This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellula...This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.展开更多
AIM:To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer(GSC).METHODS:The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center...AIM:To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer(GSC).METHODS:The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center.The prognostic factors were analyzed with Cox proportional hazard models.RESULTS:GSC tended to occur within 25 years following the primary surgery,when the initial disease is benign,whereas it primarily occurred within the first15 years post-operation for gastric cancer.Patients with regular follow-up after primary surgery had a better survival rate.The multivariate Cox regression analysis revealed that Borrmann type?Ⅰ/Ⅱ(HR=3.165,95%CI:1.055-9.500,P=0.040)and radical resection(HR=1.780,95%CI:1.061-2.987,P=0.029)were independent prognostic factors for GSC.The overall 1-,3-,and 5-year survival rates of the 92 patients were78.3%,45.6%and 27.6%,respectively.The 1-,3-,and 5-year survival rates of those undergoing radical resection were 79.3%,52.2%,and 37.8%,respectively.The 5-year survival rates for stages?Ⅰ,Ⅱ,Ⅲ,andⅣwere 85.7%,47.4%,16.0%,and 13.3%,respectively(P=0.005).CONCLUSION:The appearance of GSC occurs sooner in patients with primary malignant cancer than in patients with a primary benign disease.Therefore,close follow-up is necessary.The overall survival of patients with GSC is poor,and curative resection can improve their prognosis.展开更多
Objective:This study aimed to develop and validate a risk scoring system to identify high-risk individuals carrying malignant lesions in stomach for tailored gastric cancer screening.Methods:A gastric cancer risk scor...Objective:This study aimed to develop and validate a risk scoring system to identify high-risk individuals carrying malignant lesions in stomach for tailored gastric cancer screening.Methods:A gastric cancer risk scoring system(GC-RSS)was developed based on questionnaire-based predictors for gastric cancer derived from systematic literature review.To assess the capability of this system for discrimination,risk scores for 8,214 and 7,235 outpatient subjects accepting endoscopic examination in two endoscopy centers,and 32,630 participants in a community-based cohort in China were calculated to plot receiver operating characteristic curves and generate area under the curve(AUC).To evaluate the performance of GC-RSS,the screening proportion,sensitivity and detection rate ratio compared to universal screening were used under different risk score cutoff values.Results:GC-RSS comprised nine predictors including advanced age,male gender,low body mass index(<18.5 kg/m^(2)),family history of gastric cancer,cigarette smoking,consumption of alcohol,preference for salty food,irregularity of meals and consumption of preserved food.This tool performed well in determining the risk of malignant gastric lesions with AUCs of 0.763,0.706 and 0.696 in three validation sets.When subjects with risk scores≥5 were evaluated with endoscopy,nearly 50%of these endoscopies could be saved with a detection rate of over 1.5 times achieved.When the cutoff was set at 8,only about 10%of subjects with the highest risk would be offered endoscopy,and detection rates for gastric cancer could be increased 2-4 fold compared to universal screening.Conclusions:An effective questionnaire-based GC-RSS was developed and validated.This tool may play an important role in establishing a tailored screening strategy for gastric cancer in China.展开更多
Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested wi...Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China.The oral microbiome was evaluated with 16 S ribosomal RNA(rRNA)gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above(SDA)and 168 matched healthy controls.DESeq analysis was performed to identify taxa of differential abundance.Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.Results:A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls(all P<0.05&false discovery rate-adjusted Q<0.10).A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve(AUC)of 0.89(95%CI,0.84-0.93).Cross-validation and sensitivity analysis,excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls,or restriction to screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions:The oral microbiome may play an etiological and predictive role in esophageal cancer,and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.展开更多
The advent of three-dimensional （3-D） printed technique provides great possibility in the fabrication of customized porous titanium （Ti） implant. However, the bioinert property of the printed Ti poses an out- stan...The advent of three-dimensional （3-D） printed technique provides great possibility in the fabrication of customized porous titanium （Ti） implant. However, the bioinert property of the printed Ti poses an out- standing problem. Hybrid micro-arc oxidation and hydrothermal （MAO-HT） treatment on porous metals is able to produce multi-scaled hierarchical orthopedic implant, showing great potential for surface mod- ification of 3-D printed implant. In this study, cylindrical porous Ti6Al4V （Ti64） scaffolds with pore size of 640 lure, porosity of ？3% were 3-D printed by electron beam melting process, and their surfaces were left untreated or treated by a combined MAO-HT procedure. In vitro bioactivity was tested by immer- sion in simulated body fluid for different time points. Then, 12 scaffolds in each group were implanted into the femoral condyles of New Zealand rabbit for 8 weeks. Osseointegration was evaluated by qual- itative and quantitative histological analysis, and the bone ingrowth features were probed by sequential fluorescent labeling at 3 and 6 weeks post-surgery, Following the MAO-HT treatment, the porous Ti64 scaffold was endowed with multi-scaled micro/nano-topographies and high amounts of CaP on its surface. The treated scaffold exhibited drastically enhanced apatite forming ability compared with the un- treated one. In vivo test revealed significantly that a higher amount of bone ingrowth and bone implant contact at the treated scaffold. The 2 types of scaffolds had different patterns of bone ingrowth; the treated scaffold exhibited a pattern of contact osteogenesis, by which bone formed directly on the treated implant surface, whereas bone formed distal to the implant surface of the untreated scaffold. MAO-HT treat- ment can significantly enhance the in vitro apatite-inducing ability and in vivo osseointegration capacity of 3-D porous Ti64 scaffold and may provide as a viable approach for the fabrication of bioactive 3-D printed porous implant for orthopedic applications.展开更多
Objective： There have been few population-based studies evaluating health related quality of life（HRQOL） in rural populations in China, and this study aimed to assess the current status of and risk factors for HRQO...Objective： There have been few population-based studies evaluating health related quality of life（HRQOL） in rural populations in China, and this study aimed to assess the current status of and risk factors for HRQOL in a general rural population in high risk region of esophageal cancer in China.Methods： From November 2015 to September 2016, 12,085 permanent residents aged 45–69 years from 257 villages in the Endoscopic Screening for Esophageal Cancer in China（ESECC） trial（Clinical Trials.gov：NCT01688908） randomly selected from Hua County, Henan Province, China were interviewed. The EQ-5 D-3 L,a generic measure of HRQOL, and a questionnaire were used to assess their HRQOL and potential risk factors.Results： Among all the participants, 30.62% of the participants reported problems in at least one EQ-5 D dimension. Pain/discomfort（25.52%） was the most frequently reported problem followed by anxiety/depression（7.97%）, mobility（5.82%）, usual activities（2.61%） and self-care（1%）. These rural residents had a mean EQ-5 D index score of 0.948, and lower EQ-5 D index scores were associated with older age, female gender, lower levels of household annual per capita income, living alone, using shallow wells as main source of drinking water, exposure to family members smoking, testiness, unhealthy dietary habits, overweight or obesity, upper gastrointestinal cancer related symptoms and chronic diseases.Conclusions： Rural residents in China have a relatively low quality of life. Health promotion programs in this population should focus on the elderly, especially elderly women and the elderly living alone. Improving basic living circumstances and primary medical care services should be priorities. Results of this study will also serve as the basis for the cost-utility evaluation in our ESECC screening trial.展开更多
As important atmospheric circulation patterns in Northern Hemisphere(NH),the North Atlantic Oscillation(NAO)and the Western Pacific teleconnection(WP)affect the winter climate in Eurasia.In order to explore the combin...As important atmospheric circulation patterns in Northern Hemisphere(NH),the North Atlantic Oscillation(NAO)and the Western Pacific teleconnection(WP)affect the winter climate in Eurasia.In order to explore the combined effects of NAO and WP on East Asian(EA)temperature,the NAO and WP indices are divided into four phases from 1980−2021:the positive NAO and WP phase(NAO+/WP+),the negative NAO and WP phase(NAO−/WP−),the positive NAO and negative WP phase(NAO+/WP−),the negative NAO and positive WP phase(NAO−/WP+).In the phase of NAO+/WP+,the low geopotential height(GH)stays in north of EA at 50°−80°N;the surface air temperature anomaly(SATA)is 0.8−1℃lower than Southern Asian.In the phase of NAO−/WP−,the center of high temperature and GH locate in the northeast of EA;the cold air spreads to Southern Asia,causing the SATA decreases 1−1.5℃.In the phase of NAO+/WP−,the high GH belt is formed at 55°−80°N.Meanwhile,the center of high SATA locates in the north of Asia that increases 0.8−1.1℃.The cold airflow causes temperature dropping 0.5−1℃in the south of EA.The SATA improves 0.5−1.5℃in south of EA in the phase of NAO−/WP+.The belt of high GH is formed at 25°−50°N,and blocks the cold air which from Siberia.The NAO and WP generate two warped plate pressure structures in NH,and affect the temperature by different pressure configurations.NAO and WP form different GH,and GH acts to block and push airflow by affecting the air pressure,then causes the temperature to be different from the north and south of EA.Finally,the multiple linear regression result shows that NAO and WP are weakened by each other such as the phase of NAO+/WP+and NAO−/WP−.展开更多
Objective The aim of this study was to examine the effects of photodynamic therapy(PDT)on the expression of Nav1.7 in spinal dorsal root ganglion(DRG)neurons.Methods The primary DRG neurons from newborn SD rats were c...Objective The aim of this study was to examine the effects of photodynamic therapy(PDT)on the expression of Nav1.7 in spinal dorsal root ganglion(DRG)neurons.Methods The primary DRG neurons from newborn SD rats were cultured.The cells were identified by neuron-specific enolase immunofluorescence staining.DRG neurons were divided into four groups:control group,photosensitizer group,laser group,and PDT group.The cell viability was detected by a cell counting kit-8(CCK8)assay.qRT-PCR and Western blotting were used to determine the mRNA and protein expression levels of Nav1.7 in DRG neurons.Results The purity of the cultured primary DRG neurons was greater than 90%.Compared with the control group,no significant change was found in the cell viability of the photosensitizer group,while the viability in the laser group and the PDT group was significantly reduced.The mRNA and protein expression levels of Nav1.7 were significantly greater in the laser group and the PDT group than in the control group.At the same time,the mRNA and protein expression levels of Nav1.7 were greater in the laser group than in the PDT group.Conclusion Both laser and PDT could upregulate the expression of Nav1.7 in DRG neurons,and the promoting effect might be related to the pain induced by clinical treatment.This study provides a research basis for the use of laser and PDT to treat pain.A better understanding of the relationship between Nav1.7 and PDT can help clinicians better manage PDT-related pain.展开更多
Metasurfaces,composed of planar arrays of intricately designed meta-atom structures,possess remarkable capabilities in controlling electromagnetic waves in various ways.A critical aspect of metasurface design involves...Metasurfaces,composed of planar arrays of intricately designed meta-atom structures,possess remarkable capabilities in controlling electromagnetic waves in various ways.A critical aspect of metasurface design involves selecting suitable meta-atoms to achieve target functionalities such as phase retardation,amplitude modulation,and polarization conversion.Conventional design processes often involve extensive parameter sweeping,a laborious and computationally intensive task heavily reliant on designer expertise and judgement.Here,we present an efficient genetic algorithm assisted meta-atom optimization method for high-performance metasurface optics,which is compatible to both single-and multiobjective device design tasks.We first employ the method for a single-objective design task and implement a high-efficiency Pancharatnam-Berry phase based metalens with an average focusing efficiency exceeding 80%in the visible spectrum.We then employ the method for a dual-objective metasurface design task and construct an efficient spin-multiplexed structural beam generator.The device is capable of generating zeroth-order and first-order Bessel beams respectively under right-handed and left-handed circular polarized illumination,with associated generation efficiencies surpassing 88%.Finally,we implement a wavelength and spin co-multiplexed four-channel metahologram capable of projecting two spin-multiplexed holographic images under each operational wavelength,with efficiencies over 50%.Our work offers a streamlined and easy-to-implement approach to meta-atom design and optimization,empowering designers to create diverse high-performance and multifunctional metasurface optics.展开更多
Thermosensitive hydrogels were prepared by graft polymerization of chitosan and N-isopropylacrylamide via 60 Co ?-radiation. The effects of monomer concentration and total irradiation dose on percent grafting and graf...Thermosensitive hydrogels were prepared by graft polymerization of chitosan and N-isopropylacrylamide via 60 Co ?-radiation. The effects of monomer concentration and total irradiation dose on percent grafting and grafting efficiency were studied. The thermosensitivity and swelling properties of the hydrogels were investigated.展开更多
The problem of optimal aeroassisted symmetric transfer between elliptical orbits is concerned.The complete trajectory is assumed as consisting of two impulsive velocity changes at the beginning and the end of an inter...The problem of optimal aeroassisted symmetric transfer between elliptical orbits is concerned.The complete trajectory is assumed as consisting of two impulsive velocity changes at the beginning and the end of an interior atmospheric subarc,where the vehicle is controlled via the lift coefficient and thrust.The corresponding dynamic equations are built and bounded controls are considered.For the purpose of optimization computation,the equations are normalized.In order to minimize the total fuel consumption,the geocentric radius of initial elliptical transfer orbital perigee and controls during atmospheric flight should all be optimized.It is an optimal control problem which involves additional parameter optimization.To solve the problem,a two-level optimization method denoted by ＂genetic algorithm ＋ Gauss pseudospectral method＂ is adopted：the genetic algorithm is used for parameter optimization and the Gauss pseudospectral method is used for optimal control problems.The flow chart of simulation is given.On this basis,the issue of more realistic modeling with two finite-thrust subarcs in the nonatmospheric part of the trajectory is simultaneously addressed.The orbital transfer problem is transformed to three continuous optimal control problems,and the constraints at different times are given,which are respectively solved by using the Gauss pseudospectral method.The obtained numerical results indicate that the optimal thrust control is of bangbang type.The minimum-fuel trajectory in the atmosphere consists of aeroglide,aerocruise and aeroglide.They are compared with the results of pure impulsive model,and the conclusions that a significant fuel saving will be achieved by synergetic maneuver are drawn.展开更多
An adaptive repetitive control scheme is presented for a class of nonlinearly parameterized systems based on the fuzzy basis function network （FBFN）. The parameters of the fuzzy rules are tuned with adaptive schemes...An adaptive repetitive control scheme is presented for a class of nonlinearly parameterized systems based on the fuzzy basis function network （FBFN）. The parameters of the fuzzy rules are tuned with adaptive schemes. To attenuate chattering effectively, the discontinuous control term is approximated by an adaptive PI control structure. The bound of the discontinuous control term is assumed to be unknown and estimated by an adaptive mechanism. Based on the Lyapunov stability theory, an adaptive repetitive control law is proposed to guarantee the closed-loop stability and the tracking performance. By means of FBFNs, which avoid the nonlinear parameterization from entering into the adaptive repetitive control, the controller singularity problem is solved. The proposed approach does not require an exact structure of the system dynamics, and the proposed controller is utilized to control a model of permanent-magnet linear synchronous motor subject to significant disturbances and parameter uncertainties. The simulation results demonstrate the effectiveness of the proposed method.展开更多
Ascites syndrome is still a problem for chicken industry in various parts of the world. Despite the intensive investigations of this syndrome for many years, its pathogenesis remains unclear. The objective of this stu...Ascites syndrome is still a problem for chicken industry in various parts of the world. Despite the intensive investigations of this syndrome for many years, its pathogenesis remains unclear. The objective of this study was to analyze the difference in hepatic proteomics between ascites and healthy broilers by two-dimensional electrophoresis （2-DE） and matrix-assisted laser desorption/ionization-time of flight mass spectrometry （MALDI-TOF-MS）. Changes of biochemical parameters of liver and blood were also determined. The results indicated that red blood cell counts （RBC）, hematocrit （HCT） and haemoglobin （HGB） of ascites broilers were significantly greater than healthy broilers. Hepatic malondialdehyde （MDA） level of ascites broilers was significantly increased, and the activity of total superoxide dismutase （T-SOD） was significantly decreased. Hepatic lactic acid （LD） level of ascitic broilers were significantly lower than healthy ones, Serum glucose and cholesterol level of ascites broilers were significantly increased, and serum globulin level was significantly decreased in ascites broilers. There was no significant difference in triglyceride （TG） and blood urea nitrogen （BUN） level. The activity of liver hexokinase （HK） and succinodehydrogenase （SDH） in ascites broilers was significantly decreased, and there was no significant difference in the activity of liver pyruvate kinase （PK） and Na＋-K＋-ATPase. The hepatic proteomics analysis showed that 18 proteins expression difference were identified between ascites and healthy broilers. These proteins were mainly involved in： 1） cytoskeleton; 2） glucose, lipids and amino acid metabolism; 3） cell secretion; 4） cell apoptosis; 5） signal transduction; 6） immune and inflammatory response; and 7） cellular redox homeostasis. Mitochondrial isoform phosphoenolpyruvate carboxykinase （M-PEPCK） mainly participates in gluconeogenesis of chicken liver. In conclusion, liver oxidative damage was significantly aggravated, but antioxidant capacity was decreased in cold-induced ascites broilers. Serum glucose level was significantly increased, with liver M-PEPCK expression higher in ascites broilers, which implied that some potential regulatory reagents may reduce ascites susceptibility and mortality under cold temperature by increasing liver gluconeogenesis level.展开更多
In the last five years,great progress has been made in cloud computing,es pecially in virtualization,standardization,and automation.This has result ed in numerous cloud services,such as Infrastructure as a Service,Pla...In the last five years,great progress has been made in cloud computing,es pecially in virtualization,standardization,and automation.This has result ed in numerous cloud services,such as Infrastructure as a Service,Plat form as a Service,and Software as a Service.Many cloud technologies have matured and have been commercialized.However,issues such as information security,mobility,energy efficiency,and infrastructure optimization are becoming more serious.The key causes of these issues are increased scale of data centers,convergence of IT and CT,increased user concern about information security,展开更多
By using the technique of the split Hopkinson pressure bar（ SHPB）,impact tests at different stress wavelengths（ 0. 8-2. 0 m） and strain rates（ 20-120 s^（-1）） were conducted to study the dynamic mechanical prop...By using the technique of the split Hopkinson pressure bar（ SHPB）,impact tests at different stress wavelengths（ 0. 8-2. 0 m） and strain rates（ 20-120 s^（-1）） were conducted to study the dynamic mechanical properties and damage accumulation evolution lawof granite. Test results showthat the dynamic compressive strength and strain rate of granite have a significantly exponential correlation;the relationship between peak strain and strain rate is approximately linear,and the increase of wavelengths generally makes the level of peak strain uplift. The multiple-impacts test at a lowstrain rate indicates that at the same wavelength,the cumulative damage of granite shows an exponential increasing form with the increase of strain rate; when keeping the increase of strain rate constant and increasing the stress wavelength,the damage accumulation effect of granite is intensified and still shows an exponential increasing form; under the effect of multiple impacts,the damage development trend of granite is similar overall,but the increase rate is accelerating. Therefore the damage evolution model was established on the basis of the exponential function while the physical meaning of parameters in the model was determined. The model can reflect the effect of the wave parameters and multiple impacts. The validity of the model and the physical meaning of the parameters were verified by the test,which further offer a reference for correlational research and engineering application for the granite.展开更多
Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid(CSF)flow by beating their motile cilia coordinately.The ependymal denudation or ciliary dysfunction causes hydroce...Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid(CSF)flow by beating their motile cilia coordinately.The ependymal denudation or ciliary dysfunction causes hydrocephalus.Here,we report that the deficiency of regulator of Gprotein signaling 22(RGS22)results in severe congenital hydrocephalus in both mice and rats.Interestingly,RGS22 is specifically expressed in ependymal cells within the brain.Using conditional knock-out mice,we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus.Mechanistically,we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis.This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor(LPAR)signaling under Rgs22^(-/-)condition,as the LPAR blockade effectively alleviates hydrocephalus in Rgs22^(-/-)rats.Therefore,our findings unveil a previously unrecognized role of RGS22 in the central nervous system,and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.展开更多
Skin diseases are important factors affecting health and quality of life,especially in rural areas where medical resources are limited.Early and accurate diagnosis can reduce unnecessary health and economic losses.How...Skin diseases are important factors affecting health and quality of life,especially in rural areas where medical resources are limited.Early and accurate diagnosis can reduce unnecessary health and economic losses.However,traditional visual diagnosis poses a high demand on both doctors’experience and the examination equipment,and there is a risk of missed diagnosis and misdiagnosis.Recently,advances in artificial intelligence technology,particularly deep learning,have resulted in the use of unimodal computer-aided diagnosis and treatment technologies based on skin images in dermatology.However,due to the small amount of information contained in unimodality,this technology cannot fully demonstrate the advantages of multimodal data in the real-world medical environment.Multimodal data fusion can fully integrate various types of data to help doctors make more accurate clinical decisions.This review aimed to provide a comprehensive overview of multimodal data and deep learning methods that could help dermatologists diagnose and treat skin diseases.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
文摘This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.
基金Supported by National Natural Science Foundation of China,No.81272726Specialized Research Fund for the Doctoral Program of Higher Education,China,No.20110071120097Shanghai Municipal Health Bureau Research Project,No.20114174
文摘AIM:To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer(GSC).METHODS:The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center.The prognostic factors were analyzed with Cox proportional hazard models.RESULTS:GSC tended to occur within 25 years following the primary surgery,when the initial disease is benign,whereas it primarily occurred within the first15 years post-operation for gastric cancer.Patients with regular follow-up after primary surgery had a better survival rate.The multivariate Cox regression analysis revealed that Borrmann type?Ⅰ/Ⅱ(HR=3.165,95%CI:1.055-9.500,P=0.040)and radical resection(HR=1.780,95%CI:1.061-2.987,P=0.029)were independent prognostic factors for GSC.The overall 1-,3-,and 5-year survival rates of the 92 patients were78.3%,45.6%and 27.6%,respectively.The 1-,3-,and 5-year survival rates of those undergoing radical resection were 79.3%,52.2%,and 37.8%,respectively.The 5-year survival rates for stages?Ⅰ,Ⅱ,Ⅲ,andⅣwere 85.7%,47.4%,16.0%,and 13.3%,respectively(P=0.005).CONCLUSION:The appearance of GSC occurs sooner in patients with primary malignant cancer than in patients with a primary benign disease.Therefore,close follow-up is necessary.The overall survival of patients with GSC is poor,and curative resection can improve their prognosis.
基金supported by the National Science&Technology Fundamental Resources Investigation Program of China(No.2019FY101102)the National Natural Science Foundation of China(No.82073626,81773501)+5 种基金the National Key R&D Program of China(No.2016YFC0901404)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(No.J200016)the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(No.XXZ0204)the Beijing Hospitals Authority Youth Programme(No.QML20201101)Sanming Project of Shenzhen(No.SZSM201612061)the Beijing Nova Program(No.Z201100006820093)。
文摘Objective:This study aimed to develop and validate a risk scoring system to identify high-risk individuals carrying malignant lesions in stomach for tailored gastric cancer screening.Methods:A gastric cancer risk scoring system(GC-RSS)was developed based on questionnaire-based predictors for gastric cancer derived from systematic literature review.To assess the capability of this system for discrimination,risk scores for 8,214 and 7,235 outpatient subjects accepting endoscopic examination in two endoscopy centers,and 32,630 participants in a community-based cohort in China were calculated to plot receiver operating characteristic curves and generate area under the curve(AUC).To evaluate the performance of GC-RSS,the screening proportion,sensitivity and detection rate ratio compared to universal screening were used under different risk score cutoff values.Results:GC-RSS comprised nine predictors including advanced age,male gender,low body mass index(<18.5 kg/m^(2)),family history of gastric cancer,cigarette smoking,consumption of alcohol,preference for salty food,irregularity of meals and consumption of preserved food.This tool performed well in determining the risk of malignant gastric lesions with AUCs of 0.763,0.706 and 0.696 in three validation sets.When subjects with risk scores≥5 were evaluated with endoscopy,nearly 50%of these endoscopies could be saved with a detection rate of over 1.5 times achieved.When the cutoff was set at 8,only about 10%of subjects with the highest risk would be offered endoscopy,and detection rates for gastric cancer could be increased 2-4 fold compared to universal screening.Conclusions:An effective questionnaire-based GC-RSS was developed and validated.This tool may play an important role in establishing a tailored screening strategy for gastric cancer in China.
基金the National Natural Science Foundation of China(No.30930102,82073626,81502855,81773501)the National Key R&D program of China(No.2016YFC0901404)+4 种基金the National Special Programme of Scientific and Technological Resources Investigation(No.2019FY101102)the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(No.XXZ0204)the Beijing Natural Science Foundation(No.7182033)the Beijing Municipal Administration of Hospital’s Youth Programme(No.QML20171101)the Science Foundation of Peking University Cancer Hospital(No.2020-7)。
文摘Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China.The oral microbiome was evaluated with 16 S ribosomal RNA(rRNA)gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above(SDA)and 168 matched healthy controls.DESeq analysis was performed to identify taxa of differential abundance.Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.Results:A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls(all P<0.05&false discovery rate-adjusted Q<0.10).A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve(AUC)of 0.89(95%CI,0.84-0.93).Cross-validation and sensitivity analysis,excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls,or restriction to screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions:The oral microbiome may play an etiological and predictive role in esophageal cancer,and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.
基金the Beijing AKEC Medical Co.,LtdMedical Research Center of Peking University Third Hospitalsupported by the Project of Scientific and Technical Plan of Beijing(Nos.Z121100005312005 and Z141100002814008)
文摘The advent of three-dimensional （3-D） printed technique provides great possibility in the fabrication of customized porous titanium （Ti） implant. However, the bioinert property of the printed Ti poses an out- standing problem. Hybrid micro-arc oxidation and hydrothermal （MAO-HT） treatment on porous metals is able to produce multi-scaled hierarchical orthopedic implant, showing great potential for surface mod- ification of 3-D printed implant. In this study, cylindrical porous Ti6Al4V （Ti64） scaffolds with pore size of 640 lure, porosity of ？3% were 3-D printed by electron beam melting process, and their surfaces were left untreated or treated by a combined MAO-HT procedure. In vitro bioactivity was tested by immer- sion in simulated body fluid for different time points. Then, 12 scaffolds in each group were implanted into the femoral condyles of New Zealand rabbit for 8 weeks. Osseointegration was evaluated by qual- itative and quantitative histological analysis, and the bone ingrowth features were probed by sequential fluorescent labeling at 3 and 6 weeks post-surgery, Following the MAO-HT treatment, the porous Ti64 scaffold was endowed with multi-scaled micro/nano-topographies and high amounts of CaP on its surface. The treated scaffold exhibited drastically enhanced apatite forming ability compared with the un- treated one. In vivo test revealed significantly that a higher amount of bone ingrowth and bone implant contact at the treated scaffold. The 2 types of scaffolds had different patterns of bone ingrowth; the treated scaffold exhibited a pattern of contact osteogenesis, by which bone formed directly on the treated implant surface, whereas bone formed distal to the implant surface of the untreated scaffold. MAO-HT treat- ment can significantly enhance the in vitro apatite-inducing ability and in vivo osseointegration capacity of 3-D porous Ti64 scaffold and may provide as a viable approach for the fabrication of bioactive 3-D printed porous implant for orthopedic applications.
基金supported by the Charity Project of National Ministry of Health (No. 201202014)the Natural Science Foundation of China (No. 81473033)+2 种基金the National Key R&D Program of China (No. 2016YFC0901404)the Science Foundation of Peking University Cancer Hospital (No. 2017-4)the Open Project funded by Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing (No. 2017-10)
文摘Objective： There have been few population-based studies evaluating health related quality of life（HRQOL） in rural populations in China, and this study aimed to assess the current status of and risk factors for HRQOL in a general rural population in high risk region of esophageal cancer in China.Methods： From November 2015 to September 2016, 12,085 permanent residents aged 45–69 years from 257 villages in the Endoscopic Screening for Esophageal Cancer in China（ESECC） trial（Clinical Trials.gov：NCT01688908） randomly selected from Hua County, Henan Province, China were interviewed. The EQ-5 D-3 L,a generic measure of HRQOL, and a questionnaire were used to assess their HRQOL and potential risk factors.Results： Among all the participants, 30.62% of the participants reported problems in at least one EQ-5 D dimension. Pain/discomfort（25.52%） was the most frequently reported problem followed by anxiety/depression（7.97%）, mobility（5.82%）, usual activities（2.61%） and self-care（1%）. These rural residents had a mean EQ-5 D index score of 0.948, and lower EQ-5 D index scores were associated with older age, female gender, lower levels of household annual per capita income, living alone, using shallow wells as main source of drinking water, exposure to family members smoking, testiness, unhealthy dietary habits, overweight or obesity, upper gastrointestinal cancer related symptoms and chronic diseases.Conclusions： Rural residents in China have a relatively low quality of life. Health promotion programs in this population should focus on the elderly, especially elderly women and the elderly living alone. Improving basic living circumstances and primary medical care services should be priorities. Results of this study will also serve as the basis for the cost-utility evaluation in our ESECC screening trial.
基金The National Key Research and Development Program of China under contract No.2022YFE0140500the National Natural Science Foundation of China under contract Nos 41821004 and 42130406+2 种基金the National Natural Science Foundation of China-Shandong Joint Fund under contract No.U1906215the Open Fund of Key Laboratory of Ocean Circulation and Waves,Chinese Academy of Sciences under contract No.KLOCW2003the Project of Doctoral Found of Qingdao University of Science and Technology under contract No.210010022746.
文摘As important atmospheric circulation patterns in Northern Hemisphere(NH),the North Atlantic Oscillation(NAO)and the Western Pacific teleconnection(WP)affect the winter climate in Eurasia.In order to explore the combined effects of NAO and WP on East Asian(EA)temperature,the NAO and WP indices are divided into four phases from 1980−2021:the positive NAO and WP phase(NAO+/WP+),the negative NAO and WP phase(NAO−/WP−),the positive NAO and negative WP phase(NAO+/WP−),the negative NAO and positive WP phase(NAO−/WP+).In the phase of NAO+/WP+,the low geopotential height(GH)stays in north of EA at 50°−80°N;the surface air temperature anomaly(SATA)is 0.8−1℃lower than Southern Asian.In the phase of NAO−/WP−,the center of high temperature and GH locate in the northeast of EA;the cold air spreads to Southern Asia,causing the SATA decreases 1−1.5℃.In the phase of NAO+/WP−,the high GH belt is formed at 55°−80°N.Meanwhile,the center of high SATA locates in the north of Asia that increases 0.8−1.1℃.The cold airflow causes temperature dropping 0.5−1℃in the south of EA.The SATA improves 0.5−1.5℃in south of EA in the phase of NAO−/WP+.The belt of high GH is formed at 25°−50°N,and blocks the cold air which from Siberia.The NAO and WP generate two warped plate pressure structures in NH,and affect the temperature by different pressure configurations.NAO and WP form different GH,and GH acts to block and push airflow by affecting the air pressure,then causes the temperature to be different from the north and south of EA.Finally,the multiple linear regression result shows that NAO and WP are weakened by each other such as the phase of NAO+/WP+and NAO−/WP−.
基金supported by Natural Science Foundation of Beijing Municipality(No.7202200)Central Military Commission Health Care Project(No.20BJZ13)Air Force Equipment Scientific Research Project(No.KJ20201A050226).
文摘Objective The aim of this study was to examine the effects of photodynamic therapy(PDT)on the expression of Nav1.7 in spinal dorsal root ganglion(DRG)neurons.Methods The primary DRG neurons from newborn SD rats were cultured.The cells were identified by neuron-specific enolase immunofluorescence staining.DRG neurons were divided into four groups:control group,photosensitizer group,laser group,and PDT group.The cell viability was detected by a cell counting kit-8(CCK8)assay.qRT-PCR and Western blotting were used to determine the mRNA and protein expression levels of Nav1.7 in DRG neurons.Results The purity of the cultured primary DRG neurons was greater than 90%.Compared with the control group,no significant change was found in the cell viability of the photosensitizer group,while the viability in the laser group and the PDT group was significantly reduced.The mRNA and protein expression levels of Nav1.7 were significantly greater in the laser group and the PDT group than in the control group.At the same time,the mRNA and protein expression levels of Nav1.7 were greater in the laser group than in the PDT group.Conclusion Both laser and PDT could upregulate the expression of Nav1.7 in DRG neurons,and the promoting effect might be related to the pain induced by clinical treatment.This study provides a research basis for the use of laser and PDT to treat pain.A better understanding of the relationship between Nav1.7 and PDT can help clinicians better manage PDT-related pain.
基金support from the National Science Foundation of China(Grant Nos.62075078 and 62135004)the Knowledge Innovation Program of Wuhan-Shuguang Project(Grant No.2022010801020095).
文摘Metasurfaces,composed of planar arrays of intricately designed meta-atom structures,possess remarkable capabilities in controlling electromagnetic waves in various ways.A critical aspect of metasurface design involves selecting suitable meta-atoms to achieve target functionalities such as phase retardation,amplitude modulation,and polarization conversion.Conventional design processes often involve extensive parameter sweeping,a laborious and computationally intensive task heavily reliant on designer expertise and judgement.Here,we present an efficient genetic algorithm assisted meta-atom optimization method for high-performance metasurface optics,which is compatible to both single-and multiobjective device design tasks.We first employ the method for a single-objective design task and implement a high-efficiency Pancharatnam-Berry phase based metalens with an average focusing efficiency exceeding 80%in the visible spectrum.We then employ the method for a dual-objective metasurface design task and construct an efficient spin-multiplexed structural beam generator.The device is capable of generating zeroth-order and first-order Bessel beams respectively under right-handed and left-handed circular polarized illumination,with associated generation efficiencies surpassing 88%.Finally,we implement a wavelength and spin co-multiplexed four-channel metahologram capable of projecting two spin-multiplexed holographic images under each operational wavelength,with efficiencies over 50%.Our work offers a streamlined and easy-to-implement approach to meta-atom design and optimization,empowering designers to create diverse high-performance and multifunctional metasurface optics.
文摘Thermosensitive hydrogels were prepared by graft polymerization of chitosan and N-isopropylacrylamide via 60 Co ?-radiation. The effects of monomer concentration and total irradiation dose on percent grafting and grafting efficiency were studied. The thermosensitivity and swelling properties of the hydrogels were investigated.
基金supported by the National High Technology Research and Development Program of China(863Program)(2011AA0469)
文摘The problem of optimal aeroassisted symmetric transfer between elliptical orbits is concerned.The complete trajectory is assumed as consisting of two impulsive velocity changes at the beginning and the end of an interior atmospheric subarc,where the vehicle is controlled via the lift coefficient and thrust.The corresponding dynamic equations are built and bounded controls are considered.For the purpose of optimization computation,the equations are normalized.In order to minimize the total fuel consumption,the geocentric radius of initial elliptical transfer orbital perigee and controls during atmospheric flight should all be optimized.It is an optimal control problem which involves additional parameter optimization.To solve the problem,a two-level optimization method denoted by ＂genetic algorithm ＋ Gauss pseudospectral method＂ is adopted：the genetic algorithm is used for parameter optimization and the Gauss pseudospectral method is used for optimal control problems.The flow chart of simulation is given.On this basis,the issue of more realistic modeling with two finite-thrust subarcs in the nonatmospheric part of the trajectory is simultaneously addressed.The orbital transfer problem is transformed to three continuous optimal control problems,and the constraints at different times are given,which are respectively solved by using the Gauss pseudospectral method.The obtained numerical results indicate that the optimal thrust control is of bangbang type.The minimum-fuel trajectory in the atmosphere consists of aeroglide,aerocruise and aeroglide.They are compared with the results of pure impulsive model,and the conclusions that a significant fuel saving will be achieved by synergetic maneuver are drawn.
基金supported by the National Natural Science Foundation of China (61203041)the Chinese National Post-doctor Science Foundation (2011M500217)
文摘An adaptive repetitive control scheme is presented for a class of nonlinearly parameterized systems based on the fuzzy basis function network （FBFN）. The parameters of the fuzzy rules are tuned with adaptive schemes. To attenuate chattering effectively, the discontinuous control term is approximated by an adaptive PI control structure. The bound of the discontinuous control term is assumed to be unknown and estimated by an adaptive mechanism. Based on the Lyapunov stability theory, an adaptive repetitive control law is proposed to guarantee the closed-loop stability and the tracking performance. By means of FBFNs, which avoid the nonlinear parameterization from entering into the adaptive repetitive control, the controller singularity problem is solved. The proposed approach does not require an exact structure of the system dynamics, and the proposed controller is utilized to control a model of permanent-magnet linear synchronous motor subject to significant disturbances and parameter uncertainties. The simulation results demonstrate the effectiveness of the proposed method.
基金financed by Beijing Natural Science Foundation(6111002)the Ear-marked Fund for China Agriculture Research System
文摘Ascites syndrome is still a problem for chicken industry in various parts of the world. Despite the intensive investigations of this syndrome for many years, its pathogenesis remains unclear. The objective of this study was to analyze the difference in hepatic proteomics between ascites and healthy broilers by two-dimensional electrophoresis （2-DE） and matrix-assisted laser desorption/ionization-time of flight mass spectrometry （MALDI-TOF-MS）. Changes of biochemical parameters of liver and blood were also determined. The results indicated that red blood cell counts （RBC）, hematocrit （HCT） and haemoglobin （HGB） of ascites broilers were significantly greater than healthy broilers. Hepatic malondialdehyde （MDA） level of ascites broilers was significantly increased, and the activity of total superoxide dismutase （T-SOD） was significantly decreased. Hepatic lactic acid （LD） level of ascitic broilers were significantly lower than healthy ones, Serum glucose and cholesterol level of ascites broilers were significantly increased, and serum globulin level was significantly decreased in ascites broilers. There was no significant difference in triglyceride （TG） and blood urea nitrogen （BUN） level. The activity of liver hexokinase （HK） and succinodehydrogenase （SDH） in ascites broilers was significantly decreased, and there was no significant difference in the activity of liver pyruvate kinase （PK） and Na＋-K＋-ATPase. The hepatic proteomics analysis showed that 18 proteins expression difference were identified between ascites and healthy broilers. These proteins were mainly involved in： 1） cytoskeleton; 2） glucose, lipids and amino acid metabolism; 3） cell secretion; 4） cell apoptosis; 5） signal transduction; 6） immune and inflammatory response; and 7） cellular redox homeostasis. Mitochondrial isoform phosphoenolpyruvate carboxykinase （M-PEPCK） mainly participates in gluconeogenesis of chicken liver. In conclusion, liver oxidative damage was significantly aggravated, but antioxidant capacity was decreased in cold-induced ascites broilers. Serum glucose level was significantly increased, with liver M-PEPCK expression higher in ascites broilers, which implied that some potential regulatory reagents may reduce ascites susceptibility and mortality under cold temperature by increasing liver gluconeogenesis level.
文摘In the last five years,great progress has been made in cloud computing,es pecially in virtualization,standardization,and automation.This has result ed in numerous cloud services,such as Infrastructure as a Service,Plat form as a Service,and Software as a Service.Many cloud technologies have matured and have been commercialized.However,issues such as information security,mobility,energy efficiency,and infrastructure optimization are becoming more serious.The key causes of these issues are increased scale of data centers,convergence of IT and CT,increased user concern about information security,
基金Supported by the National Key Technologies Research&Development Program(2017YFC0804607)the National Key Basic Research Development Plan(973 Proect)(2014CB047000)
文摘By using the technique of the split Hopkinson pressure bar（ SHPB）,impact tests at different stress wavelengths（ 0. 8-2. 0 m） and strain rates（ 20-120 s^（-1）） were conducted to study the dynamic mechanical properties and damage accumulation evolution lawof granite. Test results showthat the dynamic compressive strength and strain rate of granite have a significantly exponential correlation;the relationship between peak strain and strain rate is approximately linear,and the increase of wavelengths generally makes the level of peak strain uplift. The multiple-impacts test at a lowstrain rate indicates that at the same wavelength,the cumulative damage of granite shows an exponential increasing form with the increase of strain rate; when keeping the increase of strain rate constant and increasing the stress wavelength,the damage accumulation effect of granite is intensified and still shows an exponential increasing form; under the effect of multiple impacts,the damage development trend of granite is similar overall,but the increase rate is accelerating. Therefore the damage evolution model was established on the basis of the exponential function while the physical meaning of parameters in the model was determined. The model can reflect the effect of the wave parameters and multiple impacts. The validity of the model and the physical meaning of the parameters were verified by the test,which further offer a reference for correlational research and engineering application for the granite.
基金supported by grants from the China National Natural Science Foundation(82130052 and 81925017 to Tao Li,82001690 to Hong Cai)。
文摘Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid(CSF)flow by beating their motile cilia coordinately.The ependymal denudation or ciliary dysfunction causes hydrocephalus.Here,we report that the deficiency of regulator of Gprotein signaling 22(RGS22)results in severe congenital hydrocephalus in both mice and rats.Interestingly,RGS22 is specifically expressed in ependymal cells within the brain.Using conditional knock-out mice,we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus.Mechanistically,we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis.This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor(LPAR)signaling under Rgs22^(-/-)condition,as the LPAR blockade effectively alleviates hydrocephalus in Rgs22^(-/-)rats.Therefore,our findings unveil a previously unrecognized role of RGS22 in the central nervous system,and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.
基金supported by grants from the Air Force Logistics Department(Grant No.BKJW221J009).
文摘Skin diseases are important factors affecting health and quality of life,especially in rural areas where medical resources are limited.Early and accurate diagnosis can reduce unnecessary health and economic losses.However,traditional visual diagnosis poses a high demand on both doctors’experience and the examination equipment,and there is a risk of missed diagnosis and misdiagnosis.Recently,advances in artificial intelligence technology,particularly deep learning,have resulted in the use of unimodal computer-aided diagnosis and treatment technologies based on skin images in dermatology.However,due to the small amount of information contained in unimodality,this technology cannot fully demonstrate the advantages of multimodal data in the real-world medical environment.Multimodal data fusion can fully integrate various types of data to help doctors make more accurate clinical decisions.This review aimed to provide a comprehensive overview of multimodal data and deep learning methods that could help dermatologists diagnose and treat skin diseases.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
