Renaturalizing Floodplains

This manuscript analyzes and discusses viewpoints concerning the renaturalization of floodplains as an instrument of management in large catchments, using natural flood defense schemes. Schemes consider the differentiated supply of ecosystemic services based on river channel/floodplain interactions. Conventional structural methods used to prevent flooding (e.g., longitudinal dikes) are increasingly showing themselves to be less efficient with regard to advances in the problems of environmental management of the territory, especially when combined with extreme events, where the importance of perfecting strategies for harmonizing duly controlled floodable areas and water retention can be seen. Natural flood risk reduction measures are part of a holistic solution for sustainable management of flood risk, conservation of nature, water quality and green economy. They rely upon the inherent ability of floodplains to retain water in the basin, and this can delay and reduce peak flows.

Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

Harnessing artificial intelligence for identifying conflicts of interest in research

This editorial explores the transformative potential of artificial intelligence(AI)in identifying conflicts of interest(COIs)within academic and scientific research.By harnessing advanced data analysis,pattern recognition,and natural language processing techniques,AI offers innovative solutions for enhancing transparency and integrity in research.This editorial discusses how AI can automatically detect COIs,integrate data from various sources,and streamline reporting processes,thereby maintaining the credibility of scientific findings.

Naturalizing Aliens

Invasive species have posed major economic and environmental threats to

Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

Synthetic polymers:A review of applications in drilling fluids

With the growth of deep drilling and the complexity of the well profile,the requirements for a more complete and efficient exploitation of productive formations increase,which increases the risk of various complications.Currently,reagents based on modified natural polymers(which are naturally occurring compounds)and synthetic polymers(SPs)which are polymeric compounds created industrially,are widely used to prevent emerging complications in the drilling process.However,compared to modified natural polymers,SPs form a family of high-molecular-weight compounds that are fully synthesized by undergoing chemical polymerization reactions.SPs provide substantial flexibility in their design.Moreover,their size and chemical composition can be adjusted to provide properties for nearly all the functional objectives of drilling fluids.They can be classified based on chemical ingredients,type of reaction,and their responses to heating.However,some of SPs,due to their structural characteristics,have a high cost,a poor temperature and salt resistance in drilling fluids,and degradation begins when the temperature reaches 130℃.These drawbacks prevent SP use in some medium and deep wells.Thus,this review addresses the historical development,the characteristics,manufacturing methods,classification,and the applications of SPs in drilling fluids.The contributions of SPs as additives to drilling fluids to enhance rheology,filtrate generation,carrying of cuttings,fluid lubricity,and clay/shale stability are explained in detail.The mechanisms,impacts,and advances achieved when SPs are added to drilling fluids are also described.The typical challenges encountered by SPs when deployed in drilling fluids and their advantages and drawbacks are also discussed.Economic issues also impact the applications of SPs in drilling fluids.Consequently,the cost of the most relevant SPs,and the monomers used in their synthesis,are assessed.Environmental impacts of SPs when deployed in drilling fluids,and their manufacturing processes are identified,together with advances in SP-treatment methods aimed at reducing those impacts.Recommendations for required future research addressing SP property and performance gaps are provided.

Facile synthesis of hierarchical NaX zeolite from natural kaolinite for efficient Knoevenagel condensation

Zeolite catalysts have found extensive applications in the synthesis of various fine chemicals.However,the micropores of zeolites impose diffusion limitations on bulky molecules,greatly reducing the catalytic efficiency.Herein,we explore an economic and environmentally friendly method for synthesizing hierarchical NaX zeolite that exhibits improved catalytic performance in the Knoevenagel condensation reaction for producing the useful fine chemical 2-cyano-3-phenylacrylate.The synthesis was achieved via a low-temperature activation of kaolinite and subsequent in-situ transformation strategy without any template or seed.Systematic characterizations reveal that the synthesized NaX zeolite has both intercrystalline and intra-crystalline mesopores,smaller crystal size,and larger external specific surface area compared to commercial NaX zeolite.Detailed mechanism investigations show that the inter-crystalline mesopores are generated by stacking smaller crystals formed from in-situ crystallization of the depolymerized kaolinite,and the intra-crystalline mesopores are inherited from the pores in the depolymerized kaolinite.This synthesis strategy provides an energy-saving and effective way to construct hierarchical zeolites,which may gain wide applications in fine chemical manufacturing.

Mechanical Modeling and Analysis of Stability Deterioration of Production Well During Marine Hydrate Depressurization Production

Different from oil and gas production,hydrate reservoirs are shallow and unconsolidated,whose mechanical properties deteriorate with hydrate decomposition.Therefore,the formations will undergo significant subsidence during depressurization,which will destroy the original force state of the production well.However,existing research on the stability of oil and gas production wells assumes the formation to be stable,and lacks consideration of the force exerted on the hydrate production well by formation subsidence caused by hydrate decomposition during production.To fill this gap,this paper proposes an analytical method for the dynamic evolution of the stability of hydrate production well considering the effects of hydrate decomposition.Based on the mechanical model of the production well,the basis for stability analysis has been proposed.A multi-field coupling model of the force state of the production well considering the effect of hydrate decomposition and formation subsidence is established,and a solver is developed.The analytical approach is verified by its good agreement with the results from the numerical method.A case study found that the decomposition of hydrate will increase the pulling-down force and reduce the supporting force,which is the main reason for the stability deterioration.The higher the initial hydrate saturation,the larger the reservoir thickness,and the lower the production pressure,the worse the stability or even instability.This work can provide a theoretical reference for the stability maintaining of the production well.

Predicting the friction angle of clays using a multi-layer perceptron neural network enhanced by yeo-johnson transformation and coral reefs optimization

The accurate prediction of the friction angle of clays is crucial for assessing slope stability in engineering applications.This study addresses the importance of estimating the friction angle and presents the development of four soft computing models:YJ-FPA-MLPnet,YJ-CRO-MLPnet,YJ-ACOC-MLPnet,and YJCSA-MLPnet.First of all,the Yeo-Johnson(YJ)transformation technique was used to stabilize the variance of data and make it more suitable for parametric statistical models that assume normality and equal variances.This technique is expected to improve the accuracy of friction angle prediction models.The friction angle prediction models then utilized multi-layer perceptron neural networks(MLPnet)and metaheuristic optimization algorithms to further enhance performance,including flower pollination algorithm(FPA),coral reefs optimization(CRO),ant colony optimization continuous(ACOC),and cuckoo search algorithm(CSA).The prediction models without the YJ technique,i.e.FPA-MLPnet,CRO-MLPnet,ACOC-MLPnet,and CSA-MLPnet,were then compared to those with the YJ technique,i.e.YJ-FPA-MLPnet,YJ-CRO-MLPnet,YJ-ACOC-MLPnet,and YJ-CSA-MLPnet.Among these,the YJ-CRO-MLPnet model demonstrated superior reliability,achieving an accuracy of up to 83%in predicting the friction angle of clay in practical engineering scenarios.This improvement is significant,as it represents an increase from 1.3%to approximately 20%compared to the models that did not utilize the YJ transformation technique.

Simulation of the Ecosystem Productivity Responses to Aerosol Diffuse Radiation Fertilization Effects over the Pan-Arctic during 2001–19

The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Geological conditions,genetic mechanisms and accumulation patterns of helium resources

Based on the methodology for petroleum systems and through the anatomy and geochemical study of typical helium-rich gas fields,the geological conditions,genesis mechanisms,and accumulation patterns of helium resources in natural gas are investigated.Helium differs greatly from other natural gas resources in generation,migration,and accumulation.Helium is generated due to the slow alpha decay of basement U-/Th-rich elements or released from the deep crust and mantle,and then migrates along the composite transport system to natural gas reservoirs,where it accumulates with a suitable carrier gas.Helium migration and transport are controlled by the transport system consisting of lithospheric faults,basement faults,sedimentary layer faults,and effective transport layers.Based on the analysis of the helium-gas-water phase equilibrium in underground fluids and the phase-potential coupling,three occurrence states,i.e.water-soluble phase,gas-soluble phase and free phase,in the process of helium migration and accumulation,and three migration modes of helium,i.e.mass flow,seepage,and diffusion,are proposed.The formation and enrichment of helium-rich gas reservoirs are controlled by three major factors,i.e.high-quality helium source,high-efficiency transport and suitable carrier,and conform to three accumulation mechanisms,i.e.exsolution and convergence,buoyancy-driven,and differential pressure displacement.The helium-rich gas reservoirs discovered follow the distribution rule and accumulation pattern of near helium source,adjacent to fault,low potential area,and high position".To explore and evaluate helium-rich areas,it is necessary to conduct concurrent/parallel exploration of natural gas.The comprehensive evaluation and selection of profitable helium-rich areas with the characteristics of"source-trap connected,low fluid potential and high position,and proper natural gas volume matched with helium’s"should focus on the coupling and matching of the helium"source,migration,and accumulation elements"with the natural gas"source,reservoir and caprock conditions",and favorable carrier gas trap areas in local low fluid potential and high positions.

Natural Disaster Risk Monitoring for Immovable Cultural Relics Based on Digital Twin

Natural disaster risk monitoring is an important task for disaster prevention and reduction.In the case of immovable cultural relics,however,the feedback mechanism,risk factors,monitoring logic,and monitoring indicators of natural disaster risk monitoring are complex.How to achieve intelligent perception and monitoring of natural disaster risk for immovable cultural relics has always been a focus and a challenge for researchers.Based on the analysis of the concepts and issues related to the natural disaster risk of immovable cultural relics,this paper proposes a framework for natural disaster risk monitoring for immovable cultural relics based on the digital twin.This framework focuses on risk monitoring,including the physical entities of natural disaster risk for immovable cultural relics,monitoring indicators,and virtual entity construction.A platform for monitoring the natural disaster risk of immovable cultural relics is proposed.Using the Puzhou Ancient City Site as a test bed,the proposed concept can be used for monitoring the natural disaster risk of immovable cultural relics at different scales.

Low-temperature characteristicsof rubbers and performance testsof type 120 emergencyvalve diaphragms

Purpose–The type 120 emergency valve is an essential braking component of railway freight trains,butcorresponding diaphragms consisting of natural rubber(NR)and chloroprene rubber(CR)exhibit insufficientaging resistance and low-temperature resistance,respectively.In order to develop type 120 emergency valverubber diaphragms with long-life and high-performance,low-temperatureresistant CR and NR were processed.Design/methodology/approach–The physical properties of the low-temperature-resistant CR and NRwere tested by low-temperature stretching,dynamic mechanical analysis,differential scanning calorimetryand thermogravimetric analysis.Single-valve and single-vehicle tests of type 120 emergency valves werecarried out for emergency diaphragms consisting of NR and CR.Findings–The low-temperature-resistant CR and NR exhibited excellent physical properties.The elasticityand low-temperature resistance of NR were superior to those of CR,whereas the mechanical properties of thetwo rubbers were similar in the temperature range of 0℃–150℃.The NR and CR emergency diaphragms metthe requirements of the single-valve test.In the low-temperature single-vehicle test,only the low-temperaturesensitivity test of the NR emergency diaphragm met the requirements.Originality/value–The innovation of this study is that it provides valuable data and experience for futuredevelopment of type 120 valve rubber diaphragms.

Natural rubber latex as a potential additive for water-based drilling fluids

The environmental hazards and"carbon footprint"of oil and gas drilling can be significantly reduced by replacing traditional petroleum-based chemical additives with natural materials derived from plants and animals.This paper explored for the first time the interaction mechanism between natural rubber latex(NRL)and bentonite suspensions(BTs)through a series of characterization experiments,as well as the potential applications in water-based drilling fluids(WBDF).The gel viscoelasticity experiments showed that NRL could decrease the consistency coefficient(k)and flow index(n)of BTs,and enhance the shear thinning performance of BTs as pseudo-plastic fluids.In addition,0.5 w/v%NRL not only increased the critical yield stress and strengthened the structural strength between the bentonite particles,but also facilitated the compatibility of pressure loss and flow efficiency.The evaluation of colloidal stability and WBDF performance indicated that NRL particles could promote the hydration and charge stability on the surface of BTs particles,and optimize the particle size distribution and flow resistance of WBDF under the"intercalation-exfoliation-encapsulation"synergistic interaction.Moreover,NRL can improve the rheological properties of WBDF at high temperatures(<150.C),and form a dense blocking layer by bridging and sealing the pores and cracks of the filter cake,which ultimately reduces the permeability of the cake and the filtration loss of WBDF.

Physical Experiments and Mechanism Study on the Occurrence State of Hydrogen in Clay Minerals

In recent years,natural hydrogen has been discovered in various geological environments both domestically and internationally,which has sparked a global interest among geologists and led to a surge in the exploration of hydrogen gas(Klein et al.,2019;Prinzhofer et al.,2019;Moretti and Webber,2021;Scott,2021;Bezruchko,2022).However,there is a lack of research on the occurrence state of natural hydrogen gas,which hinders a deeper understanding of its behavior in underground storage and migration.

DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.