皮下种植黑色素瘤对小鼠血液中脂肪和氨基酸代谢的影响*

目的:探讨皮下种植黑色素瘤对小鼠血液中相关脂肪和氨基酸代谢的影响。方法:野生型小鼠皮下种植B16黑色素瘤细胞,两周后观察小鼠并取不同的组织称重,检测血液中甘油三酯、葡萄糖、脂肪酸、炎症因子的水平。利用质谱方法检测血液中氨基酸的水平。结果:野生型小鼠皮下肿瘤种植2周后体重没有明显变化,脾脏和肝脏的重量明显增加,皮下脂肪组织和腹腔脂肪组织的重量没有明显变化。血液中甘油三酯的水平明显增高,葡萄糖和甘油的水平明显下降。血液中炎症因子Interleukin 6(IL6)和Interferon gamma(IFNγ)的水平明显增加。血液的质谱结果显示有四种氨基酸的水平有明显变化,其中胱氨酸(Cystine)增加了约30倍,丝氨酸(Serine)、谷氨酰胺(Glutamine)和色氨酸(Tryptophan)分别有不同程度的降低。结论:皮下黑色素瘤显著影响小鼠机体营养状态和炎症,并特异性影响血液中氨基酸的代谢。     

DNA Methylation and SNPs in VCX are Correlated with Sex Differences in the Response to Chronic Hepatitis B

The study was conducted to explore the mechanisms of sex differences in the response to chronic hepatitis B(CHB) in terms of DNA methylation, SNP genotype, and gene expression. Genomic DNA was isolated from peripheral blood mononuclear cells(PBMCs) of CHB patients and healthy controls and evaluated using the Human Methylation 450 K Assay. The DNA methylation level at hg37 chromosome(CHR) X: 7810800 was further validated using pyrosequencing.SNP genotypes, VCX m RNA expression of PBMCs, and plasma VCX protein concentration were further examined using SNaPshot, RT-qPCR, and Western blot, respectively. Results showed that a total of 5529 CpG loci were differentially methylated between male and female CHB patients. DNA methylation level and CC+CT frequency at CHR X: 7810800,VCX mRNA expression of PBMCs, and plasma VCX protein concentration were higher in female than in male CHB patients. The CHR X: 7810800 locus was hypermethylated in CHB patients with CC+CT genotypes in comparison with those with the TT genotype. In cases of CC+CT genotypes, VCX mRNA expression was negatively correlated with the DNA methylation level. CHB patients with higher levels of HBV DNA, AST, and GGT or higher GPRI scores exhibited lower VCX expression. In conclusion, SNPs and DNA methylation at the CHR X: 7810800 locus cooperatively regulate VCX expression in CHB. The upregulated VCX expression in female CHB patients might represent a mechanism of protection from more severe liver dysfunction and extensive fibrosis, as observed in male CHB patients.     

CRISPR‐LbCas12a‐mediated modification of citrus

Recently, CRISPR‐Cas12a (Cpf1) from Prevotella and Francisella was engineered to modify plant genomes. In this report, we employed CRISPR‐LbCas12a (LbCpf1), which is derived from Lachnospiraceae bacterium ND2006, to edit a citrus genome for the first time. First, LbCas12a was used to modify the CsPDS gene successfully in Duncan grapefruit via Xcc‐facilitated agroinfiltration. Next, LbCas12a driven by either the 35S or Yao promoter was used to edit the PthA4 effector binding elements in the promoter (EBE_PthA4‐CsLOBP) of CsLOB1. A single crRNA was selected to target a conserved region of both Type I and Type II CsLOBPs, since the protospacer adjacent motif of LbCas12a (TTTV) allows crRNA to act on the conserved region of these two types of CsLOBP. CsLOB1 is the canker susceptibility gene, and it is induced by the corresponding pathogenicity factor PthA4 in Xanthomonas citri by binding to EBE_PthA4‐CsLOBP. A total of seven 35S‐LbCas12a‐transformed Duncan plants were generated, and they were designated as #D₃₅s1 to #D₃₅s7, and ten Yao‐LbCas12a‐transformed Duncan plants were created and designated as #D_yao1 to #D_yao10. LbCas12a‐directed EBE_PthA4‐CsLOBP modifications were observed in three 35S‐LbCas12a‐transformed Duncan plants (#D₃₅s1, #D₃₅s4 and #D₃₅s7). However, no LbCas12a‐mediated indels were observed in the Yao‐LbCas12a‐transformed plants. Notably, transgenic line #D₃₅s4, which contains the highest mutation rate, alleviates XccΔpthA4:dCsLOB1.4 infection. Finally, no potential off‐targets were observed. Therefore, CRISPR‐LbCas12a can readily be used as a powerful tool for citrus genome editing.     

Ratiometric fluorescent detection of Cu2+ based on dual‐emission ZIF‐8@rhodamine‐B nanocomposites

Zeolitic imidazolate framework‐8 (ZIF‐8) loading rhodamine‐B (ZIF‐8@rhodamine‐B) nanocomposites was proposed and used as ratiometric fluorescent sensor to detect copper(II) ion (Cu²⁺). Scanning electron microscopy, Fourier transform infrared spectroscopy, X‐ray powder diffraction, nitrogen adsorption/desorption isotherms and fluorescence emission spectroscopy were employed to characterize the ZIF‐8@rhodamine‐B nanocomposites. The results showed the rhodamine‐B was successfully assembled on ZIF‐8 based on the π‐π interaction and the hydrogen bond between the nitrogen atom of ZIF‐8 and –COOH of rhodamine‐B. The as‐obtained ZIF‐8@rhodamine‐B nanocomposites were octahedron with size about 150–200 nm, had good water dispersion, and exhibited the characteristic fluorescence emission of ZIF‐8 at 335 nm and rhodamine‐B at 575 nm. The Cu²⁺ could quench fluorescence of ZIF‐8 rather than rhodamine‐B. The ZIF‐8 not only acted as the template to assemble rhodamine‐B, but also was employed as the signal fluorescence together with the fluorescence of rhodamine‐B as the reference to construct a novel ratiometric fluorescent sensor to detect Cu²⁺. The resulted ZIF‐8@rhodamine‐B nanocomposite fluorescence probe showed good linear range (68.4 nM to 125 μM) with a low detection limit (22.8 nM) for Cu²⁺ combined with good sensitivity and selectivity. The work also provides a better way to design ratiometric fluorescent sensors from ZIF‐8 and other fluorescent molecules.     

The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis

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ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition

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An In Situ Interface Reinforcement Strategy Achieving Long Cycle Performance of Dual‐Ion Batteries

Dual‐ion batteries (DIBs) with high operation voltage offer promising candidates for low‐cost clean energy chemistries. However, there still exist tough issues, including structural collapse of the graphite cathode due to solvent co‐intercalation and electrolyte decomposition on the electrode/electrolyte interface, which results in unsatisfactory cyclability and fast battery failure. Herein, Li₄Ti₅O₁₂ (LTO) modified mesocarbon microbeads (MCMBs) are proposed as a cathode material. The LTO layer functions as a skeleton and offers electrocatalytic active sites for in situ generation of a favorable and compatible cathode electrolyte interface (CEI) layer. The synergetic LTO‐CEI network can change the thermodynamic behavior of the PF₆^? intercalation process and maintain the structural integrity of the graphite cathode, as a “Great Wall” to protect the cathode from structural collapse and electrolyte decomposition. Such LTO‐CEI reinforced cathode exhibits a prolonged cyclability with 85.1% capacity retention after 2000 cycles even at cut‐off potential of 5.4 V versus Li⁺/Li. Moreover, the LTO‐modified MCMB (+)//prelithiated MCMB (?) full cell exhibits a high energy density of ≈200 Wh kg^?1, remarkably enhanced cyclability with 93.5% capacity retention after 1000 cycles. Undoubtedly, this work offers in‐depth insight into interface chemistry, which can arouse new originality to boost the development of DIBs.     

Chromosome‐level reference genome of X12, a highly virulent race of the soybean cyst nematode Heterodera glycines

Soybean cyst nematode (SCN, Heterodera glycines) is a major pest of soybean that is spreading across major soybean production regions worldwide. Increased SCN virulence has recently been observed in both the United States and China. However, no study has reported a genome assembly for H. glycines at the chromosome scale. Herein, the first chromosome‐level reference genome of X12, an unusual SCN race with high infection ability, is presented. Using whole‐genome shotgun (WGS) sequencing, Pacific Biosciences (PacBio) sequencing, Illumina paired‐end sequencing, 10X Genomics linked reads and high‐throughput chromatin conformation capture (Hi‐C) genome scaffolding techniques, a 141.01‐megabase (Mb) assembled genome was obtained with scaffold and contig N50 sizes of 16.27 Mb and 330.54 kilobases (kb), respectively. The assembly showed high integrity and quality, with over 90% of Illumina reads mapped to the genome. The assembly quality was evaluated using Core Eukaryotic Genes Mapping Approach and Benchmarking Universal Single‐Copy Orthologs. A total of 11,882 genes were predicted using de novo, homolog and RNAseq data generated from eggs, second‐stage juveniles (J2), third‐stage juveniles (J3) and fourth‐stage juveniles (J4) of X12, and 79.0% of homologous sequences were annotated in the genome. These high‐quality X12 genome data will provide valuable resources for research in a broad range of areas, including fundamental nematode biology, SCN–plant interactions and co‐evolution, and also contribute to the development of technology for overall SCN management.     

Genetic variations of NOD2 and MD2 genes in hepatitis B virus infection

Objectives: Nucleotide oligomerization domain 2 (NOD2) and myeloid differentiation protein 2 (MD-2) have crucial roles in the innate immune system. NOD2 is a member of the NOD-like receptor (NLR) family of pattern recognition receptors (PRRs), while MD-2 is a co-receptor for Toll-like receptor 4 (TLR4), which comprises another group of PRRs. Genetic variations in the NOD2 and MD-2 genes may be susceptibility factors to viral pathogens including hepatitis B virus (HBV). We investigated whether polymorphisms at NOD2 (rs2066845 and rs2066844) or at MD-2 (rs6472812 and rs11466004) were associated with susceptibility to HBV infection and advancement to related liver complications in a Saudi Arabian population. Methods: A total of 786 HBV-infected patients and 600 healthy uninfected controls were analyzed in the present study. HBV-infected patients were categorized into three groups based on the clinical stage of the infection: inactive HBV carriers, active HBV carriers, and patients with liver cirrhosis + hepatocellular carcinoma (HCC). Results: All four SNPs were significantly associated with susceptibility to HBV infection although none of the SNPs tested in NOD2 and MD-2 were significantly associated with persistence of HBV infection. We found that HBV-infected patients that were homozygous CC for rs2066845 in the NOD2 gene were at a significantly increased risk of progression to HBV-related liver complications (Odds Ratio = 7.443 and P = 0.044). Furthermore, haplotype analysis found that the rs2066844-rs2066845 C-G and T-G haplotypes at the NOD2 gene and four rs6472812-rs11466004 haplotypes (G-C, G-T, A-C, and A-T) at the MD-2 gene were significantly associated with HBV infection in the affected cohort compared to those found in our control group. Conclusion: We found that the single nucleotide polymorphisms rs2066844 and rs2066845 at NOD2 and rs6472812 and rs11466004 at MD-2 were associated with susceptibility to HBV infection in a Saudi population.