Occurrence and stability of anion–π interactions between phosphate and nucleobases in functional RNA molecules

We present a systematic structural and energetic characterization of phosphate(OP)–nucleobase anion…π stacking interactions in RNAs. We observed OP–nucleobase stacking contacts in a variety of structural motifs other than regular helices and spanning broadly diverse sequence distances. Apart from the stacking between a phosphate and a guanine or a uracil two-residue upstream in specific U-turns, such interactions in RNA have been scarcely characterized to date. Our QM calculations showed an energy minimum at a distance between the OP atom and the nucleobase plane centroid slightly below 3 Å for all the nucleobases. By sliding the OP atom over the nucleobase plane we localized the optimal mutual positioning of the stacked moieties, corresponding to an energy minimum below -6 kcal•mol⁻¹, for all the nucleobases, consistently with the projections of the OP atoms over the different π-rings we observed in experimental occurrences. We also found that the strength of the interaction clearly correlates with its electrostatic component, pointing to it as the most relevant contribution. Finally, as OP–uracil and OP–guanine interactions represent together 86% of the instances we detected, we also proved their stability under dynamic conditions in model systems simulated by state-of-the art DFT-MD calculations.     

DNASE1L3 inhibits proliferation,invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β‐catenin destruction complex (GSK‐3β and Axin), promotes the ubiquitination degradation of β‐catenin, and inhibits its nuclear transfer, thus, decreasing c‐Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

Decreased expression of DNASE1L3 is associated with poor prognosis in patients with HCC DNASE1L3 inhibits the proliferation and cell cycle of HCC cells in vitro and promotes the invasion and metastasis of HCC cells DNASE1L3 inhibits the tumorigenicity and metastasis of HCC cells in vivo DNASE1L3 interacts with β‐catenin and promotes its binding to the β‐catenin destroying complex DNASE1L3 interacts with P21 and stabilizes P21 by mediating the deubiquitin activity     

Effects of highly selective sensory/motor nerve injury on bone metabolism and bone remodeling in rats

Objectives:This work aimed to investigate the mechanism of selective sensory/motor nerve injury in affecting bone metabolism and remodeling.Methods:The selective sensory/motor nerve injury rat model was constructed through posterior rhizotomy (PRG), anterior rhizotomy (ARG), or anterior combined with posterior rhizotomy (APRG) at the L_4-6 sensory/motor nerves on the right side of rats. Sham-operated (SOG) rats served as control. At 8 weeks after surgery, the sciatic nerves, spinal cord segments L₅ and tibial tissues were collected for analysis.Results:the integrity of trabecular bone was damaged, the number of trabecular bone was decreased and the number of osteoclasts were increased in ARG group. ARG activated NF-κβ and PPAR-γ pathways, and inhibited Wnt/β-catenin pathway. ARG group exhibited high turnover bone metabolism. In PRG group, the trabecular bone morphology became thinner, and the number of osteoclasts was increased. NF-κβ pathway was activated and OPG/RANKL ratio was decreased in PRG group. The activated osteoclasts, reduced osteoblasts activity and lower turnover bone metabolism were observed in PRG group. Additionally, the bone metabolism in APRG group was similar to ARG group.Conclusion:The posterior rhizotomy and anterior rhizotomy induced the different degree of osteoporosis in rats, which may attribute to regulate Wnt/β-catenin, NF-κβ and PPAR-γ signalling pathways.     

Thioredoxin 1 supports colorectal cancer cell survival and promotes migration and invasion under glucose deprivation through interaction with G6PD

Overcoming energy stress is a critical step for cells in solid tumors. Under this stress microenvironment, cancer cells significantly alter their energy metabolism to maintain cell survival and even metastasis. Our previous studies have shown that thioredoxin-1 (Trx-1) expression is increased in colorectal cancer (CRC) and promotes cell proliferation. However, the exact role and mechanism of how Trx-1 is involved in energy stress are still unknown. Here, we observed that glucose deprivation of CRC cells led to cell death and promoted the migration and invasion, accompanied by upregulation of Trx-1. Increased Trx-1 supported CRC cell survival under glucose deprivation. Whereas knockdown of Trx-1 sensitized CRC cells to glucose deprivation-induced cell death and reversed glucose deprivation-induced migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we identified glucose-6-phosphate dehydrogenase (G6PD) interacting with Trx-1 by HuPortTM human protein chip, co-IP and co-localization. Trx-1 promoted G6PD protein expression and activity under glucose deprivation, thereby increasing nicotinamide adenine dinucleotide phosphate (NADPH) generation. Moreover, G6PD knockdown sensitized CRC cells to glucose deprivation-induced cell death and suppressed glucose deprivation-induced migration, invasion, and EMT. Inhibition of Trx-1 and G6PD, together with inhibition of glycolysis using 2-deoxy-D-glucose (2DG), resulted in significant anti-tumor effects in CRC xenografts in vivo. These findings demonstrate a novel mechanism and may represent a new effective therapeutic regimen for CRC.     

若尔盖人-狼冲突现状与管理研究

大中型食肉动物肇事事件导致人类与野生动物关系恶化,给生物多样性保护工作带来巨大的挑战。若尔盖湿地是我国三大湿地之一,湿地、草原分布广泛,生物多样性丰富,畜牧业发达,但近年来狼(Canis lupus)捕杀牲畜的肇事事件时有发生。为了解若尔盖野生狼肇事件的空间分布以及牧民对人-狼冲突管理的看法,本研究于2022年对若尔盖县13个乡镇83个行政村进行走访调查。结果表明：(1)多数受访者(66.0%)认为在过去5年内,若尔盖县野生狼数量有所增加;(2)狼肇事事件具有明显的空间分异性,最严重的是包座乡。包座乡临近山区,该区域牧场面积广阔、牧民饲养牲畜数量多等原因导致该镇发生狼肇事事件较多;(3)对于狼肇事,绝大多数牧民(85.0%)更希望采取经济补偿或者驱赶措施,只有少数牧民(9.4%)希望采取捕杀的措施;(4)影响牧民对狼肇事管理措施的偏好因子中,受教育程度、年龄、民族以及被杀牲畜数量有显著影响。建议加强狼种群监测管理,采取措施减少狼捕杀牲畜,优化补偿机制,缓解当地牧民与狼之间的矛盾。本研究为当前若尔盖县野生动物保护和管理决策提供了依据,对其他地区大型食肉动物与当地居民冲突管理具有借鉴意义。     

不同农业土地利用方式和管理对土壤有机碳的影响 ——以北京市延庆盆地为例

自20世纪80年代以来,我国农业土地利用方式和农田管理发生了巨大变化,由此引起的土壤有机碳（SOC）含量、密度及其垂直分布发生了相应的变化,研究不同土地利用方式和管理对土壤有机碳的影响对于探讨农田生态系统的固碳作用具有重要的意义.以北京市延怀盆地为典型研究地区,选择6种农业土地利用和管理模式,共计42块样地,在1m深土体内分层采集197个土壤样品.研究结果表明：（1） 不同农业土地利用和管理方式对SOC含量的影响主要发生在0～25 cm土层中,剖面中SOC含量自上向下明显降低.（2） 通过对6种土地利用和管理方式下土壤SOC含量进行比较,结果发现果园和高投入的玉米地土壤在0～100 cm土层中SOC含量均较高,变化范围分别为4.16～10.00 g kg^-1和4.73～9.31 g kg^-1; 菜地土壤在0～40 cm土层中SOC含量较高,变化范围为6.42～9.67 g kg^-1;大豆地、中、低投入玉米地土壤在0～100 cm土层中SOC含量较低,变化范围分别为3.27～7.73 g kg^-1、3.14～8.33 g kg^-1和1.83～7.67 g kg^-1. （3） 不同农业土地利用方式对SOC密度影响的趋势与对SOC含量影响的趋势基本一致,在0～100 cm土壤中,SOC密度的顺序为果园＞菜地＞高投入玉米地＞中投入玉米地＞大豆地＞低投入玉米地,变化范围为4.15～8.22 kg m^-2.