表观“阅读器”BET蛋白家族对哺乳动物发育和iPSC重编程的调控

溴结构域和超末端结构域(bromodomain and extra-terminal,BET)蛋白家族作为表观"阅读器",在哺乳动物发育过程中起着至关重要的作用。其家族内的各成员通过识别各种表观修饰并募集相应的功能复合物,对相关基因进行精密调控,促使早期胚胎向特定方向分化和发育。另外,随着诱导性多潜能干细胞(induced pluripotent stem cell,iPSC)重编程技术发展,越来越多的研究发现BET蛋白家族在体细胞重编程中可能也占据着核心地位。本文总结了BET蛋白家族在哺乳动物发育和iPSC重编程中的作用,并对BET家族调控重编程的新机制进行了展望。

机械敏感蛋白PC1调控破骨细胞及骨吸收的作用机制

Mechanical loading is required for bone homeostasis,but the underlying mechanism is still unclear.Our previous studies revealed that the mechanical protein polycystin-1(PC1,encoded by Pkd1)is critical for bone formation.However,the role of PC1 in bone resorption is unknown.Here,we found that PC1directly regulates osteoclastogenesis and bone resorption.The conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts,decreased bone resorption,and increased bone mass.A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease,which is mainly caused by loss-of-function mutation of the PKD1 gene,is associated with a lower risk of hip fracture than those with other chronic kidney diseases.Moreover,mice with osteoclastspecific knockout of Pkd1 showed complete resistance to unloading-induced bone loss.A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass.Pharmacological regulation of the PC1-TAZ axis alleviated unloading-and estrogen deficiency-induced bone loss.Thus,the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.

Innovations in functional genomics and molecular breeding of pea:exploring advances and opportunities

The garden pea(Pisum sativum L.)is a significant cool-season legume,serving as crucial food sources,animal feed,and industrial raw materials.The advancement of functional genomics over the past two decades has provided substantial theoretical foundations and progress to pea breeding.Notably,the release of the pea reference genome has enhanced our understanding of plant architecture,symbiotic nitrogen fixation(SNF),flowering time,floral organ development,seed development,and stress resistance.However,a considerable gap remains between pea functional genomics and molecular breeding.This review summarizes the current advancements in pea functional genomics and breeding while highlighting the future challenges in pea molecular breeding.

Flexible CuCo_(2)O_(4)@Ni-Co-S hybrids as electrode materials for high-performance energy storage devices

Rational design of electrode meterials with unique core-shell nanostructures is of great significance for improving the electrochemical performance of supercapacitors. In this work, we prepare several CuCo_(2)O_(4)@Ni-Co-S composite electrodes by a controllable hydrothermal and electrodeposition route. Onedimensional nanowires can shorten the ions transport path, while two-dimensional nanosheets expose many active sites. This enables three-dimensional structured composite with high electrochemical activity. The as-prepared heterostructured materials show a specific of 1048 C/g at 1 A/g. It still maintains 75.6% of initial capacity after 20000 cycles at 10 A/g. The device delivers an energy density of 79.2 Wh/kg when the power density reaches to 2280 W/kg. Moreover, it possesses an excellent mechanical stability after repeated folding at different angles.

Self-supported high-entropy alloy electrocatalyst for highly efficient H_(2) evolution in acid condition

Developing non-precious catalysts as Pt substitutes for electrochemical hydrogen evolution reaction(HER)with superior stability in acidic electrolyte is of critical importance for large-scale,low-cost hydrogen production from water.Herein,we report a CoCrFeNiAl high-entropy alloy(HEA)electrocatalyst with self-supported structure synthesized by mechanical alloying and spark plasma sintering(SPS)consolidation.The HEA after HF treatment and in situ electrochemical activation for 4000 cycles of cyclic voltammetry(HF-HEAa2)presents favourable activity with overpotential of 73 mV to reach a current density of 10 mA cm^(2) and a Tafel slope of 39.7 mV dec1.The alloy effect of Al/Cr with Co/Fe/Ni at atomic level,high-temperature crystallization,as well as consolidation by SPS endow CoCrFeNiAl HEA with high stability in 0.5 M H2SO4 solution.The superior performance of HF-HEAa2 is related with the presence of metal hydroxides/oxides groups on HEA.

Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer

Metformin is currently a strong candidate anti-tumor agent in multiple cancers.However,its anti-tumor effectiveness varies among different cancers or sub-populations,potentially due to tumor heterogeneity.It thus remains unclear which hepatocellular carcinoma(HCC)patient subpopulation(s)can benefit from met-formin treatment.Here,through a genome-wide CRISPR-Cas9-based knockout screen,we find that DOCK1 levels determine the anti-tumor effects of met-formin and that DOCK1 is a synthetic lethal target of metformin in HCC.Mechanistically,metformin promotes DOCK1 phosphorylation,which activates RAC1 to facilitate cell survival,leading to metformin resistance.The DOCK1-selective inhibitor,TBOPP,potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids,and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models.Notably,metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression.This study shows that metformin effective-ness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for met-formin-resistant HCC patients.

Hydroxylated high-entropy alloy as highly efficient catalyst for electrochemical oxygen evolution reaction

Oxygen evolution reaction(OER),a half reaction involved in electrochemical water splitting,CO2 reduction,and metal–air batteries,restricts the efficiency of these energy conversion systems due to sluggish reaction kinetics[1,2].To accelerate OER,highly efficient electrocatalysts are required.However,large-scale applications of the normally used OER catalysts(i.e.RuO2 and IrO2)are hampered by their instability and low abundance.It is highly desirable to develop earth-abundant catalysts with low cost,high activity and long-term stability.Co(Ni,Fe)(oxy)hydroxides(Co(Ni)-(O)OH)have emerged as promising OER catalysts in recent years[3].

β-cell dynamics in type 2 diabetes and in dietary and exercise interventions

Pancreaticβ-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes(T2D).Recent clinical and experimental studies have suggested that the functional capacity ofβ-cells,particularly in the first phase of insulin secretion,is a primary contributor to the progression of T2D and its associated complications.Pancreaticβ-cells undergo dynamic compensation and decompensation processes during the development of T2D,in which metabolic stresses such as endoplasmic reticulum stress,oxidative stress,and inflammatory signals are key regulators ofβ-cell dynamics.Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D,especially in the early stages.Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague,accumulating evidence has implicated the improvement ofβ-cell functional capacity.In this review,we summarize recent advances in the understanding of the dynamic adaptations ofβ-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions onβ-cell dysfunction in T2D.This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D,and more importantly,it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.

Co_(3)O_(4)@NiMoO_(4)composite electrode materials for flexible hybrid capacitors

Co_(3)O_(4)nanomaterials as electrodes have been studied widely in the past decade due to their unique structural characteristics.However,their performance does not yet reach the level required for practical applications.It is,nevertheless,an effective strategy to synthesize hybrid electrode materials with high energy density.Herein we prepare Co_(3)O_(4)@NiMoO_(4)nanowires by a two-step hydrothermal method.The as-obtained sample can be directly used as cathode material of supercapacitors;with specific capacitance of 600 C/g at 1 A/g.An assembled capacitor delivers an energy density of 36.1 Wh/kg at 2700 W/kg,and retains 98.2%of the initial capacity after 8000 cycles.

Bifunctional Fe-doped CoP@Ni_(2)P heteroarchitectures for highefficient water electrocatalysis

It is important to develop economical and durable electrocatalysts for sustainable energy conversion technology.However,the current catalysts still suffer from insufficient hydrogen adsorption energy.Herein,we report a kind of novel bi-phosphide catalyst through constructing heterogeneous structures and cation doping.The obtained sample delivers an outstanding hydrogen evolution reaction(HER)performance at all pH range.As oxygen evolution reaction(OER)electrocatalyst,Fe-CoP@Ni_(2)P samples show an overpotential of 237 mV at 50 mA·cm^(−2) in alkaline solution.For electrolysis of water,Fe-CoP@Ni_(2)P catalysts deliver a cell voltage of 1.59 V at 50 mA·cm^(−2) and long durability.Furthermore,density functional theory(DFT)calculation further confirms that the doped heterostructure promotes Gibbs free energy for hydrogen adsorption.And the significant increase in the density of total states(DOS)also enhances the catalytic activity of HER.