1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrie...1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrient malnutrition and yield reductions from climate change with sufficient speed or precision[1].Consequently,agriculture is transitioning from selection-based breeding to designbased engineering.Synthetic biology enables the precision modification of metabolic pathways and the construction of novel trait combinations[1,2].This special issue,Synthetic Biology for Crop Improvement,brings together 26 articles that showcase the field’s transition from laboratory curiosity to field-validated agricultural technology.The collection spans 13 plant species,from staple grains and major industrial crops to horticultural and medicinal plants,demonstrating the universal applicability of metabolic engineering.These studies reveal maturation toward field readiness:independent groups achieving reproducible results in identical pathways,greenhouse concepts advancing to multi-season field trials,and engineered traits delivering measurable agronomic value.This progression answers the central question in crop synthetic biology,shifting the paradigm from asking“can it work?”to demonstrating“how it works,and here are the yields”.This transformation is grounded in understanding and manipulating plant metabolism at molecular resolution[3].展开更多
Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remai...Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.展开更多
Chilo suppressalis(Walker)is one of the most important rice pests worldwide,posing a significant challenge to effective control.To develop a precision-timed,eco-friendly management strategy,overwintering population in...Chilo suppressalis(Walker)is one of the most important rice pests worldwide,posing a significant challenge to effective control.To develop a precision-timed,eco-friendly management strategy,overwintering population investigation and dynamic monitoring of C.suppressalis populations were conducted in the Meishan region of Sichuan,China,from 2023 to 2024.The optimal timing for insecticide application was estimated,followed by field trials evaluating the efficacy of different insecticides.Results demonstrated that the peak emergence of first-generation adults typically occurred in early July(under the environmental conditions of the Meishan region),with the ambient humidity below 75%and temperature around 29◦C.Pesticide efficacy trials show that insecticide combinations exhibited superior control.Notably,a combined treatment of emamectin benzoate⋅methoxyfenozide+chlorantraniliprole achieved the highest control efficacy(90.05%)and a corresponding yield of 12,491.55 kg/ha.All tested treatments were determined to be safe for rice growth.Furthermore,this optimized strategy resulted in notable economic benefits,including a 50%reduction in pesticide usage and cost savings of 4796.15 CNY compared to conventional practices.This study provides valuable insights into sustainable rice production and pest management and,for the first time,proposes a precision application time window based on intelligent monitoring.展开更多
The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid ...The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid syntheses of aromatic scaffolds that contains deuterium remain an important yet elusive task.State-of-the-art approaches mainly relied on the transition metal-catalyzed C-H deuteration via the assistance of directing groups(DGs),which often suffered from over-deuteration and lengthy step counts required for installation and/or removal of DG.Herein,we report a generalizable synthetic linchpin strategy for the facile preparation of the ortho-deuterated aromatic core.Through capture of aryne-derived 1,3-zwitterion with heavy water,we synthesized an array of ortho-deuterated aryl sulfonium salts.These novel linchpins not only participated the transition metal catalyzed cross-coupling reaction as nucleophiles,but also served as aryl radical reservoirs under photochemical or electrochemical conditions,enabling facile and precise access to structurally diverse deuterated aromatics.Moreover,we have disclosed a novel EDA complex enabled direct arylation of phosphines under visible-light irradiation,further expanding the utility of our platform approach.展开更多
Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing can...Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.展开更多
With the continuous advancement of bionanomaterial technology,the design and fabrication strategies of biomimetic nanocarriers have undergone significant strategic transformations and innovations.This article systemat...With the continuous advancement of bionanomaterial technology,the design and fabrication strategies of biomimetic nanocarriers have undergone significant strategic transformations and innovations.This article systematically reviews the evolution from single-cell membrane nanovesicles to hybrid cell membrane nanovesicles integrating multiple cell membranes,culminating in cell membrane hybrid lipid nanoparticles(CM-LNPs)combining natural cell membranes or membrane proteins with engineered synthetic phospholipids.This technological progression enables the synergistic retention of multicellular biological functions and the incorporation of advantageous synthetic material properties,such as enhanced engineering flexibility and surface modifiability.Additionally,the article discusses the advantages and limitations of traditional extrusion and ultrasonication methods in the preparation of cell membrane nanovesicles,highlights the benefits and development prospects of novel microfluidic techniques in the preparation of CM-LNPs,and explores the future application prospects and challenges of CM-LNPs in the biomedical field.展开更多
Phosphatase and tensin homolog deleted on chromosome 10(PTEN)messenger RNA(mRNA)delivery has fueled a great hope for tumor immunotherapy via augmenting the immune sensitivity in many human cancers.However,therapeutic ...Phosphatase and tensin homolog deleted on chromosome 10(PTEN)messenger RNA(mRNA)delivery has fueled a great hope for tumor immunotherapy via augmenting the immune sensitivity in many human cancers.However,therapeutic efficacy and clinical translation are limited by inadequate mRNA expression,insufficient immune stimulation and stringent storage requirements.Herein,inspired by the intrinsic properties of metal ions and exosomes,we developed a biomimetic delivery system(Mn-NP@PM)with superior stability for precise colorectal cancer immunotherapy.This platform employs adjuvant-metal-ion chelation for PTEN mRNA loading and PD-L1 antibodies(αPD-L1)-modified monocyte-macrophage membrane coating for mRNA protection and tumor targeting.Mn^(2+) was specifically selected due to its capacity for reversible mRNA binding through weak non-electrostatic interactions,facilitating efficient release,while simultaneously activating the stimulator of interferon genes(STING)pathway.Importantly,Mn-NP@PM exhibited membrane fusion for immediate cytosolic mRNA delivery,bypassing endo-lysosomal escape,optimizing transportation efficiency.Clinical-data-driven analyses further demonstrated that Mn-NP@PM-mediated PTEN restoration significantly increased T-cell infiltration and strengthened antitumor immunity in humanized patient derived xenograft(PDX)models.Collectively,this biomimetic,metal-ion-chelating,membrane-coated mRNA delivery system represents a versatile and clinically translatable strategy for personalized cancer immunotherapy.展开更多
Controllable photoreaction transition of photosensitizers(PSs)provides a highly promising approach for achieving efficient photodynamic therapy(PDT).However,tumor microenvironment-triggered phototransition remains a s...Controllable photoreaction transition of photosensitizers(PSs)provides a highly promising approach for achieving efficient photodynamic therapy(PDT).However,tumor microenvironment-triggered phototransition remains a significant challenge and has not yet been reported.In this work,we develop a hydrogen bond self-assembly(HBSA)strategy that is triggered by the acidic tumor microenvironment to enable the photodynamic transition of tetra(4-carboxylphenyl)porphyrin(TCPP)PSs from type Ⅱ to type Ⅰ reactions.Upon self-assembly of TCPP monomers into TCPP assemblies(TCPP-ass),the generated reactive oxygen species shift from singlet oxygen to superoxide anions,which induces caspase-3/GSDME-mediated programmed pyroptosis,enabling rapid and complete solid tumor elimination with minimized adverse effects and enhanced therapeutic efficacy.Crucially,the HBSA process occurs exclusively within tumor cells,and this tumor-specific self-assembly strategy not only utilizes high tissue penetration of TCPP molecular-PSs,but also avoids phototoxicity caused by the formation and accumulation of TCPP-ass nano-PSs in normal tissue,providing an innovative approach for precise cancer therapy.展开更多
High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging ...High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging foundation models and multimodal learning frameworks are enabling scalable and transferable representations of cellular states,while advances in interpretability and real-world data integration are bridging the gap between discovery and clinical application.This paper outlines a concise roadmap for AI-driven,transcriptome-centered multi-omics integration in precision medicine(Figure 1).展开更多
Doping is essential for modulating semiconductor conductivity,forming p-n junctions,and reducing contact resistance[1].Notably,as organic semiconductors(OSCs)advance toward high performance,flexibility,and miniaturiza...Doping is essential for modulating semiconductor conductivity,forming p-n junctions,and reducing contact resistance[1].Notably,as organic semiconductors(OSCs)advance toward high performance,flexibility,and miniaturization,achieving precise regionally selective doping becomes critical for building complex,highly integrated devices[2].In inorganic semiconductors(e.g.,silicon),sub-100-nanometer regional doping is achievable through photolithography and ion implantation—techniques foundational to modern complementary metaloxide-semiconductor(CMOS)technology[3].展开更多
Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal ce...Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.展开更多
In the dynamic landscape of modern healthcare and precision medicine,the digital revolution is reshaping medical industries at an unprecedented pace,and traditional Chinese medicine(TCM)is no exception[1-4].The paper...In the dynamic landscape of modern healthcare and precision medicine,the digital revolution is reshaping medical industries at an unprecedented pace,and traditional Chinese medicine(TCM)is no exception[1-4].The paper“From digits towards digitization:the past,present,and future of traditional Chinese medicine”by Academician&TCM National Master Qi WANG(王琦).展开更多
The management of breast cancer,one of the most common and heterogeneous malignancies,has transformed with the advent of precision medicine.This review explores current developments in genetic profiling,molecular diag...The management of breast cancer,one of the most common and heterogeneous malignancies,has transformed with the advent of precision medicine.This review explores current developments in genetic profiling,molecular diagnostics,and targeted therapies that have revolutionized breast cancer treatment.Key innovations,such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors,antibodydrug conjugates(ADCs),and immune checkpoint inhibitors(ICIs),have improved outcomes for hormone receptor-positive(HR+),HER2-positive(HER2+),and triple-negative breast cancer(TNBC)subtypes remarkably.Additionally,emerging treatments,such as PI3K inhibitors,poly(ADP-ribose)polymerase(PARP)inhibitors,and m RNA-based therapies,offer new avenues for targeting specific genetic mutations and improving treatment response,particularly in difficult-to-treat breast cancer subtypes.The integration of liquid biopsy technologies provides a non-invasive approach for real-time monitoring of tumor evolution and treatment response,thus enabling dynamic adjustments to therapy.Molecular imaging and artificial intelligence(AI)are increasingly crucial in enhancing diagnostic precision,personalizing treatment plans,and predicting therapeutic outcomes.As precision medicine continues to evolve,it has the potential to significantly improve survival rates,decrease recurrence,and enhance quality of life for patients with breast cancer.By combining cutting-edge diagnostics,personalized therapies,and emerging treatments,precision medicine can transform breast cancer care by offering more effective,individualized,and less invasive treatment options.展开更多
In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trau...In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trauma can be decreased,and patients’quality of life can be improved by ensuring safety.Herein,we explore the axillary de-escalation surgery model for breast cancer.展开更多
Expanding the specific surface area of substrates and carrying out precise surface engineering of imprinted nanocavities are crucial methods for enhancing the identification efficiency of molecularly imprinted polymer...Expanding the specific surface area of substrates and carrying out precise surface engineering of imprinted nanocavities are crucial methods for enhancing the identification efficiency of molecularly imprinted polymers(MIPs).To implement this synergistic strategy,bioinspired surface engineering was used to incorporate dual covalent receptors via precise post-imprinting modifications(PIMs)onto mesoporous silica nanosheets.The prepared sorbents(denoted as‘‘D-PMIPs”)were utilized to improve the specific identification of adenosine 5-monophosphate(AMP).Significantly,the mesoporous silica nanosheets possess a high surface area of approximately 498.73 m^(2)·g^(-1),which facilitates the formation of abundant specific recognition sites in the D-PMIPs.The dual covalent receptors are valuable for estab-lishing the spatial orientation and arrangement of AMP through multiple cooperative interactions.PIMs enable precise site-specific functionalization within the imprinted cavities,leading to the tailor-made formation of complementary binding sites.The maximum number of high-affinity binding sites(Nmax)of the D-PMIPs is 39.99 lmol·g^(-1),which is significantly higher than that of imprinted sorbents with a sin-gle receptor(i.e.,S-BMIPs or S-PMIPs).The kinetic data of the D-PMIPs can be effectively described by a pseudo-second-order model,indicating that the main binding mechanism involves synergistic chemisorption from boronate affinity and the pyrimidine base.This study suggests that using dual cova-lent receptors and PIMs is a reliable approach for creating imprinted sorbents with high selectivity,allow-ing for the controlled engineering of imprinted sites.展开更多
Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids pres...Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids preserve the complex tissue architecture and cellular diversity of human cancers,enabling more accurate predictions of tumor growth,metastasis,and drug responses.Integration with microfluidic platforms,such as organ-on-a-chip systems,further enhances the ability to model tumor-environment interactions in real-time.Organoids facilitate in-depth exploration of tumor heterogeneity,molecular mechanisms,and the development of personalized treatment strategies when coupled with multi-omics technologies.Organoids provide a platform for investigating tumor-immune cell interactions,which aid in the design and testing of immune-based therapies and vaccines.Taken together,these features position organoids as a transformative tool in advancing cancer research and precision medicine.展开更多
Artificial intelligence(AI)is driving a paradigm shift in gastroenterology and hepa-tology by delivering cutting-edge tools for disease screening,diagnosis,treatment,and prognostic management.Through deep learning,rad...Artificial intelligence(AI)is driving a paradigm shift in gastroenterology and hepa-tology by delivering cutting-edge tools for disease screening,diagnosis,treatment,and prognostic management.Through deep learning,radiomics,and multimodal data integration,AI has achieved diagnostic parity with expert cli-nicians in endoscopic image analysis(e.g.,early gastric cancer detection,colorectal polyp identification)and non-invasive assessment of liver pathologies(e.g.,fibrosis staging,fatty liver typing)while demonstrating utility in personalized care scenarios such as predicting hepatocellular carcinoma recurrence and opti-mizing inflammatory bowel disease treatment responses.Despite these advance-ments challenges persist including limited model generalization due to frag-mented datasets,algorithmic limitations in rare conditions(e.g.,pediatric liver diseases)caused by insufficient training data,and unresolved ethical issues related to bias,accountability,and patient privacy.Mitigation strategies involve constructing standardized multicenter databases,validating AI tools through prospective trials,leveraging federated learning to address data scarcity,and de-veloping interpretable systems(e.g.,attention heatmap visualization)to enhance clinical trust.Integrating generative AI,digital twin technologies,and establishing unified ethical/regulatory frameworks will accelerate AI adoption in primary care and foster equitable healthcare access while interdisciplinary collaboration and evidence-based implementation remain critical for realizing AI’s potential to redefine precision care for digestive disorders,improve global health outcomes,and reshape healthcare equity.展开更多
Artificial intelligence(AI)and machine learning(ML)are transforming spine care by addressing diagnostics,treatment planning,and rehabilitation challenges.This study highlights advancements in precision medicine for sp...Artificial intelligence(AI)and machine learning(ML)are transforming spine care by addressing diagnostics,treatment planning,and rehabilitation challenges.This study highlights advancements in precision medicine for spinal pathologies,leveraging AI and ML to enhance diagnostic accuracy through deep learning algorithms,enabling faster and more accurate detection of abnormalities.AIpowered robotics and surgical navigation systems improve implant placement precision and reduce complications in complex spine surgeries.Wearable devices and virtual platforms,designed with AI,offer personalized,adaptive therapies that improve treatment adherence and recovery outcomes.AI also enables preventive interventions by assessing spine condition risks early.Despite progress,challenges remain,including limited healthcare datasets,algorithmic biases,ethical concerns,and integration into existing systems.Interdisciplinary collaboration and explainable AI frameworks are essential to unlock AI’s full potential in spine care.Future developments include multimodal AI systems integrating imaging,clinical,and genetic data for holistic treatment approaches.AI and ML promise significant improvements in diagnostic accuracy,treatment personalization,service accessibility,and cost efficiency,paving the way for more streamlined and effective spine care,ultimately enhancing patient outcomes.展开更多
Zenith Tropospheric Delay(ZTD)is an important factor that restricts the high-precision positioning of global navigation satellite system(GNSS),and it is of great significance in establishing a real-time and highprecis...Zenith Tropospheric Delay(ZTD)is an important factor that restricts the high-precision positioning of global navigation satellite system(GNSS),and it is of great significance in establishing a real-time and highprecision ZTD model.However,existing ZTD models only consider the impact of linear terms on ZTD estimation,whereas the nonlinear factors have rarely been investigated before and thus become the focus of this study.A real-time and high-precision ZTD model for large height difference area is proposed by considering the linear and nonlinear characteristics of ZTD spatiotemporal variations and is called the realtime linear and nonlinearity ZTD(RLNZ)model.This model uses the ZTD estimated from the Global Pressure and Temperature 3(GPT3)model as the initial value.The linear impacts of periodic term and height on the estimation of ZTD difference between GNSS and GPT3 model are first considered.In addition,nonlinear factors such as geographical location and time are further used to fit the remaining nonlinear ZTD residuals using the general regression neural network method.Finally,the RLNZ-derived ZTD is obtained at an arbitrary location.The western United States,with height difference ranging from-500 to 4000 m,is selected,and the hourly ZTD of 484 GNSS stations provided by the Nevada Geodetic Laboratory(NGL)and the data of 9 radiosonde(RS)stations in the year 2021 are used.Experiment results show that a better performance of ZTD estimation can be retrieved from the proposed RLNZ model when compared with the GPT3 model.Statistical results show the averaged root mean square(RMS),Bias,and mean absolute error(MAE)of ZTD from GPT3 and RLNZ models are 33.7/0.8/25.7 mm and 22.6/0.1/17.4 mm,respectively.The average improvement rate of the RLNZ model is 33% when compared to the GPT3 model.Finally,the application of the proposed RLNZ model in simulated real-time Precise Point Positioning(PPP)indicates that the accuracy of PPP in N,E and U components is improved by 8%,2%,and 6% when compared with that from the GPT3-based PPP.Meanwhile,the convergence time in N and U components is improved by 23% and 7%,respectively.Such results verify the superiority of the proposed RLNZ model in retrieving realtime ZTD maps for GNSS positioning and navigation applications.展开更多
文摘1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrient malnutrition and yield reductions from climate change with sufficient speed or precision[1].Consequently,agriculture is transitioning from selection-based breeding to designbased engineering.Synthetic biology enables the precision modification of metabolic pathways and the construction of novel trait combinations[1,2].This special issue,Synthetic Biology for Crop Improvement,brings together 26 articles that showcase the field’s transition from laboratory curiosity to field-validated agricultural technology.The collection spans 13 plant species,from staple grains and major industrial crops to horticultural and medicinal plants,demonstrating the universal applicability of metabolic engineering.These studies reveal maturation toward field readiness:independent groups achieving reproducible results in identical pathways,greenhouse concepts advancing to multi-season field trials,and engineered traits delivering measurable agronomic value.This progression answers the central question in crop synthetic biology,shifting the paradigm from asking“can it work?”to demonstrating“how it works,and here are the yields”.This transformation is grounded in understanding and manipulating plant metabolism at molecular resolution[3].
基金supported by grants from the Open Research Fund of the Zhejiang Key Laboratory of Precision Psychiatry(2025A2)the Natural Science Foundation of Zhejiang Province(LY23C090002)。
文摘Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.
基金funded by the National Key R&D Project‘Innovation and Integration of Key Technologies for Integration of Agricultural Machinery and Agronomy in Weak Links of Hybrid Mid-season Rice in Hilly Areas of Southwest China’(2023YFD2301901).
文摘Chilo suppressalis(Walker)is one of the most important rice pests worldwide,posing a significant challenge to effective control.To develop a precision-timed,eco-friendly management strategy,overwintering population investigation and dynamic monitoring of C.suppressalis populations were conducted in the Meishan region of Sichuan,China,from 2023 to 2024.The optimal timing for insecticide application was estimated,followed by field trials evaluating the efficacy of different insecticides.Results demonstrated that the peak emergence of first-generation adults typically occurred in early July(under the environmental conditions of the Meishan region),with the ambient humidity below 75%and temperature around 29◦C.Pesticide efficacy trials show that insecticide combinations exhibited superior control.Notably,a combined treatment of emamectin benzoate⋅methoxyfenozide+chlorantraniliprole achieved the highest control efficacy(90.05%)and a corresponding yield of 12,491.55 kg/ha.All tested treatments were determined to be safe for rice growth.Furthermore,this optimized strategy resulted in notable economic benefits,including a 50%reduction in pesticide usage and cost savings of 4796.15 CNY compared to conventional practices.This study provides valuable insights into sustainable rice production and pest management and,for the first time,proposes a precision application time window based on intelligent monitoring.
基金supported by the National Natural Science Foundation of China (Nos.22271010 and 21702013)。
文摘The deuterium labeling has garnered significant interest in drug discovery due to its critical role on improving pharmacokinetic and metabolic properties.However,despite its pharmaceutical value,the general and rapid syntheses of aromatic scaffolds that contains deuterium remain an important yet elusive task.State-of-the-art approaches mainly relied on the transition metal-catalyzed C-H deuteration via the assistance of directing groups(DGs),which often suffered from over-deuteration and lengthy step counts required for installation and/or removal of DG.Herein,we report a generalizable synthetic linchpin strategy for the facile preparation of the ortho-deuterated aromatic core.Through capture of aryne-derived 1,3-zwitterion with heavy water,we synthesized an array of ortho-deuterated aryl sulfonium salts.These novel linchpins not only participated the transition metal catalyzed cross-coupling reaction as nucleophiles,but also served as aryl radical reservoirs under photochemical or electrochemical conditions,enabling facile and precise access to structurally diverse deuterated aromatics.Moreover,we have disclosed a novel EDA complex enabled direct arylation of phosphines under visible-light irradiation,further expanding the utility of our platform approach.
文摘Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.
基金financially supported by the National Natural Science Foundation of China(32371475)。
文摘With the continuous advancement of bionanomaterial technology,the design and fabrication strategies of biomimetic nanocarriers have undergone significant strategic transformations and innovations.This article systematically reviews the evolution from single-cell membrane nanovesicles to hybrid cell membrane nanovesicles integrating multiple cell membranes,culminating in cell membrane hybrid lipid nanoparticles(CM-LNPs)combining natural cell membranes or membrane proteins with engineered synthetic phospholipids.This technological progression enables the synergistic retention of multicellular biological functions and the incorporation of advantageous synthetic material properties,such as enhanced engineering flexibility and surface modifiability.Additionally,the article discusses the advantages and limitations of traditional extrusion and ultrasonication methods in the preparation of cell membrane nanovesicles,highlights the benefits and development prospects of novel microfluidic techniques in the preparation of CM-LNPs,and explores the future application prospects and challenges of CM-LNPs in the biomedical field.
基金supported by the Basic Science Center Project of the National Natural Science Foundation of China(22388101)New Cornerstone Science Foundation(NCI202318)+6 种基金the National Natural Science Foundation of China(32171398 and T242200557)the National Key R&D Program of China(2023YFA1610200 and 2022YFA1603701)Beijing Nova Program(20220484060,20230484426,and 20240484661)Beijing Natural Science Foundation(F251001)Chinese Academy of Sciences Project for Young Scientists in Basic Research(YSBR-036)the One Hundred Talents Program of Chinese Academy of Sciences(E3G551R1ZX)Chinese Academy of Medical Sciences(CAMS)and Innovation Fund for Medical Sciences(CIFMS2019-I2M-5-018).
文摘Phosphatase and tensin homolog deleted on chromosome 10(PTEN)messenger RNA(mRNA)delivery has fueled a great hope for tumor immunotherapy via augmenting the immune sensitivity in many human cancers.However,therapeutic efficacy and clinical translation are limited by inadequate mRNA expression,insufficient immune stimulation and stringent storage requirements.Herein,inspired by the intrinsic properties of metal ions and exosomes,we developed a biomimetic delivery system(Mn-NP@PM)with superior stability for precise colorectal cancer immunotherapy.This platform employs adjuvant-metal-ion chelation for PTEN mRNA loading and PD-L1 antibodies(αPD-L1)-modified monocyte-macrophage membrane coating for mRNA protection and tumor targeting.Mn^(2+) was specifically selected due to its capacity for reversible mRNA binding through weak non-electrostatic interactions,facilitating efficient release,while simultaneously activating the stimulator of interferon genes(STING)pathway.Importantly,Mn-NP@PM exhibited membrane fusion for immediate cytosolic mRNA delivery,bypassing endo-lysosomal escape,optimizing transportation efficiency.Clinical-data-driven analyses further demonstrated that Mn-NP@PM-mediated PTEN restoration significantly increased T-cell infiltration and strengthened antitumor immunity in humanized patient derived xenograft(PDX)models.Collectively,this biomimetic,metal-ion-chelating,membrane-coated mRNA delivery system represents a versatile and clinically translatable strategy for personalized cancer immunotherapy.
基金supported by the National Natural Science Foundation of China(22176058)the Science and Technology Commission of Shanghai Municipality(24DX1400200,23ZR1416100,25ZR1401082)+1 种基金the Program of Introducing Talents of Discipline to Universities(B16017)the Fundamental Research Funds for the Central Universities(222201717003)。
文摘Controllable photoreaction transition of photosensitizers(PSs)provides a highly promising approach for achieving efficient photodynamic therapy(PDT).However,tumor microenvironment-triggered phototransition remains a significant challenge and has not yet been reported.In this work,we develop a hydrogen bond self-assembly(HBSA)strategy that is triggered by the acidic tumor microenvironment to enable the photodynamic transition of tetra(4-carboxylphenyl)porphyrin(TCPP)PSs from type Ⅱ to type Ⅰ reactions.Upon self-assembly of TCPP monomers into TCPP assemblies(TCPP-ass),the generated reactive oxygen species shift from singlet oxygen to superoxide anions,which induces caspase-3/GSDME-mediated programmed pyroptosis,enabling rapid and complete solid tumor elimination with minimized adverse effects and enhanced therapeutic efficacy.Crucially,the HBSA process occurs exclusively within tumor cells,and this tumor-specific self-assembly strategy not only utilizes high tissue penetration of TCPP molecular-PSs,but also avoids phototoxicity caused by the formation and accumulation of TCPP-ass nano-PSs in normal tissue,providing an innovative approach for precise cancer therapy.
文摘High-throughput transcriptomics has evolved from bulk RNA-seq to single-cell and spatial profiling,yet its clinical translation still depends on effective integration across diverse omics and data modalities.Emerging foundation models and multimodal learning frameworks are enabling scalable and transferable representations of cellular states,while advances in interpretability and real-world data integration are bridging the gap between discovery and clinical application.This paper outlines a concise roadmap for AI-driven,transcriptome-centered multi-omics integration in precision medicine(Figure 1).
文摘Doping is essential for modulating semiconductor conductivity,forming p-n junctions,and reducing contact resistance[1].Notably,as organic semiconductors(OSCs)advance toward high performance,flexibility,and miniaturization,achieving precise regionally selective doping becomes critical for building complex,highly integrated devices[2].In inorganic semiconductors(e.g.,silicon),sub-100-nanometer regional doping is achievable through photolithography and ion implantation—techniques foundational to modern complementary metaloxide-semiconductor(CMOS)technology[3].
基金the Scientific and Technological Research Council of Türkiye(TÜBİTAK)Under the International Postdoctoral Research Fellowship Program(2219),No.1059B192400980the National Postdoctoral Research Fellowship Program(2218),No.122C158.
文摘Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.
文摘In the dynamic landscape of modern healthcare and precision medicine,the digital revolution is reshaping medical industries at an unprecedented pace,and traditional Chinese medicine(TCM)is no exception[1-4].The paper“From digits towards digitization:the past,present,and future of traditional Chinese medicine”by Academician&TCM National Master Qi WANG(王琦).
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82103614 and 32171363)Natural Science Foundation of Fujian Province of China(Grant No.2021J05007)+4 种基金funding from the start-up fund for Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast CancerXiamen’s Key Laboratory of Precision Medicine for Endocrine-Related Cancersstart-up and supporting funds from the Third Affiliated Hospital of Kunming Medical University,Yunnan Cancer Hospital for Guo-Jun Zhang and Jing-Wen BaiKey Research and development program for social development of Yunnan Science and Technology Department(Grant No.202403AC100014-2)horizontal project funding from the Third Affiliated Hospital of Kunming Medical University(Grant Nos.20233160A0866 and 20243160A0511)。
文摘The management of breast cancer,one of the most common and heterogeneous malignancies,has transformed with the advent of precision medicine.This review explores current developments in genetic profiling,molecular diagnostics,and targeted therapies that have revolutionized breast cancer treatment.Key innovations,such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors,antibodydrug conjugates(ADCs),and immune checkpoint inhibitors(ICIs),have improved outcomes for hormone receptor-positive(HR+),HER2-positive(HER2+),and triple-negative breast cancer(TNBC)subtypes remarkably.Additionally,emerging treatments,such as PI3K inhibitors,poly(ADP-ribose)polymerase(PARP)inhibitors,and m RNA-based therapies,offer new avenues for targeting specific genetic mutations and improving treatment response,particularly in difficult-to-treat breast cancer subtypes.The integration of liquid biopsy technologies provides a non-invasive approach for real-time monitoring of tumor evolution and treatment response,thus enabling dynamic adjustments to therapy.Molecular imaging and artificial intelligence(AI)are increasingly crucial in enhancing diagnostic precision,personalizing treatment plans,and predicting therapeutic outcomes.As precision medicine continues to evolve,it has the potential to significantly improve survival rates,decrease recurrence,and enhance quality of life for patients with breast cancer.By combining cutting-edge diagnostics,personalized therapies,and emerging treatments,precision medicine can transform breast cancer care by offering more effective,individualized,and less invasive treatment options.
基金supported by grants from the Natural Science Foundation of Shandong Province(Grant No.ZR2024QH058).
文摘In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trauma can be decreased,and patients’quality of life can be improved by ensuring safety.Herein,we explore the axillary de-escalation surgery model for breast cancer.
基金supported by the National Natural Science Foundation of China(22078132,22108103,and U22A20413)the Open Funding Project of the National Key Labora-tory of Biochemical Engineering(2021KF-02)+3 种基金China Postdoctoral Science Foundation(2021M691301)Jiangsu Key Research and Development Program(BE2022356)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(CPSF)(GZ20230989)Jiangsu Agricultural Independent Innovation Fund Project(CX(21)3079).
文摘Expanding the specific surface area of substrates and carrying out precise surface engineering of imprinted nanocavities are crucial methods for enhancing the identification efficiency of molecularly imprinted polymers(MIPs).To implement this synergistic strategy,bioinspired surface engineering was used to incorporate dual covalent receptors via precise post-imprinting modifications(PIMs)onto mesoporous silica nanosheets.The prepared sorbents(denoted as‘‘D-PMIPs”)were utilized to improve the specific identification of adenosine 5-monophosphate(AMP).Significantly,the mesoporous silica nanosheets possess a high surface area of approximately 498.73 m^(2)·g^(-1),which facilitates the formation of abundant specific recognition sites in the D-PMIPs.The dual covalent receptors are valuable for estab-lishing the spatial orientation and arrangement of AMP through multiple cooperative interactions.PIMs enable precise site-specific functionalization within the imprinted cavities,leading to the tailor-made formation of complementary binding sites.The maximum number of high-affinity binding sites(Nmax)of the D-PMIPs is 39.99 lmol·g^(-1),which is significantly higher than that of imprinted sorbents with a sin-gle receptor(i.e.,S-BMIPs or S-PMIPs).The kinetic data of the D-PMIPs can be effectively described by a pseudo-second-order model,indicating that the main binding mechanism involves synergistic chemisorption from boronate affinity and the pyrimidine base.This study suggests that using dual cova-lent receptors and PIMs is a reliable approach for creating imprinted sorbents with high selectivity,allow-ing for the controlled engineering of imprinted sites.
基金supported by the Chinese Academy of Medical Sciences(Grant No.2021RU002)Beijing Natural Science Foundation(Grant No.Z240013)+2 种基金National Natural Science Foundation of China(Grant Nos.82450111,82388102,82373416,and 92259303)Beijing Research Ward Excellence Program(Grant Nos.BRWEP2024W034080200 and BRWEP2024W034080204)Peking University People’s Hospital Research and Development Funds(Grant No.RZG2024-02).
文摘Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids preserve the complex tissue architecture and cellular diversity of human cancers,enabling more accurate predictions of tumor growth,metastasis,and drug responses.Integration with microfluidic platforms,such as organ-on-a-chip systems,further enhances the ability to model tumor-environment interactions in real-time.Organoids facilitate in-depth exploration of tumor heterogeneity,molecular mechanisms,and the development of personalized treatment strategies when coupled with multi-omics technologies.Organoids provide a platform for investigating tumor-immune cell interactions,which aid in the design and testing of immune-based therapies and vaccines.Taken together,these features position organoids as a transformative tool in advancing cancer research and precision medicine.
基金Supported by the Natural Science Foundation of Jilin Province,No.YDZJ202401182ZYTSJilin Provincial Key Laboratory of Precision Infectious Diseases,No.20200601011JCJilin Provincial Engineering Laboratory of Precision Prevention and Control for Common Diseases,Jilin Province Development and Reform Commission,No.2022C036.
文摘Artificial intelligence(AI)is driving a paradigm shift in gastroenterology and hepa-tology by delivering cutting-edge tools for disease screening,diagnosis,treatment,and prognostic management.Through deep learning,radiomics,and multimodal data integration,AI has achieved diagnostic parity with expert cli-nicians in endoscopic image analysis(e.g.,early gastric cancer detection,colorectal polyp identification)and non-invasive assessment of liver pathologies(e.g.,fibrosis staging,fatty liver typing)while demonstrating utility in personalized care scenarios such as predicting hepatocellular carcinoma recurrence and opti-mizing inflammatory bowel disease treatment responses.Despite these advance-ments challenges persist including limited model generalization due to frag-mented datasets,algorithmic limitations in rare conditions(e.g.,pediatric liver diseases)caused by insufficient training data,and unresolved ethical issues related to bias,accountability,and patient privacy.Mitigation strategies involve constructing standardized multicenter databases,validating AI tools through prospective trials,leveraging federated learning to address data scarcity,and de-veloping interpretable systems(e.g.,attention heatmap visualization)to enhance clinical trust.Integrating generative AI,digital twin technologies,and establishing unified ethical/regulatory frameworks will accelerate AI adoption in primary care and foster equitable healthcare access while interdisciplinary collaboration and evidence-based implementation remain critical for realizing AI’s potential to redefine precision care for digestive disorders,improve global health outcomes,and reshape healthcare equity.
文摘Artificial intelligence(AI)and machine learning(ML)are transforming spine care by addressing diagnostics,treatment planning,and rehabilitation challenges.This study highlights advancements in precision medicine for spinal pathologies,leveraging AI and ML to enhance diagnostic accuracy through deep learning algorithms,enabling faster and more accurate detection of abnormalities.AIpowered robotics and surgical navigation systems improve implant placement precision and reduce complications in complex spine surgeries.Wearable devices and virtual platforms,designed with AI,offer personalized,adaptive therapies that improve treatment adherence and recovery outcomes.AI also enables preventive interventions by assessing spine condition risks early.Despite progress,challenges remain,including limited healthcare datasets,algorithmic biases,ethical concerns,and integration into existing systems.Interdisciplinary collaboration and explainable AI frameworks are essential to unlock AI’s full potential in spine care.Future developments include multimodal AI systems integrating imaging,clinical,and genetic data for holistic treatment approaches.AI and ML promise significant improvements in diagnostic accuracy,treatment personalization,service accessibility,and cost efficiency,paving the way for more streamlined and effective spine care,ultimately enhancing patient outcomes.
基金supported by the National Natural Science Foundation of China(42274039)Shaanxi Provincial Innovation Capacity Support Plan Project(2023KJXX-050)+2 种基金The Open Grants of the State Key Laboratory of Severe Weather(2023LASW-B18)Scientific and technological research projects for major issues in military medicine and aviation medicine(2022ZZXM012)Local special scientific research plan project of Shaanxi Provincial Department of Education(22JE012)。
文摘Zenith Tropospheric Delay(ZTD)is an important factor that restricts the high-precision positioning of global navigation satellite system(GNSS),and it is of great significance in establishing a real-time and highprecision ZTD model.However,existing ZTD models only consider the impact of linear terms on ZTD estimation,whereas the nonlinear factors have rarely been investigated before and thus become the focus of this study.A real-time and high-precision ZTD model for large height difference area is proposed by considering the linear and nonlinear characteristics of ZTD spatiotemporal variations and is called the realtime linear and nonlinearity ZTD(RLNZ)model.This model uses the ZTD estimated from the Global Pressure and Temperature 3(GPT3)model as the initial value.The linear impacts of periodic term and height on the estimation of ZTD difference between GNSS and GPT3 model are first considered.In addition,nonlinear factors such as geographical location and time are further used to fit the remaining nonlinear ZTD residuals using the general regression neural network method.Finally,the RLNZ-derived ZTD is obtained at an arbitrary location.The western United States,with height difference ranging from-500 to 4000 m,is selected,and the hourly ZTD of 484 GNSS stations provided by the Nevada Geodetic Laboratory(NGL)and the data of 9 radiosonde(RS)stations in the year 2021 are used.Experiment results show that a better performance of ZTD estimation can be retrieved from the proposed RLNZ model when compared with the GPT3 model.Statistical results show the averaged root mean square(RMS),Bias,and mean absolute error(MAE)of ZTD from GPT3 and RLNZ models are 33.7/0.8/25.7 mm and 22.6/0.1/17.4 mm,respectively.The average improvement rate of the RLNZ model is 33% when compared to the GPT3 model.Finally,the application of the proposed RLNZ model in simulated real-time Precise Point Positioning(PPP)indicates that the accuracy of PPP in N,E and U components is improved by 8%,2%,and 6% when compared with that from the GPT3-based PPP.Meanwhile,the convergence time in N and U components is improved by 23% and 7%,respectively.Such results verify the superiority of the proposed RLNZ model in retrieving realtime ZTD maps for GNSS positioning and navigation applications.
