Research progress on natural products against hepatocellular carcinoma

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

Updating targets for natural killer/T-cell lymphoma immunotherapy

Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.

Current therapeutic modalities and chemopreventive role of natural products in liver cancer:Progress and promise

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

Natural Products and Derivatives Targeting at Cancer Energy Metabolism:A Potential Treatment Strategy

In the 1920s,Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells.Tumor cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic conditions.Investigation on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the world.In recent years,plentiful studics suggest that targeting the peculiar cancer energy metabolic pathways,including glycolysis,mitochondrial respiration,amino acid metabolism,and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential nutrients.Natural products (NPs)are considered as the “treasure trove of small molecules drugs” and have played an extremely remarkable role in the discovery and development of anticancer drugs.And numerous NPs have been reported to act on cancer energy metabolism targets.Herein,a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared.

Potential application of proteolysis targeting chimera(PROTAC)modification technology in natural products for their targeted protein degradation

There are numerous evaluations of natural products,of which majority are food bioactives,performed up to date for their various health beneficial activities via targeting specific proteins.However,the direct identification of a targeted protein remains unexplored for natural occurring compounds.Proteolysis targeting chimera(PROTAC)is a type of bifunctional chimeric molecules that can directly degrade the binding proteins targeted by bioactive molecules in an ubiquitin-proteasome pathway.As the agents in protein degradation dependent on ubiquitin ligase,the bifunctional molecule connects the target protein ligand and E3 ligase ligand together via an appropriate linker.It is highly selective and efficient to induce the ubiquitin-mediated degradation of targeted binding proteins.Therefore,it has been demonstrated that the PROTAC technology has broad application in the modulation of the target protein level.In this review,we outlined the advances in PROTAC combined molecule compounds,summarized its quantitative structure-activity relationship,and finally reviewed the methods applied in identifying the target proteins of natural products.We hope it will provide an insightful application of PROTAC techniques in the target protein identification of natural products including food bioactive molecules.

Naturally derived anti-hepatitis B virus agents and their mechanism of action

Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.

Natural products as a crucial source of anti-inflammatory drugs: recent trends and advancements

Natural active molecules are key sources of modern innovative drugs. Particularly, a great amount of natural active molecules have been reported to possess promising therapeutic effects on inflammatory diseases, including asthma, rheumatoid arthritis, hepatitis, enteritis, metabolic disorders and neurodegenerative diseases. However, these natural active molecules with various molecular structures usually exert anti-inflammatory effects through diversiform pharmacological mechanisms, which is necessary to be summarized systematically. In this review, we introduced the current major anti-inflammatory natural active molecules based on their chemical structures, and discussed their pharmacological mechanisms including anti-inflammatory molecular signaling pathways and potential target proteins, which providing a referential significance on the development of novel anti-inflammatory drugs, and also revealing new therapeutic strategies for inflammatory diseases.

Marine natural products with anti-inflammation effects

The ocean possesses a complex setting with high pressure,high salinity,oligotrophy,low temperature and weak illumination conditions.To survive and evolve in such harsh surroundings,marine organisms metabolize a series of chemicals known as secondary metabolites which indicate structural and functional diversity to adapt interspecific survival competition.During recent decades,the anti-inflammatory property of marine natural products has come under scrutiny as inflammation involves in the vast majority of diseases.Correspondingly,a myriad of marine bioactive molecules including terpenes,polypeptides,polysaccharides,sterols and many others may bring a new insight into inflammation therapies with multifarious sources and minimal side effects.And a better understanding of their mechanisms of anti-inflammation may lead to better treatments for numerous diseases.Herein,the research progress of marine-derived anti-inflammation compounds and the relevant mechanisms were reviewed,to provide a basis for the research and development of anti-inflammatory marine drugs.

基于改进YOLOv5s的不同成熟度苹果目标检测方法

[目的]本文旨在解决在自然环境下不同成熟度苹果目标检测精度较低的问题。[方法]提出了一种改进的YOLOv5s模型SODSTR-YOLOv5s(YOLOv5s with small detection layer and omni-dimensional dynamic convolution and swin transformer block),用于不同成熟度苹果检测。首先改进YOLOv5s的多尺度目标检测层,在Prediction中构建检测160×160特征图的检测头,提高小尺寸的不同成熟度苹果的检测精度;其次在Backbone结构中融合Swin Transformer Block,加强同级成熟度的苹果纹理特征融合,弱化纹理特征分布差异带来的消极影响,提高模型泛化能力;最后将Neck结构的Conv模块替换为动态卷积模块ODConv,细化局部特征映射,实现局部苹果细粒度特征的充分提取。基于不同成熟度苹果数据集进行试验,验证改进模型的性能。[结果]改进模型SODSTR-YOLOv5s检测的精确率、召回率、平均精度均值分别为89.1%、95.5%、93.6%,高、中、低成熟度苹果平均精度均值分别为94.1%、93.1%、93.7%,平均检测时间为16 ms,参数量为7.34 M。相比于YOLOv5s模型,改进模型SODSTR-YOLOv5s精确率、召回率、平均精度均值分别提高了3.8%、5.0%、2.9%,参数量和平均检测时间分别增加了0.32 M和5 ms。[结论]改进模型SODSTR-YOLOv5s提升了在自然环境下对不同成熟度苹果的检测能力,能较好地满足实际采摘苹果的检测要求。

自然科学版期刊新增栏目选题策划

《佳木斯大学学报(自然科学版)》是一家省级期刊,致力于提供深度和多样化的学术交流平台,旨在激发作者和读者对自然科学领域的深刻理解,并鼓励提出新的学术观点。该期刊拟新设立栏目《自然科学探索》。新栏目将包括环境变化研究、生物多样性保护、地球科学研究和环保倡导与可持续发展等主题。目标读者涵盖科学家、教育工作者、学生、环保倡导者及对自然科学感兴趣的广泛读者群体。栏目计划每季度出版一次,力求在提高读者对自然科学的兴趣、传播科学知识、鼓励环保行动和成为自然科学领域的权威知识来源等方面取得重要效果。

中药及其天然产物通过靶向铁死亡治疗癌症研究进展

铁死亡是一种独特的铁依赖性的细胞死亡方式,一种不同于细胞凋亡、各种形式的坏死和自噬的新型死亡表型。许多从中药中提取的活性成分可在不同癌症中通过诱导铁死亡发挥抗癌作用。越来越多的研究发现,对铁死亡的调控可影响肿瘤细胞对药物的敏感性,甚至逆转耐药。一些天然产物与化学治疗药物如顺铂、氟尿嘧啶、吉西他滨等联用可通过诱导铁死亡增强癌细胞对药物的敏感性。该文主要总结了可以通过诱导铁死亡发挥抗癌作用的中药及其天然产物,可为癌症治疗和逆转耐药提供新思路,同时也为发掘中药的潜在优势、拓宽中药的应用范围提供参考。

功能化脂质体及其在植物源天然产物递送中的应用

植物源天然产物具有广泛的药理特性,在药物发现中占据关键地位,同时以植物膳食补充剂的形式满足人体营养需求。植物源天然产物功效强大,但普遍存在溶解性低、稳定性差、缺乏靶向性、有毒副作用、有特殊气味等限制因素,为临床药物转化带来了挑战。近年来,纳米技术的发展为植物源天然产物的应用提供了新途径。其中,脂质体是一种由两亲性物质合成的双分子层纳米囊泡,具有高载药量、稳定性强等优势。与其他纳米颗粒相比,脂质体易于制备和扩展,它的扩展基于脂质体能被灵活修饰的表面特性。通过在脂质体表面修饰具备不同功能的元件可以使脂质体功能化,这些功能体现在靶向递送、药物控释、局部释放、改善药代动力学等。使用不同类型的功能化脂质体负载植物源天然产物不仅可以增强天然产物的稳定性、提高靶向性、减少副作用,还可以掩盖天然产物的刺激性气味,提升大众的接受度。本综述围绕当前植物源天然产物面临的典型问题,结合功能化脂质体在其中的具体应用做出总结。此外,本文还将回顾功能化脂质体进入临床治疗所面临的机遇和挑战,并探讨克服这些问题的机会,以期更好地实现植物纳米药物的精准控制,为相关领域研究人员及相关产业工作人员提供思路与启发。

钼锝靶件辐照装置堆外自然循环实验研究

钼锝同位素辐照装置的堆外热工水力研究,对于确定靶件的辐照参数和辐照安全具有重要意义,相关结果可为靶件的设计验证和入堆辐照提供技术支持。本文针对自主研发的钼得靶件辐照装置,设计了堆外传热实验台架,开展了钼锝靶件辐照装置堆外传热验证实验,对比分析了不同热流密度、不同模拟靶件外径、不同辐照装置结构等条件下实验段的温度分布。结果表明,辐照装置内导流管的设计可有效提高装置的自然循环能力,证明了所设计辐照装置的安全性。

文库构建与基因簇靶向筛选驱动的微生物天然产物高效发现

微生物天然产物作为小分子药物的主要来源,已被广泛应用于医药与农业等领域。随着全球抗生素耐药性与其他公共健康问题的加剧,新结构、新靶点微生物天然产物发现迫在眉睫。大规模(宏)基因组测序揭示微生物蕴含了巨大的生物合成潜力,相继催生了多种不同类型的天然产物挖掘策略。然而,目前仍然缺乏将天然产物合成基因簇与编码产物快速关联的高效方案。近年来,(宏)基因组文库构建在获取批量天然产物合成基因簇方面展现出明显优势,结合高效的基因簇靶向筛选方法,显著加速了新结构天然产物系统发现。本文综述了三类基于(宏)基因组文库构建与靶向筛选驱动天然产物创新发现的策略,主要从克隆载体类型、文库构建方式、基因簇靶向筛选方法等角度进行了阐述,并对Cosmid/Fosmid文库、BAC/PAC文库、FAC/YAC文库等不同文库类型的优缺点及应用范围进行了对比,最后对这些策略的发展前景进行了展望。未来,基于文库构建与基因簇靶向筛选策略将极大驱动不同生境微生物来源的活性天然产物挖掘,预期大量新靶点、新结构天然产物将不断涌现。

自然资源视频监测目标检测关键技术研究与应用

随着机器视觉技术的突飞猛进,智能视频监测为自然资源监管提供了可实时响应的新执法手段。运用基于深度学习的域自适应目标识别技术和基于DEM辅助的高精度单目定位技术,对自然资源违法行为与线索进行快速目标检测;并在此基础上设计了自然资源视频执法监测系统技术架构,在广东开展了实地应用测试。结果表明,该方法对重型机械、土堆、建筑板材、在建砖房、新建板房、红砖堆等类别的识别准确率均高于80%,在1 200 m监测距离内平均定位误差小于3%。

基于改进YOLOv3的自然场景中未成熟青苹果识别研究

为研究适合当前生产实际的苹果自动套袋技术,实现真实环境中未成熟青苹果的精准识别,提出一种基于改进YOLOv3的自然场景中未成熟青苹果图像识别方法。首先,为提高含干扰因素图像中未成熟青苹果识别准确率,基于YOLOv3算法利用残差网络和多尺度特征融合检测小目标的思想,对YOLOv3特征提取网络进行改进与试验验证,利用尺寸为(104,104,128)的特征图代替原尺寸为(13,13,1024)的特征图作为输出,提出改进YOLOv3的未成熟青苹果目标检测模型,通过增大特征提取网络输出特征图尺寸,减小感受野尺寸,提高算法网络对图像中未成熟青苹果的捕捉能力与识别准确率。其次,设计不同算法、不同品种和不同环境下的识别对比试验并对结果进行对比分析。改进YOLOv3在整体数据集上的检测均值平均精确率mAP值和召回率R值分别为92.46%、87.6%,较原YOLOv3分别提高3.22%、14.57%,改进模型性能提升主要体现在检测正确目标数量的能力上;在含光照影响、重叠和遮挡影响图像测试集上改进YOLOv3的mAP值较原YOLOv3分别提高3.58%、2.74%。改进YOLOv3模型对整体数据集和含干扰因素图像测试集的检测准确率较高,检测正确目标的数量较多,抗干扰能力较强。

自然杀伤细胞家族2成员D受体-配体轴在血液瘤中的作用研究进展

自然杀伤细胞家族2成员D(NKG2D)受体通过表达在自然杀伤(NK)细胞和细胞毒性T淋巴(CTLs)细胞上激活这些免疫细胞对抗肿瘤。肿瘤细胞通过降低自然杀伤细胞家族2成员D配体(NKG2DLs)的表达来逃避免疫系统的监视,从而促进肿瘤的免疫逃逸。最新的研究揭示了NKG2D受体-配体轴在血液瘤的发展、免疫监视和治疗中的关键作用,尤其是在阐明免疫逃逸机制和开发新的治疗策略方面显示出巨大潜力。现从NKG2D受体-配体轴在血液瘤发病机制、免疫监测及治疗中的作用进行阐述,在加深对血液瘤病理机制理解的同时,为提升治疗效果开辟了新的策略。

Click chemistry and natural products

The 2022 Nobel Prize in Chemistry was awarded to American scientists Carolyn Bertozzi,K.Barry Sharpless,and Danish scientist Morten P.Merdahl for their contributions to the development of click chemistry and bioorthogonal chemistry.

Role of marine natural products in the development of antiviral agents against SARS‑CoV‑2:potential and prospects

A novel coronavirus,known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has surfaced and caused global concern owing to its ferocity.SARS-CoV-2 is the causative agent of coronavirus disease 2019;however,it was only discovered at the end of the year and was considered a pandemic by the World Health Organization.Therefore,the develop-ment of novel potent inhibitors against SARS-CoV-2 and future outbreaks is urgently required.Numerous naturally occurring bioactive substances have been studied in the clinical setting for diverse disorders.The intricate infection and replication mechanism of SARS-CoV-2 offers diverse therapeutic drug targets for developing antiviral medicines by employing natural products that are safer than synthetic compounds.Marine natural products(MNPs)have received increased attention in the development of novel drugs owing to their high diversity and availability.Therefore,this review article investigates the infection and replication mechanisms,including the function of the SARS-CoV-2 genome and structure.Furthermore,we highlighted anti-SARS-CoV-2 therapeutic intervention efforts utilizing MNPs and predicted SARS-CoV-2 inhibitor design.

基于双重多视角表示的目标级隐性情感分类

目标级隐性情感分类是自然语言处理中一项重要的情感分析任务。目前多数研究主要侧重于对上下文感知的目标进行建模,且建模信息源较为单一,难以充分捕获到目标词在文本中的隐性情感。针对该问题,提出基于双重多视角表示学习的目标级隐性情感分类方法,采用3种视角对目标和输入文本进行建模,分别设计文本自身的表示学习、图视角下的表示学习以及外部知识视角下的表示学习,并通过卷积神经网络将3种视角下的表示进行深度融合。此外,同时采用上述3种视角对目标进行表示学习,将文本的语义表示和目标的语义表示相结合,并输入到情感极性分类器中。在5个公共数据集上进行实验并与8个基线模型的对比结果表明,该方法性能达到了最优水平,在News MTSC-mt和News MTSC-rw隐性情感分析数据集上的F1_m值分别比最好模型提高1.0%和2.6%,在Laptop14、Restaurant14和Twitter显性情感分析数据集上的F1_m值分别比最好模型提高3.6%、1.4%和1.6%。