Methyltransferase-like 3-mediated N6-methyladenosine modification of miR-7212-5p drives osteoblast differentiation and fracture healing

N6-methyladenosine (m6A) modification has been reported in various diseases and implicated in increasing numbers of biological processes. However, previous studies have not focused on the role of m6A modification in fracture healing. Here, we demonstrated that m6A modifications are decreased during fracture healing and that methyltransferase-like 3 (METTL3) is the main factor involved in the abnormal changes in m6A modifications. Down-regulation of METTL3 promotes osteogenic processes both in vitro and in vivo, and this effect is recapitulated by the suppression of miR-7212-5p maturation. Further studies have shown that miR-7212-5p inhibits osteoblast differentiation in MC3T3-E1 cells by targeting FGFR3. The present study demonstrated an important role of the METTL3/miR-7212-5p/FGFR3 axis and provided new insights on m6A modification in fracture healing.     

Surface display of ACC deaminase on endophytic <Emphasis Type="Italic">Enterobacteriaceae</Emphasis> strains to increase saline resistance of host rice sprouts by regulating plant ethylene synthesis

Background

Most endophytic bacteria in consortia, which provide robust and broad metabolic capacity, are attractive for applications in plant metabolic engineering. The aim of this study was to investigate the effects of engineered endophytic bacterial strains on rice sprout ethylene level and growth under saline stress. A protocol was developed to synthesize engineered strains by expressing bacterial 1-aminocyclopropane-1-carboxylate (ACC) deaminase gene on cells of endophytic Enterobacter sp. E5 and Kosakonia sp. S1 (denoted as E5P and S1P, respectively).

Results

Results showed that ACC deaminase activities of the engineered strains E5P and S1P were significantly higher than those of the wild strains E5 and S1. About 32–41% deaminase was expressed on the surface of the engineered strains. Compared with the controls without inoculation, inoculation with the wild and engineered strains increased the deaminase activities of sprouts. Inoculation with the engineered strains increased 15–21% more deaminase activities of sprouts than with the wild strains, and reduced the ethylene concentrations of sprouts more significantly than with wild strains (P < 0.05). Inoculation with the wild and engineered strains promoted the growth of sprouts, while the promoting effects were more profound with the engineered strains than with the wild strains. The engineered strains improved saline resistance of sprouts under salt concentrations from 10 to 25 g L^?1. The engineered strains promoted longer roots and shoots than the wild strains under the salt stresses, indicating that the ACC deaminases on the endophytic bacterial cells could result in plant-produced ACC degradation and inhibit plant ethylene formation.

Conclusions

The protocols of expressing enzymes on endophytic bacterial cells showed greater potentials than those of plant over-expressed enzymes to increase the efficiency of plant metabolic pathways.

     

PVP Treatment Induced Gradient Oxygen Doping in In2S3 Nanosheet to Boost Solar Water Oxidation of WO3 Nanoarray Photoanode

The photoelectrochemical performance of the WO₃ photoanode is limited by the severe charge recombination in the bulk phase and at the WO₃/electrolyte interface. Herein, In₂S₃ nanosheets are integrated onto the surface of the WO₃ nanowall array photoanode, followed by a facile polyvinylpyrrolidone (PVP) solution treatment. The PVP treatment results in sulfur vacancies and a gradient oxygen doping into In₂S₃ from surface to interior, which induces the formation of a gradient energy band distribution. The gradient band structured In₂S₃ and type II band alignment at the WO₃/In₂S₃ interface simultaneously create a channel that favors photogenerated electrons to migrate from the surface to the conductive substrate, thereby suppressing bulk carrier recombination. Meanwhile, the sulfur vacancies and oxygen doping contribute to increased charge carrier concentration, prolonged carrier lifetime, more active sites, and small interfacial transfer impedance. As a consequence, the PVP treated WO₃/In₂S₃ heterostructure photoanode exhibits a significantly enhanced photocurrent of 1.61 mA cm^?2 at 1.23 V versus reversible hydrogen electrode (RHE) and negative onset potential of 0.02 V versus RHE.     

2021年膜翅目新增分类单元

本文对2021年发表的膜翅目昆虫新分类单元进行了梳理和总结。结合数据库检索, 基于标本记录, 全球膜翅目学者于2021年发表该目新分类单元的期刊论文355篇, 新增分类单元条目共1,152条, 隶属于21总科66科416属, 包括5新科4新亚科83新属3新亚属1,054新种和3新亚种。现生类群相关期刊论文309篇, 新增分类单元条目980条, 隶属于18总科52科332属, 包括2新科26新属3新亚属946新种和3新亚种。绝灭类群相关期刊论文46篇, 新增分类单元条目172条, 隶属于14总科27科86属, 包括3新科4新亚科57新属和108新种。2021年中国膜翅目新增分类单元的相关期刊论文83篇, 新增分类单元条目235条, 隶属于17总科34科91属, 包括3新属(绝灭类群1新属)和232新种(绝灭类群2新种); 现生类群中新增的2属分别记录自台湾和浙江, 新种数量排前五位的省级行政单位有云南(54个)、浙江(42个)、福建(18个)、西藏(18个)和新疆(16个)。在全球现生、绝灭和中国现生膜翅目总科新物种数量的对比中, 姬蜂总科新种数量最多, 分别约占全球现生、绝灭和中国现生膜翅目新种总数的32.5% (307个/946个)、19.4% (21个/108个)和37.0% (85个/230个)。有关现生膜翅目新种发表情况, 在洲级地理单元中, 亚洲发表新种数量最多, 约占56.9% (538个); 在洲级地理亚单元中, 东亚发表新种数量最多, 约占28.6% (271个); 在国家和地区行政单元中, 中国发表新种数量最多, 约占24.3% (230个)。在76种期刊的355篇论文中, 有348篇英文论文、4篇中文论文和3篇法语论文。这些结果表明, 中国膜翅目分类在全球膜翅目分类中发挥着十分重要的作用。     

MicroRNA‐183‐5p is stress‐inducible and protects neurons against cell death in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons. A fundamental pathogenesis of ALS is the prolonged cell stress in neurons, which is caused by either accumulation of protein aggregates or reactive oxygen species. However, the mechanistic link between stress sensing and cell death is unsettled. Here, we identify that miR‐183‐5p, a neuron‐enriched miRNA, couples stress sensing and cell death programming in ALS. miR‐183‐5p is immediately induced by hydrogen peroxide, tunicamycin or TNF‐α in neurons. The overexpression of miR‐183‐5p increases neuron survival under stress conditions, whereas its knockdown causes neuron death. miR‐183‐5p coordinates apoptosis and necroptosis pathways by directly targeting PDCD4 and RIPK3, and thus protects neurons against cell death under stress conditions. The consistent reduction of miR‐183‐5p in ALS patients and mouse models enhances the notion that miR‐183‐5p is a central regulator of motor neuron survival under stress conditions. Our study supplements current understanding of the mechanistic link between cell stress and death/survival, and provides novel targets for clinical interventions of ALS.     

Identification, mapping, and application of polymorphic DNA associated with resistance gene Pm21 of wheat.

A new powdery mildew resistance gene designated Pm21, from Haynaldia villosa, a relative of wheat, has been identified and incorporated into wheat through an alien translocation line. Cytogenetic and biochemical analyses showed that chromosome arms 6VS and 6AL were involved in this translocation. Random amplified polymorphic DNA (RAPD) analysis was performed on recipient wheat cultivar Yangmai 5, the translocation line, and H. villosa with 180 random primers. Eight of the 180 primers amplified polymorphic DNA in the translocation line, and the same results were obtained in four replications. Furthermore, RAPD analysis was reported for substitution line 6V, seven addition lines (1V-7V), and the F1, as well as F2 plants of (translocation line x 'Yangmai 5'), using two of the eight random primers. One RAPD marker, specific to chromosome arm 6VS, OPH17-1900, could be used as a molecular marker for the detection of gene Pm21 in breeding materials with powdery mildew resistance introduced from H. villosa. Key words : RAPD analysis, 6VS-specific marker, Pm21, Erysiphe graminis f.sp. tritici, Triticum aestivum - Haynaldia villosa translocation.     

Solution structure of BmKalphaIT01, an alpha-insect toxin from the venom of the Chinese scorpion Buthus martensii Karsch

The solution structure of an alpha-insect toxin from Buthus martensii Karsch, BmKalphaIT01, has been determined by two-dimensional NMR spectroscopy and molecular modeling techniques. Combining the sequence homology comparison and toxicity bioassays, BmKalphaIT01 has been suggested to be a natural mutant of alpha-insect toxins and so can serve as a tool to study the relationship of structure-function among this group of toxins. The overall structure of BmKalphaIT01 shares a common core structure consisting of an alpha-helix packed against a three-stranded antiparallel beta-sheet, which exhibits distinctive local conformations within the loops connecting these secondary structure elements. The solution structure of BmKalphaIT01 features a non-proline cis peptide bond between Asn9 and Tyr10, which is proposed to mediate the spatial closing of the five-residue turn (Gln8-Cys12) and the C-terminal segment (Arg58-His64) to form the NC domain and confer the toxin insect-specific bioactivity. Conformational heterogeneity is observed in the solution of BmKalphaIT01 and could be attributed to the cis-trans isomerization of the peptide bond between residues 9 and 10. The minor conformation of BmKalphaIT01 with a trans peptide bond between Asn9 and Tyr10 may be responsible for its moderate bioactivity against mammals. The cis-trans isomerization of the peptide bond between residues 9 and 10 may be the structural basis of dual pharmacological activities of alpha-insect and alpha-like scorpion toxins, which is supported by the fact that conformational heterogeneity occurs in the solution structures of LqhalphaIT, LqqIII, and LqhIII and by comparison of the solution structure of BmKalphaIT01 with those of some relevant alpha-type toxins.     

Metabolomic approach to evaluating adriamycin pharmacodynamics and resistance in breast cancer cells

Continuous exposure of breast cancer cells to adriamycin induces high expression of P-gp and multiple drug resistance. However, the biochemical process and the underlying mechanisms for the gradually induced resistance are not clear. To explore the underlying mechanism and evaluate the anti-tumor effect and resistance of adriamycin, the drug-sensitive MCF-7S and the drug-resistant MCF-7Adr breast cancer cells were used and treated with adriamycin, and the intracellular metabolites were profiled using gas chromatography mass spectrometry. Principal components analysis of the data revealed that the two cell lines showed distinctly different metabolic responses to adriamycin. Adriamycin exposure significantly altered metabolic pattern of MCF-7S cells, which gradually became similar to the pattern of MCF-7Adr, indicating that metabolic shifts were involved in adriamycin resistance. Many intracellular metabolites involved in various metabolic pathways were significantly modulated by adriamycin treatment in the drug-sensitive MCF-7S cells, but were much less affected in the drug-resistant MCF-7Adr cells. Adriamycin treatment markedly depressed the biosynthesis of proteins, purines, pyrimidines and glutathione, and glycolysis, while it enhanced glycerol metabolism of MCF-7S cells. The elevated glycerol metabolism and down-regulated glutathione biosynthesis suggested an increased reactive oxygen species (ROS) generation and a weakened ability to balance ROS, respectively. Further studies revealed that adriamycin increased ROS and up-regulated P-gp in MCF-7S cells, which could be reversed by N-acetylcysteine treatment. It is suggested that adriamycin resistance is involved in slowed metabolism and aggravated oxidative stress. Assessment of cellular metabolomics and metabolic markers may be used to evaluate anti-tumor effects and to screen for candidate anti-tumor agents.