G-quadruplex inducer/stabilizer pyridostatin targets SUB1 to promote cytotoxicity of a transplatinum complex

Pyridostatin (PDS) is a well-known G-quadruplex (G4) inducer and stabilizer, yet its target genes have remained unclear. Herein, applying MS proteomics strategy, we revealed PDS significantly downregulated 22 proteins but upregulated 16 proteins in HeLa cancer cells, of which the genes both contain a number of G4 potential sequences, implying that PDS regulation on gene expression is far more complicated than inducing/stabilizing G4 structures. The PDS-downregulated proteins consequently upregulated 6 proteins to activate cyclin and cell cycle regulation, suggesting that PDS itself is not a potential anticancer agent, at least toward HeLa cancer cells. Importantly, SUB1, which encodes human positive cofactor and DNA lesion sensor PC4, was downregulated by 4.76-fold. Further studies demonstrated that the downregulation of PC4 dramatically promoted the cytotoxicity of trans-[PtCl₂(NH₃)(thiazole)] (trans-PtTz) toward HeLa cells to a similar level of cisplatin, contributable to retarding the repair of 1,3-trans-PtTz crosslinked DNA lesion mediated by PC4. These findings not only provide new insights into better understanding on the biological functions of PDS but also implicate a strategy for the rational design of novel multi-targeting platinum anticancer drugs via conjugation of PDS as a ligand to the coordination scaffold of transplatin for battling drug resistance to cisplatin.     

灌水时间对冬小麦生长发育及水肥利用效率的影响

研究秸秆还田后不同越冬前灌水时间(11月10日、11月25日、12月10日)和春季灌水时间(3月5日,返青期;4月5日,拔节期)对冬小麦生长发育、干物质运转及水肥利用效率的影响.结果表明： 越冬前灌水时间主要影响冬前和拔节期群体大小,而春灌时间对冬小麦成穗数、产量、干物质运转和水肥利用效率的影响较大,而且越冬前灌水时间对冬小麦产量构成的影响与春灌时间密切相关.在春季返青期灌水条件下,越冬前灌水时间越早,成穗数和产量越高;在拔节期灌水条件下,随越冬前灌水时间的推迟,成穗数和产量呈先升高再降低的趋势,而穗粒数逐渐增加,千粒重受影响较小.水分利用效率、养分吸收量和肥料利用率均随越冬前灌水时间的推迟而降低,随春季灌水时间的推迟而升高.因此,在秸秆还田足墒播种条件下,将越冬前灌水时间适当提前,可以塌实土壤,促进冬小麦冬前分蘖,增加群体大小;配合拔节期增量灌水,可以控制早春无效分蘖,提高成穗率,稳定粒重,提高水肥利用效率,实现节水高产高效栽培.     

Natural Killer Cells Are Characterized by the Concomitantly Increased Interferon-γ and Cytotoxicity in Acute Resolved Hepatitis B Patients

Natural killer (NK) cells are abundant in the liver and have been implicated in inducing hepatocellular damage in patients with chronic hepatitis B virus (HBV) infection. However, the role of NK cells in acute HBV infection remains to be elucidated. We comprehensively characterized NK cells and investigated their roles in HBV clearance and liver pathology in 19 chronic hepatitis B (CHB) patients and 21 acute hepatitis B (AHB) patients as well as 16 healthy subjects. It was found that NKp46⁺ NK cells were enriched in the livers of AHB and CHB patients. We further found that peripheral NK cells from AHB patients expressed higher levels of activation receptors and lower levels of inhibitory receptors than those from CHB patients and HC subjects, thus displaying the increased cytolytic activity and interferon-γ production. NK cell activation levels were also correlated positively with serum alanine aminotransferase levels and negatively with plasma HBV DNA levels in AHB patients, which is further confirmed by the longitudinal follow-up of AHB patients. Serum pro-inflammatory cytokine and chemokine levels were also increased in AHB patients as compared with CHB and HC subjects. Thus, the concomitantly increased interferon-γ and cytotoxicity of NK cells were associated with liver injury and viral clearance in AHB patients.     

长期施肥对NO3^——N深层积累和土壤剖面中水分分布的影响

研究了旱地农业系统中,长期不同施肥条件下,降水对NO3^--N积累、剖面水分分布以及N有收量、回收率影响及其相互之间的关系。结果表明,降水和氮肥施用量显著影响作物产量。施用氮肥在土壤剖面中造成NO3^--N深层积累,其中NPM处理累积层位于60－120cm,累积量相当于3.0年的年度施肥量（120kg·hm^-2）,NP处理累积层位于80－140cm,相当于1.4年施肥量。随着降水的年际间波动,进化论在丰水年、平水年还是干旱年,NPM处理耗水量＞NP处理＞M处理＞P,CK处理。12年不同施肥造成了土壤剖面水分差异。冬小麦播种前不同施肥处理0－100cm水分剖面分布差别不大,NPM处理、NP处理（除丰水年外）,土壤100－300cm含水量迅速降低,干旱年M处理缓慢降低,P和CK处理在任何年份变化都不大,氮肥回收率随着降水的波动也呈现相应的高低变化,NPM、NP处理的高低波动幅度最大。NPM、NP处理NO3^-－N累积与N素回收率的降低、土壤水分亏缺基本吻合。由此也反映了水分－作物－施肥三者之间存在的内在制约关系。     

短葶飞蓬云南三个种群的核型与等位酶分析

通过核型和等位酶分析,对短葶飞蓬（Erigeron breviscapus)种群遗传结构进行了较全面的研究。研究材料来自丽江,昆明,邱北,核型分析表明,这3个种群都为二倍体种群（2n=2x=18),以丽江种群为例,短葶飞蓬核型为2n=2x=18=6m 10sm(2SAT) 2st,10种酶的等位酶分析表明,短葶飞蓬的遗传变异存在于种群内,种群间遗传一致度高（I=0.9172),遗传距离小（D=0.0876),遗传距离与空间距离大致成正相关。     

西北干旱荒漠区植物属的区系分析

为了分析西北干旱荒漠区种子植物属的组成及其区系特点 ,探讨其起源与演化 ,作者根据多年的调查结果并查阅大量相关资料 ,研究表明 :西北干旱荒漠区分布有种子植物 4 84属 ,其区系特征为单种属、寡种属多 ,优势现象明显 ;植物区系具有强烈的旱生性和古老性 ;区系地理成分复杂多样 ,包含 1 4个分布区类型和 1 4个变型 ,地中海区 -西亚 -中亚分布、北温带分布、旧世界分布、中亚分布类型占据前四位 ,分别占总属的 2 2 .33%、1 7.98%、1 0 .6 9%、7.36 % ;特有成分比较低 ,中国特有成分仅 6属 ,只占总属数的 1 .5 7% ;起源古老 ,多为本土发生     

Mitochondrial ND6 T14502C variant may modulate the phenotypic expression of LHON-associated G11778A mutation in four Chinese families

We report here the clinical, genetic, and molecular evaluations of four Han Chinese families with Leber’s hereditary optic neuropathy. Thirty-one (20 males/11 females) of 83 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual impairment. The average age-of-onset of vision loss was 22 years old. Strikingly, these penetrances of visual impairment in these Chinese families were higher than those in other 11 Chinese pedigrees carrying the only ND4 G11778A mutation. Molecular analysis identified the known G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M10a and M7c2. Of these, the T14502C mutation caused the substitution of a highly conserved isoleucine for valine at position 58 in ND6. This mutation has been associated with LHON in other Chinese families with very low penetrance of LHON. Thus, the deficient activities of complex I, caused by G11778A mutation, would be worsened by the T14502C mutation in these four Chinese families. As a result, mitochondrial dysfunctions would lead to the high penetrance and expressivity of visual loss in these Chinese families carrying both G11778A and T14502C mutations than other 11 Chinese families carrying only G11778A mutation. These data suggested that the T14502C variant may modulate the phenotypic manifestation of the G11778A mutation in these Chinese pedigrees.     

Repeated measures random forests (RMRF): Identifying factors associated with nocturnal hypoglycemia

Nocturnal hypoglycemia is a common phenomenon among patients with diabetes and can lead to a broad range of adverse events and complications. Identifying factors associated with hypoglycemia can improve glucose control and patient care. We propose a repeated measures random forest (RMRF) algorithm that can handle nonlinear relationships and interactions and the correlated responses from patients evaluated over several nights. Simulation results show that our proposed algorithm captures the informative variable more often than naïvely assuming independence. RMRF also outperforms standard random forest and extremely randomized trees algorithms. We demonstrate scenarios where RMRF attains greater prediction accuracy than generalized linear models. We apply the RMRF algorithm to analyze a diabetes study with 2524 nights from 127 patients with type 1 diabetes. We find that nocturnal hypoglycemia is associated with HbA1c, bedtime blood glucose (BG), insulin on board, time system activated, exercise intensity, and daytime hypoglycemia. The RMRF can accurately classify nights at high risk of nocturnal hypoglycemia.     

玉米蛋白粉替代鱼粉对大黄鱼生长、血清生化指标及肝脏组织学的影响

为探讨玉米蛋白粉替代鱼粉对大黄鱼(Larimichthys crocea) 幼鱼生长、血清生化指标及肝脏组织形态的影响, 进行了为期56d的养殖试验, 探索玉米蛋白粉替代大黄鱼幼鱼饲料鱼粉的适当比例。以初始体重为(10.49±0.03) g的大黄鱼幼鱼为研究对象, 用玉米蛋白粉替代基础饲料(含40%鱼粉)0、15%、30%、45%、60%和75%的鱼粉来配制6种等氮(粗蛋白含量45%)等脂(粗脂肪含量10%)的实验饲料, 分别标记为C0、C15、C30、C45、C60、C75组。除C0以外的替代组分别添加了适量的晶体氨基酸(赖氨酸和蛋氨酸)。结果表明, 玉米蛋白粉替代水平对大黄鱼幼鱼存活率、试验鱼特定生长率、饲料系数均无显著性差异(P>0.05)。C45和C60组肌肉粗蛋白含量显著高于C0组(P<0.05), 肌肉粗脂肪含量C45组显著高于C0、C15和C75组 (P<0.05), C45、C60和C75组肌肉水分显著低于C0组(P<0.05), 全鱼粗蛋白、粗脂肪、水分含量无显著差异(P>0.05); 灰分含量有上升趋势, C75组显著高于其他组(P<0.05)。各替代组的血清白蛋白、白球比、谷草转氨酶、葡萄糖均无显著性差异(P>0.05); 随着替代比例的升高, 总胆固醇有降低的趋势, 除C15组与C0无显著性差异外(P>0.05), 4组均显著低于CO组(P<0.05); 实验探讨替代后对鱼的影响, C75组血清总蛋白和球蛋白含量显著低于C0组(P<0.05); C75组血清谷草转氨酶含量显著高于C0(P<0.05)。各处理组总抗氧化能力、过氧化氢酶、谷胱甘肽过氧化氢酶均没有显著性影响(P>0.05), 但替代组总抗氧化能力含量均高于C0; 丙二醛在C75组显著高于C0组(P<0.05)。通过肝组织学观察表明, 当替代比例高于45%时, 呈现肝细胞核偏位、胞浆内脂肪滴较多、细胞透明空泡化等症状。综上所述, 在实验条件下, 研究认为玉米蛋白粉替代鱼粉对大黄鱼幼鱼的适宜添加量为45%。