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To investigate the association between outcomes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and common modifiable vascular risk factors. Studies published between 1993 and February 2023 from PubMed, Embase, Cochrane, CNKI, and WanFang, along with their references, were systematically examined. Cross-sectional analyzes in patients with CADASIL with information on modifiable cerebrovascular risk factors and outcomes were included. Meta-analysis was conducted if at least three studies were available for each risk factor and outcome. We included nine studies and 1687 samples in the analysis. The results of the meta-analysis showed that hypertension was positively associated with stroke in patients with CADASIL (OR = 2.69; 95 % CI: 2.02–3.57). Other vascular risk factors, including diabetes mellitus, dyslipidemia, hyperhomocysteinemia, smoking, alcohol drinking, and obesity, did not show stable correlations between the three outcomes (stroke, dementia, and disability). Hypertension was significantly associated with stroke in patients with CADASIL. The role of other vascular risk factors in CADASIL and its outcomes: stroke, dementia, and disability, remains ambiguous. [ABSTRACT FROM AUTHOR]

A new pestalotiopsin C ( 1 ) with three known compounds ( 2 – 4 ) are obtained from the fermentation broth of fungus of Trichoderma KK19L1 sp. Pestalotiopsin C ( 1 ) has two atropisomers with mole ratio of 1.2/1 in chloroform at room temperature. Its structure was well established by 1D and 2D NMR, and further confirmed by X-ray diffraction. Its absolute configuration (AC) was determined by comparing its experimental electronic circular dichroism (ECD) and optical rotation (OR) value with the calculated ECD and OR data using quantum methods. The bioactivity of compound 1 was tested against five cell-lines HL-60, SMMC-7721, A-549, MCF-7, SW480, respectively. [ABSTRACT FROM AUTHOR]

Four new highly unsaturated pyranone derivatives A–D ( 1 – 4 ), together with one known compound 5 (−)-nitidon were isolated from cultures of the fungus Junghuhnianitida . Planar structures of the new compounds were elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses. Absolute configurations of the new compounds were determined on the basis of biosynthetic considerations and quantum chemistry theory. Compound 1 exhibited almost the same cytotoxic activities as cis -platin. [ABSTRACT FROM AUTHOR]

The palladium-catalyzed cross-couplings of alkylindium reagents with diaryliodonium salts proceeded efficiently in the presence of tetrakis(triphenylphosphine)palladium [Pd(PPh 3) 4 ], 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos), lithium tert -butoxide, and lithium chloride in DMA/THF (1:1) at 100 °C, leading to the corresponding cross-coupling products in moderate to good yield with broad substrate scope and wide functional group tolerance. [Display omitted] • Pd efficiently catalyzed couplings of alkylindiums with diaryliodonium salts. • Aryliodonium salts served as efficient aryl transfer reagents in cross-couplings. • The reactions showed broad substrate scope and wide functional group tolerance. The palladium-catalyzed cross-couplings of alkylindium reagents with diaryliodonium salts proceeded efficiently in the presence of tetrakis(triphenylphosphine)palladium [Pd(PPh 3) 4 ], 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos), lithium tert -butoxide, and lithium chloride in DMA/THF (1:1) at 100 °C, leading to the corresponding cross-coupling products in moderate to good yield with broad substrate scope and wide functional group tolerance. [ABSTRACT FROM AUTHOR]

Abstract: Oxidized and polished multi-walled carbon nanotubes (MWCNTs) were dispersed in aqueous solution, providing a highly stable suspension of purified, shortened, and functionalized carboxylic acid nanotubes. A gonadotrophin releasing hormone (GnRH), which was overexpressed in the plasma membrane of several types of cancer cells, was covalently anchored onto the surface of the oxidized MWCNTs via an amide linkage. The MWCNTs modified with GnRH (MWCNTs–GnRH) were characterized by UV–vis and emission spectra, and elemental analysis. Red-shift in the optical spectra consisting of the UV–vis absorption and emission spectra with the attraction of GnRH on the surface of the MWCNTs was observed due to the attraction of GnRH on the surface of the MWCNTs via π stacking, however, there was no property for a direct mixture of MWCNTs and GnRH, supporting the successful modification. Elemental analysis revealed that the sidewall coverage of MWCNTs by the GnRH was about 0.7% of the available surface area. The non toxic GnRH and MWCNTs can separately enter the DU 145 cells. In contrast, GnRH–MWCNTs entered the cells and showed toxicity in the malignant cells. These results showed that the newly formed toxic material had potential ability to kill the malignant cells with just a simple covalent bonding of the two. [Copyright &y& Elsevier]

Abstract: Scorpion venom is composed of a large repertoire of biologically active polypeptides. However, most of these peptides remain to be identified and characterized. In this paper, we report the identification and characterization of four novel disulfide-bridged venom peptides (named BmKBTx, BmKITx, BmKKx1 and BmKKx2, respectively) from the Chinese scorpion, Mesobuthus martensii (also named Buthus martensii Karsch). BmKBTx is composed of 58 amino acid residues and cross-linked by three disulfide bridges. The sequence of BmKBTx shows some similarities to that of the toxin, birtoxin, and its analogs. It is likely that BmKBTx is a β-toxin active on Na+ channels, which is toxic to either insects or mammals. BmKITx is composed of 71 amino acid residues with four disulfide bridges. It is the longest venom peptide identified from M. martensii so far. BmKITx shows little sequence identity with scorpion α-toxins toxic to insects. It is likely that BmKITx is a new type of Na+-channel specific toxin active on both insects and mammals. BmKKx1 contains 38 amino acid residues cross-linked by three disulfide bridges and shows 84% sequence identity with BmTx3, an inhibitor of A-type K+ channel and HERG currents. BmKKx1 has been classified as α-KTx-15.8. BmKKx2 is composed of 36 residues and stabilized by three disulfide bridges. BmKKx2 is a new member of the γ-K+-channel toxin subfamily (classified as γ-KTx 2.2). The venoms of scorpions thus continue to provide novel toxins with potential novel actions on targets. [Copyright &y& Elsevier]

Abstract: A novel cDNA clone (named BmKT-u) which is a hybrid molecule of the 5′-terminal region of BmKT’ cDNA and the 3′-terminal region of an undocumented cDNA (named BmKu), was isolated from a cDNA library made from the venom gland of scorpion Buthus martensii Karsch. BmKT-u codes for a 30 amino acid residue precursor peptide composed of a 20-residue signal sequence, and a putative 10-residue novel mature peptide. Northern blot hybridization showed BmKT-u cDNA is generated from a transcript. RT-PCR experiments excluded the possibility that BmKT-u cDNA is an artifact generated during reverse transcription. Genomic amplifications performed with three pairs of BmKT-u gene-specific primers showed the BmKT-u gene does not exist in the genome of the scorpion as a single transcriptional unit. Genomic cloning for BmKT’ showed that the BmKT’ gene contains an intron of 509bp inserted into the region encoding the C-terminal region of the signal peptide. A sequence alignment comparison of the cDNA of BmKT-u with genomic BmKT’ revealed that the junction site of the hybrid molecule is located at the 5′-splicing site of the intron. The data suggest that the BmKT-u transcript is a naturally occurring mature mRNA that is generated by trans-splicing. Trans-splicing may contribute to the diversity of venom peptides from venomous animals. [Copyright &y& Elsevier]

A novel cDNA sequence encoding a new type of scorpion venom peptide (BmKAPi) was first isolated from the venom gland of Buthus martensii Karsch by cDNA library screening combined with 5′-race. The encoded precursor of BmKAPi consisted of 89 amino acid residues including a signal peptide of 24 residues, a putative mature peptide of 64 residues (BmKAPi) and an extra basic residue at the C-terminus which might be removed in the post-translational processing. BmKAPi is stabilized by five disulfide bridges, whereas all other disulfide-bridged scorpion toxins described are cross-linked by three or four disulfide bridges. It suggested the three-dimensinal scaffold of BmKAPi might be different from other scorpion toxins. The amino acid sequence of BmKAPi showed no homology with other scorpion venom peptides, but shared a little similarity with some anticoagulant peptides and proteinase inhibitors isolated from hookworm, honeybee or European frog, respectively. RT-PCR analysis showed that BmKAPi mRNA could be induced by venom extraction suggesting BmKAPi might be a component of scorpion venom. These results suggest that BmKAPi is a new type of scorpion venom peptide different from other described scorpion toxins in structural and functional aspects. [Copyright &y& Elsevier]

Abstract The absolute configuration of cepharanthine (1), a strongly bioactive bisbenzylisoquinoline alkaloid exhibiting 12 specific bioactivities without any reported negative side-effects, has been reassigned from (1 R ,1′ S) to (1 R ,1′ R) using quantum theory. The absolute configurations (ACs) of 13 other analogues of 1 were also systematically reassigned. Six quaternary salts were prepared from 1 and one exhibited strong anti-bacterial activity against Bacillus subtilis with MIC 0.31 μ M, while Ciprofloxacin, the positive control medicine was 3.88 μ M. This work established the critical importance of correlating chiroptical experimental spectra with their quantum mechanically predicted spectra for accurate stereogenic center assignments. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Graphical abstract Four binuclear Cu(I) complexes of neutral or deprotonated 2-(2-pyridyl)imidazo[4,5- f ][1,10]-phenanthroline (pipH) and diphosphine were synthesized. The two Cu(I) complexes with deprotonated pipH show obvious blue shift and stronger emission compare to the other two with neutral pipH. Abstract Reaction of 2-(2-pyridyl)imidazo[4,5- f ][1,10]-phenanthroline (pipH), [Cu(MeCN) 4 ]ClO 4 and diphosphine ligand bis[(2-diphenylphosphino)phenyl] ether (POP) or 9,9-dimethyl-4,5-bis(diphenylphosphino)-9H-xanthene (xantphos) in a 1:2:2 ratio generated four binuclear copper(I) complexes, [Cu 2 (pipH)(PP) 2 ](ClO 4) 2 (PP = POP, 1a ; xantphos, 2a) and [Cu 2 (pip)(PP) 2 ]ClO 4 (PP = POP, 1b ; xantphos, 2b) in neutral and strong alkaline media, respectively. Complexes 1b and 2b containing deprotonated pipH show obvious blue shift and stronger emission compared to complexes 1a and 2a with neutral pipH due to the stronger binding ability, the higher rigidity and conjugate degree resulting from anionic pip ligand and less vibrational quenching due to the loss of N H bond. [ABSTRACT FROM AUTHOR]

[Display omitted] • The first example of RCF of fermentation residues was illustrated. • The fermented stover residues are abundant renewable lignin-rich bioresources. • Lignins of fermented residues contain lower molecular weight and β- O -4′ linkages. • 28.5 wt% yield of phenolic monomers was obtained at 220 °C over a Pd/C catalyst. The fermented corn stover residues are abundant renewable lignin-rich bioresources that show great potential to produce aromatic phenols. However, selective catalytic hydrogenolysis of this residual material still remains challenge to obtain high yields. Herein, a novel strategy to produce monophenolic compounds from the fermented stover over a commercial Pd/C catalyst was proposed. Taking the reaction temperature as the key variable, the highest monomer yield was 28.5 wt% at 220 °C in compaction with that of the pristine corn stover (22.8 wt%). The enhanced monophenol yield was due to the higher contents of lignin and less recalcitrance in the fermented stover. Moreover, the van Krevelen diagram revealed a slight selective C O bond scission of lignin macromolecular during fermentation as well as the dehydration and deoxygenation in hydrogenolysis reaction. Overall, this work opens a new avenue for the valorization of lignin through reductive catalytic fractionation of agricultural wastes. [ABSTRACT FROM AUTHOR]

Abstract: ZNF300, which plays the role in human embryonic development and some diseases, is a typical KRAB/C2H2 zinc finger gene expressed only in higher mammalians. Our data showed that expression of ZNF300 changed significantly in various leukemia blasts in the bone marrow aspirates of newly diagnosed leukemia patients. To investigate the potential relationship between expression of ZNF300 and the progression of leukemia development and hematopoietic differentiation, we cloned and characterized the putative human ZNF300 gene promoter and identified its transcription start sites (TSSs). Deletion and mutagenesis analysis demonstrated that a myeloid-specific transcription factor PU.1 binding site was responsible for myeloid-specific regulation of ZNF300 promoter activity. Furthermore, electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that PU.1 bound to the PU.1 binding site within ZNF300 promoter region in vitro and in vivo. Overexpression of PU.1 elevated ZNF300 promoter activity, whereas silencing of PU.1 expression significantly reduced the activity in myeloid-derived HL-60 cell but not in T-cell Jurkat. In vitro induced HL-60 cells into CD11b expressing cells by DMSO demonstrated that ZNF300 was upregulated along with upregulation of PU.1 expression. These results demonstrated that ZNF300 was activated by PU.1 and suggested that the regulation may be involved in the progression of leukemia development and hematopoietic differentiation. [Copyright &y& Elsevier]

Abstract: An important biologically-relevant property of fullerenol is its ability to quench free radicals. Carbon tetrachloride (CCl4)-induced hepatotoxicity and nephrotoxicity model was used to investigate the possible mechanisms of fullerenol protection in Sprague–Dawley rats in this study. Rats were administrated with fullerenol (0, 1, 1.5 and 5mg/kgd) by intravenous or intraperitoneal injection for 3days before CCl4 challenge, 24h following the CCl4 challenge, all the rats were assessed using serum and tissue homogenates biomarkers as well as the pathological evaluation. All results showed that CCl4 caused significant increasing serum activity of alanine aminotransferase and aspartate aminotransferase, as well as the concentration of blood urea nitrogen and creatinine. Malondialdehyde level was also increased significantly, whereas the ratio of reduced glutathione to oxidized glutathione was decreased in tissue homogenates. The pathological evaluation indicated the liver and kidney were damaged by CCl4. Fullerenol-pretreatment alleviated biomarker changes as well as histological changes significantly, and fullerenol-pretreatment alone can increase the ratio of reduced glutathione to oxidized glutathione, which indicated fullerenol could protect tissues against CCl4-induced oxidative stress by improving the antioxidant ability. [Copyright &y& Elsevier]

Abstract: An increasing number of studies have been devoted to studying the respiratory toxicity of carbon nanomaterials, but little information is known, thus far, on the biodistribution of these nanomaterials after inhalation or intratracheal instillation. We synthesized and labeled a polyhydroxylated derivative of fullerene C60(OH) x (x =22,24) with 99mTc. With single photon emission computed tomography imaging and 〈gamma〉-ray counting techniques, the biodistribution of 99mTc-C60(OH) x in Sprague–Dawley rats after intratracheal instillation was studied. It was found that, besides the highest retention in the lung, 99mTc-C60(OH) x is distributed mainly in the liver, bone, and spleen, with no uptake found in brain. The long-term retention in the lung and the very fast clearance from the blood revealed a transient characteristic of penetrating the alveolar-capillary barrier. The dimensions and size distribution, as well as in vivo aggregation of 99mTc-C60(OH) x , may affect the capability and kinetic process of penetrating the alveolar-capillary barrier. The results provide guidance for further study of the respiratory toxicity of carbon nanomaterials. [Copyright &y& Elsevier]

Human ZNF268 gene is a typical Kruppel-associated box! C2H2 zinc finger gene whose homolog has been found only in higher mammals and not in lower mammals such as mouse. Its expression profiles have suggested that it plays a role in the differentiation of blood cells during early human embryonic development and the pathogenesis of leukemia. To gain additional insight into the molecular mechanisms controlling the expression of the ZNF268 gene and to provide the necessary tools for further genetic studies of leukemia, we have mapped the 5′-end of the human ZNF268 mRNA by reverse transcription-PCR and primer extension assays. We then cloned the 5′-flanking genomic DNA containing the putative ZNF268 gene promoter and analyzed its function in several different human and mouse tissue culture cell lines. Interestingly, our studies show that the ZNF268 gene lacks a typical eukaryotic promoter that is present upstream of the transcription start site and directs a basal level of transcription. Instead, the functional promoter requires an essential element that is located within the first exon of the gene. Deletion and mutational analysis reveals the requirement for a cAMP response-element-binding protein (CREB)-binding site within this element for promoter function. Gel mobility shift and chromatin immunoprecipitation assays confirm that CREB-2 binds to the site in vitro and in vivo. Furthermore, over- expression of CREB-2 enhances the promoter activity. These results demonstrate that the human ZNF268 gene promoter is atypical and requires an intragenic element located within the first exon that mediates the effect of CREB for its activity. [ABSTRACT FROM AUTHOR]

Abstract: At least 25 nondisulfide-bridged peptides (NDBPs) have been identified and characterized from scorpions. However, the genomic organization of the genes that encode these peptides have not been reported yet. BmKa1, BmKa2 and BmKb1 are three novel genes that code for NDBPs identified by our group from Mesobuthus martensii Karsch. Based on their cDNA sequences, the genomic DNA sequences encoding these peptides were obtained using the PCR method. Sequence analysis showed that three distinct genomic structural patterns are used to encode these three peptides. The BmKa1 gene is not interrupted by any introns. However, the BmKa2 gene is composed of two exons, interrupted by a 67bp intron that is located in the DNA region encoding the mature peptide. Two genomic homologues of the BmKb1 cDNA sequence, named BmKb1′ and BmKb2, respectively, were obtained. The BmKb1′ gene contains one intron of 593bp, inserted into the DNA region that encodes the signal peptide. Similarly, the BmKb2 gene also contains an intron that interrupts the exon that encodes the NDBP signal peptide. The amino acid sequences deduced for BmKb2 and BmKb1′ differ only at one position. The data suggest that the genomic organizational pattern of NDBPs displays more divergence than that exhibited by the genes that encode disulfide-bridged peptides from scorpions. [Copyright &y& Elsevier]

The scorpion venom peptides with no disulfide bridge are rarely identified and poorly characterized so far. Here, we report the identification and characterization of four novel disulfide-bridge-free venom peptides (BmKa1, BmKa2, BmKb1 and BmKn2) from Buthus martensii Kasch. BmKa1 and BmKa2 are very acidic and hydrophilic, showing no any similarity to other proteins, whereas BmKb1 and BmKn2 both are basic, α-helical peptide with an amidated C-terminus, showing a little homology with other peptides. Functional tests with synthetic peptide showed that BmKn2 has strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, whereas BmKb1 has weak activity in inhibiting the growth of these bacteria. [Copyright &y& Elsevier]

A new imine ligand and its ionic and neutral cuprous complexes were synthesized, and their structures and naked-eye phosphorescence were studied. The ionic complexes show a weak emission in solution, but display a good emission in the solid state, while the neutral complexes exhibit good naked-eye phosphorescence both in solution and in the solid state. [Display omitted] Here, a new imine ligand, 2-(6-methoxynaphthyl)-1 H -imidazo[4,5-f][1,10]phenanthroline (mipH), and three pairs of its ionic and neutral Cu(I) complexes were synthesized. Their crystal structures and naked-eye phosphorescence were studied. All the Cu(I) complexes show good phosphorescence emissive properties in the solid state in the visible region, but in dichloromethane solutions, only the neutral Cu(I) complexes emit good naked-eye phosphorescence, which contrasts sharply with the weak luminescence of the ionic Cu(I) complexes. [ABSTRACT FROM AUTHOR]