子囊菌交配型位点与交配型基因研究进展

有性生殖是真菌的生殖方式之一,是真菌遗传重组的重要驱动力。交配型(mating-type,MAT)位点控制真菌性别,在有性生殖过程中起决定性作用。不同类型真菌MAT位点的基因组成、排列方式和编码蛋白不尽相同。近年来,MAT位点和MAT基因的功能与调控网络研究进展较快。本文对子囊菌交配型位点的基因组成及分布、MAT基因的功能、MAT位点与有性生殖调控通路的关系等进行了综述。     

Vitamin D supplementation worsens Alzheimer's progression: Animal model and human cohort studies

Vitamin D deficiency has been epidemiologically linked to Alzheimer''s disease (AD) and other dementias, but no interventional studies have proved causality. Our previous work revealed that the genomic vitamin D receptor (VDR) is already converted into a non‐genomic signaling pathway by forming a complex with p53 in the AD brain. Here, we extend our previous work to assess whether it is beneficial to supplement AD mice and humans with vitamin D. Intriguingly, we first observed that APP/PS1 mice fed a vitamin D‐sufficient diet showed significantly lower levels of serum vitamin D, suggesting its deficiency may be a consequence not a cause of AD. Moreover, supplementation of vitamin D led to increased Aβ deposition and exacerbated AD. Mechanistically, vitamin D supplementation did not rescue the genomic VDR/RXR complex but instead enhanced the non‐genomic VDR/p53 complex in AD brains. Consistently, our population‐based longitudinal study also showed that dementia‐free older adults (n = 14,648) taking vitamin D₃ supplements for over 146 days/year were 1.8 times more likely to develop dementia than those not taking the supplements. Among those with pre‐existing dementia (n = 980), those taking vitamin D₃ supplements for over 146 days/year had 2.17 times the risk of mortality than those not taking the supplements. Collectively, these animal model and human cohort studies caution against prolonged use of vitamin D by AD patients.     

城市绿色开敞空间可达性研究——以南京市中心城区为例

城市绿色开敞空间是城市公共空间的重要组成部分,合理配置城市绿色开敞空间对城市宜居环境建设至关重要。空间可达性常用于评价公共服务设施空间布局的合理性,两步移动搜索法即是一种直观、运算简便、应用广泛的可达性计算方法,但该方法未考虑需求主体之间的差异性。本研究以南京市中心城区为例,利用手机信令数据提取需求者属性特征以及空间分布,通过分类细化需求主体改进搜索策略,改善两步移动搜索法传统研究未考虑不同群体差异性、统计数据滞后、空间尺度粗等弊端。结果表明,南京市中心城区绿色开敞空间可达性呈现出明显的空间分异特征,江南主城可达性总体比江北新区高,低值区集中在人口密度高、绿色开敞空间资源规模小的中心城区周边;不同人群的绿色开敞空间可达性总体格局相似,但在数值上老年人可达性均值是其他年龄段的14.60%,工作人群可达性均值是居住人群的86.02%,老年人作为弱势群体在享受绿色开敞空间服务中被边缘化。研究结果可为优化南京市绿色开敞空间布局提供科学依据,也可为其他公共服务设施可达性评价提供借鉴。     

MicroRNA-363-3p/sphingosine-1-phosphate receptor 1 axis inhibits sepsis-induced acute lung injury via the inactivation of nuclear factor kappa-B ligand signaling

Infection-associated inflammation and coagulation are critical pathologies in sepsis-induced acute lung injury (ALI). This study aimed to investigate the effects of microRNA-363-3p (miR-363-3p) on sepsis-induced ALI and explore the underlying mechanisms. A cecal ligation and puncture-induced septic mouse model was established. The results of this study suggested that miR-363-3p was highly expressed in lung tissues of septic mice. Knockdown of miR-363-3p attenuated sepsis-induced histopathological damage, the inflammation response and oxidative stress in lung tissues. Furthermore, knockdown of miR-363-3p reduced the formation of platelet-derived microparticles and thrombin generation in blood samples of septic mice. Downregulation of miR-363-3p suppressed sphingosine-1-phosphate receptor 1 (S1PR1) expression in lung tissues and subsequently inactivated the nuclear factor kappa-B ligand (NF-κB) signaling. A luciferase reporter assay confirmed that miR-363-3p directly targeted the 3’-untranslated region of the mouse S1pr1 mRNA. Collectively, our study suggests that inactivation of NF-κB signaling is involved in the miR-363-3p/S1PR1 axis-mediated protective effect on septic ALI.     

Purinergic signaling in myocardial ischemia–reperfusion injury

Purines and their derivatives, extensively distributed in the body, act as a class of extracellular signaling molecules via a rich array of receptors, also known as purinoceptors (P1, P2X, and P2Y). They mediate multiple intracellular signal transduction pathways and participate in various physiological and pathological cell behaviors. Since the function in myocardial ischemia–reperfusion injury (MIRI), this review summarized the involvement of purinergic signal transduction in diversified pathological processes, including energy metabolism disorder, oxidative stress injury, calcium overload, inflammatory immune response, platelet aggregation, coronary vascular dysfunction, and cell necrosis and apoptosis. Moreover, increasing evidence suggests that purinergic signaling also mediates the prevention and treatment of MIRI, such as ischemic conditioning, pharmacological intervention, and some other therapies. In conclusion, this review exhibited that purinergic signaling mediates the complex processes of MIRI which shows its promising application and prospecting in the future.     

The insulin receptor family in the heart: new light on old insights

Insulin was discovered over 100 years ago. Whilst the first half century defined many of the physiological effects of insulin, the second emphasised the mechanisms by which it elicits these effects, implicating a vast array of G proteins and their regulators, lipid and protein kinases and counteracting phosphatases, and more. Potential growth-promoting and protective effects of insulin on the heart emerged from studies of carbohydrate metabolism in the 1960s, but the insulin receptors (and the related receptor for insulin-like growth factors 1 and 2) were not defined until the 1980s. A related third receptor, the insulin receptor-related receptor remained an orphan receptor for many years until it was identified as an alkali-sensor. The mechanisms by which these receptors and the plethora of downstream signalling molecules confer cardioprotection remain elusive. Here, we review important aspects of the effects of the three insulin receptor family members in the heart. Metabolic studies are set in the context of what is now known of insulin receptor family signalling and the role of protein kinase B (PKB or Akt), and the relationship between this and cardiomyocyte survival versus death is discussed. PKB/Akt phosphorylates numerous substrates with potential for cardioprotection in the contractile cardiomyocytes and cardiac non-myocytes. Our overall conclusion is that the effects of insulin on glucose metabolism that were initially identified remain highly pertinent in managing cardiomyocyte energetics and preservation of function. This alone provides a high level of cardioprotection in the face of pathophysiological stressors such as ischaemia and myocardial infarction.     

植物光信号途径重要新调控因子TZP的研究进展

TZP(TANDEM ZINC-FINGER/PLUS3)是近年来鉴定到的一个光信号转导途径新组分,在光介导的植物生长发育过程中发挥重要调控作用。TZP不仅负调控蓝光信号途径,参与光敏色素B(phyB)介导的开花调控过程,还参与调控phyA在体内的蛋白质磷酸化。对TZP生化活性和作用机制的深入研究,不仅有助于进一步完善光信号调控网络,也可为设计和培育具有耐密理想株型及高光效作物新品种提供理论依据。该文系统总结了TZP在植物光信号途径中发挥的重要调控作用,并提出未来TZP功能研究的重要问题。