The natural flavanone hesperidin and its aglycone hesperetin were identified as human aldo-keto reductase family 1 member C1 (AKR1C1) and AKR1C2 inhibitors via chemoproteomic profiling, which provides mechanistic insight into their chemosensitization effects in cancer therapy.

Developing aramid membranes with favorable processability and structural tunability for critical separation applications remains a challenging endeavor. This study reports a bottom-up strategy to prepare heterocyclic aramid nanofibers (HANFs) through polymerization-induced self-assembly (PISA), which enables the development of a new category of aramid aerogel membranes with distinctive self-healing behaviors. By manipulating the dynamic assembly of the building blocks driven by non-covalent interactions under thermal annealing, the morphology, texture and porosity of the aerogel membranes can be modified. Tunable mass-transfer property across the membranes is thus achieved, allowing effective decontamination of simulated high-level radioactive waste (HLRW) containing abundant fission products and rare earth metals. Particularly, the aerogel membranes demonstrate excellent structural stability under intense gamma-ray irradiation (up to 50 kGy) in strong-acid solutions (8 mol/L nitric acid, 72 h). Overall, this study provides molecular-level insights into the supramolecular assembly of aramid nanofibers, and the methodology established here opens up opportunities for the customized preparation of functional aramid membranes adaptable for separation applications in extreme environments.

Colorectal cancer remains the second leading cause of cancer-related mortalities worldwide. While artemisinin (ART), a key active compound from the traditional Chinese medicinal herb Artemisia annua, has been recognized for its antiproliferative activity against colon cancer cells, its underlying molecular underpinnings remain elusive. Whereas promiscuity of heme-dependent alkylating of macromolecules, mainly proteins, has been seen pivotal as a universal and primary mode of action of ART in cancer cells, accumulating evidence suggests the existence of unique targets and mechanisms of actions contingent on cell or tissue specificities. Here, we employed photoaffinity probes to identify the specific targets responsible for ART's anti-colon cancer actions. Upon validation, microsomal prostaglandins synthase-2 emerged as a specific and reversible target of ART in HCT116 colorectal cancer cells, whose inhibition resulted in reduced cellular prostaglandin E-2 biosynthesis and cell growth. Our discovery opens new opportunities for pharmacological treatment of colon cancer.

The regeneration of tendon and bone junctions (TBJs), a fibrocartilage transition zone between tendons and bones, is a challenge due to the special triphasic structure. In our study, a silk fibroin (SF)-based triphasic scaffold consisting of aligned type I collagen (Col I), transforming growth factor beta (TGF-beta), and hydroxyapatite (HA) was fabricated to mimic the compositional gradient feature of the native tendon-bone architecture. Rat tendon-derived stem cells (rTDSCs) were loaded on the triphasic SF scaffold, and the high cell viability suggested that the scaffold presents good biocompatibility. Meanwhile, increased expressions of tenogenic-, chondrogenic-, and osteogenic-related genes in the TBJs were observed. The in vivo studies of the rTDSC-seeded scaffold in a rat TBJ rupture model showed tendon tissue regeneration with a clear transition zone within 8 weeks of implantation. These results indicated that the biomimetic triphasic SF scaffolds seeded with rTDSCs have great potential to be applied in TBJ regeneration. The regeneration of tendon and bone junction (TBJ), a fibrocartilage transition zone between tendons and bones, is a challenge due to the special triphasic structure. A silk fibroin (SF)-based triphasic scaffold mimics native TBJ architecture.

Uranium extraction from seawater (UES), a potential approach to securing the long-term uranium supply and sustainability of nuclear energy, has experienced significant progress in the past decade. Promising adsorbents with record-high capacities have been developed by diverse innovative synthetic strategies, and scale-up marine field tests have been put forward by several countries. However, significant challenges remain in terms of the adsorbents' properties in complex marine environments, deployment methods, and the economic viability of current UES systems. This review presents an up-to-date overview of the latest advancements in the UES field, highlighting new insights into the mechanistic basis of UES and the methodologies towards the function-oriented development of uranium adsorbents with high adsorption capacity, selectivity, biofouling resistance, and durability. A distinctive emphasis is placed on emerging electrochemical and photochemical strategies that have been employed to develop efficient UES systems. The most recent achievements in marine tests by the major countries are summarized. Challenges and perspectives related to the fundamental, technical, and engineering aspects of UES are discussed. This review is envisaged to inspire innovative ideas and bring technical solutions towards the development of technically and economically viable UES systems.

Developing polymeric adsorbents for uranium harvesting from high-salinity environments remains a daunting challenge due to the ‘polyelectrolyte effect’-induced conformational collapse compromising the ligand availability. A catalyst-free, visible light-controlled radical polymerization has been presented here for the tailor-made synthesis of zwitterionic block copolymers (BCPs) bearing uranophilic ligands. The novel anti-polyelectrolyte uranium harvesters exhibited significant salinity resistance. The facile and robust photosynthetic strategy offers a significantly high monomer conversion ( α > 95%) that facilitates “one-pot” chain extension to develop the BCPs. Metal catalyst residues, as found in conventional controlled radical polymerizations, are avoided and promoted to synthesize fascinating polymeric materials. We also highlight the first study, by integrating computational modeling with QCM-D analysis, on the interplay between polymer conformational dynamics and chemical adsorption behaviors. With zwitterionic polymer segments as conformational regulators, the BCPs exhibit remarkable ‘anti-polyelectrolyte effect’ by maintaining stretched conformations in saline solutions. Improved ligand accessibility and promotion of diffusional mass transfer are achieved, enabling a high adsorption capacity toward uranium with remarkably fast kinetics in spiked natural seawater and salt lake brines. Graphical Abstract A catalyst-free, visible light-regulated RAFT polymerization method is established to develop zwitterionic block copolymers bearing uranophilic ligands as new-generation uranium harvesters adaptable in high-salinity environments.

Metal–organic frameworks with well-organized low-dimensional architectures provide significant thermodynamic and/or kinetic benefits for diverse applications. We present here the controlled synthesis of a novel class of hierarchical zirconium-porphyrin frameworks ( ZrPHPs ) with nanosheet-assembled hexagonal prism morphology. The crystal growth behaviors and structural evolution of ZrPHPs in an additive-modulated solvothermal synthesis are examined, showing an “assembly-hydrolysis-reassembly” mechanism towards the formation of 2D nanosheets with ordered arrangement. Because of the highly-accessible active sites harvesting broadband photons, ZrPHPs serve as adaptable photocatalysts to regulate macromolecular synthesis under full-range visible light and natural sunlight. An initiator-free, oxygen-tolerant photopolymerization system is established, following a distinctive mechanism involving direct photo-induced electron transfer to dormant species and hole-mediated reversible deactivation. Specifically, ZrPHPs provide a surface-confined effect towards the propagating chains which inhibits their recombination termination, enabling the highly-efficient synthesis of ultrahigh molecular weight polymers ( M n >1,500,000) with relatively low dispersity ( Đ ≈1.5).

The cycling stability of high-energy-density lithium (Li) metal batteries is severely hindered by uneven Li deposition, which is caused by the heterogeneous transport of Li ions in solid electrolyte interphase (SEI) on the surface of Li metal anodes. LiF-rich SEI emerges as a promising solution to improve homogeneous transport of Li ions. Herein, constructing LiF-rich SEI by regulating the interaction between the polymer coating on Li metal anode and fluoroethylene carbonate (FEC) in electrolytes was demonstrated. The polymer coating with uniformly distributed polar functional groups can interact with intermediate decomposition products of FEC, promoting the formation of LiF. LiF-rich SEI ensures improved uniformity of Li deposition, which promises stable operation of Li metal batteries under practical conditions for 143 cycles in comparison with 89 cycles of control group. Moreover, a prototype pouch cell of 1.0 Ah maintains a capacity retention of 90% after 180 cycles. This work provides a fresh attempt to construct LiF-rich SEI by regulating the interaction between solvent and polymer for long-cycling Li metal batteries.

Inhibitor of beta-catenin and TCF (ICAT) is a key protein in the Wnt-β-catenin signaling pathway. However, its role in acute myeloid leukemia (AML) remains unknown. In this study, we evaluated its expression level as well as its prognostic value in AML patients. A total of 72 patients with AML and 30 control subjects were enrolled in this study during the period of January 2017 and December 2019 at Zhongshan Hospital of SunYat-sen University. ICAT and β-catenin expression levels in peripheral blood were determined via enzyme-linked immunosorbent assays. ICAT levels in AML patients were significantly lower and β-catenin levels were higher than those of the control group. After the first course of standard chemotherapy, the concentration of ICAT in the partial remission group (93.79 ng/mL) was significantly higher than that in the initial diagnosis group (49.38 ng/mL) and the no response group (39.94 ng/mL). AML subtypes had lower ICAT expression levels than controls, and ICAT levels were significantly correlated with body mass index, bone marrow/peripheral blood blast cell proportions, and white blood cell and red blood cell counts at initial diagnosis. Furthermore, low ICAT expression was found to be associated with poor disease-free survival and overall survival in AML. ICAT is closely associated with AML progression and can be used as an indicator to monitor AML treatment efficacy.

天然产物因其结构新颖性、生物相容性和功能多样性成为现代药物研发创新的重要源泉.传统植物来源的天然产物生物合成途径研究主要基于基因组学和生物信息学联合分析和生物学功能验证,具有一定局限性.基于小分子探针的化学蛋白质组学技术的飞速发展为植物天然产物的生物合成途径解析提供了新的机遇.本文以胆固醇、原花青素、桑白皮中Deils-A del类型天然产物和甜菊糖苷等天然产物为例,简要概括了近10年来分子探针和化学蛋白质组学在天然产物生物合成途径解析中的应用.

By integrating multi-scale computational simulation with photo-regulated macromolecular synthesis, this study presents a new paradigm for smart design while customizing polymeric adsorbents for uranium harvesting from seawater. A dissipative particle dynamics (DPD) approach, combined with a molecular dynamics (MD) study, is performed to simulate the conformational dynamics and adsorption process of a model uranium grabber, i.e., PAO m - b -PPEGMA n , suggesting that the maximum adsorption capacity with atomic economy can be achieved with a preferred block ratio of 0.18. The designed polymers are synthesized using the PET-RAFT polymerization in a microfluidic platform, exhibiting a record high adsorption capacity of uranium (11.4 ± 1.2 mg/g) in real seawater within 28 days. This study offers an integrated perspective to quantitatively assess adsorption phenomena of polymers, bridging metal-ligand interactions at the molecular level with their spatial conformations at the mesoscopic level. The established protocol is generally adaptable for target-oriented development of more advanced polymers for broadened applications.

We report a quantitative chemoproteomic approach that utilizes a clickable photoreactive probe for global profiling of celastrol targets, which may significantly improve the current understanding of celastrol's mode of action.

Background: Diverse clinical and serological manifestations of systemic lupus erythematosus (SLE) compromise its diagnosis and treatment. A more reliable biomarker for SLE, which can play a critical role in either diagnosis, monitoring the disease progress or evaluating the response to treatment for individualized therapeutic, is necessary. DNA sensor is an important mediator of inflammation in systemic autoimmune diseases. However, the potential role for DNA sensor as disease activity biomarkers for SLE remained obscure. We detected the aberrant activation of DNA sensors and the corresponding IFN-beta response in SLE patients, and to evaluate their potential role as disease biomarkers for SLE.Methods: We quantified the expressions of IFN-I and DNA sensor, such as cGAS, IFI16, DDX41, DAI and their down-stream adaptor STING in PBMC derived from patients with SLE (n = 100), healthy controls (HCs) (n = 62) by real-time PCR. The relationships between the expression of cGAS or IFI16 and clinical features in SLE patients were investigated. ROC curve analysis was performed to examine the predictive value of cGAS and IFI16 in SLE diagnosis, disease activity monitoring, specific organ manifestation and therapeutic response. RNA interferencemediated depletion of IFI16 or cGAS was conducted to evaluate their impact on IFN-I response.Results: The expressions of cGAS and IFI16 were significantly higher in PBMC from SLE patients, closely correlated with the SLEDAI scores and high anti-dsDNA antibody titers. While the AUC for cGAS (0.767) was less than that of IFI16 and IFN-beta, the AUC for IFI16 (0.856) and IFN-beta (0.856) were similar. Expression of cGAS and IFI16 combine with IFN-beta in PBMC showed high sensitivity (89.2%) and specificity (89.1%) for discrimination between mild and moderate/severe disease activity in SLE. Higher expression of IFI16 was association with ocular disorder in SLE patients. Neither IFI16 nor cGAS was a reliable indicator of therapeutic response. RNA interference-mediated depletion of IFI16 or cGAS prevented active SLE serum-induced upregulating in both IFN alpha and IFN-beta.Conclusions: High expression levels of cGAS and IFI16 in PBMC from SLE patients correlated strongly with disease activity. Both cGAS and IFI16 mediated signaling pathway were account for the robust production of IFN-beta. Expression of cGAS and IFI16 combined with IFN-beta in PBMC might serve as potential biomarkers for early diagnosis and monitoring disease activity in SLE.

Since several "red oil" explosion accidents have occurred in the spent fuel reprocessing process, which is mainly due to the mix of HNO3 and organic solvent at high temperature, the reaction between HNO3, TBP and n-dodecane at different conditions were studied to simulate the evaporation concentration process. The temperature and pressure changes were observed, and the main liquid and gas components were analyzed qualitatively and quantitatively by using FTIR and GC/MS. Furthermore, the reaction mechanism is also concluded. It is hope to provide some basic data to design the standards and safety limits in evaporation concentration process of spent fuel reprocessing.

骨质疏松症(osteoporosis,OP)是一组代谢性骨病,其原因复杂,主要特点为骨微结构破坏、骨量低下、骨脆性增加.随着社会生产力的稳步提升,老龄化社会成为多数发达国家及部分发展中国家的社会形态.正因为老年人在人口结构的占比不断攀升,骨质疏松症的占比也不断增高,所以如何防治骨质疏松症已成为当前人们关注的重点和难点.为了研制更为有效的临床药物及推广正确的诊疗康复方案,构建行之有效的骨质疏松实验动物模型起着关键的作用,这也将推进临床转换这一过程.本文就如何构建骨质疏松动物模型进行系统的讲述,对涵盖动物模型的造模方法进行了详细的综述.

在"互联网+"的背景下,医院档案管理工作的模式向信息化、电子化管理的转变成为发展趋向.本文分析了医院档案管理信息化建设的重要性,提出了医院档案信息化建设的合理措施,旨在有助于医院档案管理建设水平的提升.

Senile osteoporosis (SOP) is a worldwide age-related disease characterized by the loss of bone mass and decrease in bone strength. Bone mesenchymal stem cells (BMSCs) play an important role in the pathology of senile osteoporosis. Abnormal expression and regulation of non-coding RNA (ncRNA) are involved in a variety of human diseases. In the present study, we aimed to identify differentially expressed mRNAs and ncRNAs in senile osteoporosis patient-derived BMSCs via high-throughput transcriptome sequencing in combination with bioinformatics analysis. As a result, 415 mRNAs, 30 lncRNAs, 6 circRNAs and 27 miRNAs were found to be significantly changed in the senile osteoporosis group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to analyze the function of differentially expressed mRNAs and ncRNAs. The circRNA–miRNA–mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Interestingly, circRNA008876-miR-150-5p-mRNA was the sole predicted circRNA-miRNA-mRNA network. The differential expression profile of this ceRNA network was further verified by qRT-PCR. The biological function of this network was validated by overexpression and knockdown experiments. In conclusion, circRNA008876-miR-150-5p-mRNA could be an important ceRNA network involved in senile osteoporosis, which provides potential biomarkers and therapeutic targets for senile osteoporosis.

目的 探讨Wnt/β-catenin信号通路在1,25-二羟基维生素D3[1,25-(OH)2-hydroxyvitamin D3,1,25-(OH)2 D3]诱导人急性早幼粒细胞HL-60向单核系分化中的作用.方法 分别采用不同浓度的1,25-(OH)2 D3在不同时间诱导HL-60细胞向单核系分化,确定最佳药物浓度和诱导时间;使用最佳药物浓度0.1μmol/L 1,25-(OH)2 D3诱导HL-60细胞72 h,采用流式细胞技术、细胞化学染色技术检测并观察HL-60细胞的分化方向、分化程度及细胞增殖受抑情况;western blot检测ICAT、TCF1、c-Myc、cyclin D1、β-catenin蛋白的表达水平及pRB蛋白的磷酸化水平;采用免疫荧光法检测β-catenin在细胞内的分布情况.结果 0.1μmol/L 1,25-(OH)2 D3于72 h时可有效诱导HL-60细胞向单核系分化;G0/G1期细胞增殖明显受抑(t=4.769,P<0.001),且细胞增殖抑制率升高(t=4.84,P<0.001);瑞氏染色结果 发现,与对照组比较,成熟单核细胞比例显著升高[(61.2±13.6)％vs(0.8±0.2)％,t=7.49,P=0.001];western blot结果 表明,ICAT蛋白表达上调(t=9.917,P<0.01),TCF1、c-Myc和cyclin D1蛋白表达下调(t分别为54.54,54.64和29.24,P均<0.001);此外,pRB蛋白的磷酸化水平亦下调(t=150.6,P<0.001);细胞β-catenin蛋白表达水平无显著性变化(P>0.99),但其在核内的表达水平下降(t=9.77,P=0.01);免疫荧光检测结果 显示,β-catenin蛋白呈胞浆聚集状态.结论 1,25-(OH)2 D3通过抑制Wnt/β-catenin信号通路,抑制HL-60细胞增殖并促进其单核系分化.

Frozen shoulder is a common shoulder disorder characterized by a gradual increase of pain and a limited range of motion. However, its pathophysiologic mechanisms remain unclear and there is no consensus as to the most effective treatment. The purpose of the study was to investigate the effect of transforming growth factor‐β (TGF‐β) on fibrosis and inflammatory response of the shoulder joint of rat models and to explore the therapeutic effect of the peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonist. In the study, the effect of PPAR‐γ agonist CDDO‐IM treatment on cell proliferation, migration, and extracellular matrix proteins synthesis (vimentin, α‐smooth muscle actin, collagen I, and collagen III) were tested by cell proliferation test, scratches test, real‐time quantitative polymerase chain reaction, and Western blot analysis. The frozen shoulder was also established on the rat model by injecting adenovirus‐TGF‐β1 into rats' shoulder capsule. Pathological changes of the frozen shoulder tissue of the experimental group and PPAR‐γ agonist treatment group were evaluated. The stiffness of joints of the three groups was tested. Inflammatory mediators' expression including cyclooxygenase‐1, interleukin‐1β, and tumor necrosis factor‐α of the shoulder was tested by enzyme‐linked immunosorbent assay, and the expression of extracellular matrix proteins was evaluated by hematoxylin and eosin staining and immunohistochemistry. The results showed that pathological changes of the frozen shoulder in the rat model include an abnormal proliferation of fibroblasts, infiltration of inflammatory cells, and disorder of fibrous structure, while rosiglitazone reduced the severity of the frozen shoulder in the treatment group. Clinically, PPAR‐γ agonists may be a promising target for the treatment of the frozen shoulder.

背景:冻结肩是一种以肩关节疼痛和活动受限为主要特征的疾病,目前病因不明,治疗效果欠佳.目的:研究转化生长因子-β1(TGF-β1)对大鼠肩关节囊纤维化及炎症反应等病理改变的影响,以及过氧化物酶体增殖剂激活受体-γ(PPAR-γ)激动剂对大鼠冻结肩的治疗作用,为临床治疗冻结肩提供新思路.方法:利用TGF-β1诱导人皮肤成纤维细胞(HSF)异常纤维化,PPAR-γ激动剂三萜类化合物(CDDO-IM)作为治疗药物,检测细胞增殖、迁移情况及细胞外基质蛋白的表达情况.向SD大鼠的肩关节腔注射TGF-β1过表达的腺病毒构建大鼠冻结肩模型.2周后,其中一半大鼠用罗格列酮灌胃饲养2周,作为罗格列酮治疗组.检测大鼠肩关节活动度,利用ELISA检测关节腔炎症因子,HE染色和免疫组织化学法检测大鼠肩关节囊组织细胞外基质蛋白的表达情况.结果:在细胞实验中,TGF-β1组的增殖率为83.6％,TGF-β1+CDDO-IM组增殖率为19.3％(P<0.01);TGF-β1组的迁移率为84.9％,TGF-β1+CDDO-IM组迁移率为44.1％(P<0.05);TGF-β1能够诱导HSF增殖、迁移及异常纤维化.动物实验成功构建了TGF-β1诱导的大鼠冻结肩模型,免疫组织化学结果提示,罗格列酮能够抑制大鼠冻结肩的炎症形成,减少基质蛋白生成,重塑纤维组织结构.结论:冻结肩的病理改变主要是纤维细胞异常增生,炎症细胞浸润,纤维结构紊乱,而PPAR-γ激动剂可以缓解大鼠冻结肩关节僵硬,减弱炎症反应,抑制异常纤维化.