Yeast-based models have become a powerful platform in pharmaceutical research,offering significant potential for producing complex drugs,vaccines,and therapeutic agents.While many current drugs were discovered before ...Yeast-based models have become a powerful platform in pharmaceutical research,offering significant potential for producing complex drugs,vaccines,and therapeutic agents.While many current drugs were discovered before fully understanding their molecular mechanisms,yeast systems now provide valuable insights for drug discovery and personalized medicine.Recent advancements in genetic engineering,metabolic engineering,and synthetic biology have improved the efficiency and scalability of yeast-based production systems,enabling more sustainable and cost-effective manufacturing processes.This paper reviews the latest developments in yeast-based technologies,focusing on their use as model organisms to study disease mechanisms,identify drug targets,and develop novel therapies.We highlight key platforms such as the yeast two-hybrid system,surface display technologies,and optimized expression systems.Additionally,we explore the future integration of yeast engineering with artificial intelligence(AI),machine learning(ML),and advanced genome editing technologies like CRISPR/Cas9,which are expected to accelerate drug discovery and enable personalized therapies.Furthermore,yeast-based systems are increasingly employed in largescale drug production,vaccine development,and therapeutic protein expression,offering promising applications in clinical and industrial settings.This paper discusses the practical implications of these systems and their potential to revolutionize drug development,paving the way for safer,more effective therapies.展开更多
Many evolved biomolecular functions such as ion pumping or redox catalysis rely on controlled charge transport through the polypeptide matrix, which can be regulated by shifts in molecular protonation states and depen...Many evolved biomolecular functions such as ion pumping or redox catalysis rely on controlled charge transport through the polypeptide matrix, which can be regulated by shifts in molecular protonation states and dependent supramolecular packing modes in response to environmental cues. However, the exact roles of such dynamic, non-covalent interactions in peptide charge transport have remained elusive. To tackle this challenge, here we report the modulation of charge transport in a series of lysine(Lys)-substituted hepta-glycine(Gly) peptide self-assembled monolayers(SAMs) on template-striped gold(Au^(TS)) bottom electrodes with eutectic gallium-indium(EGaIn) liquid metal top electrodes. We demonstrate systematic modulation of hydrogen bonding and more general electrostatic interactions by shifting the position of the charged Lys-residue and creating different protonation patterns by changing the environmental pH in the Au^(TS)/peptide//Ga Ox/EGa In junctions. The effective modulation is evidenced by current density-voltage(J-V) measurements combined with SAM characterization using ultraviolet photoelectron spectroscopy(UPS) and angle-resolved X-ray photoelectron spectroscopy(ARXPS), polarization modulation-infrared reflection-absorption spectroscopy(PM-IRRAS), and molecular dynamics(MD) simulations. Decreasing the hydrogen bonding inside the peptide SAMs and increasing the electrostatic interactions by environmental counterions amplifies the charge transport differently with Lys-position, which means that the sensitive electrical response of peptide SAMs can be tuned by the peptide sequence. Our results provide insights into the relationship between molecular design and in situ modulation of charge transport properties for the development of bionanoelectronics.展开更多
Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination...Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion.This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence,aiming to provide general guidance on appropriate imaging examination selection,comprehensive and accurate imaging assessment for early orthodontic treatment patients.展开更多
The relationship between socioeconomic development and the environment is intimately linked with the level of regional sustainable development.Clarifying the evolution pattern of this relationship during the sustainab...The relationship between socioeconomic development and the environment is intimately linked with the level of regional sustainable development.Clarifying the evolution pattern of this relationship during the sustainable development progress is crucial for achieving all of the Sustainable Development Goals(SDGs),but less research has focused on this problem.Here,we have utilized statistical and remote sensing data from 290 municipal units in China to analyze the evolution of the coupling coordination degree(CCD)between socioeconomic development and the environment along a progression of sustainable development measured by the SDG Index.The results show that the hotspot areas of CCD are concentrated in coastal regions,gradually decreasing as they move inland.Additionally,as sustainable development progresses,both socioeconomic and environment levels exhibit a nonlinear rise.The coupling coordination between the two demonstrates a pattern of initial increasing,then decreasing,and finally increasing again,which may be related to changes in industrial structure.Our study delves deeply into the patterns of evolution in the relationship between socioeconomic and environments,exploring the challenges and opportunities faced by regions at different stages of sustainable development.The findings can deepen our understanding of sustainable development and provide policy suggestions and theoretical support for achieving SDGs.展开更多
ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the...ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells （MSCs） was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.展开更多
Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children...Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.展开更多
Runt-related transcription factor-1(Runxl)is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development.However,the potential role of Runx...Runt-related transcription factor-1(Runxl)is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development.However,the potential role of Runxl in joint diseases is not well known.In the current study,we aimed to explore the role of Runxl in osteoarthritis induced by anterior cruciate ligament transaction(ACLT)surgery.We showed that chondrocyte-specific Runxl knockout(Runx1f/fCol2a1-Cre)aggravated cartilage destruction by accelerating the loss of proteoglycan and collagen II in early osteoarthritis.Moreover,we observed thinning and ossification of the growth plate,a decrease in chondrocyte proliferative capacity and the loss of bone matrix around the growth plate in late osteoarthritis.We overexpressed Runxl by adeno-associated virus(AAV)in articular cartilage and identified its protective effect by slowing the destruction of osteoarthritis in cartilage in early osteoarthritis and alleviating the pathological progression of growth plate cartilage in late osteoarthritis.ChIP-seq analysis identified new targets that interacted with Runxl in cartilage pathology,and we confirmed the direct interactions of these factors with Runxl by ChIP-qPCR.This study helps us to understand the function of Runxl in osteoarthritis and provides new clues for targeted osteoarthritis therapy.展开更多
This study proposes a new generation network based on transformers and guided by the music theory to produce high-quality music work.In this study,the decoding block of the transformer is used to learn the internal in...This study proposes a new generation network based on transformers and guided by the music theory to produce high-quality music work.In this study,the decoding block of the transformer is used to learn the internal information of single-track music,and cross-track transformers are used to learn the information amongst the tracks of different musical instruments.A reward network based on the music theory is proposed,which optimizes the global and local loss objective functions while training and discriminating the network so that the reward network can provide a reliable adjustment method for the generation of the network.The method of combining the reward network and cross entropy loss is used to guide the training of the generator and produce high-quality music work.Compared with other multi-track music generation models,the experimental results verify the validity of the model.展开更多
A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau （MAPT） gene was significantly associated with sp...A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau （MAPT） gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population. We screened the mutation-susceptible regions of MAPT- the 3＇ and 5＇ untranslated regions as well as introns 9, 10, 11, and 12 - by direct sequencing, and identified 33 genetic variations. Two of these, 105788 A 〉 G in intron 9 and 123972 T 〉 A in intron 11, were not present in the control group. The age of onset in patients with the 105788 A 〉 G and/or the 123972 T 〉 A variant was younger than that in patients without either genetic variation. Moreover, the pa- tients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.展开更多
As Volatile Organic Compounds(VOCs)are one of the precursors of ozone,their distribution and variable concentrations are highly related to local ozone pollution control.In this study,we obtained vertical profiles of V...As Volatile Organic Compounds(VOCs)are one of the precursors of ozone,their distribution and variable concentrations are highly related to local ozone pollution control.In this study,we obtained vertical profiles of VOCs in Shanghai’s Jinshan district on 8 September and 9 September in 2016 to investigate their distribution and impact on local atmospheric oxidation in the near surface layer.Vertical samples were collected from heights between 50 m and 400 m by summa canisters using an unmanned aerial vehicle(UAV).Concentrations of VOCs(VOCs refers to the 52 species measured in this study)varied minimally below 200 m,and decreased by 21.2%from 100 m to 400 m.The concentrations of VOCs above 200 m decreased significantly in comparison to those below 200 m.The proportions of alkanes and aromatics increased from 55.2%and 30.5%to 57.3%and 33.0%,respectively.Additionally,the proportion of alkenes decreased from 13.2%to 8.4%.Toluene and m/p-xylene were the key species in the formation of SOA and ozone.Principal component analysis(PCA)revealed that the VOCs measured in this study mainly originated from industrial emissions.展开更多
In this study,the oxidation behavior of Ti42Al5Mn,Ti42Al5Mn0.5 W,Ti42Al5Mn0.5W0.1B,and Ti42Al5Mn0.8 W was investigated at 800℃.Due to the inability to form a dense protective Al2O_(3) layer,Ti42Al5Mn suffered severe ...In this study,the oxidation behavior of Ti42Al5Mn,Ti42Al5Mn0.5 W,Ti42Al5Mn0.5W0.1B,and Ti42Al5Mn0.8 W was investigated at 800℃.Due to the inability to form a dense protective Al2O_(3) layer,Ti42Al5Mn suffered severe spallation during oxidation at 800℃and the mass gain was significant.The intermediate layer between the scale and the substrate was first composed of Laves/Z phase but changed toα2/Z phase with prolonged oxidation.The intermediate layer with high Ti/Al ratio favors the forma-tion of a thick Al2O_(3)+TiO_(2) mixed layer in the oxide scale which is prone to initiate cracks and cause the spalling of oxides.The doping of W in TiO_(2) effectively inhibited its generation and promoted the for-mation of a dense Al2O_(3) layer,resulting in a significant improvement in the oxidation resistance of the alloy.Compared to Ti42Al5Mn alloy,Ti42Al5Mn0.8 W showed no spallation after 300 h cyclic oxidation and the kinetic curve changed from liner law to parabolic law.The intermediate layer of Ti42Al5Mn0.8 W alloy was composed of a single Laves phase and remained unchanged even after 1000 h oxidation at 800℃,offering a favorable basis for the generation of a stable protective oxide layer in the alloy.The addi-tion of 0.1 at.%B to Ti42Al5Mn0.5 W alloy refined its microstructure and further improved its spallation resistance to a level close to that of Ti42Al5Mn0.8 W alloy.展开更多
Direct reduction based on hydrogen metallurgical gas-based shaft furnace is a promising technology for the efficient and low-carbon smelting of vanadium-titanium magnetite.However,in this process,the sticking of pelle...Direct reduction based on hydrogen metallurgical gas-based shaft furnace is a promising technology for the efficient and low-carbon smelting of vanadium-titanium magnetite.However,in this process,the sticking of pellets occurs due to the aggregation of metal-lic iron between the contact surfaces of adjacent pellets and has a serious negative effect on the continuous operation.This paper presents a detailed experimental study of the effect of TiO2 on the sticking behavior of pellets during direct reduction under different conditions.Results showed that the sticking index(SI)decreased linearly with the increasing TiO2 addition.This phenomenon can be attributed to the increase in unreduced FeTiO3 during reduction,leading to a decrease in the number and strength of metallic iron interconnections at the sticking interface.When the TiO2 addition amount was raised from 0 to 15wt%at 1100°C,the SI also increased from 0.71%to 59.91%.The connection of the slag phase could be attributed to the sticking at a low reduction temperature,corresponding to the low sticking strength.Moreover,the interconnection of metallic iron became the dominant factor,and the SI increased sharply with the increase in re-duction temperature.TiO2 had a greater effect on SI at a high reduction temperature than at a low reduction temperature.展开更多
The mineral species in soils vary in a wide variety of places,thus resulting in the petroleumcontaminated soil(PCS)with complex characters.Thus,the research on the effect of mineral species on oil-soil interactions in...The mineral species in soils vary in a wide variety of places,thus resulting in the petroleumcontaminated soil(PCS)with complex characters.Thus,the research on the effect of mineral species on oil-soil interactions in PCS takes on a critical significance.In this study,the desorption and adsorption behaviors of aromatic hydrocarbons(Ar)on two minerals surfaces were examined.Meanwhile,the interfacial forces between minerals and Ar were studied and the sources of these forces were analyzed.Moreover,molecular dynamics(MD)simulations were conducted to gain insight into the interfacial interaction mechanisms.As revealed by the results of this study,in comparison with Qs-Ar(quartz sand,Qs),Mnt-Ar(montmorillonite,Mnt)contaminants required higher temperature and activation energies for thermal desorption(201.95 kJ·mol^(-1)vs.127.82 kJ·mol^(-1))The above difference was generated since the adhesive forces between Ar and Mnt surfaces were greater than those between Ar and Qs.As indicated by the analysis of the adhesion force sources,the van der Waals forces were responsible for facilitating oil adhesion to mineral surfaces,even though the electrostatic force prevented oil-mineral adhesion.Furthermore,the hydrophobic forces facilitated adhesion in 3 nm.The MD results demonstrated that compared with the Qs system,there existed larger binding energies between Ar and Mnt,a lower diffusion coefficient for Ar on the Mnt surface,as well as more significant adsorption of Ar on Mnt.In general,the different mineral species affect the strength of the interaction at the oil-soil interface,which is a guideline for proposing targeted oil-soil separation measures.展开更多
With the continuous miniaturization of integrated circuit(IC)devices,Co is recognized as the most promising alternative to Cu as an interconnecting metal.During IC processing,Co surfaces need to be flattened.This work...With the continuous miniaturization of integrated circuit(IC)devices,Co is recognized as the most promising alternative to Cu as an interconnecting metal.During IC processing,Co surfaces need to be flattened.This work describes dynamic polishing experiments and static corrosion experiments on the electrical,chemical,and mechanical factors involved in cobalt electrochemical mechanical polishing(ECMP).Then,the impact and proportion of individual and combined factors on the Co-ECMP are quantitatively analyzed.The experimental results show that mechanical action,rather than individual chemical or electrical action,plays a primary role in Co-ECMP.The ratios of individual mechanical,chemical,and electrical action proportions are 50.46%,11.17%,and 6.20%,respectively.However,chemical and electrical assistance with mechanical action can achieve twofold efficiency and high-quality polishing of Co.For example,the ratios of mechanical–chemical or electrical–chemical–mechanical cooperation are 72.05% or 100%,respectively.In addition,polarization curves,energy dispersive spectroscopy(EDS),and X-ray photoelectron spectroscopy(XPS)were used to analyze the Co-ECMP process and products.Atomic-level mechanism analysis is performed for each factor.The results indicate that in Co-ECMP,the oxides formed on the Co surface are mainly CoO,Co(OH)_(2),and Co_(3)O_(4).The oxides react with the complexing agents to form loose and porous Co-benzotriazole(Co-BTA)complexes.Mechanical,chemical,and electrical factors collaborate to form and remove Co-BTA constantly,achieving rapid material removal and obtaining smooth atomic-level surfaces.展开更多
Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiolog...Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, wesummarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.展开更多
Artificial intelligence generated content(AIGC)has been a research hotspot in the field of artificial intelligence in recent years.It is expected to replace humans in performing some of the work of content generation ...Artificial intelligence generated content(AIGC)has been a research hotspot in the field of artificial intelligence in recent years.It is expected to replace humans in performing some of the work of content generation at a low cost and a high volume,such as music,painting,multimodal content generation,news articles,summary reports,stock commentary summaries,and even content and digital people generated in the meta-universe.AIGC provides a new technical path for the development and implementation of AI in the future.展开更多
Exploration of the QCD phase diagram and critical point is one of the main goals in current relativistic heavy-ion collisions.The QCD critical point is expected to belong to a three-dimensional(3D)Ising universality c...Exploration of the QCD phase diagram and critical point is one of the main goals in current relativistic heavy-ion collisions.The QCD critical point is expected to belong to a three-dimensional(3D)Ising universality class.Machine learning techniques are found to be powerful in distinguishing different phases of matter and provide a new way to study the phase diagram.We investigate phase transitions in the 3D cubic Ising model using supervised learning methods.It is found that a 3D convolutional neural network can be trained to effectively predict physical quantities in different spin configurations.With a uniform neural network architecture,it can encode phases of matter and identify both second-and first-order phase transitions.The important features that discriminate different phases in the classification processes are investigated.These findings can help study and understand QCD phase transitions in relativistic heavy-ion collisions.展开更多
Previous studies have shown that DWARFIO （D10） is a rice ortholog of MAX41RMS1/DAD1, encoding a carotenoid cleavage dioxygenase and functioning in strigolactones/strigolactone-derivatives （SL） biosynthesis. Here w...Previous studies have shown that DWARFIO （D10） is a rice ortholog of MAX41RMS1/DAD1, encoding a carotenoid cleavage dioxygenase and functioning in strigolactones/strigolactone-derivatives （SL） biosynthesis. Here we use DIO. RNA interference （RNAi） transgenic plants similar to dlO mutant in phenotypes to investigate the interactions among DIO, auxin and cytokinin in regulating rice shoot branching. Auxin levels in node 1 of both decapitated DIO.RNAi and wild type plants decreased significantly, showing that decapitation does reduce endogenous auxin concentration, but decapitation has no clear effects on auxin levels in node 2 of the same plants. This implies that node 1 may be the location where a possible interaction between auxin and DIO gene would be detected. DIO expression in node 1 is inhibited by decapitation, and this inhibition can be restored by exogenous auxin application, indicating that DIO may play an important role in auxin regulation of SL. The decreased expression of most OsPINs in shoot nodes of DIO-RNAi plants may cause a reduced auxin transport capacity. Furthermore, effects of auxin treatment of decapitated plants on the expression of cytokinin biosynthetic genes suggest that DIO promotes cytokinin biosynthesis by reducing auxin levels. Besides, in DIO-RNAi plants, decreased storage cytokinin levels in the shoot node may partly account for the increased active cytokinin contents, resulting in more tillering phenotypes.展开更多
The effects of simulated microgravity on matrix mineralization of chondrocytes were examined using cultured chicken embryonic chondrocytes as the model. In four days, there was a time course decrease in alkaline phosp...The effects of simulated microgravity on matrix mineralization of chondrocytes were examined using cultured chicken embryonic chondrocytes as the model. In four days, there was a time course decrease in alkaline phosphatase activity of chondrocytes, a marker of matrix mineralization.Meanwhile, in two days, there was a significant drop in intracellular calcium concentration in contrast to the control. These results indicate that simulated microgravity can suppress matrix calcification of cultured chondrocytes, and intracellular calcium may be involved in the regulation of matrix calcification as the second messenger.展开更多
Proton transport(PT)in solid-state materials is crucial for applications in energy conversion and protonic devices.Nevertheless,the highly complex and disordered structures of conventional proton-conducting materials,...Proton transport(PT)in solid-state materials is crucial for applications in energy conversion and protonic devices.Nevertheless,the highly complex and disordered structures of conventional proton-conducting materials,such as polymers and proteins,hinder a clear understanding of the mechanisms underlying PT,particularly the formation of hydrogen bond(H-bond)networks and their role in mediating PT.Here,we show that self-assembling monolayers(SAMs)of oligopeptides provide a promising platform for elucidating the key factors that modulate PT related H-bonds,including amide bond interactions,peptide sequence,and chain length.Combined with structural characterizations of SAMs,the electrical measurements under both direct and alternating current modes demonstrate that longer and more extended oligopeptide chains in SAMs result in an ordered molecular arrangement,leading to a more pronounced response of current density(J)to increasing relative humidity(RH).Moreover,this increase in molecular order also shifts the transition from electron-dominated to proton-dominated charge transport to a higher RH.The synergy between carrier concentration and mobility is a key factor contributing to the increase in J.This study not only elucidates the critical role of ordered H-bonds in PT but also expands the application of SAM technology in controlling molecular conformation and enhancing proton conduction.展开更多
基金funded by 2024 Scientific Research Project of Chongqing Medical and Pharmaceutical College(No.ygzrc2024101)Chongqing Education Commission Natural Science Foundation(No.KJQN202402821)+2 种基金Chongqing Shapingba District Science and Technology Bureau Project(No.2024071)2024 Chongqing Medical and Pharmaceutical College Innovation Research Group Project(No.ygz2024401)Chongqing Science and Health Joint Medical Research Project(No.2024SQKWLHMS051),respectively.
文摘Yeast-based models have become a powerful platform in pharmaceutical research,offering significant potential for producing complex drugs,vaccines,and therapeutic agents.While many current drugs were discovered before fully understanding their molecular mechanisms,yeast systems now provide valuable insights for drug discovery and personalized medicine.Recent advancements in genetic engineering,metabolic engineering,and synthetic biology have improved the efficiency and scalability of yeast-based production systems,enabling more sustainable and cost-effective manufacturing processes.This paper reviews the latest developments in yeast-based technologies,focusing on their use as model organisms to study disease mechanisms,identify drug targets,and develop novel therapies.We highlight key platforms such as the yeast two-hybrid system,surface display technologies,and optimized expression systems.Additionally,we explore the future integration of yeast engineering with artificial intelligence(AI),machine learning(ML),and advanced genome editing technologies like CRISPR/Cas9,which are expected to accelerate drug discovery and enable personalized therapies.Furthermore,yeast-based systems are increasingly employed in largescale drug production,vaccine development,and therapeutic protein expression,offering promising applications in clinical and industrial settings.This paper discusses the practical implications of these systems and their potential to revolutionize drug development,paving the way for safer,more effective therapies.
基金supported by the National Natural Science Foundation of China(Nos.21974102 and 21705019)the National Key R&D Program of China(No.2018YFA0703700)support from Science Foundation Ireland(SFI,No.12/RC/2275_P2)。
文摘Many evolved biomolecular functions such as ion pumping or redox catalysis rely on controlled charge transport through the polypeptide matrix, which can be regulated by shifts in molecular protonation states and dependent supramolecular packing modes in response to environmental cues. However, the exact roles of such dynamic, non-covalent interactions in peptide charge transport have remained elusive. To tackle this challenge, here we report the modulation of charge transport in a series of lysine(Lys)-substituted hepta-glycine(Gly) peptide self-assembled monolayers(SAMs) on template-striped gold(Au^(TS)) bottom electrodes with eutectic gallium-indium(EGaIn) liquid metal top electrodes. We demonstrate systematic modulation of hydrogen bonding and more general electrostatic interactions by shifting the position of the charged Lys-residue and creating different protonation patterns by changing the environmental pH in the Au^(TS)/peptide//Ga Ox/EGa In junctions. The effective modulation is evidenced by current density-voltage(J-V) measurements combined with SAM characterization using ultraviolet photoelectron spectroscopy(UPS) and angle-resolved X-ray photoelectron spectroscopy(ARXPS), polarization modulation-infrared reflection-absorption spectroscopy(PM-IRRAS), and molecular dynamics(MD) simulations. Decreasing the hydrogen bonding inside the peptide SAMs and increasing the electrostatic interactions by environmental counterions amplifies the charge transport differently with Lys-position, which means that the sensitive electrical response of peptide SAMs can be tuned by the peptide sequence. Our results provide insights into the relationship between molecular design and in situ modulation of charge transport properties for the development of bionanoelectronics.
基金supports by the National Natural Science Foundation of China(Nos.82201135)"2015"Cultivation Program for Reserve Talents for Academic Leaders of Nanjing Stomatological School,Medical School of Nanjing University(No.0223A204).
文摘Early correction of childhood malocclusion is timely managing morphological,structural,and functional abnormalities at different dentomaxillofacial developmental stages.The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion.This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence,aiming to provide general guidance on appropriate imaging examination selection,comprehensive and accurate imaging assessment for early orthodontic treatment patients.
基金supported by the National Natural Sci-ence Foundation of China(Grant No.42271291)China Postdoctoral Science Foundation(Certificate No.2024M750219)the Project Supported by State Key Laboratory of Earth Surface Processes and Re-source Ecology(Grant No.2022-ZD-02).
文摘The relationship between socioeconomic development and the environment is intimately linked with the level of regional sustainable development.Clarifying the evolution pattern of this relationship during the sustainable development progress is crucial for achieving all of the Sustainable Development Goals(SDGs),but less research has focused on this problem.Here,we have utilized statistical and remote sensing data from 290 municipal units in China to analyze the evolution of the coupling coordination degree(CCD)between socioeconomic development and the environment along a progression of sustainable development measured by the SDG Index.The results show that the hotspot areas of CCD are concentrated in coastal regions,gradually decreasing as they move inland.Additionally,as sustainable development progresses,both socioeconomic and environment levels exhibit a nonlinear rise.The coupling coordination between the two demonstrates a pattern of initial increasing,then decreasing,and finally increasing again,which may be related to changes in industrial structure.Our study delves deeply into the patterns of evolution in the relationship between socioeconomic and environments,exploring the challenges and opportunities faced by regions at different stages of sustainable development.The findings can deepen our understanding of sustainable development and provide policy suggestions and theoretical support for achieving SDGs.
基金supported by grants from the National Natural Science Foundation of China (No.81271178 and 81470777)
文摘ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells （MSCs） was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.
基金supported by the National Natural Science Foundation of China(82171001,82222015)Research Funding from West China School/Hospital of Stomatology Sichuan University(RCDWJS2023-1)Align Technology Specialized Scientific Research Fund(21H0922).
文摘Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.
基金This work was supported by the National Natural Science Foundation of China(81771047 to J.X.,81901040 to CZ.)the China Postdoctoral Science Foundation(2019M653440)+1 种基金the Sichuan Provincial Science and Technology Department(2019YJ0101)the Young Elite Scientist Sponsorship Program by CAST(2020QNR001).
文摘Runt-related transcription factor-1(Runxl)is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development.However,the potential role of Runxl in joint diseases is not well known.In the current study,we aimed to explore the role of Runxl in osteoarthritis induced by anterior cruciate ligament transaction(ACLT)surgery.We showed that chondrocyte-specific Runxl knockout(Runx1f/fCol2a1-Cre)aggravated cartilage destruction by accelerating the loss of proteoglycan and collagen II in early osteoarthritis.Moreover,we observed thinning and ossification of the growth plate,a decrease in chondrocyte proliferative capacity and the loss of bone matrix around the growth plate in late osteoarthritis.We overexpressed Runxl by adeno-associated virus(AAV)in articular cartilage and identified its protective effect by slowing the destruction of osteoarthritis in cartilage in early osteoarthritis and alleviating the pathological progression of growth plate cartilage in late osteoarthritis.ChIP-seq analysis identified new targets that interacted with Runxl in cartilage pathology,and we confirmed the direct interactions of these factors with Runxl by ChIP-qPCR.This study helps us to understand the function of Runxl in osteoarthritis and provides new clues for targeted osteoarthritis therapy.
基金the research project funded by the National Natural Science Foundation of China(Grant No.61631016 and 61901421)the National Key R&D Program of China(Grant No.2018YFB1403903)supported by the Fundamental Research Funds for the Central Universities(Grant No.CUC210B011).
文摘This study proposes a new generation network based on transformers and guided by the music theory to produce high-quality music work.In this study,the decoding block of the transformer is used to learn the internal information of single-track music,and cross-track transformers are used to learn the information amongst the tracks of different musical instruments.A reward network based on the music theory is proposed,which optimizes the global and local loss objective functions while training and discriminating the network so that the reward network can provide a reliable adjustment method for the generation of the network.The method of combining the reward network and cross entropy loss is used to guide the training of the generator and produce high-quality music work.Compared with other multi-track music generation models,the experimental results verify the validity of the model.
基金funded by the National Natural Science Foundation of China,No.30560042 and 81260194Jiangxi Provincial Health Bureau of Science and Technology Program,No.20111028
文摘A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau （MAPT） gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population. We screened the mutation-susceptible regions of MAPT- the 3＇ and 5＇ untranslated regions as well as introns 9, 10, 11, and 12 - by direct sequencing, and identified 33 genetic variations. Two of these, 105788 A 〉 G in intron 9 and 123972 T 〉 A in intron 11, were not present in the control group. The age of onset in patients with the 105788 A 〉 G and/or the 123972 T 〉 A variant was younger than that in patients without either genetic variation. Moreover, the pa- tients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.41830106,21607104)the National Key Research and Development Plan(Grant Nos.2017YFC0210004,2018YFC0213801)+1 种基金the Shanghai Science and Technology Commission of Shanghai Municipality(18QA 403600)the Shanghai Environmental Protection Bureau(2017-2).
文摘As Volatile Organic Compounds(VOCs)are one of the precursors of ozone,their distribution and variable concentrations are highly related to local ozone pollution control.In this study,we obtained vertical profiles of VOCs in Shanghai’s Jinshan district on 8 September and 9 September in 2016 to investigate their distribution and impact on local atmospheric oxidation in the near surface layer.Vertical samples were collected from heights between 50 m and 400 m by summa canisters using an unmanned aerial vehicle(UAV).Concentrations of VOCs(VOCs refers to the 52 species measured in this study)varied minimally below 200 m,and decreased by 21.2%from 100 m to 400 m.The concentrations of VOCs above 200 m decreased significantly in comparison to those below 200 m.The proportions of alkanes and aromatics increased from 55.2%and 30.5%to 57.3%and 33.0%,respectively.Additionally,the proportion of alkenes decreased from 13.2%to 8.4%.Toluene and m/p-xylene were the key species in the formation of SOA and ozone.Principal component analysis(PCA)revealed that the VOCs measured in this study mainly originated from industrial emissions.
基金National Natural Science Foundation of China(Grant No.51971215).
文摘In this study,the oxidation behavior of Ti42Al5Mn,Ti42Al5Mn0.5 W,Ti42Al5Mn0.5W0.1B,and Ti42Al5Mn0.8 W was investigated at 800℃.Due to the inability to form a dense protective Al2O_(3) layer,Ti42Al5Mn suffered severe spallation during oxidation at 800℃and the mass gain was significant.The intermediate layer between the scale and the substrate was first composed of Laves/Z phase but changed toα2/Z phase with prolonged oxidation.The intermediate layer with high Ti/Al ratio favors the forma-tion of a thick Al2O_(3)+TiO_(2) mixed layer in the oxide scale which is prone to initiate cracks and cause the spalling of oxides.The doping of W in TiO_(2) effectively inhibited its generation and promoted the for-mation of a dense Al2O_(3) layer,resulting in a significant improvement in the oxidation resistance of the alloy.Compared to Ti42Al5Mn alloy,Ti42Al5Mn0.8 W showed no spallation after 300 h cyclic oxidation and the kinetic curve changed from liner law to parabolic law.The intermediate layer of Ti42Al5Mn0.8 W alloy was composed of a single Laves phase and remained unchanged even after 1000 h oxidation at 800℃,offering a favorable basis for the generation of a stable protective oxide layer in the alloy.The addi-tion of 0.1 at.%B to Ti42Al5Mn0.5 W alloy refined its microstructure and further improved its spallation resistance to a level close to that of Ti42Al5Mn0.8 W alloy.
基金the National Natural Science Foundation of China(No.51904063)the Science and Technology Plan Project of Liaoning Province,China(No.2022JH24/10200027)+1 种基金the Key Research and Development Project of Hebei Province,China(No.21314001D)the seventh batch of the Ten Thousand Talents Plan(No.ZX20220553).
文摘Direct reduction based on hydrogen metallurgical gas-based shaft furnace is a promising technology for the efficient and low-carbon smelting of vanadium-titanium magnetite.However,in this process,the sticking of pellets occurs due to the aggregation of metal-lic iron between the contact surfaces of adjacent pellets and has a serious negative effect on the continuous operation.This paper presents a detailed experimental study of the effect of TiO2 on the sticking behavior of pellets during direct reduction under different conditions.Results showed that the sticking index(SI)decreased linearly with the increasing TiO2 addition.This phenomenon can be attributed to the increase in unreduced FeTiO3 during reduction,leading to a decrease in the number and strength of metallic iron interconnections at the sticking interface.When the TiO2 addition amount was raised from 0 to 15wt%at 1100°C,the SI also increased from 0.71%to 59.91%.The connection of the slag phase could be attributed to the sticking at a low reduction temperature,corresponding to the low sticking strength.Moreover,the interconnection of metallic iron became the dominant factor,and the SI increased sharply with the increase in re-duction temperature.TiO2 had a greater effect on SI at a high reduction temperature than at a low reduction temperature.
基金supported by the National Key Research and Development Program of China(2019YFE0115600)the National Natural Science Foundation of China(52074290)。
文摘The mineral species in soils vary in a wide variety of places,thus resulting in the petroleumcontaminated soil(PCS)with complex characters.Thus,the research on the effect of mineral species on oil-soil interactions in PCS takes on a critical significance.In this study,the desorption and adsorption behaviors of aromatic hydrocarbons(Ar)on two minerals surfaces were examined.Meanwhile,the interfacial forces between minerals and Ar were studied and the sources of these forces were analyzed.Moreover,molecular dynamics(MD)simulations were conducted to gain insight into the interfacial interaction mechanisms.As revealed by the results of this study,in comparison with Qs-Ar(quartz sand,Qs),Mnt-Ar(montmorillonite,Mnt)contaminants required higher temperature and activation energies for thermal desorption(201.95 kJ·mol^(-1)vs.127.82 kJ·mol^(-1))The above difference was generated since the adhesive forces between Ar and Mnt surfaces were greater than those between Ar and Qs.As indicated by the analysis of the adhesion force sources,the van der Waals forces were responsible for facilitating oil adhesion to mineral surfaces,even though the electrostatic force prevented oil-mineral adhesion.Furthermore,the hydrophobic forces facilitated adhesion in 3 nm.The MD results demonstrated that compared with the Qs system,there existed larger binding energies between Ar and Mnt,a lower diffusion coefficient for Ar on the Mnt surface,as well as more significant adsorption of Ar on Mnt.In general,the different mineral species affect the strength of the interaction at the oil-soil interface,which is a guideline for proposing targeted oil-soil separation measures.
基金supported by the National Natural Science Foundation of China(Nos.52165025 and 51865030)the Jiangxi Province Key Laboratory of Light Alloy(No.2024SSY05031).
文摘With the continuous miniaturization of integrated circuit(IC)devices,Co is recognized as the most promising alternative to Cu as an interconnecting metal.During IC processing,Co surfaces need to be flattened.This work describes dynamic polishing experiments and static corrosion experiments on the electrical,chemical,and mechanical factors involved in cobalt electrochemical mechanical polishing(ECMP).Then,the impact and proportion of individual and combined factors on the Co-ECMP are quantitatively analyzed.The experimental results show that mechanical action,rather than individual chemical or electrical action,plays a primary role in Co-ECMP.The ratios of individual mechanical,chemical,and electrical action proportions are 50.46%,11.17%,and 6.20%,respectively.However,chemical and electrical assistance with mechanical action can achieve twofold efficiency and high-quality polishing of Co.For example,the ratios of mechanical–chemical or electrical–chemical–mechanical cooperation are 72.05% or 100%,respectively.In addition,polarization curves,energy dispersive spectroscopy(EDS),and X-ray photoelectron spectroscopy(XPS)were used to analyze the Co-ECMP process and products.Atomic-level mechanism analysis is performed for each factor.The results indicate that in Co-ECMP,the oxides formed on the Co surface are mainly CoO,Co(OH)_(2),and Co_(3)O_(4).The oxides react with the complexing agents to form loose and porous Co-benzotriazole(Co-BTA)complexes.Mechanical,chemical,and electrical factors collaborate to form and remove Co-BTA constantly,achieving rapid material removal and obtaining smooth atomic-level surfaces.
基金supported by the National Natural Science Foundation of China(Nos.81770562,81602166 and 81703807)grants from the Science and Technology Planning Project of Luzhou,Sichuan Province,China(Nos.2016LZXNYD-Z04 and 2017LZXNYD-J02)
文摘Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, wesummarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
文摘Artificial intelligence generated content(AIGC)has been a research hotspot in the field of artificial intelligence in recent years.It is expected to replace humans in performing some of the work of content generation at a low cost and a high volume,such as music,painting,multimodal content generation,news articles,summary reports,stock commentary summaries,and even content and digital people generated in the meta-universe.AIGC provides a new technical path for the development and implementation of AI in the future.
基金Supported by the National Natural Science Foundation of China(12275102)the National Key Research and Development Program of China(2022YFA1604900)。
文摘Exploration of the QCD phase diagram and critical point is one of the main goals in current relativistic heavy-ion collisions.The QCD critical point is expected to belong to a three-dimensional(3D)Ising universality class.Machine learning techniques are found to be powerful in distinguishing different phases of matter and provide a new way to study the phase diagram.We investigate phase transitions in the 3D cubic Ising model using supervised learning methods.It is found that a 3D convolutional neural network can be trained to effectively predict physical quantities in different spin configurations.With a uniform neural network architecture,it can encode phases of matter and identify both second-and first-order phase transitions.The important features that discriminate different phases in the classification processes are investigated.These findings can help study and understand QCD phase transitions in relativistic heavy-ion collisions.
基金supported by the National Natural Science Foundation of China (30623011)
文摘Previous studies have shown that DWARFIO （D10） is a rice ortholog of MAX41RMS1/DAD1, encoding a carotenoid cleavage dioxygenase and functioning in strigolactones/strigolactone-derivatives （SL） biosynthesis. Here we use DIO. RNA interference （RNAi） transgenic plants similar to dlO mutant in phenotypes to investigate the interactions among DIO, auxin and cytokinin in regulating rice shoot branching. Auxin levels in node 1 of both decapitated DIO.RNAi and wild type plants decreased significantly, showing that decapitation does reduce endogenous auxin concentration, but decapitation has no clear effects on auxin levels in node 2 of the same plants. This implies that node 1 may be the location where a possible interaction between auxin and DIO gene would be detected. DIO expression in node 1 is inhibited by decapitation, and this inhibition can be restored by exogenous auxin application, indicating that DIO may play an important role in auxin regulation of SL. The decreased expression of most OsPINs in shoot nodes of DIO-RNAi plants may cause a reduced auxin transport capacity. Furthermore, effects of auxin treatment of decapitated plants on the expression of cytokinin biosynthetic genes suggest that DIO promotes cytokinin biosynthesis by reducing auxin levels. Besides, in DIO-RNAi plants, decreased storage cytokinin levels in the shoot node may partly account for the increased active cytokinin contents, resulting in more tillering phenotypes.
文摘The effects of simulated microgravity on matrix mineralization of chondrocytes were examined using cultured chicken embryonic chondrocytes as the model. In four days, there was a time course decrease in alkaline phosphatase activity of chondrocytes, a marker of matrix mineralization.Meanwhile, in two days, there was a significant drop in intracellular calcium concentration in contrast to the control. These results indicate that simulated microgravity can suppress matrix calcification of cultured chondrocytes, and intracellular calcium may be involved in the regulation of matrix calcification as the second messenger.
基金supported by the financial support from the National Natural Science Foundation of China(22374109 and 21974102)the National Key R&D Program of China(2018YFA0703700).
文摘Proton transport(PT)in solid-state materials is crucial for applications in energy conversion and protonic devices.Nevertheless,the highly complex and disordered structures of conventional proton-conducting materials,such as polymers and proteins,hinder a clear understanding of the mechanisms underlying PT,particularly the formation of hydrogen bond(H-bond)networks and their role in mediating PT.Here,we show that self-assembling monolayers(SAMs)of oligopeptides provide a promising platform for elucidating the key factors that modulate PT related H-bonds,including amide bond interactions,peptide sequence,and chain length.Combined with structural characterizations of SAMs,the electrical measurements under both direct and alternating current modes demonstrate that longer and more extended oligopeptide chains in SAMs result in an ordered molecular arrangement,leading to a more pronounced response of current density(J)to increasing relative humidity(RH).Moreover,this increase in molecular order also shifts the transition from electron-dominated to proton-dominated charge transport to a higher RH.The synergy between carrier concentration and mobility is a key factor contributing to the increase in J.This study not only elucidates the critical role of ordered H-bonds in PT but also expands the application of SAM technology in controlling molecular conformation and enhancing proton conduction.
