Highly Stable 72-Nuclearity Nanocages for Efficient Synthesis of Aryl Nitriles via Ni/Cu Synergistic Catalysis.

Seeking noble-metal-free catalysts for efficient synthesis of aryl nitriles under mild conditions poses a significant challenge due to the use of hypertoxic cyanides or high-pressure/temperature NH3/O2 in conventional synthesis processes. Herein, we developed a novel framework 1 assembled by [Ni72] nanocages with excellent solvents/pH stability. To investigate the structure-activity relationship of catalytic performance, several isostructural MOFs with different molar ratios of Ni/Cu by doping Cu2+ into framework 1 (Ni0.59Cu0.41 (2), Ni0.81Cu0.19 (3), Ni0.88Cu0.12 (4), and Ni0.92Cu0.08 (5)) were prepared. Catalytic studies revealed that catalyst 3 exhibited remarkable performance in the synthesis of aryl nitriles, utilizing a formamide alternative to hypertoxic NaCN/KCN. Notably, catalyst 3 achieved an excellent TOF value of 9.8 h-1. Furthermore, catalyst 3 demonstrated its applicability in a gram-scale experiment and maintained its catalytic performance even after six recycling cycles, owing to its high stability resulting from significant electrostatic and orbital interactions between the Ni center and ligands as well as a large SOMO-LUMO energy gap supported by DFT calculations. Control experiments and DFT calculations further revealed that the excellent catalytic performance of catalyst 3 originated from the synergistic effect of Ni/Cu. Importantly, this work not only provides a highly feasible method to construct highly stable MOFs containing multinuclear nanocages with exceptional catalytic performance but also represents the first example of a heterogeneous catalyst for the synthesis of aryl nitriles using formamide as the cyanide source.

R-loop and diseases: the cell cycle matters.

The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.

Discovery of Selective and Potent ATR Degrader for Exploration its Kinase-Independent Functions in Acute Myeloid Leukemia Cells.

ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader. Its kinase-independent regulatory functions in acute myeloid leukemia (AML) cells were elucidated using this proteolysis-targeting chimera (PROTAC) molecule as a probe. The ATR degrader, 8 i, exhibited significantly different cellular phenotypes compared to the ATR kinase inhibitor 1. Mechanistic studies revealed that ATR deletion led to breakdown in the nuclear envelope, causing genome instability and extensive DNA damage. This would increase the expression of p53 and triggered immediately p53-mediated apoptosis signaling pathway, which was earlier and more effective than ATR kinase inhibition. Based on these findings, the in vivo anti-proliferative effects of ATR degrader 8 i were assessed using xenograft models. The degrader significantly inhibited the growth of AML cells in vivo, unlike the ATR inhibitor. These results suggest that the marked anti-AML activity is regulated by the kinase-independent functions of the ATR protein. Consequently, developing potent and selective ATR degraders could be a promising strategy for treating AML.

Dihydroartemisinin abolishes cisplatin-induced nephrotoxicity in vivo.

Dihydroartemisinin (DHA), a derivative of artemisinin which is primarily used to treat malaria in clinic, also confers protective effect on lipopolysaccharide-induced nephrotoxicity. While, the activities of DHA in cisplatin (CDDP)-caused nephrotoxicity are elusive. To investigate the role and underlying mechanism of DHA in CDDP-induced nephrotoxicity. Mice were randomly separated into four groups: normal, CDDP, and DHA (25 and 50 mg/kg were orally injected 1 h before CDDP for consecutive 10 days). All mice except the normal were single injected intraperitoneally with CDDP (22 mg/kg) for once on the 7th day. Combined with quantitative proteomics and bioinformatics analysis, the impact of DHA on renal cell apoptosis, oxidative stress, biochemical indexes, and inflammation in mice were investigated. Moreover, a human hepatocellular carcinoma cells xenograft model was established to elucidate the impact of DHA on tumor-related effects of CDDP. DHA reduced the levels of creatinine (CREA) (p < 0.01) and blood urea nitrogen (BUN) (p < 0.01), reversed CDDP-induced oxidative, inflammatory, and apoptosis indexes (p < 0.01). Mechanistically, DHA attenuated CDDP-induced inflammation by inhibiting nuclear factor κB p65 (NFκB p65) expression, and suppressed CDDP-induced renal cell apoptosis by inhibiting p63-mediated endogenous and exogenous apoptosis pathways. Additionally, DHA alone significantly decreased the tumor weight and did not destroy the antitumor effect of CDDP, and did not impact AST and ALT. In conclusion, DHA prevents CDDP-triggered nephrotoxicity via reducing inflammation, oxidative stress, and apoptosis. The mechanisms refer to inhibiting NFκB p65-regulated inflammation and alleviating p63-mediated mitochondrial endogenous and Fas death receptor exogenous apoptosis pathway.

An Efficient Homologous Recombination-Based In Situ Protein-Labeling Method in Verticillium dahliae.

Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.

Hierarchically core-shell structured nanocellulose/carbon nanotube hybrid aerogels for patternable, self-healing and flexible supercapacitors.

The flexible and self-healing supercapacitors (SCs) are considered to be promising smart energy storage devices. Nevertheless, the SCs integrated with flexibility, lightweight, pattern editability, self-healing capabilities and desirable electrochemical properties remain a challenge. Herein, an all-in-one self-healing SC fabricated with the free-standing hybrid film (TCMP) composed of the 2,2,6,6-tetramethylpiperidin-1-yloxy-oxidized cellulose nanofibers (TOCNs) carried carbon nanotubes (CNTs), manganese dioxide (MnO2) and polyaniline (PANI) as the electrode, polyvinyl alcohol/sulfuric acid (PVA/H2SO4) gel as the electrolyte and dynamically cross-linked cellulose nanofibers/PVA/sodium tetraborate decahydrate (CNF/PB) hydrogel as the self-healing electrode matrix is developed. The TCMP film electrodes are fabricated through a facile in-situ polymerization of MnO2 and PANI in TOCNs-dispersed CNTs composite networks, exhibiting lightweight, high electrical conductivity, flexibility, pattern editability and excellent electrochemical properties. Benefited from the hierarchically porous structure and high mechanical properties of TOCNs, excellent electrical conductivity of CNTs and the desirable synergistic effect of pseudocapacitance induced by MnO2 and PANI, the assembled SC with an interdigital structure demonstrated a high areal capacitance of 1108 mF cm-2 at 2 mA cm-2, large areal energy density of 153.7 µWh cm-2 at 1101.7 µW cm-2. A satisfactory bending cycle performance (capacitance retention up to 95 % after 200 bending deformations) and self-healing characteristics (∼90 % capacitance retention after 10 cut/repair cycles) are demonstrated for the TCMP-based symmetric SC, delivering a feasible strategy for electrochemical energy storage devices with excellent performance, designable patterns and desirable safe lifespan.

The role of ADAR1 through and beyond its editing activity in cancer.

Adenosine-to-inosine (A-to-I) editing of RNA, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, is a prevalent RNA modification in mammals. It has been shown that A-to-I editing plays a critical role in multiple diseases, such as cardiovascular disease, neurological disorder, and particularly cancer. ADARs are the family of enzymes, including ADAR1, ADAR2, and ADAR3, that catalyze the occurrence of A-to-I editing. Notably, A-to-I editing is mainly catalyzed by ADAR1. Given the significance of A-to-I editing in disease development, it is important to unravel the complex roles of ADAR1 in cancer for the development of novel therapeutic interventions.In this review, we briefly describe the progress of research on A-to-I editing and ADARs in cancer, mainly focusing on the role of ADAR1 in cancer from both editing-dependent and independent perspectives. In addition, we also summarized the factors affecting the expression and editing activity of ADAR1 in cancer.

GetPrimers: A generalized PCR-based genetic targeting primer designer enabling easy and standardized targeted gene modification across multiple systems.

Genetic targeting (e.g., gene knockout and tagging) based on polymerase chain reaction (PCR) is a simple yet powerful approach for studying gene functions. Although originally developed in classic budding and fission yeast models, the same principle applies to other eukaryotic systems with efficient homologous recombination. One-step PCR-based genetic targeting is conventionally used but the sizes of the homologous arms that it generates for recombination-mediated genetic targeting are usually limited. Alternatively, gene targeting can also be performed via fusion PCR, which can create homologous arms that are orders of magnitude larger, therefore substantially increasing the efficiency of recombination-mediated genetic targeting. Here, we present GetPrimers (https://www.evomicslab.org/app/getprimers/), a generalized computational framework and web tool to assist automatic targeting and verification primer design for both one-step PCR-based and fusion PCR-based genetic targeting experiments. Moreover, GetPrimers by design runs for any given genetic background of any species with full genome scalability. Therefore, GetPrimers is capable of empowering high-throughput functional genomic assays at multipopulation and multispecies levels. Comprehensive experimental validations have been performed for targeting and verification primers designed by GetPrimers across multiple organism systems and experimental setups. We anticipate GetPrimers to become a highly useful and popular tool to facilitate easy and standardized gene modification across multiple systems.

Andrographolide anti-proliferation and metastasis of hepatocellular carcinoma through LncRNA MIR22HG regulation.

Hepatocellular carcinoma (HCC) treatment is a major challenge. Although andrographolide (Andro) has an anti-proliferation effect on HCC, its underlying mechanism is not yet elucidated, and whether Andro can inhibit HCC metastasis has not been reported. The present study aimed to clarify whether Andro inhibits SK-Hep-1 cell proliferation and HCC metastasis, and the mechanisms. The results showed that Andro significantly reduced the survival of HCC cells and tumor weight and volume in tumor-bearing nude mice. Andro also triggered apoptosis of HCC cells and upregulated MIR22HG, Cleaved Caspase 9/7/3 expression levels, and downregulated BCL-2 mRNA, BCL-2 expression levels. Knockdown of MIR22HG or overexpression of HuR attenuated the effects of Andro on the signal transduction of mitochondrial apoptotic pathway and proliferation ability in HCC cells. Moreover, Andro significantly reduced the invasive ability of the cells and the level of HCC cell lung metastasis, upregulated miR-22-3p expression level and downregulated HMGB1 and MMP-9 expression levels. MIR22HG or miR-22-3p knockdown attenuated the effects of Andro on the signaling of HMGB1/MMP-9 pathway and invasive ability in HCC cells, while the overexpression of HMGB1 attenuated the inhibitory effects of Andro on the MMP-9 expression level and invasive ability in HCC cells. Thus, the regulation of MIR22HG-HuR/BCL-2 and MIR22HG/HMGB1 signaling pathways is involved in the anti-HCC proliferation and metastasis effects of Andro. This study provided a new pharmacological basis for Andro in HCC treatment and, for the first time, identified a natural product molecule capable of positively regulating MIR22HG, which has a robust biological function.

Detection of Various Traditional Chinese Medicinal Metabolites as Angiotensin-Converting Enzyme Inhibitors: Molecular Docking, Activity Testing, and Surface Plasmon Resonance Approaches.

Angiotensin-converting enzyme 1 (ACE1) is a peptide involved in fluid and blood pressure management. It regulates blood pressure by converting angiotensin I to angiotensin II, which has vasoconstrictive effects. Previous studies have shown that certain compounds of natural origin can inhibit the activity of angiotensin-converting enzymes and exert blood pressure-regulating effects. Surface Plasmon Resonance (SPR) biosensor technology is the industry standard method for observing biomolecule interactions. In our study, we used molecular simulation methods to investigate the docking energies of various herbal metabolites with ACE1 proteins, tested the real-time binding affinities between various herbal metabolites and sACE1 by SPR, and analyzed the relationship between real-time binding affinity and docking energy. In addition, to further explore the connection between inhibitor activity and real-time binding affinity, several herbal metabolites' in vitro inhibitory activities were tested using an ACE1 activity test kit. The molecular docking simulation technique's results and the real-time affinity tested by the SPR technique were found to be negatively correlated, and the virtual docking technique still has some drawbacks as a tool for forecasting proteins' affinities to the metabolites of Chinese herbal metabolites. There may be a positive correlation between the enzyme inhibitory activity and the real-time affinity detected by the SPR technique, and the results from the SPR technique may provide convincing evidence to prove the interaction between herbal metabolites and ACE1 target proteins.

Trifolium repens L.-Like Periodic Micronano Structured Superhydrophobic Surface with Ultralow Ice Adhesion for Efficient Anti-Icing/Deicing.

Wind turbine blades are often covered with ice and snow, which inevitably reduces their power generation efficiency and lifetime. Recently, a superhydrophobic surface has attracted widespread attention due to its potential values in anti-icing/deicing. However, the superhydrophobic surface can easily transition from Cassie-Baxter to Wenzel at low temperature, limiting its wide applications. Herein, inspired by the excellent water resistance and cold tolerance of Trifolium repens L. endowed by its micronano structure and low surface energy, a fresh structure was prepared by combining femtosecond laser processing technology and a boiling water treatment method. The prepared icephobic surface aluminum alloy (ISAl) mainly consists of a periodic microcrater array, nonuniform microclusters, and irregular nanosheets. This three-scale structure greatly promotes the stability of the Cassie-Baxter state. The critical Laplace pressure of ISAl is up to 1437 Pa, and the apparent water contact angle (CA) is higher than 150° at 0 °C. Those two factors contribute to its excellent anti-icing and deicing performances. The results show that the static icing delay time reaches 2577 s, and the ice adhesion strength is only 1.60 kPa. Furthermore, the anti-icing and deicing abilities of the proposed ISAl were examined under the environment of low temperature and high relative humidity to demonstrate its effectiveness. The dynamic anti-icing time of ISAl in extreme environments is up to 5 h, and ice can quickly fall with a speed of 34 r/min when it is in a horizontal rotational motion. Finally, ISAl has excellent reusability and mechanical durability, with the ice adhesion strength still being less than 6 kPa and the CA greater than 150° after 15 cycles of icing-deicing tests. The proposed structure would offer a promising strategy for the efficient anti-icing and deicing of wind turbine blades.

Endoscopic diagnosis and treatment of superficial non-ampullary duodenal epithelial tumors: A review.

The surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics. To date, white light endoscopy (WLE) remains the cornerstone of endoscopic diagnosis for SNADETs. Besides, narrow-band imaging (NBI) techniques and magnifying endoscopy (ME) have been widely used in the clinic and endorsed by multiple guidelines and consensuses for SNADETs' evaluation. Confocal laser endomicroscopy (CLE), endocytoscopy (ECS), and artificial intelligence (AI) are also up-and-coming methods, showing an exceptional value in the diagnosis of SNADETs. Similar to the endoscopic treatment for colorectal polyps, the choices for SNADETs mainly include cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and laparoscopic endoscopic cooperative surgery (LECS). However, owing to the narrow lumen, rich vascularity, weak muscle layer, abundant Brunner's gland, and the hardship of endoscope control, the duodenum ranks as one of the most dangerous operating areas in the digestive tract. Therefore, endoscopists must anticipate the difficulties in endoscopic maneuverability, remain aware of the increased risk of complications, and then select the appropriate treatment according to the advantages and disadvantages of each method.

Biomass-Derived Carbon Aerogels for ORR/OER Bifunctional Oxygen Electrodes.

The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are crucial electrochemical reactions that play vital roles in energy conversion and storage technologies, such as fuel cells and metal-air batteries. Typically, noble-metal-based catalysts are required to enhance the sluggish kinetics of the ORR and OER, but their high costs restrict their practical commercial applications. Thus, highly active and strong non-noble metal catalysts are essential to address the cost and durability challenge. Based on previous research, carbon-based catalysts may present the best alternatives to these precious metals in the future owing to their affordability, very large surface areas, and superior mechanical and electrical qualities. In particular, carbon aerogels prepared using biomass as the precursors are referred to as biomass-derived carbon aerogels. They have sparked broad attention and demonstrated remarkable performance in the energy conversion and storage sectors as they are ecologically beneficial, affordable, and have an abundance of precursors. Therefore, this review focuses on various nanostructured materials based on biomass-derived carbon aerogels as ORR/OER catalysts, including metal atoms, metal compounds, and alloys.

Impact of Insect-Resistant Transgenic Maize 2A-7 on Diversity and Dynamics of Bacterial Communities in Rhizosphere Soil.

Artificial modification of Bacillus thuringiensis (Bt) proteins can effectively improve their resistance to target pests, but the effect of such modification on the diversity of rhizosphere microorganisms remains unclear. Transgenic maize 2A-7 contains two artificially modified Bt proteins, mCry1Ab and mCry2Ab. These proteins can enter soil and pose a potential threat to soil microbial diversity. To assess their impacts on rhizosphere bacteria communities, the contents of the two Bt proteins and changes in bacterial community diversity in the rhizosphere soils of transgenic maize 2A-7 and its control variety were analyzed at different growth stages in 2020. The results showed that the two Bt proteins were detected at low levels in the rhizosphere soils of 2A-7 plants. No significant differences in soil bacterial diversity were detected between 2A-7 and its control variety at any of the growth stages. Bioinformatics analysis indicated that the growth stage, rather than the cultivar, was the main factor causing changes in bacterial communities. This research provides valuable data for understanding the impact of Bt crops on the soil microbiome, and establishes a theoretical basis for evaluation of their safety.

The presence of copper ions alters tetracycline removal pathway in aerobic granular sludge: Performance and mechanism.

This study investigated the removal characteristics of tetracycline (TC) in the presence of copper ions (Cu2+) in aerobic granular sludge by analyzing the TC removal pathway, composition and functional group changes of extracellular polymeric substances (EPS), and microbial community structure. The TC removal pathway changed from cell biosorption to EPS biosorption, and the microbial degradation rate of TC was reduced by 21.37% in the presence of Cu2+. Cu2+ and TC induced enrichment of denitrifying bacteria and EPS-producing bacteria by regulating the expression of signaling molecules and amino acid synthesis genes to increase the content of EPS and -NH2 groups in EPS. Although Cu2+ reduced the content of acidic hydroxyl functional groups (AHFG) in EPS, an increase in TC concentration stimulated the secretion of more AHFG and -NH2 groups in EPS. The long-term presence of TC presence of the relative abundances of Thauera, Flavobacterium and Rhodobacter and improved the removal efficiency.

Effect of 3-Dimensional Imaging Device on Polyp and Adenoma Detection During Colonoscopy: A Randomized Controlled Trial.

INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.

The performance and mechanism of tetracycline and ammonium removal by Pseudomonas sp. DX-21.

To remove ammonium and tetracycline (TC) from wastewater, a new strain, DX-21, was isolated and exhibited simultaneous removal ability. The performance of DX-21 in TC removal, its removal mechanism, and the potential toxicities of the degradation products were investigated with genomics, mass spectrometry, density functional theory calculations, quantitative structure-activity relationship analyses, and Escherichia coli exposure experiments. DX-21 exhibited removal of ammonium (9.64 mg·L-1·h-1) via assimilation, and TC removal (0.85 mg·L-1·h-1) primarily occurred through cell surface bio-adsorption and biodegradation. Among the 12 identified degradation products, the majority exhibited lower toxicities than TC. Moreover, potential degradation pathways were proposed, including hydroxylation and deamination. Furthermore, DX-21 possessed TC resistance genes, various oxygenases and peroxidases that could potentially contribute to TC degradation. DX-21 colonized activated sludge and significantly enhanced the biodegradation of TC. Therefore, DX-21 showed potential for treating wastewater containing both ammonium and TC.

Design and discovery of new selective and potent VEGF receptor 2 tyrosine kinase inhibitors.

A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared by 3D modeling as potential inhibitors of VEGFR-2. Evaluation of VEGFR inhibitory activities suggested that compound I10 was a more potent (IC50 = 0.11 nM) VEGFR-2 inhibitor than most of the listed drugs. Kinase panel assays demonstrated that compound I10 was the selective VEGFR-2 inhibitor. The prediction of 3D modeling unveiled a unique binding mode of this lead compound to VEGFR-2. Compound I10 exhibited remarkable anti-angiogenesis and anti-proliferation in HUVEC at low nanomolar concentrations. PK studies indicated that the lead compound possessed adequate oral bioavailability in various species. In vivo subcutaneous tumor model demonstrated that oral administration of I10 demonstrated potent efficacy in inhibiting tumor growth and angiogenesis. All these results suggested compound I10 is a potential drug candidate for cancer treatment.

Effects of stacking breeding on the methylome and transcriptome profile of transgenic rice with glyphosate tolerance.

MAIN CONCLUSION: Transcriptomics and methylomics were used to identify the potential effects resulting from GM rice breeding stacks, which provided scientific data for the safety assessment strategy of stacked GM crops in China. Gene interaction is one of the main concerns for stacked genetically modified crop safety. With the development of technology, the combination of omics and bioinformatics has become a useful tool to evaluate the unintended effects of genetically modified crops. In this study, transcriptomics and methylomics were used as molecular profiling techniques to identify the potential effects of stack through breeding. Stacked transgenic rice En-12 × Ec-26 was used as material, which was obtained through hybridization using parents En-12 and Ec-26, in which the foreign protein can form functional EPSPS protein by intein-mediated trans-splitting. Differentially methylated region (DMR) analysis showed that the effect of stacking breeding on methylation was less than that of genetic transformation at the methylome level. Differentially expressed gene (DEG) analysis showed that the DEGs between En-12 × Ec-26 and its parents were far fewer than those between transgenic rice and Zhonghua 11 (ZH11), and no unintended new genes were found in En-12 × Ec-26. Statistical analysis of gene expression and methylation involved in shikimic acid metabolism showed that there was no difference in gene expression, although there were 16 and 10 DMR genes between En-12 × Ec-26 and its parents (En and Ec) in methylation, respectively. The results indicated that the effect of stacking breeding on gene expression and DNA methylation was less than the effect of genetic transformation. This study provides scientific data supporting safety assessments of stacked GM crops in China.

Microbial communities and their roles in the Cenozoic sulfurous oil reservoirs in the Southwestern Qaidam Basin, Western China.

The latest discovery of sulfurous natural gas marked a breakthrough in the Cenozoic natural gas exploration in the southwestern margin of Qaidam Basin. The 16S rRNA analyses were performed on the crude oil samples from H2S-rich reservoirs in the Yuejin, Shizigou and Huatugou profiles, to understand the sulfurous gas origin, which was also integrated with carbon and hydrogen isotopes of alkane and sulfur isotopes of H2S collected from the Yingxiongling Area. Results show that the microorganisms in samples can survive in the hypersaline reservoirs, and can be classified into multiple phyla, including Proteobacteria, Planctomycetes, Firmicutes, Bacteroidetes, and Haloanaerobiaeota. Methanogens are abundant in all of the three profiles, while sulfate-reducing bacteria are abundant in Yuejin and Huatugou profiles, contributing to the methane and H2S components in the natural gas. The carbon, hydrogen and sulfur isotopes of sulfurous natural gas in the Yingxiongling Area show that the natural gas is a mixture of coal-type gas and oil-type gas, which was primarily derived from thermal degradation, and natural gas from the Yuejin and Huatugou profiles also originated from biodegradation. The isotopic analysis agrees well with the 16S rRNA results, i.e., H2S-rich natural gas from the Cenozoic reservoirs in the southwest margin of the Qaidam Basin was primarily of thermal genesis, with microbial genesis of secondary importance.