Phase separation and transcriptional regulation in cancer development

Liquid-liquid phase separation,a novel biochemical phenomenon,has been increasingly studied for its medical applications.It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes.During transcriptional regulation,dynamic condensates are formed through interactions between transcriptional elements,such as transcription factors,coactivators,and mediators.Cancer is a disease characterized by uncontrolled cell proliferation,but the precise mechanisms underlying tumorigenesis often remain to be elucidated.Emerging evidence has linked abnormal transcriptional condensates to several diseases,especially cancer,implying that phase separation plays an important role in tumorigenesis.Condensates formed by phase separation may have an effect on gene transcription in tumors.In the present review,we focus on the correlation between phase separation and transcriptional regulation,as well as how this phenomenon contributes to cancer development.

Flexible bidirectional pulse charging regulation achieving long-life lithium-ion batteries

Typical application scenarios,such as vehicle to grid(V2G)and frequency regulation,have imposed significant long-life demands on lithium-ion batteries.Herein,we propose an advanced battery life-extension method employing bidirectional pulse charging(BPC)strategy.Unlike traditional constant current charging methods,BPC strategy not only achieves comparable charging speeds but also facilitates V2G frequency regulation simultaneously.It significantly enhances battery cycle ampere-hour throughput and demonstrates remarkable life extension capabilities.For this interesting conclusion,adopting model identification and postmortem characterization to reveal the life regulation mechanism of BPC:it mitigates battery capacity loss attributed to loss of lithium-ion inventory(LLI)in graphite anodes by intermittently regulating the overall battery voltage and anode potential using a negative charging current.Then,from the perspective of internal side reaction,the life extension mechanism is further revealed as inhibition of solid electrolyte interphase(SEI)and lithium dendrite growth by regulating voltage with a bidirectional pulse current,and a semi-empirical life degradation model combining SEI and lithium dendrite growth is developed for BPC scenarios health management,the model parameters are identified by genetic algorithm with the life simulation exhibiting an accuracy exceeding 99%.This finding indicates that under typical rate conditions,adaptable BPC strategies can extend the service life of LFP battery by approximately 123%.Consequently,the developed advanced BPC strategy offers innovative perspectives and insights for the development of long-life battery applications in the future.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)globally.However,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated.This study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer settings.Methods:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each CPG.We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types.Results:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR A.Overall,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous versions.The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current version.In the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)recommendations.Significant variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer types.Conclusion:One-third of the current ESMO CPG recommendations are supported by the highest level of evidence.More well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

Systematic Security Guideline Framework through Intelligently Automated Vulnerability Analysis

This research aims to propose a practical framework designed for the automatic analysis of a product’s comprehensive functionality and security vulnerabilities,generating applicable guidelines based on real-world software.The existing analysis of software security vulnerabilities often focuses on specific features or modules.This partial and arbitrary analysis of the security vulnerabilities makes it challenging to comprehend the overall security vulnerabilities of the software.The key novelty lies in overcoming the constraints of partial approaches.The proposed framework utilizes data from various sources to create a comprehensive functionality profile,facilitating the derivation of real-world security guidelines.Security guidelines are dynamically generated by associating functional security vulnerabilities with the latest Common Vulnerabilities and Exposure(CVE)and Common Vulnerability Scoring System(CVSS)scores,resulting in automated guidelines tailored to each product.These guidelines are not only practical but also applicable in real-world software,allowing for prioritized security responses.The proposed framework is applied to virtual private network(VPN)software,wherein a validated Level 2 data flow diagram is generated using the Spoofing,Tampering,Repudiation,Information Disclosure,Denial of Service,and Elevation of privilege(STRIDE)technique with references to various papers and examples from related software.The analysis resulted in the identification of a total of 121 vulnerabilities.The successful implementation and validation demonstrate the framework’s efficacy in generating customized guidelines for entire systems,subsystems,and selected modules.

A review of public health guidelines for postpartum physical activity and sedentary behavior from around the world

Background:The period following pregnancy is a critical time window when future habits with respect to physical activity(PA) and sedentary behavior(SB) are established;therefore,it warrants guidance.The purpose of this scoping review was to summarize public health-oriented country-specific postpartum PA and SB guidelines worldwide.Methods:To identity guidelines published since 2010,we performed a(a) systematic search of 4 databases(CINAHL,Global Health,PubMed,and SPORTDiscus),(b) structured repeatable web-based search separately for 194 countries,and(c) separate web-based search.Only the most recent guideline was included for each country.Results:We identified 22 countries with public health-oriented postpartum guidelines for PA and 11 countries with SB guidelines.The continents with guidelines included Europe(n=12),Asia(n=5),Oceania(n=2),Africa(n=1),North America(n=1),and South America(n=1).The most common benefits recorded for PA included weight control/management(n=10),reducing the risk of postpartum depression or depressive symptoms(n=9),and improving mood/well-being(n=8).Postpartum guidelines specified exercises to engage in,including pelvic floor exercises(n=17);muscle strengthening,weight training,or resistance exercises(n=13);aerobics/general aerobic activity(n=13);walking(n=11);cycling(n=9);and swimming(n=9).Eleven guidelines remarked on the interaction between PA and breastfeeding;several guidelines stated that PA did not impact breast milk quantity(n=7),breast milk quality(n=6),or infant growth(n=3).For SB,suggestions included limiting long-term sitting and interrupting sitting with PA.Conclusion:Country-specific postpartum guidelines for PA and SB can help promote healthy behaviors using a culturally appropriate context while providing specific guidance to public health practitioners.

Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

Contract Mechanism of Water Environment Regulation for Small and Medium Sized Enterprises Based on Optimal Control Theory

The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.

Dynamic regulation of the irrigation-nitrogen-biochar nexus for the synergy of yield,quality,carbon emission and resource use efficiency in tomato

Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water shortages and the overuse of fertilizers.The field experiment had twelve treatments and a control(CK)trial including two irrigation amounts(I1,100%ETm;I2,60%ETm;where ETm is the maximum evapotranspiration),two nitrogen applications(N1,360 kg ha^(−1);N2,120 kg ha^(−1))and three biochar application levels(B1,60 t ha^(−1);B_(2),30 t ha^(−1)and B3,0 t ha^(−1)).A multi-objective synergistic irrigation-nitrogen-biochar application system for improving tomato yield,quality,water and nitrogen use efficiency,and greenhouse emissions was developed by integrating the techniques of experimentation and optimization.First,a coupled irrigation-nitrogen-biochar plot experiment was arranged.Then,tomato yield and fruit quality parameters were determined experimentally to establish the response relationships between irrigation-nitrogen-biochar dosage and yield,comprehensive quality of tomatoes(TCQ),irrigation water use efficiency(IWUE),partial factor productivity of nitrogen(PFPN),and net greenhouse gas emissions(NGE).Finally,a multi-objective dynamic optimization regulation model of irrigation-nitrogen-biochar resource allocation at different growth stages of tomato was constructed which was solved by the fuzzy programming method.The results showed that the application of irrigation and nitrogen to biochar promoted increase in yield,IWUE and PFPN,while it had an inhibitory effect on NGE.In addition,the optimal allocation amounts of water and fertilizer were different under different scenarios.The yield of the S1 scenario increased by 8.31%compared to the B_(1)I_(1)N_(2) treatment;TCQ of the S2 scenario increased by 5.14%compared to the B_(2)I_(2)N_(1) treatment;IWUE of the S3 scenario increased by 10.01%compared to the B1I2N2 treatment;PFPN of the S4 scenario increased by 9.35%compared to the B_(1)I_(1)N_(2) treatment;and NGE of the S5 scenario decreased by 11.23%compared to the B_(2)I1N1 treatment.The optimization model showed that the coordination of multiple objectives considering yield,TCQ,IWUE,PFPN,and NGE increased on average from 4.44 to 69.02%compared to each treatment when the irrigation-nitrogen-biochar dosage was 205.18 mm,186 kg ha^(−1)and 43.31 t ha^(−1),respectively.This study provides a guiding basis for the sustainable management of water and fertilizer in greenhouse tomato production under drip irrigation fertilization conditions.

A short overview of the lead iodide residue impact and regulation strategies in perovskite solar cells

Lead iodide(PbI2) is a vital raw material for preparing perovskite solar cells(PSCs),and it not only takes part in forming the light absorption layer but also remains in the grain boundary as a passivator.In other words,the PbI2 content in the precursor and as formed film will affect the efficiency and stability of the PSCs.With moderate residual PbI2,it passivates the bulk/surface defects of perovskite,reduces the interfacial recombination,promotes the perovskite stability,minimizes the device hysteresis,and so on.Deficient PbI2 residue will reduce the interfacial passivation effect and device performance.In addition to facilitating the non-radiative recombination,over PbI2 residue can also lead to electronic insulation in the grain boundary and deteriorate the device performance.However,the impact and regulation of PbI2 residue on the device performance and stability is still not fully understood.Herein,a comprehensive and detailed review is presented by discussing the PbI2 residue impact and its regulation strategies(i.e., elimination,facilitation and conversion of the residue PbI2) to manipulate the PbI2 content,distribution and forms.Finally,we also show future outlooks in this field,with an aim to help further the progression of high-efficiency and stable PSCs.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese medicine and Western medicine

Integrated traditional Chinese medicine(TCM)and Western medicine(WM)is a new medical science grounded in the knowledge bases of both TCM and WM,which then forms a unique modern medical system in China.Integrated TCM and WM has a long history in China,and has made important achievements in the process of clinical diagnosis and treatment.However,the methodological defects in currently published clinical practice guidelines(CPGs)limit its development.The organic integration of TCM and WM is a deeper integration of TCM and WM.To realize the progression of"integration"to"organic integration",a targeted and standardized guideline development methodology is needed.Therefore,the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Rice melatonin deficiency causes premature leaf senescence via DNA methylation regulation

In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogramming,especially of genes involved in chlorophyll and carbon metabolism,redox regulation,and transcriptional regulation,during dark-induced leaf senescence.Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes.Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin.A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.

Investigation on mechanical properties regulation of rock-like specimens based on 3D printing and similarity quantification

3D printing is widely adopted to quickly produce rock mass models with complex structures in batches,improving the consistency and repeatability of physical modeling.It is necessary to regulate the mechanical properties of 3D-printed specimens to make them proportionally similar to natural rocks.This study investigates mechanical properties of 3D-printed rock analogues prepared by furan resin-bonded silica sand particles.The mechanical property regulation of 3D-printed specimens is realized through quantifying its similarity to sandstone,so that analogous deformation characteristics and failure mode are acquired.Considering similarity conversion,uniaxial compressive strength,cohesion and stress–strain relationship curve of 3D-printed specimen are similar to those of sandstone.In the study ranges,the strength of 3D-printed specimen is positively correlated with the additive content,negatively correlated with the sand particle size,and first increases then decreases with the increase of curing temperature.The regulation scheme with optimal similarity quantification index,that is the sand type of 70/140,additive content of 2.5‰and curing temperature of 81.6℃,is determined for preparing 3D-printed sandstone analogues and models.The effectiveness of mechanical property regulation is proved through uniaxial compression contrast tests.This study provides a reference for preparing rock-like specimens and engineering models using 3D printing technology.

Recent Progress and Regulation Strategies of Layered Materials as Cathode of Aqueous Zinc-Ion Batteries

Aqueous zinc-ion batteries(ZIBs)have shown great potential in the fields of wearable devices,consumer electronics,and electric vehicles due to their high level of safety,low cost,and multiple electron transfer.The layered cathode materials of ZIBs hold a stable structure during charge and discharge reactions owing to the ultrafast and straightforward(de)intercalation-type storage mechanism of Zn^(2+)ions in their tunable interlayer spacing and their abilities to accommodate other guest ions or molecules.Nevertheless,the challenges of inadequate energy density,dissolution of active materials,uncontrollable byproducts,increased internal pressure,and a large de-solvation penalty have been deemed an obstacle to the development of ZIBs.In this review,recent strategies on the structure regulation of layered materials for aqueous zinc-ion energy storage devices are systematically summarized.Finally,critical science challenges and future outlooks are proposed to guide and promote the development of advanced cathode materials for ZIBs.

Research on the Legal Framework of Content Regulations for Network Platforms

In the era of the Internet,various network platforms have evolved into new hubs for information dissemination.Currently,China has established a platform-centered content regulation framework,wherein platforms proactively enforce content regulations in accordance with legal censorship obligations.Additionally,platform policies and user agreements augment their authority in content regulation.The platforms can achieve cost-effective and highly efficient content regulation by leveraging their strategic advantages enabled by their own technical capabilities and extensive coverage.The platform self-regulation model,however,still faces challenges.First,accurately evaluating content remains a formidable task;second,ensuring effective platform publicity through self-regulation poses difficulties;third,users may potentially face disadvantages due to the platform’s right of self-regulation;and fourth,digital copyright owners face challenges when defending digital copyright disputes under the safe harbor rule.Therefore,it is imperative to establish,review,and revise the legal framework for content regulation of network platforms in order to enhance the efficiency of their governance systems.The formulation of the legal framework for content regulation of network platforms may encompass the following aspects:rationalizing obligations pertaining to platform content regulations,enhancing supervision over platform self-regulation,and establishing a dual-track responsibility system for digital copyright content regulation.This will ensure a harmonious balance among public interests,users’personal rights and interests,and commercial benefits through regulating the content on network platforms.

Retaining the self-released chalcogenate at reconstructed cobalt sites by self-transformed carbonate regulation for boosted oxygen evolution

The in-situ generated oxyanions at electrochemically reconstructed catalysts from metal-based nonoxide compounds have been proven to significantly accelerate oxygen evolution reaction(OER)kinetics.However,it remains a challenge to retain these self-released oxyanions at reconstructed catalysts,hindering its utilization as a tool to develop efficient OER catalysts.Here,we demonstrate a versatile selftransformed carbonate regulation strategy to efficiently retain the self-released chalcogenate at Co oxyhydroxides reconstructed from carbon-incorporated Co selenides under OER conditions.These selftransformed CO_(3)^(2-)can induce electron accumulation and narrow d bond at Co sites to facilitate the Co3d-O 2p orbital hybridization between Co sites and SeO_(x)^(2-)for enhanced SeO_(x)^(2-)retention,which can accelerate the rate-limiting step for^(*)OOH formation during OER.Relative to CoOOH-SeO_(x)^(2-)with limited SeO_(x)^(2-)residues,CoOOH-CO_(3)^(2-)/SeO_(x)^(2-)with elevated SeO_(x)^(2-)retention by CO_(3)^(2-)regulation exhibited a 5.6-fold increase in current density and a remarkable lower Tafel slope towards OER.This strategy paves a rational avenue to design efficient catalysts for electrooxidation reactions through finely regulating self-released oxyanions at reconstructed structures.

Primary and Secondary Microplastic and Nanoplastic Regulations: Perspectives on Water Industry Impacts

Plastic pollution, both primary and secondary, is an environmental challenge, prompting regulatory actions at global and regional levels. With increasing research about the impacts of micro- and nanoplastics on ecosystems and human health, governments worldwide have undertaken efforts to address this issue. The global community has advanced regulatory efforts that have led to the implementation of national laws or regulations in numerous countries. These measures ban or restrict the use of primary and secondary microplastics and nanoplastics. An overview of global and European regulatory frameworks is presented to provide context for the United States (US). In the endeavor to document plastics regulation development in the US, a description of regulatory agencies and their roles in advancing policy and rules as well as future direction and areas for improvement in regulating plastics are introduced. A discussion of what emerging regulations mean to utilities and industries is also provided along with a comparison of regulatory frameworks.

Exploring the combination of biochar‐amended soil and automated irrigation technology for water regulation and preservation in green infrastructure

Biochar is a carbon sink material with the potential to improve water retention in various soils.However,for the long‐term maintenance of green infrastructure,there is an additional need to regulate the water contents in the covers to maintain vegetation growth in semiarid conditions.In this study,biochar‐amended soil was combined with subsurface drip irrigation,and the water preservation characteristics of this treatment were investigated through a series of one‐dimensional soil column tests.To ascertain the best treatment method specific to semiarid climatic conditions,the test soil was amended with 0%,1%,3%,and 5%biochar.Automatic irrigation devices equipped with soil moisture sensors were used to control the subsurface water content with the aim of enhancing vegetation growth.Each soil column test lasted 150 h,during which the volumetric water contents and soil suction data were recorded.The experimental results reveal that the soil specimen amended with 3%biochar is the most water‐saving regardless of the time cost.Soil with a higher biochar content(e.g.,5%)consumes a more significant amount of water due to the enhancement of the water‐holding capacity.Based on the experimental results,it can be concluded that the appropriate ratio can be determined within 1%–3%,which can reduce not only the amount of irrigated/used water but also the time cost.Such technology can be explored for water content regulation in green infrastructure and the development of barriers for protecting the environment around deep underground waste containment.

New food sources and production systems:a comparison of international regulations and China’s advancements in novel foods with synthetic biology

The global shift towards sustainable food systems has sparked innovations in food sources and production systems,including cell-based meat,plant-based food products,precision fermentation,and 3D food printing.These advancements pose regulatory challenges and opportunities,with China emerging as a critical player in adopting and regulating new food technologies.This review explores the international landscape of new food sources and production systems(NFPS),focusing on China’s role and regulatory approaches compared to global practices.Through this comparative analysis,we aim to contribute to the ongoing dialogue on food safety regulation,offering insights and recommendations for policymakers,industry stakeholders,and researchers engaged in the global food system’s evolution.This comprehensive overview underscores the dynamic nature of regulatory frameworks governing NFPS,highlighting the international efforts to ensure food safety,consumer protection,and the sustainable evolution of the food industry.

Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

Membrane tension plays a crucial role in various fundamental cellular processes,with one notable example being the T cell-mediated elimination of tumor cells through perforin-induced membrane perforation by amplifying cellular force.However,the mechanisms governing the regulation of biomolecular activities at the cell interface by membrane tension remain elusive.In this study,we investigated the correlation between membrane tension and poration activity of melittin,a prototypical pore-forming peptide,using dynamic giant unilamellar vesicle leakage assays combined with flickering tension analysis,molecular dynamics simulations,and live cell assays.The results demonstrate that an increase in membrane tension enhances the activity of melittin,particularly near its critical pore-forming concentration.Moreover,peptide actions such as binding,insertion,and aggregation in the membrane further influence the evolution of membrane tension.Live cell experiments reveal that artificially enhancing membrane tension effectively enhances melittin’s ability to induce pore formation and disrupt membranes,resulting in up to a ten-fold increase in A549 cell mortality when exposed to a concentration of 2.0-μg·mL^(-1)melittin.Our findings elucidate the relationship between membrane tension and the mechanism of action as well as pore-forming efficiency of melittin,while providing a practical mechanical approach for regulating functional activity of molecules at the cell-membrane interface.