MiR‐155 promotes interleukin‐1β‐induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1‐mediated PI3K/Akt pathway

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA‐155 (miR‐155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR‐155 is associated with OA pathology remain unexplored. We report here that miR‐155 level is significantly up‐regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin‐1β (IL‐1β), a pivotal pro‐catabolic factor promoting cartilage degradation. Moreover, miR‐155 inhibition attenuates and its overexpression promotes IL‐1β‐induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3‐kinase (PI3K)) is a target of miR‐155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR‐155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR‐155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR‐155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1‐mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR‐155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression.     

Membrane‐Free Zn/MnO2 Flow Battery for Large‐Scale Energy Storage

The traditional Zn/MnO₂ battery has attracted great interest due to its low cost, high safety, high output voltage, and environmental friendliness. However, it remains a big challenge to achieve long‐term stability, mainly owing to the poor reversibility of the cathode reaction. Different from previous studies where the cathode redox reaction of MnO₂/MnOOH is in solid state with limited reversibility, here a new aqueous rechargeable Zn/MnO₂ flow battery is constructed with dissolution–precipitation reactions in both cathodes (Mn²⁺/MnO₂) and anodes (Zn²⁺/Zn), which allow mixing of anolyte and catholyte into only one electrolyte and remove the requirement for an ion selective membrane for cost reduction. Impressively, this new battery exhibits a high discharge voltage of ≈1.78 V, good rate capability (10C discharge), and excellent cycling stability (1000 cycles without decay) at the areal capacity ranging from 0.5 to 2 mAh cm^‐2. More importantly, this battery can be readily enlarged to a bench scale flow cell of 1.2 Ah with good capacity retention of 89.7% at the 500th cycle, displaying great potential for large‐scale energy storage.     

陕北白绒山羊DRB1基因外显子2遗传变异分析

本研究通过对123只陕北白绒山羊DRB1基因外显子2的遗传变异分析,旨在获得陕北白绒山羊DRB1基因的多态性及变异信息,为山羊抗病基因的挖掘研究提供基础资料。本研究共获得6条陕北白绒山羊DRB1基因外显子2序列,其中4条为首次发现。生物信息学分析表明DRB1位点具有较高的多态性,6条等位基因可能起源于2个祖先基因。在长期的进化过程中,DRB1位点受到了明显的选择压力作用,这种选择作用有助于陕北白绒山羊对当地气候的适应。蛋白质结构的预测证实了DRB1*1与其它等位基因间的差异性,说明核苷酸变异可能会引起蛋白质结构的改变,最终可能影响宿主对病原体的免疫应答。本次对陕北白绒山羊DRB1基因多态性的调查与分析有助于筛选疾病抗性和易感性MHC (Major histocompatibility complex)候选基因,进而可加速绒山羊抗病品系的改良与培育进程。     

From signaling to function: how strigolactones regulate plant development

Science China Life Sciences -     

Base excision repair but not DNA double‐strand break repair is impaired in aged human adipose‐derived stem cells

The decline in DNA repair capacity contributes to the age‐associated decrease in genome integrity in somatic cells of different species. However, due to the lack of clinical samples and appropriate tools for studying DNA repair, whether and how age‐associated changes in DNA repair result in a loss of genome integrity of human adult stem cells remains incompletely characterized. Here, we isolated 20 eyelid adipose‐derived stem cell (ADSC) lines from healthy individuals (young: 10 donors with ages ranging 17–25 years; old: 10 donors with ages ranging 50–59 years). Using these cell lines, we systematically compared the efficiency of base excision repair (BER) and two DNA double‐strand break (DSB) repair pathways—nonhomologous end joining (NHEJ) and homologous recombination (HR)—between the young and old groups. Surprisingly, we found that the efficiency of BER but not NHEJ or HR is impaired in aged human ADSCs, which is in contrast to previous findings that DSB repair declines with age in human fibroblasts. We also demonstrated that BER efficiency is negatively associated with tail moment, which reflects a loss of genome integrity in human ADSCs. Mechanistic studies indicated that at the protein level XRCC1, but not other BER factors, exhibited age‐associated decline. Overexpression of XRCC1 reversed the decline of BER efficiency and genome integrity, indicating that XRCC1 is a potential therapeutic target for stabilizing genomes in aged ADSCs.     

Ultrasensitive Deep-Ultraviolet Surface Plasmon Resonance Sensors Using Aluminum-Graphene Metasurface: a Theoretical Insight

Plasmonics - This study investigates a versatile deep-ultraviolet (DUV) surface plasmon resonance (SPR) sensor by integrating a few graphene layers into low-cost aluminum (Al) thin film. The...     

HIF‐1α forms regulatory loop with YAP to coordinate hypoxia‐induced adriamycin resistance in acute myeloid leukemia cells

Despite the improvement in acute myeloid leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemoresistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found that AML cells showed less susceptibility to adriamycin (ADR) in the presence of hypoxia, while inhibition of hypoxia‐inducible factor 1α (HIF‐1α) by CdCl₂ can make AML cells re‐susceptibile to ADR even under hypoxia. Moreover, HIF‐1α is overexpressed and plays an important role in ADR‐resistance maintenance in resistant AML cells. We further found hypoxia or induction of HIF‐1α can significantly upregulate yes‐associated protein (YAP) expression in AML cells, and resistant cells express a high level of YAP. Finally, we found that YAP may not only enhance HIF‐1α stability but also promote HIF‐1α's activity on the target gene pyruvate kinase M2. In conclusion, our data indicate that HIF‐1α or YAP may represent a therapeutic target for overcoming resistance toward adriamycin‐based chemotherapy in AML.