天津市地下水生态系统服务价值演变

基于千年生态系统评估对生态系统服务的分类方法，将天津市地下水生态系统服务功能划分为供给、调节、 支持和文化 4 个方面，以此为基础建立地下水生态系统服务价值评估指标体系，采用价值量评估方法构建货币化 的价值评估模型，对地下水生态系统服务价值进行测算，并重点分析南水北调中线工程通水前后天津市地下水生 态系统服务价值演变特征。结果表明：2008—2019 年，天津市地下水生态系统年均总服务价值为 83.71 亿元，其 中，南水北调中线工程通水前（2008—2014 年）为 69.81 亿元，通水后（2015—2019 年）为 103.18 亿元；通水后，地 下水调节服务价值、支持服务价值增大，供给服务价值减小；南水北调中线工程对地下水生态系统服务价值的贡 献呈增大趋势，由 2015 年 2.64 亿元增加至 2019 年 24.01 亿元。     

气候变化背景下滇中引水工程水源区与受水区 降水丰枯遭遇分析

基于历史实测降水数据与全球气候模型预估数据，使用 Morlet 小波方法分析滇中引水工程水源区与受水区 降水序列的周期变化和未来的降水趋势。同时，采用 Copula 函数计算历史时期（1960—2021 年）与未来时期 （2022—2100 年）水源区与受水区降水丰枯异步或丰枯同步的概率。结果表明：1960—2021 年降水序列存在 26~39?a、18~25?a、4~7?a 的 3 类时间尺度的周期变化，2022—2100 年降水序列存在 38~55?a、18~30?a、5~12?a 的 3 类时间尺度的周期变化，降水量呈现“多—少—多”的循环交替，预计未来 10~20?a 将持续处于降水较多的时期； 过去 62?a，水源区和受水区降水丰枯异步频率 36.4%，同期丰水年频率为 25.3%，同期枯水年频率小于 30%，水源区 和受水区具有水量互补的引水条件，两区域之间存在着水量补偿特征；与历史丰枯遭遇对比，未来降水量丰枯同 步频率均呈现减小的趋势，丰枯异步呈现增加的趋势，同枯和源枯受丰的频率减少，未来有利于调水的降水丰枯 组合概率平均增加 3.75%；在近、中、远期预估中，从 SSP1-2.6 情景过渡到 SSP5-8.5 情景，SSP5-8.5 情景下降水量 丰枯异步频率比 SSP1-2.6 情景大，说明水源区与受水区的降水区域差异变大，降水时空差异更加显著。通过对滇 中引水工程水源区与受水区降水量丰枯遭遇的综合分析、定量评估和模拟预测，为滇中引水工程水资源调度协同 一体化提供数据支撑及参考依据。     

Hydrogen storage performance of methyl-substituted mesoporous silica with tailored textural characteristics

Journal of Porous Materials - The present study reports a systematic analysis of morphology and hydrogen sorption capacity of mesoporous organic-inorganic silica prepared by varying the silica...     

Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

SmartBone^® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β.     

Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.     

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.