中药天然产物代谢活化的化学性质可能与其毒性相关

确保中药(TCM)的安全性一直是医疗保健领域中长期存在的普遍挑战。对天然产品的毒理学复杂性进行细致的研究至关重要,特别是这些物质的代谢转化以及随后产生的反应性中间体。这一生化过程是多种毒性表现的起源,包括肝毒性、肾毒性、肺毒性和遗传毒性。在TCM中分类的化合物,包括吡咯里西啶生物碱、蒽醌、呋喃萜类、烯基苯、双苄基异喹啉生物碱、黄酮类和甲氧基二苯基衍生物,在代谢激活后表现出一系列有害机制。这篇综述提供了这些化合物通过代谢激活引起毒性的途径的全面描述。这篇综述强调了天然产物代谢激活中涉及的化学机制,这些机制可能触发毒性级联反应,而不仅仅是表面现象。此外,这项研究通过深入探讨代谢激活引起的毒性机制,丰富了现有文献。总之,这篇综述强调了仔细研究毒性机制的重要性,并为合理和安全使用中药提供了见解。

Real-time data processing method for CO_(2) dispersion interferometer on EAST

A real-time data processing system is designed for the carbon dioxide dispersion interferometer(CO_(2)-DI)on EAST.The system utilizes the parallel and pipelining capabilities of an fieldprogrammable gate array(FPGA)to digitize and process the intensity of signals from the detector.Finally,the real-time electron density signals are exported through a digital-to-analog converter(DAC)module in the form of analog signals.The system has been successfully applied in the CO_(2)-DI system to provide low-latency electron density input to the plasma control system on EAST.Experimental results of the latest campaign with long-pulse discharges on EAST(2022–2023)demonstrate that the system can respond effectively in the case of rapid density changes,proving its reliability and accuracy for future electron density calculation.

First results of CO_(2) dispersion interferometer on EAST tokamak

A dispersion interferometer(DI)has been installed and operates on the Experimental Advanced Superconducting Tokamak(EAST).This DI system utilizes a continuous-wave 9.3μm CO_(2)laser source to measure line-averaged electron densities accurately.In contrast to conventional interferometers,the DI does not require substantial vibration isolations or compensating systems to reduce the impact of vibrations in the optical path.It also employs a ratio of modulation amplitudes,ensuring it remains immune to the variations in detected intensities.Without a variation compensation system,the DI system on EAST reaches a density resolution of less than1.8×10^(-2)πrad and a temporal resolution of 20μs.The measurements made by the POlarimeterINTerferometer(POINT)system and the far-infrared hydrogen cyanide(HCN)interferometer are remarkably consistent with the DI’s results.The possibility of fringe jumps and the impact of refraction in high-density discharge can be significantly decreased using a shorter wavelength laser source.A rapid density change of 3×10^(19)m^(-3)during 0.15 s has been measured accurately in shot No.114755 of EAST.Additionally,the DI system demonstrates dependability and stability under 305 s long-pulse discharges in shot No.122054.

产业数字化转型与居民消费结构升级——效应、路径与机理

产业数字化转型是利用数字经济构建核心竞争力的关键,居民消费结构升级是人们寻求更高层次需求满足的结果,也是经济高质量发展的重要特征。理论模型上,本文构建了一个多部门一般均衡模型,考察了产业数字化转型对居民消费结构升级的影响。结果显示,产业数字化可以通过影响两类消费品之间的相对价格促进消费结构高级化,通过长尾效应促进消费结构多样化。实证部分利用面板固定效应模型,肯定了前述的主要结论与作用机制,并且在进一步分析中发现,产业数字化对消费结构升级的推动作用在经济发展程度较低的地区更为明显,对收入水平较低的居民也更为明显,体现出了一定的包容性。本文的主要结论有深刻的政策含义:产业数字化转型是供给方面的重要转变,它代表着未来中国产业生态的重构方向;居民消费结构升级是需求方面的变化,因此,利用产业数字化转型推动居民消费结构升级可以成为以供给侧结构性改革拉动内需、以新发展格局引领经济高质量发展的有效途径。同时,产业数字化转型对于推动居民消费结构升级的积极作用也从供需结合的角度证实了数字经济与经济高质量发展的相合性。

苯并三氮唑基乙酸HOF的制备及质子导电性能研究——推荐一个绿色综合化学实验

氢键有机框架(HOFs)是一类由有机构筑单元通过分子间氢键自组装而成的新型晶态固体材料,具有孔径可调、低密度、含有丰富氢键网络的结构特点,因而在质子导电研究领域备受关注。本实验切合该领域的研究前沿,以水为溶剂,采用一步法制备苯并三氮唑基乙酸HOF (简称HOF1),通过元素分析、红外光谱、粉末X射线衍射等手段对其组成和结构进行表征。之后采用交流阻抗法测试其在三种相对湿度(75%、85%以及98%RH)和60–100℃之间的质子导电率,进而通过计算活化能推断其质子导电机理。本实验难度适中,综合多种测试手段,可以使学生了解质子导电领域的研究前沿知识、激发科研兴趣,训练科研能力。

肿瘤电场治疗仪治疗复发脑胶质母细胞瘤的前瞻性单中心单臂探索性研究

目的:评价肿瘤电场治疗仪用于治疗复发胶质母细胞瘤患者的初步安全性和有效性。方法:选取2020年4月至2020年8月期间中南大学湘雅医院和解放军总医院6例受试者,均为男性,中位年龄53(48~68)岁。入组复发胶质母细胞瘤受试者并收集临床资料,通过观察受试者治疗期间不良事件的发生率、肿瘤进展时间(time to progression,TTP)和总生存时间(overall survival,OS)评估治疗的安全性和有效性。结果:入组6例受试者中位随访时间10.9(8.4~22.7)个月,所有受试者发生肿瘤进展,5例随访至死亡,截至随访截止1例生存。中位肿瘤进展时间(median time to progression,m TTP)为4.7个月(95%CI:3.62~5.78),中位无进展生存时间(median progression-free survival,mPFS)为4.7个月(95%CI:3.62~5.78),中位总生存时间(median overall survival,mOS)为10.9个月(95%CI:8.86~12.94)。客观缓解率(CR+PR)33.3%;疾病控制率(SD+PR+CR)83.3%。治疗相关的不良事件主要为头皮皮疹,发生率为66.7%,经调整电极片黏贴位置、保持创口干燥、涂抹类固醇类软膏或抗生素软膏后均可有效缓解。结论:肿瘤电场治疗仪用于治疗复发胶质母细胞瘤的受试者在电场治疗过程中呈现良好的初步安全性和有效性。

Reviving and characterizing three species of dinoflagellate cysts dormant for about 70 years in the East China Sea:Biecheleria brevisulcata,Biecheleriopsis adriatica,and Scrippsiella donghaienis

Many marine dinoflagellates can form resting cysts as a part of their life cycle,and the cysts could be buried in sediment and remained viable for as long as over 150 years.However,only a very limited number of cyst species have been revived from long-buried sediments and investigated in regard to a possible shift in the intra-specific genetic structure of a species detected from the historical record at a particular location.Here,we report a successful germination of three species of resting cysts that were sampled from the depth dated back to 1941±18 AD from a 44-cm sediment core from the East China Sea.Seven isolates were established from germination of single cyst isolation or multi-cyst germinations.LSU rRNA gene or ITS sequences of these strains were obtained,then they were identified to be Biecheleria brevisulcata(five strains),Biecheleriopsis adriatica(one strain),and Scrippsiella donghaienis(one strain)in terms of morphology and rRNA gene sequence.Biecheleria brevisulcata strain 1,Bps.adriatica strain 21,and S.donghaienis strain 23 were examined in detail with light microscope(LM)and scanning electron microscope(SEM),and analyzed with high performance liquid chromatography(HPLC)for their pigment compositions,and genetic diversity.We also confirmed the presence of a resting cyst of Bps.adriatica in the field for the first time.The LSU rRNA gene-based genetic distances of Bps.adriatica from that obtained from water sample,single-cell PCR sequencing for the cysts isolated from the surface sediment of the same sea area and that reported from other regions during the recent years,and ITS-based genetic distances of S.donghaienis from that obtained from cysts isolated from the surface sediment of the same location and that reported from other regions during the recent years indicated that the intra-specific genetic structure of each species in the sampling area may have shifted during the last 70 years.Our work confirms that B.brevisulcata,Bps.adriatica,and S.donghaienis,all described as new species around 2010,have inhabited the East China Sea for about 70 years.The present work reports for the first time the revival of dinoflagellate resting cysts long-buried in the coastal sediments of China,which facilitates further study on the historical occurrences of other harmful dinoflagellates and their relevance to the regional climate and environmental changes in China.

肺动脉高压右心重构中心肌细胞的细胞死亡途径:探索重塑之路

细胞死亡对于机体生长、发育和调节稳态非常关键,是心脏病理学中的一个基本过程.证据表明,在各种心血管系统疾病中,细胞凋亡、坏死性凋亡、线粒体通透性改变驱动的坏死、焦亡、铁死亡以及自噬等死亡方式在心脏重构、心力衰竭过程中起着重要作用.随着肺动脉高压的进展,右心室发生失代偿性肥大,最终导致心室衰竭并伴随着心肌细胞死亡.因此,探讨此过程中心肌细胞死亡的具体机制对于改善患者预后意义重大.本文综述了各种心肌细胞死亡方式的信号通路和各种细胞死亡方式的检测、评估方法,总结了肺动脉高压中心肌细胞死亡方式的有关研究现况,讨论了针对不同细胞死亡方式研究对于肺动脉高压靶向治疗的研究前景.

Digitalization for supply chain resilience and robustness: The roles of collaboration and formal contracts

Black swan events such as the coronavirus (COVID-19) outbreak cause substantial supply chain disruption risks to modern companies. In today’s turbulent and complex business environment, supply chain resilience and robustness as two critical capabilities for firms to cope with disruptions have won substantial attention from both the academia and industry. Accordingly, this study intends to explore how digitalization helps build supply chain resilience and robustness. Adopting organizational information processing theory, it proposes the mediating effect of supply chain collaboration and the moderating effect of formal contracts. Using survey data of Chinese manufacturing firms, the study applied structural equation modelling to test the research model. Results show that digitalization has a direct effect on supply chain resilience, and supply chain collaboration can directly facilitate both resilience and robustness. Our study also indicates a complementary mediating effect of supply chain collaboration on the relationship between digitalization and supply chain resilience and an indirect-only mediation effect on the relationship between digitalization and supply chain robustness. Findings reveal the differential roles of digitalization as a technical factor and supply chain collaboration as an organizational factor in managing supply chain disruptions. Paradoxically, formal contracts enhance the relationship between digitalization and supply chain resilience but weaken the relationship between supply chain collaboration and supply chain resilience. The validation of moderating effects determines the boundary conditions of digitalization and supply chain collaboration and provides insights into governing supply chain partners’ behavior. Overall, this study enhances the understanding on how to build a resilient and robust supply chain.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk:a single-center study

Low-density lipoprotein cholesterol(LDL-C)is an independent risk factor for atherosclerotic cardiovascular disease(ASCVD).Even after lipid-lowering therapy(LLT)with statins or statin–ezetimibe,a large proportion of patients at very high risk still do not reach the LDL-C targets(<1.4 mmol/L and≥50%reduction).[1,2]Proprotein convertase subtilisin/kexin type 9 inhibitor(PCSK9i)is recommended for patients at high or very high cardiovascular risk inwhom LDL-C reduction is not adequate with statin therapy or in those with statin intolerance.Limited data are available regarding the use of PCSK9i in China.

A novel graphene oxide-carbon nanotubes anchored α-FeOOH hybrid activated persulfate system for enhanced degradation of Orange Ⅱ

Persulfate activation has been applied as one of the efficient advanced oxidation processes(AOPs) to remediate polluted environments. In this study, a novel α-FeOOH anchored by graphene oxide(GO)-carbon nanotubes(CNTs) aerogel(α-FeOOH@GCA) nanocomposite activated persulfate system(α-FeOOH@GCA + K2S2O8) was applied for decolorization of Orange Ⅱ(OⅡ). The decolorization of OⅡ was remarkably enhanced to a level of ~ 99% in this system compared with that of pristine α-FeOOH(~ 44%) or GO-CNTs(~18%). The enhanced catalytic activity of α-FeOOH@GCA was due to the formation of a heterojunction byα-FeOOH and GO-CNTs as confirmed by the presence of Fe–O–C chemical bonds. The degradation intermediates of OⅡ were comprehensively identified. The proposed degradation pathway of OⅡ begins with the destruction of the conjugated structures of OⅡ by the dominant reactive oxygen species, surface-bound SO4·-. The decolorization efficiency of OⅡ by the α-FeOOH@GCA activated persulfate system decreased from the first to third cycle of recycling. Ultraviolet(UV) irradiation or introduction of a small amount of Fe2+ could restore the activation of this system. The results show that the α-FeOOH@GCA persulfate activation system promises to be a highly efficient environmental remediation method for organic pollutants.

Effects of linker amino acids on the potency and selectivity of dimeric antimicrobial peptides

Dimerization is an effective strategy for designing antimicrobial peptides that combine the advantages of different native peptides. In this study, we explored the effects of different linker amino acids, including leucine, proline and aminocaproic acid, on the anticancer, antimicrobial and hemolytic activities of the heteromeric antimicrobial peptides AM-1, AM-2, and AM-3. Proline and aminocaproic acid are ideal linkers for increasing the potency and selectivity of heteromeric antimicrobial peptides. The results of MD simulations provided a rationalization for this observation. Both AM-2, which had a proline linker,and AM-3, which had an aminocaproic acid linker, adopted a compact conformation in water and a bent conformation in membranes. This change in the flexible structures of AM-2 and AM-3 could have resulted in decreased binding of these peptides to zwitterionic lipid bilayers and increased damage to mixed lipid bilayers containing acidic phospholipids. In short, these findings obtained via assessing the effects of linker amino acids will contribute to the design of ideal heteromeric antimicrobial peptides with high selectivity and potency.

Bottlenecks and opportunities in immunotherapy for glioma:a narrative review

Glioma is the most aggressive brain tumor having invasive ability and a highly heterogeneous phenotype.Many patients with glioma respond poorly to traditional surgery or temozolomide-based chemotherapy.Over the past few decades,developments in immunotherapeutic strategies have provided newer insights into the treatment of gliomas.Immunotherapy is based on the principle of normalization or recovery of T cell-mediated anti-tumor immunoreaction.Different innovative strategies have been used;these include enhancement of immunogenicity by administration of tumor antigens or dendritic cell vaccines,replenishment of cytotoxic T cells by adoptive T cell transfer,repair of exhausted T cells by immune checkpoint inhibitors,and the use of other immune activators such as oncolytic viruses.However,many immunotherapy-based clinical trials did not meet the expected therapeutic endpoints in patients with glioma.Gliomas use unique strategies to generate an immune-suppressive microenvironment;these include limiting immunogenicity and repressing T cell infiltration or activation.This may be addressed by the incorporation of immunotherapy with standard therapy or by use of certain innovative approaches such as tumor-treating fields.In this review,we summarize the updated immunotherapies in glioma and discuss current limitations and future prospects.