Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evi...Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.展开更多
New precisely cooperative attacks, such as the coordi- nated cross plane session termination （CXPST） attack, need thou- sands upon thousands machines to attack diverse selected links simultaneously with the given ra...New precisely cooperative attacks, such as the coordi- nated cross plane session termination （CXPST） attack, need thou- sands upon thousands machines to attack diverse selected links simultaneously with the given rate. However, almost all command and control（C＆C） mechanisms only provide publishing one com- mand to the whole once, so-called one-to-all C＆C model, and are not productive to support CXPST-alike attacks. In this paper, we present one-to-any C＆C model on coordination among the unco- operative controlled nodes. As an instance of one-to-any C＆C model, directional command publishing （DCP） mechanism lever- aging on Kademlia is provided with a range-mapping key creating algorithm for commands to compute the publishing range and a statistically stochastic node querying scheme to obtain the com- mands immediately. With theoretical analysis and simulation, it is indicated that one-to-any C＆C model fits for precisely coordi- nated operation on uncooperative controlled nodes with least complexity, better accuracy and efficiency. Furthermore, DCP mechanism can support one-to-all command publishing at the same time. As an example of future C＆C model, studying on one-to-any C＆C model may help to promote the development of more efficient countermeasures.展开更多
China launched the NigComSat-1R communications satellite with a Long March 3B/E from the Xichang Satellite Launch Center (XSLC) at 00:41 on December 20.Twenty six minutes after the lift-off,the satellite separated wit...China launched the NigComSat-1R communications satellite with a Long March 3B/E from the Xichang Satellite Launch Center (XSLC) at 00:41 on December 20.Twenty six minutes after the lift-off,the satellite separated with the rocket and entered precisely into a geostationary transfer orbit with a perigee of 203km,an apogee of 42007km and an inelination of 24.8 degrees.展开更多
Irregular craniofacial bone defects caused by craniofacial fractures always result in craniofacial bone and contour asymmetry and should therefore be reconstructed.Polyetheretherketone(PEEK)is an ideal substitute for ...Irregular craniofacial bone defects caused by craniofacial fractures always result in craniofacial bone and contour asymmetry and should therefore be reconstructed.Polyetheretherketone(PEEK)is an ideal substitute for autologous bone grafts and has been widely used in craniofacial bone defect reconstruction.The precise design of custom-made PEEK implants is particularly important to optimise reconstruction.Herein,the workflow and principles for the design and manufacture of PEEK implants are summarised,and a protocol for the precise design of an irregular craniofacial bone defect PEEK implant is presented.According to the method and principles,the design flow was efficient and could be standardised,and design errors could be avoided as much as possible.展开更多
CONSPECTUS:Nanozymes are nanomaterials with intrinsic enzyme-like properties that can overcome the current limitations of natural enzymes,such as high preparation cost,instability,restricted application scenarios,etc....CONSPECTUS:Nanozymes are nanomaterials with intrinsic enzyme-like properties that can overcome the current limitations of natural enzymes,such as high preparation cost,instability,restricted application scenarios,etc.Since the Fe3O4 nanoparticles(NPs)were shown to possess the peroxidase(POD)-like activity in 2007,thousands of nanomaterials were reported to mimic the catalytic properties of various types of enzymes including catalase(CAT),haloperoxidase,superoxide dismutase(SOD),glucose oxidase,glutathione peroxidase,hydrolase,nuclease,nitroreductase,and others.展开更多
The development of accurate and efficient interatomic potentials using machine learning has emerged as an important approach in materials simulations and discovery.However,the systematic construction of diverse,conver...The development of accurate and efficient interatomic potentials using machine learning has emerged as an important approach in materials simulations and discovery.However,the systematic construction of diverse,converged training sets remains challenging.展开更多
Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The pr...Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)model.This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S.typhimurium A1-R with first-line chemotherapy using the CUP PDOX model.The present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic course.We found that a carboplatinum(CAR)-based regimen was effective for this CUP patient.We also demonstrated that S.typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy.Our results indicate that S.typhimurium A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.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
Plant synthetic biology has emerged as a transformative field in agriculture,offering innovative solutions to enhance food security,provide resilience to climate change,and transition to sustainable farming practices....Plant synthetic biology has emerged as a transformative field in agriculture,offering innovative solutions to enhance food security,provide resilience to climate change,and transition to sustainable farming practices.By integrating advanced genetic tools,computational modeling,and systems biology,researchers can precisely modify plant genomes to enhance traits such as yield,stress tolerance,and nutrient use efficiency.The ability to design plants with specific characteristics tailored to diverse environmental conditions and agricultural needs holds great potential to address global food security challenges.Here,we highlight recent advancements and applications of plant synthetic biology in agriculture,focusing on key areas such as photosynthetic efficiency,nitrogen fixation,drought tolerance,pathogen resistance,nutrient use efficiency,biofortification,climate resilience,microbiology engineering,synthetic plant genomes,and the integration of artificial intelligence with synthetic biology.These innovations aim to maximize resource use efficiency,reduce reliance on external inputs,and mitigate environmental impacts associated with conventional agricultural practices.Despite challenges related to regulatory approval and public acceptance,the integration of synthetic biology in agriculture holds immense promise for creating more resilient and sustainable agricultural systems,contributing to global food security and environmental sustainability.Rigorous multi-field testing of these approaches will undoubtedly be required to ensure reproducibility.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
In the era of precision medicine,the classification of diabetes mellitus has evolved beyond the traditional categories.Various classification methods now account for a multitude of factors,including variations in spec...In the era of precision medicine,the classification of diabetes mellitus has evolved beyond the traditional categories.Various classification methods now account for a multitude of factors,including variations in specific genes,type ofβ-cell impairment,degree of insulin resistance,and clinical characteristics of metabolic profiles.Improved classification methods enable healthcare providers to formulate blood glucose management strategies more precisely.Applying these updated classification systems,will assist clinicians in further optimising treatment plans,including targeted drug therapies,personalized dietary advice,and specific exercise plans.Ultimately,this will facilitate stricter blood glucose control,minimize the risks of hypoglycaemia and hyperglycaemia,and reduce long-term complications associated with diabetes.展开更多
Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently b...Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation(ELRA), ante-situm liver resection and autotransplantation(ALRA) and auxiliary partial liver autotransplantation(APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous effort s done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.展开更多
This paper introduces a high-precision bandgap reference(BGR)designed for battery management systems(BMS),fea-turing an ultra-low temperature coefficient(TC)and line sensitivity(LS).The BGR employs a current-mode sche...This paper introduces a high-precision bandgap reference(BGR)designed for battery management systems(BMS),fea-turing an ultra-low temperature coefficient(TC)and line sensitivity(LS).The BGR employs a current-mode scheme with chopped op-amps and internal clock generators to eliminate op-amp offset.A low dropout regulator(LDO)and a pre-regula-tor enhance output driving and LS,respectively.Curvature compensation enhances the TC by addressing higher-order nonlinear-ity.These approaches,effective near room temperature,employs trimming at both 20 and 60°C.When combined with fixed cur-vature correction currents,it achieves an ultra-low TC for each chip.Implemented in a CMOS 180 nm process,the BGR occu-pies 0.548 mm²and operates at 2.5 V with 84μA current draw from a 5 V supply.An average TC of 2.69 ppm/℃ with two-point trimming and 0.81 ppm/℃ with multi-point trimming are achieved over the temperature range of-40 to 125℃.It accommo-dates a load current of 1 mA and an LS of 42 ppm/V,making it suitable for precise BMS applications.展开更多
Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in re...Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.展开更多
In recent years,advancements in single-cell and spatial transcriptomics,which are highly regarded developments in the current era,particularly the emerging integration of single-cell and spatiotemporal transcriptomics...In recent years,advancements in single-cell and spatial transcriptomics,which are highly regarded developments in the current era,particularly the emerging integration of single-cell and spatiotemporal transcriptomics,have enabled a detailed molecular comprehension of the complex regulation of cell fate.The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine.Currently,single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors.Start-ing from the perspective of RNA sequencing technology,this review outlined the signifcance of single-cell RNA sequencing(scRNA-seq)in prostate cancer research,encompassing preclinical medicine and clinical applications.We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies,as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis,treatment,and drug resistance characteristics of prostate cancer.These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer.Furthermore,we explore the potential clinical applications stemming from other single-cell technologies in this review,paving the way for future research in precision medicine.展开更多
With the continuous development of wearable electronics,wireless sensor networks and other micro-electronic devices,there is an increasingly urgent need for miniature,flexible and efficient nanopower generation techno...With the continuous development of wearable electronics,wireless sensor networks and other micro-electronic devices,there is an increasingly urgent need for miniature,flexible and efficient nanopower generation technology.Triboelectric nanogenerator(TENG)technology can convert small mechanical energy into electricity,which is expected to address this problem.As the core component of TENG,the choice of electrode materials significantly affects its performance.Traditional metal electrode materials often suffer from problems such as durability,which limits the further application of TENG.Graphene,as a novel electrode material,shows excellent prospects for application in TENG owing to its unique structure and excellent electrical properties.This review systematically summarizes the recent research progress and application prospects of TENGs based on graphene electrodes.Various precision processing methods of graphene electrodes are introduced,and the applications of graphene electrode-based TENGs in various scenarios as well as the enhancement of graphene electrodes for TENG performance are discussed.In addition,the future development of graphene electrode-based TENGs is also prospectively discussed,aiming to promote the continuous advancement of graphene electrode-based TENGs.展开更多
The gears of new energy vehicles are required to withstand higher rotational speeds and greater loads,which puts forward higher precision essentials for gear manufacturing.However,machining process parameters can caus...The gears of new energy vehicles are required to withstand higher rotational speeds and greater loads,which puts forward higher precision essentials for gear manufacturing.However,machining process parameters can cause changes in cutting force/heat,resulting in affecting gear machining precision.Therefore,this paper studies the effect of different process parameters on gear machining precision.A multi-objective optimization model is established for the relationship between process parameters and tooth surface deviations,tooth profile deviations,and tooth lead deviations through the cutting speed,feed rate,and cutting depth of the worm wheel gear grinding machine.The response surface method(RSM)is used for experimental design,and the corresponding experimental results and optimal process parameters are obtained.Subsequently,gray relational analysis-principal component analysis(GRA-PCA),particle swarm optimization(PSO),and genetic algorithm-particle swarm optimization(GA-PSO)methods are used to analyze the experimental results and obtain different optimal process parameters.The results show that optimal process parameters obtained by the GRA-PCA,PSO,and GA-PSO methods improve the gear machining precision.Moreover,the gear machining precision obtained by GA-PSO is superior to other methods.展开更多
Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are des...Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.展开更多
Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understan...Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.展开更多
The rapid evolution of laser micro/nano-manufacturing techniques has transformed precision manufacturing,enabling the creation of complex micro/nano-structures.These techniques are crucial for multiple industries,incl...The rapid evolution of laser micro/nano-manufacturing techniques has transformed precision manufacturing,enabling the creation of complex micro/nano-structures.These techniques are crucial for multiple industries,including electronics,photonics,and biomedical engineering,owing to their unmatched precision and versatility.The ability to manipulate materials at such scales has unlocked new possibilities for innovation,thereby facilitating the development of advanced components and devices with enhanced performance and functionalities.展开更多
基金financially supported by the Liaoning Revitalization Talents Program (No. XLYC1907129)the Excellent Youth Science Foundation of Liaoning Province (No. 2020-YQ-06)the China Postdoctoral Science Foundation (No. 2020M670794)。
文摘Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.
基金Supported by the National Natural Science Foundation of China(61402526,61502528)
文摘New precisely cooperative attacks, such as the coordi- nated cross plane session termination （CXPST） attack, need thou- sands upon thousands machines to attack diverse selected links simultaneously with the given rate. However, almost all command and control（C＆C） mechanisms only provide publishing one com- mand to the whole once, so-called one-to-all C＆C model, and are not productive to support CXPST-alike attacks. In this paper, we present one-to-any C＆C model on coordination among the unco- operative controlled nodes. As an instance of one-to-any C＆C model, directional command publishing （DCP） mechanism lever- aging on Kademlia is provided with a range-mapping key creating algorithm for commands to compute the publishing range and a statistically stochastic node querying scheme to obtain the com- mands immediately. With theoretical analysis and simulation, it is indicated that one-to-any C＆C model fits for precisely coordi- nated operation on uncooperative controlled nodes with least complexity, better accuracy and efficiency. Furthermore, DCP mechanism can support one-to-all command publishing at the same time. As an example of future C＆C model, studying on one-to-any C＆C model may help to promote the development of more efficient countermeasures.
文摘China launched the NigComSat-1R communications satellite with a Long March 3B/E from the Xichang Satellite Launch Center (XSLC) at 00:41 on December 20.Twenty six minutes after the lift-off,the satellite separated with the rocket and entered precisely into a geostationary transfer orbit with a perigee of 203km,an apogee of 42007km and an inelination of 24.8 degrees.
基金the Program of Shanghai Municipal Commission of Health and Family Planning(No.20194Y0033)。
文摘Irregular craniofacial bone defects caused by craniofacial fractures always result in craniofacial bone and contour asymmetry and should therefore be reconstructed.Polyetheretherketone(PEEK)is an ideal substitute for autologous bone grafts and has been widely used in craniofacial bone defect reconstruction.The precise design of custom-made PEEK implants is particularly important to optimise reconstruction.Herein,the workflow and principles for the design and manufacture of PEEK implants are summarised,and a protocol for the precise design of an irregular craniofacial bone defect PEEK implant is presented.According to the method and principles,the design flow was efficient and could be standardised,and design errors could be avoided as much as possible.
基金supported by the National Key R&D Program of China(No.2022YFA1205801)the National Natural Science Foundation of China(Nos.T2225026,82172087,52202344,82071308)the Beijing Institute of Technology Research Fund Program for Young Scholars.
文摘CONSPECTUS:Nanozymes are nanomaterials with intrinsic enzyme-like properties that can overcome the current limitations of natural enzymes,such as high preparation cost,instability,restricted application scenarios,etc.Since the Fe3O4 nanoparticles(NPs)were shown to possess the peroxidase(POD)-like activity in 2007,thousands of nanomaterials were reported to mimic the catalytic properties of various types of enzymes including catalase(CAT),haloperoxidase,superoxide dismutase(SOD),glucose oxidase,glutathione peroxidase,hydrolase,nuclease,nitroreductase,and others.
基金supported by the National Natural Science Foundation of China(11874307).
文摘The development of accurate and efficient interatomic potentials using machine learning has emerged as an important approach in materials simulations and discovery.However,the systematic construction of diverse,converged training sets remains challenging.
文摘Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)model.This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S.typhimurium A1-R with first-line chemotherapy using the CUP PDOX model.The present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic course.We found that a carboplatinum(CAR)-based regimen was effective for this CUP patient.We also demonstrated that S.typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy.Our results indicate that S.typhimurium A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.
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 the Strategic Priority Research Program of the Chinese Academy of Sciences(Category B,XDB1090000).
文摘Plant synthetic biology has emerged as a transformative field in agriculture,offering innovative solutions to enhance food security,provide resilience to climate change,and transition to sustainable farming practices.By integrating advanced genetic tools,computational modeling,and systems biology,researchers can precisely modify plant genomes to enhance traits such as yield,stress tolerance,and nutrient use efficiency.The ability to design plants with specific characteristics tailored to diverse environmental conditions and agricultural needs holds great potential to address global food security challenges.Here,we highlight recent advancements and applications of plant synthetic biology in agriculture,focusing on key areas such as photosynthetic efficiency,nitrogen fixation,drought tolerance,pathogen resistance,nutrient use efficiency,biofortification,climate resilience,microbiology engineering,synthetic plant genomes,and the integration of artificial intelligence with synthetic biology.These innovations aim to maximize resource use efficiency,reduce reliance on external inputs,and mitigate environmental impacts associated with conventional agricultural practices.Despite challenges related to regulatory approval and public acceptance,the integration of synthetic biology in agriculture holds immense promise for creating more resilient and sustainable agricultural systems,contributing to global food security and environmental sustainability.Rigorous multi-field testing of these approaches will undoubtedly be required to ensure reproducibility.
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In the era of precision medicine,the classification of diabetes mellitus has evolved beyond the traditional categories.Various classification methods now account for a multitude of factors,including variations in specific genes,type ofβ-cell impairment,degree of insulin resistance,and clinical characteristics of metabolic profiles.Improved classification methods enable healthcare providers to formulate blood glucose management strategies more precisely.Applying these updated classification systems,will assist clinicians in further optimising treatment plans,including targeted drug therapies,personalized dietary advice,and specific exercise plans.Ultimately,this will facilitate stricter blood glucose control,minimize the risks of hypoglycaemia and hyperglycaemia,and reduce long-term complications associated with diabetes.
基金supported by grants from the Beijing Hospitals Authority Youth Program (12022B4010)BTCH Young Talent En-lightenment Program (2024QMRC24)CAMS Innovation Fund for Medical Sciences (2019-I2M-5–056)。
文摘Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation(ELRA), ante-situm liver resection and autotransplantation(ALRA) and auxiliary partial liver autotransplantation(APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous effort s done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.
基金supported by the National Natural Science Foundation of China(NSFC)under grant No.62204235。
文摘This paper introduces a high-precision bandgap reference(BGR)designed for battery management systems(BMS),fea-turing an ultra-low temperature coefficient(TC)and line sensitivity(LS).The BGR employs a current-mode scheme with chopped op-amps and internal clock generators to eliminate op-amp offset.A low dropout regulator(LDO)and a pre-regula-tor enhance output driving and LS,respectively.Curvature compensation enhances the TC by addressing higher-order nonlinear-ity.These approaches,effective near room temperature,employs trimming at both 20 and 60°C.When combined with fixed cur-vature correction currents,it achieves an ultra-low TC for each chip.Implemented in a CMOS 180 nm process,the BGR occu-pies 0.548 mm²and operates at 2.5 V with 84μA current draw from a 5 V supply.An average TC of 2.69 ppm/℃ with two-point trimming and 0.81 ppm/℃ with multi-point trimming are achieved over the temperature range of-40 to 125℃.It accommo-dates a load current of 1 mA and an LS of 42 ppm/V,making it suitable for precise BMS applications.
基金supported by the National Natural Science Foun-dation of China(Grant Nos.:32170680 and T2122018)the Natural Science Foundation of Shanghai,China(Grant No.:21ZR1476000)the CAS Youth Innovation Promotion Association,China(Grant No.:Y2022076).
文摘Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.
基金Chinese Scholarship Council(202206240086)National Natural Science Foundation of China(81974099,82170785,81974098,82170784)+4 种基金National Key Research and Development Program of China(2021YFC2009303)programs from Science and Technology Department of Sichuan Province(2021YFH0172)Young Investigator Award of Sichuan University 2017(2017SCU04A17)Technology Innovation Research and Development Project of Chengdu Science and Technology Bureau(2019-YF05-00296-SN)Sichuan University-Panzhihua science and technology cooperation special fund(2020CDPZH-4).
文摘In recent years,advancements in single-cell and spatial transcriptomics,which are highly regarded developments in the current era,particularly the emerging integration of single-cell and spatiotemporal transcriptomics,have enabled a detailed molecular comprehension of the complex regulation of cell fate.The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine.Currently,single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors.Start-ing from the perspective of RNA sequencing technology,this review outlined the signifcance of single-cell RNA sequencing(scRNA-seq)in prostate cancer research,encompassing preclinical medicine and clinical applications.We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies,as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis,treatment,and drug resistance characteristics of prostate cancer.These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer.Furthermore,we explore the potential clinical applications stemming from other single-cell technologies in this review,paving the way for future research in precision medicine.
基金supported by the National Natural Science Foundation of China(grant No.52422511,U20A6004)the Guangdong Basic and Applied Basic Research Foundation(grant No.2022B1515120011)Guangzhou Basic and Applied Basic Research Foundation(grant No.2024A04J6362).
文摘With the continuous development of wearable electronics,wireless sensor networks and other micro-electronic devices,there is an increasingly urgent need for miniature,flexible and efficient nanopower generation technology.Triboelectric nanogenerator(TENG)technology can convert small mechanical energy into electricity,which is expected to address this problem.As the core component of TENG,the choice of electrode materials significantly affects its performance.Traditional metal electrode materials often suffer from problems such as durability,which limits the further application of TENG.Graphene,as a novel electrode material,shows excellent prospects for application in TENG owing to its unique structure and excellent electrical properties.This review systematically summarizes the recent research progress and application prospects of TENGs based on graphene electrodes.Various precision processing methods of graphene electrodes are introduced,and the applications of graphene electrode-based TENGs in various scenarios as well as the enhancement of graphene electrodes for TENG performance are discussed.In addition,the future development of graphene electrode-based TENGs is also prospectively discussed,aiming to promote the continuous advancement of graphene electrode-based TENGs.
基金Projects(U22B2084,52275483,52075142)supported by the National Natural Science Foundation of ChinaProject(2023ZY01050)supported by the Ministry of Industry and Information Technology High Quality Development,China。
文摘The gears of new energy vehicles are required to withstand higher rotational speeds and greater loads,which puts forward higher precision essentials for gear manufacturing.However,machining process parameters can cause changes in cutting force/heat,resulting in affecting gear machining precision.Therefore,this paper studies the effect of different process parameters on gear machining precision.A multi-objective optimization model is established for the relationship between process parameters and tooth surface deviations,tooth profile deviations,and tooth lead deviations through the cutting speed,feed rate,and cutting depth of the worm wheel gear grinding machine.The response surface method(RSM)is used for experimental design,and the corresponding experimental results and optimal process parameters are obtained.Subsequently,gray relational analysis-principal component analysis(GRA-PCA),particle swarm optimization(PSO),and genetic algorithm-particle swarm optimization(GA-PSO)methods are used to analyze the experimental results and obtain different optimal process parameters.The results show that optimal process parameters obtained by the GRA-PCA,PSO,and GA-PSO methods improve the gear machining precision.Moreover,the gear machining precision obtained by GA-PSO is superior to other methods.
文摘Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.
基金funded by NIH-NIA R01AG061708 (to PHO)Patrick Grange Memorial Foundation (to PHO)+1 种基金A Long Swim (to PHO)CureSPG4 Foundation (to PHO)。
文摘Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.
文摘The rapid evolution of laser micro/nano-manufacturing techniques has transformed precision manufacturing,enabling the creation of complex micro/nano-structures.These techniques are crucial for multiple industries,including electronics,photonics,and biomedical engineering,owing to their unmatched precision and versatility.The ability to manipulate materials at such scales has unlocked new possibilities for innovation,thereby facilitating the development of advanced components and devices with enhanced performance and functionalities.
