified on chromosome arm 6BS, which explained up to 84.0% of the phenotypic variation and was contributed by Chokwang. Two RILs showed recombination in the candidate interval of QHf.hwwg-6BS, which delimited QHf.hwwg-6BS to a 4.75 Mb physical interval between 6,028,601 bp and 10,779,424 bp on chromosome arm 6BS of IWGSC Chinese Spring reference genome RefSeq v2.0. Seven GBS-SNPs in the candidate interval were converted into Kompetitive allele specific polymerase chain reaction (KASP) markers. Two of them, KASP-6B112698 and KASP- 6B7901215, were validated in a U.S. winter wheat panel. KASP-6B112698 was nearly diagnostic, thus can be used to screen QHf.hwwg-6BS and pyramid it with other resistance genes in breeding programs. [ABSTRACT FROM AUTHOR]

The major forms of Chinese utopia include "the Land of Bliss", the Taoist "small country with few inhabitants", the Confucian "Great Unity", Tao Yuanming's "Peach Blossom Spring", Kang Youwei's "World of Great Unity" and its modern variations. Chinese utopia has evolved from reactive poetic retreat to active political remolding. It has developed from pastness to nowness in terms of temporal orientation, and from "nowhere" to "somewhere" and then to hereness in terms of spatial orientation. Chinese utopia has strong poetic anchorage, which is determined by the Heaven-Earth-man unity. Through the mechanism of texperience shift, Chinese utopia in the modern context is often transformed into a usable cultural or spiritual icon, or national political vision, policies, blueprints and concrete social practice. A comprehensive insight into the Chinese utopian tradition helps to understand the utopian-poetic-political entanglement in China. [ABSTRACT FROM AUTHOR]

As one of the most promising technologies for next-generation lighting and displays, white organic light-emitting diodes (WOLEDs) have received enormous worldwide interest due to their outstanding properties, including high efficiency, bright luminance, wide viewing angle, fast switching, lower power consumption, ultralight and ultrathin characteristics and flexibility. In this invited review, the main parameters which are used to characterize the performance of WOLEDs are introduced. Subsequently, the state-of-the-art strategies to achieve high-performance WOLEDs in recent years are summarized. Specifically, the manipulation of charges and excitons distribution in the four types of WOLEDs (fluorescent WOLEDs, phosphorescent WOLEDs, thermally activated delayed fluorescent WOLEDs and fluorescent/phosphorescent hybrid WOLEDs) are comprehensively highlighted. Moreover, doping-free WOLEDs are described. Finally, issues and ways to further enhance the performance of WOLEDs are briefly clarified. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the association between breast cancer susceptibility gene 1 (BRCA1) expression and drug resistance in colon cancer, with the specific aim of elucidating the underlying molecular mechanisms of vincristine (VCR) resistance in tumor cells. The HCT‑8 human colon cancer cell line was used to establish the VCR‑resistant HCT‑8/V line by gradually increasing the concentration of VCR during cell culture. The relative mRNA and protein expression levels of BRCA1 in these colon cancer cell lines was assessed by reverse transcriptase‑quantitative polymerase chain reaction (RT‑qPCR) analysis and western blotting, respectively. Resistance to VCR was established in the HCT‑8/V colon cancer cells, and RT‑qPCR and western blot analysis revealed the expression of BRCA1 to be significantly higher in the VCR‑resistant cells compared with their drug‑sensitive counterparts (P<0.05). The decreased BRCA1 expression in these VCR‑resistant cells may be associated with the drug resistance frequently observed in colon cancer. [ABSTRACT FROM AUTHOR]

Twelve novel three-dimensional (3D) lanthanide metal-organic frameworks with formula {[LnK(C4N2O4S)2(H2O)2](H2O)0.5}( L n=L a(1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6), Gd (7), Tb (8)), {[Ln2K2(C4N2O4S)2(C4O4H2)2(H2O)4](H2O)} (Ln = La (9), Ce (10)), and {[Ln2(C4N2O4S)3(H2O)](H2O)} (Ln = La (11), Ce (12)), are solvothermally synthesized by reacting the 1,2,5-thiadiazole-3,4-dicarboxylate (H2tdc) ligand with the corresponding lanthanide nitrate. These compounds exhibit three different types of structures which changed from nonporous to open-framework MOFs by adjusting the reaction condi- tions. Compounds 1-8 (type I) with a moc topology are constructed of 1D zigzag chains and pillared water molecules. Fumaric acid (Fac) as the coligand is introduced in the reaction to replace the pillared water and link similar zigzag chains to assemble compounds 9 and 10 (type II) with a dia topology. Compounds 11 and 12 (type III) with the chiral space group exhibit 1D right/left helical chains along the b axis, and the helical chains alternatively link together to form 3D frameworks with a new (3,4,5)- connected topology. The luminescence study shows that compounds 5, 6, 8 display intense orange, red and green luminescence and exhibit typical Sm3+, Eu3+ and Tb3+ ion emission, respectively. Furthermore, compounds 1, 7, 9 and 11 also exhibit intense green and blue luminescence arising from the H2tdc ligand. [ABSTRACT FROM AUTHOR]

HIV-1 Tat stimulates transcription elongation by recruiting the P-TEFb (positive transcription elongation factor-b) (CycT1:CDK9) C-terminal domain (CTD) kinase to the HIV-1 promoter. Here we show that Tat transactivation also requires the Ssu72 CTD Ser5P (S5P)-specific phosphatase, which mediates transcription termination and intragenic looping at eukaryotic genes. Importantly, HIV-1 Tat interacts directly with Ssu72 and strongly stimulates its CTD phosphatase activity. We found that Ssu72 is essential for Tat:P-TEFb-mediated phosphorylation of the S5P-CTD in vitro. Interestingly, Ssu72 also stimulates nascent HIV-1 transcription in a phosphatasedependent manner in vivo. Chromatin immunoprecipitation (ChIP) experiments reveal that Ssu72, like P-TEFb and AFF4, is recruited by Tat to the integrated HIV-1 proviral promoter in TNF-a signaling 2D10 T cells and leaves the elongation complex prior to the termination site. ChIP-seq (ChIP combined with deep sequencing) and GROseq (genome-wide nuclear run-on [GRO] combined with deep sequencing) analysis further reveals that Ssu72 predominantly colocalizes with S5P-RNAPII (RNA polymerase II) at promoters in human embryonic stem cells, with a minor peak in the terminator region. A few genes, like NANOG, also have high Ssu72 at the terminator. Ssu72 is not required for transcription at most cellular genes but has a modest effect on cotranscriptional termination. We conclude that Tat alters the cellular function of Ssu72 to stimulate viral gene expression and facilitate the early S5P-S2P transition at the integrated HIV-1 promoter. [ABSTRACT FROM AUTHOR]

Two new metal–organic frameworks [Cd3(H2O)2(C5N2O4H)2·H2O] 1and [KCd(C7N2O4H5)] 2have been hydrothermally synthesized employing 4,5-imidazoledicarboxylic acid (IMDC) and 2-ethyl-4,5-imidazoledicarboxylic acid (2-EtIMDC) as organic ligands. The single-crystal structure analysis reveals that compound 1exhibits a 3-D framework, which is generated from 2-D layers pillared by 1-D chains along the c-axis. Compound 2presents a 3-D structure with 1-D channels, which are connected in a cross-like fashion by [CdN2O3] trigonal bipyramid units and 2-EtIMDC ligands. [ABSTRACT FROM AUTHOR]

Rh(tmp) reacted with two diazo compounds to give rhodium(III) porphyrin alkyls in high yields under mild conditions. Mechanistic studies showed that Rh(tmp) was coordinated with a diazo compound, which then underwent a rapid hydrogen atom abstraction via carbon−hydrogen bond activation to give Rh(tmp)H. Rh(tmp)H subsequently reacted with a second molecule of the diazo compound in the rate-determining step to give Rh(tmp) alkyl and N2. The rate law revealed that rate kRh(tmp)EDA2for ethyl diazoacetate. [ABSTRACT FROM AUTHOR]

Examines the structural transformation of manganese-containing coordination polymers using conformation change of carboxylate ligand. Selection of maleate and fumarate as ligands; Impact of ligand selection on the coordination features to manganese ions; Crystal characterization of the coordination features of manganese ions.

To enhance the therapeutic efficiency and reduce side effects from drug delivery and chemotherapy, image-guided nanoscale systems have attracted tremendous attention in recent decades. In this study, we developed a novel method to fabricate a colchicine/gadolinium-loaded tubulin self-assembly nanocarrier (Col-Gd@Tub NC) for the image-guided chemotherapy of glioma. The Col-Gd@Tub NCs were spontaneously formed via tubulin self-assembly and were subsequently functionalized by colchicine and gadolinium elements. These resultant Col-Gd@Tub NCs with a diameter of 45 nm exhibited uniform particle size distribution and favorable stability without any leakage of gadolinium in water. Meanwhile, the introduction of gadolinium endowed Col-Gd@Tub NCs with high T1-weighted MRI performance in vitro. After tail vein injection, Col-Gd@Tub NCs exhibited excellent MRI contrast capability and relatively long circulation time (∼12 h) and were finally cleared out from the bladder. More significantly, the binding colchicine still exerted an anti-tumor effect after the Col-Gd@Tub NCs were taken up by the tumor cells. These results show that the Col-Gd@Tub NCs may be served as a versatile nanoscale platform for the integration of biomedical imaging probes and therapeutic molecules for tumor therapy. [ABSTRACT FROM AUTHOR]

Leucine-rich α-2 glycoprotein 1 (LRG1), a secreted glycoprotein, has been identified as significantly upregulated in renal fibrosis, potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pathways. Herein, utilizing our developed LRG1-targeting peptide for LRG1 recruitment and lenalidomide for E3 ubiquitin ligase engagement, we developed an advanced proteolysis targeting chimera, ET TAC-2, specifically designed for LRG1 degradation. Our cellular degradation assays validated that ET TAC-2 effectively degraded LRG1 through a proteasome-dependent mechanism, achieving halfmaximal degradation at a concentration of 8.38 μM. Furthermore, anti-fibrotic experiments conducted both in vitro and in vivo revealed that ET TAC-2 efficiently induced LRG1 degradation in fibrotic kidneys. This action effectively inhibited the TGF-β-Smad3 signaling pathway and diminished the secretion of fibrosis-associated proteins, consequently attenuating the progression of renal fibrosis. Our study highlights the pivotal role of LRG1 in renal fibrosis and positions ET TAC-2 as a promising therapeutic candidate for targeted LRG1 intervention. [ABSTRACT FROM AUTHOR]

Wheat leaf rust, caused by Puccinia triticina ( Pt ), is one of the most severe fungal diseases on wheat globally. Rational utilization of wheat leaf rust resistance ( Lr ) genes is still the best choice for control this disease. Wheat seedlings carrying Lr19 showed a high resistance phenotype to all Pt races in China. So far, all the cloned seedling Lr genes including Lr1 , Lr10 and Lr21 , encode protein with NBS-LRR domain. In this study, a wheat gene with NBS-LRR domain from previously established Lr19 -resistance-related cDNA library was cloned and designated as TaRGA19 . Full length of this gene was amplified by rapid amplification of cDNA ends (RACE). By blast against IWGSC wheat genome database, we have noticed that TaRGA19 was located on chromosome 2DS, which was different from Lr19 located on chromosome 7DL. Compared with susceptible Thatcher line, expression level of TaRGA19 was upregulated in wheat isogenic lines carrying Lr19 (TcLr19) after inoculation of Pt race THTS. By particle bombardment, TaRGA19-GFP fused protein was localized on plasma membrane of epidermal cells. Using virus-induced gene silencing (VIGS), TaRGA19 -knockdown plants of TcLr19 showed reduced resistance and few sporulation phenotype upon Pt challenge. Further histological observation indicated that Pt hyphal growth at the infection sites was less suppressed in the TaRGA19 -knockdown plants. In conclusion, we speculate this TaRGA19 gene was involved in the Lr19- mediated resistance to wheat leaf rust along with other components. [ABSTRACT FROM AUTHOR]

The Ski-interacting protein SKIP/SNW1 functions as both a splicing factor and a transcriptional coactivator for induced genes. We showed previously that transcription elongation factors such as SKIP are dispensable in cells subjected to DNA damage stress. However, we report here that SKIP is critical for both basal and stress-induced expression of the cell cycle arrest factor p21Cip1. RNAi chromatin immunoprecipitation (RNAi-ChIP) and RNA immunoprecipitation (RNA-IP) experiments indicate that SKIP is not required for transcription elongation of the gene under stress, but instead is critical for splicing and p21Cip1 protein expression. SKIP interacts with the 3' splice site recognition factor U2AF65 and recruits it to the p21Cip1 gene and mRNA. Remarkably, SKIP is not required for splicing or loading of U2AF65 at other investigated p53-induced targets, including the proapoptotic gene PUMA. Consequently, depletion of SKIP induces a rapid down-regulation of p21Cip1 and predisposes cells to undergo p53-mediated apoptosis, which is greatly enhanced by chemotherapeutic DNA damage agents. ChIP experiments reveal that SKIP is recruited to the p21Cip1, and not PUMA, gene promoters, indicating that p21Cip1 gene-specific splicing is predominantly cotranscriptional. The SKIP-associated factors DHX8 and Prp19 are also selectively required for p21Cip1 expression under stress. Together, these studies define a new step that controls cancer cell apoptosis. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that Bit1 exerts different roles in the development and progression of human cancers. Although Bit1 was highly exhibited in ESCC tissues in our previous study, its roles and molecular mechanisms implicated in development and progression of ESCC remain unknown. Methods: Bit1 protein expression in ESCC cell lines and normal esophageal epithelial cell was detected by Western blotting. Bit1 protein expression mediated by Bit1 shRNA was investigated by Western blotting. MTT, migration assay, invasion experiment, ELISA and Flow cytometry were utilized to determine the effects of Bit1 knockdown on cell proliferation, migration, invasion and apoptosis, respectively. A xenograft model was used to examine in vivo tumourigenicity, and immunohistochemistry and TUNEL were utilized to evaluate the related protein expression and apoptosis. Gene microarray was determined by Agilent SurePrint G3 Human GE 8 × 60 K Microarray, the interaction of Bit1 and FAK proteins were detected by Immunoprecipitation and the key protein expressions of FAK-paxillin pathway were detected by Western blotting. Results: We found Bit1 expression in all human ESCC cell lines tested was significantly higher than that in normal esophageal epithelial cell Het-1A (P < 0.05), in which EC9706 presented the highest Bit1 level. Bit1 protein level was significantly downregulated at day 1 after transfection with specific shRNA against Bit1 (P < 0.05). At days 2 and 3, Bit1 level reached the lowest value after transfection with Bit1 shRNA. Moreover, Bit1 depletion contributed to growth inhibition in vitro and in vivo, reduced cell migration and invasion abilities, and induced cell apoptosis in EC9706 and TE1 cells. More importantly, Bit1 downregulation significantly lowered Bcl-2 and MMP-2 levels in EC9706 xenografted tumor tissues, meanwhile triggered apoptosis after treatment with different doses of Bit1 shRNA. Further gene microarray revealed that 23 genes in Bit1-RNAi group were markedly downregulated, whereas 16 genes were obviously upregulated. Notably, Bit1 intrinsically interacted with FAK protein in EC9706 cells. Moreover, paxillin was downregulated at mRNA and protein levels in Bit1 shRNA group, coupled with the decreases of FAK mRNA and protein expressions. Conclusion: Bit1 may be an important regulator in cell growth, apoptosis, migration and invasion of ESCC via targeting FAK-paxillin pathway, and thereby combinative manipulation of Bit1 and FAK-paxillin pathway may be the novel and promising therapeutic targets for the patients with ESCC. [ABSTRACT FROM AUTHOR]

Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats. Methods: Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots. Results: The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats. Conclusions: BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain. [ABSTRACT FROM AUTHOR]

Because of the fluorescence properties, lanthanide metal-organic framework (Ln-MOF) materials have potential applications in the detection of metal ions and nitro-aromatic explosives. Herein, a series of isostructural Ln-MOFs [Ln2IJPIA)3IJDMF)3IJCH3OH)] (JLU-MOF201-Ln, Ln = Y, Tb, Yb, Ho and Er, H2PIA = 5-(1H-pyrazol-3-yl)isophthalic acid), and DMF = N,N-dimethylformamide) were successfully synthesized. In these compounds, binuclear secondary building units (SBUs) are formed by two adjacent Ln3+ ions and H2PIA ligands, further linking together to build a 2D structure. The 2D framework can be simplified as a (3,4)-connected network with 3,4L83 topology. The luminescence sensing tests indicated that JLUMOF201-Y and JLU-MOF201-Tb show high sensitivity for Fe3+, 2,4-dinitrophenol (2,4-DNP) and 4-hydroxyderricin (4-NP), respectively. JLU-MOF201-Y and JLU-MOF201-Tb also exhibit high selectivity for detecting Fe3+ among other metal ions in DMF solution. The limits of detection (LOD) toward Fe3+, 2,4-DNP, and 4-NP are calculated to be 2.21, 0.46, and 1.15 µM for JLU-MOF201-Y and 2.17, 2.29, and 1.01 µM for JLU-MOF201-Tb, respectively. [ABSTRACT FROM AUTHOR]

family of lamellar mesostructured hydroxyapatites are synthesized using five terminal linear aliphatic carboxylic acids (capric acid, lauric acid, myristic acid, palmitic acid, and stearic acid with the general formula of CHCOH, n = 10, 12, 14, 16, 18). The study of X-ray diffraction shows that the hydroxyapatite samples exhibit similar multi-lamellar mesostructure and their interlamellar spacing is proportional to the carbon numbers of carboxylic acids. The transmission electron microscopic images on the products prove the parallel aligned configuration. Fourier transform infrared spectra displays the characteristic components of hydroxyapatite in as-prepared samples. Thermogravimetric analysis, elemental analysis (C, H), and inductively coupled plasma analysis were further used to confirm the organic and inorganic composition of the products. [ABSTRACT FROM AUTHOR]

A new 2D layered gallium phosphite Ga(HPO3)F3·(trans-C6N2H16) 1, possessing left- and right-handed helical chains, has been solvothermally synthesized in the presence of 1,2-diaminocyclohexane (DACH) as a structure-directing agent. The inorganic framework of compound 1 consists of [Ga2O4F6] dimers and HPO3groups. The dimers are linked up viaHPO3groups to give rise to left- and right-handed helical chains along the b-axis, further these two types of helical chains are alternately connected, with [Ga2O4F6] dimer units functioning as hinges to form a novel 2D layered network in the bc-plane. Interestingly, although a mixture of cisand transisomers of DACH are used in the synthesis, only the transisomer is found to direct the formation of compound 1. Moreover, the chirality of the racemic transisomers of DACH can be transferred into the inorganic framework by hydrogen-bond. The crystal data are as follow: Ga(HPO3)F3·(trans-C6N2H16); M= 322.91; Monoclinic; P21/c(14); a= 11.2635(5) Å; b= 9.8212(5) Å; c= 10.1458(3) Å; β= 102.981(2)°; Z= 4. [ABSTRACT FROM AUTHOR]

Three compounds have been isolated from solvothermal reactions of a transition metal(ii) (Ni(ii), Co(ii)) with N,N-bis(phosphonomethyl)aminoacetic acid [(HO2CCH2)N(CH2PO3H2)2] (H5L), namely [NH3(CH2)3NH3](NH4)4[Ni(L)(H2O)]2(1), (H3O)3[Ni(L)(H2O)2]·4H2O (2) and (H3O)[Co(H2L)(H2O)2]·2H2O (3). These compounds were characterized by single crystal and powder X-ray diffraction, infrared spectroscopy, thermal analysis, elemental analysis, fluorescent spectroscopy and magnetic measurements. The structure of compound 1is composed of binuclear [Ni2O6N2]n4−units, which are further interconnected into a 3D supramolecular network by hydrogen bonds. Compounds 2and 3are both mononuclear and consist of similar octahedral [MO5N] units. A 1D dendritic water chain is formed by hydrogen bond interactions in the supramolecular network of compound 2. Compounds 1and 2show ferromagnetic properties, while weak antiferromagnetic properties are observed in compound 3. Compounds 1and 2also display fluorescent emission excited at 235 nm. [ABSTRACT FROM AUTHOR]

SOX genes encode a family of high-mobility group transcription factors that play critical roles in organogenesis. The functional specificity of different SOX proteins and the tissue specificity of a particular SOX factor are largely determined by the differential partnership of SOX transcription factors with other transcription regulators, many of which have not yet been discovered. Virtually all members of the SOX family have been found to be deregulated in a wide variety of tumors. However, little is known about the cellular and molecular behaviors involved in the oncogenic potential of SOX proteins. Using cell culture experiments, tissue analysis, molecular profiling, and animal studies, we report here that SOX2 promotes cell proliferation and tumorigenesis by facilitating the G1/S transition and through its transcription regulation of the CCNDJ gene in breast cancer cells. In addition, we identified β-catenin as the transcription partner for SOX2 and demonstrated that SOX2 and β-catenin act in synergy in the transcription regulation of CCNDJ in breast cancer cells. Our experiments not only determined a role for SOX2 in mammary tumorigenesis but also revealed another activity of the multifunctional protein, ~3-catenin. [ABSTRACT FROM AUTHOR]

The C(sp3)−C(sp3) bonds of a series of -alkylacetonitriles, 2-silylacetonitriles and 2-alkylbenzonitriles, have been activated by Rh(tmp) using Ph3P as the optimized promoter ligand at 130 °C. Selective aliphatic−aliphatic carbon−carbon bond activation (CCA) occurred for -alkylacetonitriles and 2-alkylbenzonitriles without aromatic−aliphatic or aromatic−cyanide bond activation. Competitive activations of C−Si and C−C bonds were observed for 2-silylacetonitriles. The yields of Rh(tmp) alkyls were affected by bond energy and steric hindrance of the nitriles. Kinetic studies for the carbon−carbon bond activation (CCA) of tBuCN at 130 °C revealed the rate law:  rate k‘K1Rh(tmp)mPh3Pnk3K2(K1Ph3P)/(1 K1Ph3P)Rh(tmp)tBuCN. The CCA is proposed to occur at the coordinated tBuCN with Rh(tmp) in a 1:1 ratio in the transition state. [ABSTRACT FROM AUTHOR]

The chromosomal t(4;14) (p16;q32) translocation drives high expression of histone methyltransferase nuclear SET domain-containing 2 (NSD2) and plays vital roles in multiple myeloma (MM) evolution and progression. However, the mechanisms of NSD2-driven epigenomic alterations in chemoresistance to proteasome inhibitors (PIs) are not fully understood. Using a CRISPR/Cas9 sgRNA library in a bone marrow-bearing MM model, we found that hepatoma-derived growth factor 2 (HRP2) was a suppressor of chemoresistance to PIs and that its downregulation correlated with a poor response and worse outcomes in the clinic. We observed suppression of HRP2 in bortezomib-resistant MM cells, and knockdown of HRP2 induced a marked tolerance to PIs. Moreover, knockdown of HRP2 augmented H3K27me3 levels, consequentially intensifying transcriptome alterations promoting cell survival and restriction of ER stress. Mechanistically, HRP2 recognized H3K36me2 and recruited the histone demethylase MYC-induced nuclear antigen (MINA) to remove H3K27me3. Tazemetostat, a highly selective epigenetic inhibitor that reduces H3K27me3 levels, synergistically sensitized the anti-MM effects of bortezomib both in vitro and in vivo. Collectively, these results provide a better understanding of the origin of chemoresistance in patients with MM with the t(4;14) translocation and a rationale for managing patients with MM who have different genomic backgrounds. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although many studies have suggested that air cells may play an important role in sigmoid sinus diverticulum and/or dehiscence (SSDD)-induced pulsatile tinnitus (PT), the exact effects remain unclear. This study aims to quantitatively investigate the effect of different degrees of pneumatization of temporal bone on sound transmission from the sigmoid sinus to the tympanic cavity. METHODS: In the clinical study, 25 patients were enrolled to measure the sound intensity and frequency of SSDD-induced PT. In the experimental study, sound inputs at different frequencies at the dehiscent sigmoid plate were measured and compared among realistic object models of different degrees of pneumatization, when sound intensity in the tympanic cavity was fixed as the level of the PT sound intensity sensed by patients. RESULTS: The sound intensity sensed by PT patients was 34.0 ± 13.0 dB SPL, which represented the sound intensity in the tympanic cavity transmitted from the dehiscent sigmoid plate. In the experimental study, when sound received in the tympanic cavity was fixed at 34 dB SPL, the mean inputs of sound intensity at the dehiscent sigmoid plate were 46.9, 46.2, 45.2, 47.1, 57, 57.4, and 74.1 dB SPL in a hypo-pneumatized model; 42.6, 43, 41.5, 43.2, 47.3, 58.2, and 78.8 dB SPL in a moderately pneumatized model; 52.6, 52.8, 48.1, 61, 64.2, 82.4, and >87.3 dB SPL in a well-pneumatized model; and 47.2, 46.2, 45.4, 49.4, 54.9, 66.6, and 77.7 dB SPL in hyper-pneumatized model, with increased sound frequencies (125-8000 Hz). The mean sound transmission distances were 41.7 mm, 45.2 mm, 47.6 mm, and 48.4 mm in successively better pneumatized models. CONCLUSION: Sound reduces while passing through air cells and attenuation is lowest in the moderately pneumatized temporal bone, followed by the hypo- and hyper-pneumatized temporal bones, and the highest in the well-pneumatized temporal bone. Lower-frequency sound attenuation (=1000 Hz) is less than that of higher-frequency sound (>1000 Hz). [ABSTRACT FROM AUTHOR]

The article discusses about the Glutamine constitutes an essential source of both carbon and nitrogen for numerous biosynthetic processes. It mentions about the first and rate-limiting step of glutaminolysis involves the generation of glutamate from glutamine, catalyzed by glutaminase-1 (GLS1). It discusses how shortages of glutamine result in reductions in GLS1.

Thyroid cancer is the most frequent endocrine tumor with a growing incidence worldwide. However, common diagnostic strategy for thyroid cancer classification is hardly to make a proper diagnosis in some cases. To assist classical appr oach, this study used metabolomics to screen and validate biomarkers from serum and urinary for papillary thyroid cancer (PTC). Overall, 124 untreated PTC, 76 untreated benign thyroid nodule (BTN), and 116 healthy control (HC) were collected in this stud y. Thirty-six differential metabolites were screened from non-targeted metabolomics with a discovery sample set in comparison with HC and BTN. Serum ß-hydroxybutyrate (BHB), docosahexaenoic acid (DHA), 1-methyladenosine (1-MedA), pregnanediol-3-glucuronide (PdG), urinary nicotinic acid mononucleotide (NAM) and xanthosine (Xan) were validated to be significantly differential by targeted metabolomics in validation set. The logistic regression model incorporating six biomarkers had excellent discrimination from receiver-operating characteristics (ROC) analysis, with area under the receiver-operating characteristic curve (AUC) of 0.943 (95% CI 0.902 to 0.983) and 0.952 (95% CI 0.921 to 0.983) for female alone and female + male samples, respectively. The prediction accuracy and false-negative rate in the real setting of one PTC to ten suspicious nodules were 8 4.7 and 17.7% with the threshold at probablity of 0.5. Results of a double-blind study for PTC and BTN had true positive value of 100% and true negative value of 91.7%. To con clude, BHB, DHA, 1-MedA, PdG, NAM and Xan are suitable biomarkers for PTC, and logistic regression models with the six biomarkers can be potentially used as clinical diagnosis. [ABSTRACT FROM AUTHOR]

The article discusses the positive transcription elongation factor b (P-TEFb) functions as a central regulator of transcription elongation and notes the mechanisms of signal-regulated P-TEFb activation and its roles in human diseases. The article discusses cAMP pathway roles in the development of autosomal dominant polycystic kidney disease (ADPKD) and pharmacological inhibition of P-TEFb attenuates cyst development by suppressing the pathological gene expression program in ADPKD mice.

Dance and music are expressive art forms. Previous behavioural studies have reported that dancers/musicians show a better sensorimotor ability and emotional representation of others. However, the neural mechanism behind this phenomenon is not completely understood. Recently, intensive researches have identified that the insula is highly enrolled in the empathic process. Thus, to expand the knowledge of insular function associated with empathy under the dance/music training background, we mapped the insular network and its associated brain regions in 21 dancers, 20 musicians, and 24 healthy controls using resting-state functional connectivity (FC) analysis. Whole brain voxel-based analysis was performed using seeds from the posterior insula (PI), the ventral anterior insula (vAI), and the dorsal anterior insula (dAI). The training effects of dance and music on insular subnetworks were then evaluated using one-way analysis of variance ANOVA. Increased insular FC with those seeds was found in dancers/musicians, including PI and anterior cingulated cortex (ACC), vAI and middle temporal gyrus (MTG) and middle cingulated cortex (MCC), and dAI and ACC and MTG. In addition, significant associations were found between discrepant insular FC patterns and empathy scores in dancers and musicians. These results indicated that dance/music training might enhance insular subnetwork function, which would facilitate integration of intero/exteroceptive information and result in better affective sensitivity. Those changes might finally facilitate the subjects' empathic ability. [ABSTRACT FROM AUTHOR]

Two novel porous MOFs, [Zn5(DpImDC)2(DMF)4(H2O)3]·H2O·DMF (JLU-MOF48, H5DpImDC = 2-(3,5-dicarboxyphenyl)-1H-imidazole-4,5-dicarboxylic acid) and [Co5(DpImDC)2(DMF)4(H2O)6]·DMF (JLU-MOF49), have been solvothermally synthesized by using a ligand consisting of a 4,5-imidazoledicarboxylic acid part and an isophthalic acid part. Two compounds have similar structures and connections, but with significant differences in symmetry (monoclinic and orthorhombic) due the cis-trans isomerism in a mononuclear metal node. Moreover, JLU-MOF48 exhibits notable luminescent properties and owns outstanding performance for detecting nitroaromatic explosives, especially for 2,4,6-trinitrophenol (Ksv = 1.0 × 105 M-1). [ABSTRACT FROM AUTHOR]

Cytochrome P450 3A4 (CYP3A4) is the most abundant cytochrome P450 enzyme in human liver and intestine, contributing to the metabolism of >60% of all pharmaceuticals. The expression levels of hepatic CYP3A4 show great inter-individual variation. However, the detailed regulatory mechanism of CYP3A4 expression has remained largely elusive. It has been reported that the non-coding RNA small vault (sv)RNAb targets the 3' untranslated region (3'UTR) of CYP3A4 in MCF7 cells. However, to date, the role of svRNAb has not been examined in human liver tissue and hepatic cell lines such as HepG2, which was the aim of the present study. Polymerase chain reaction analysis indicated that the expression of CYP3A4 was significantly different within a study cohort (n=19). In addition, a significant negative correlation was observed between svRNAb and CYP3A4 expression in human liver tissue samples. Furthermore, a luciferase assay on HepG2 cells verified that svRNAb directly targets CYP3A4 and regulates the expression of CYP3A4 by interacting with the validated binding sites of the CYP3A4 3'UTR. The results provided insight into the variation of the expression of CYP3A4 among individuals and provided a novel method for the adjustment of personalized drug treatment. Furthermore, the present study provided a mechanism of the regulatory role of svRNAb in multidrug-resistant cells. [ABSTRACT FROM AUTHOR]

Background c-Jun NH2-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogenactivated protein kinase (p38 MAPK) are important components of cellular signal transduction pathways, which have been reported to be involved in viral replication. However, little is known about signaling pathways in enterovirus 71 (EV71)-infected immature dendritic cells (iDCs). Thus, iDCs were induced from peripheral blood mononuclear cells (PBMC) and performed to explore the expressions and phosphorylation of molecules in the two signaling pathways as well as secretions of inflammatory cytokines and interferons during EV71 replication. Results We showed that EV71 infection could activate both JNK1/2 and p38 MAPK in iDCs and phosphorylate their downstream transcription factors c-Fos and c-Jun, which further promoted the production of IL-2, IL-6, IL-10, and TNF-α. Moreover, EV71 infection also increased the release of IFN-β and IL-12 p40. Pretreatment of iDCs with SP600125 and SB203580 (20 μM) could severely impair viral replication and its induced phosphorylation of JNK1/2,p38 MAPK, c-Fos and c-Jun. In addition, treatment of EV71-infected iDCs with SP600125 and SB203580 could inhibit secretions of IL-6, IL-10 and TNF-α. Conclusion JNK1/2 and p38 MAPK signaling pathways are beneficial to EV71 infection and positively regulate secretions of inflammatory cytokines in iDCs. [ABSTRACT FROM AUTHOR]

CYP3A4 metabolizes more than 50% of the drugs on the market. The large inter-individual differences of CYP3A4 expression may contribute to the variability of human drug responses. Post-transcriptional regulation of CYP3A4 is poorly understood, whereas transcriptional regulation has been studied much more thoroughly. In this study, we used multiple software programs to predict miRNAs that might bind to CYP3A4 and identified 112 potentially functional miRNAs. Then a luciferase reporter system was used to assess the effect of the overexpression of each potentially functional miRNA in HEK 293T cells. Fourteen miRNAs that significantly decreased reporter activity were measured in human liver samples (N = 27) as candidate miRNAs. To establish a more effective way to analyze in vivo data for miRNA candidates, the relationship between functional miRNA and target mRNA was modeled mathematically. Taking advantage of this model, we found that hsa-miR-577, hsa-miR-1, hsa-miR-532-3p and hsa-miR-627 could significantly downregulate the translation efficiency of CYP3A4 mRNA in liver. This study used in silico, in vitro and in vivo methods to progressively screen functional miRNAs for CYP3A4 and to enhance our understanding of molecular events underlying the large inter-individual differences of CYP3A4 expression in human populations. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) or cancer-initiating cells (CICs) play an important role in tumor initiation, progression, metastasis, chemoresistance, and recurrence. It is important to construct an effective method to identify and isolate CSCs for biotherapy of cancer. During the past years, many researchers had paid more attention to it; however, this method was still on seeking. Therefore, compared to the former methods that were used to isolate the cancer stem cell, in the present study, we tried to use modified transwell system to isolate and enrich CSCs from human pancreatic cancer cell lines (Panc-1). Our results clearly showed that the lower chamber cells in modified transwell system were easily forming spheres; furthermore, these spheres expressed high levels of stemcellmarkers (CD133/CD44/CD24/Oct-4/ESA) and exhibited chemoresistance, underwent epithelial-to-mesenchymal transition (EMT), and possessed the properties of self-renewal in vitro and tumorigenicity in vivo. Therefore, we speculated that modified transwell assay system, as a rapid and effective method, can be used to isolate and enrich CSCs. [ABSTRACT FROM AUTHOR]

The initiation and progression of various solid tumors, including pancreatic carcinoma, are driven by a population of cells with stem cell properties, namely cancer stem cells (CSCs). Like their normal counterparts, CSCs are also believed to rely on their own microenvironment termed niches to sustain the population. Hypoxia-inducible factor-1α (HIF-1α) is a major actor in the cell survival response to hypoxia. Recently, several researchers proposed that non-stem cancer cells can convert to stem-like cells to maintain equilibrium. The present study focuses on whether non-stem pancreatic cancer cells can convert to stem-like cells and the role of HIF-1α and autophagy in modulating this conversation. The non-stem pancreatic cancer cells and pancreatic cancer stem-like cells were separated by magnetic sorting column. Intermittent hypoxia enhanced stem-like properties of non-stem pancreatic cancer cells and stimulated the levels of HIF-1α, LC3-II and Beclin. Enhanced autophagy was associated with the elevated level of HIF-1α. The conversation of non-stem pancreatic cancer cells into pancreatic cancer stem-like cells was induced by HIF- 1α and autophagy. This novel finding may indicate the specific role of HIF-1α and autophagy in promoting the dynamic equilibrium between CSCs and non-CSCs. Also, it emphasizes the importance of developing therapeutic strategies targeting cancer stem cells as well as the microenvironmental influence on the tumor. [ABSTRACT FROM AUTHOR]

The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N1-acetyl- N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxy-kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy-AMK and glucuronide-conjugated hydroxy-AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Embryonic stem (ES) cells have attracted significant attention from researchers around the world because of their ability to undergo indefinite self-renewal and produce derivatives from the three cell lineages, which has enormous value in research and clinical applications. Until now, many ES cell lines of different mammals have been established and studied. In addition, recently, AS-ES1 cells derived from Apodemus sylvaticus were established and identified by our laboratory as a new mammalian ES cell line. Hence further research, in the application of AS-ES1 cells, is warranted. Results: Herein we report the generation of multiple mesodermal AS-ES1 lineages via embryoid body (EB) formation by the hanging drop method and the addition of particular reagents and factors for induction at the stage of EB attachment. The AS-ES1 cells generated separately in vitro included: adipocytes, osteoblasts, chondrocytes and cardiomyocytes. Histochemical staining, immunofluorescent staining and RT-PCR were carried out to confirm the formation of multiple mesodermal lineage cells. Conclusions: The appropriate reagents and culture milieu used in mesodermal differentiation of mouse ES cells also guide the differentiation of in vitro AS-ES1 cells into distinct mesoderm-derived cells. This study provides a better understanding of the characteristics of AS-ES1 cells, a new species ES cell line and promotes the use of Apodemus ES cells as a complement to mouse ES cells in future studies. [ABSTRACT FROM AUTHOR]