Traditional inverse neural network(INN)approaches for inverse design typically require auxiliary feedforward networks,leading to increased computational complexity and architectural dependencies.This study introduces ...Traditional inverse neural network(INN)approaches for inverse design typically require auxiliary feedforward networks,leading to increased computational complexity and architectural dependencies.This study introduces a standalone INN methodology that eliminates the need for feedforward networks while maintaining high reconstruction accuracy.The approach integrates Principal Component Analysis(PCA)and Partial Least Squares(PLS)for optimized feature space learning,enabling the standalone INN to effectively capture bidirectionalmappings between geometric parameters and mechanical properties.Validation using established numerical datasets demonstrates that the standalone INN architecture achieves reconstruction accuracy equal or better than traditional tandem approaches while completely eliminating the workload and training time required for Feedforward Neural Networks(FNN).These findings contribute to AI methodology development by proving that standalone invertible architectures can achieve comparable performance to complex hybrid systems with significantly improved computational efficiency.展开更多
Diisobutylaluminium hydride （DIBAL-H） promotes secondary rim regioselective bis-de-O-methylation of permethylated β- cyclodextrin （β-CD） to give diol 2. To gain an insight into the mechanism of this remarkable r...Diisobutylaluminium hydride （DIBAL-H） promotes secondary rim regioselective bis-de-O-methylation of permethylated β- cyclodextrin （β-CD） to give diol 2. To gain an insight into the mechanism of this remarkable regioselective behavior, two corresponding permethylated β-CDs with an alcohol function at either 2- or 3-position were synthesized in our previous study. As a step further to this work, the two compounds were subjected to deoxygenation reaction with tributyltin hydride in the present of 2,2＇- azobisisobutyronitrile affording the corresponding 2- and 3-deoxy permethylated β-CD derivatives （19 and 16）. The structures of these two compounds were characterized by 1D and 2D NMR and HRMS. Compounds 16 and 19 were unable to react with DIBAL- H which suggests that O-2A and O-3B are necessary for DIBAL-H promoted bis-de-O-methylation reaction of permethylated β-CD.展开更多
Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk t...Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk toxicity,treatment failure,and emergence of resistance,there is an urgent clinical need to perform therapeutic drug monitoring(TDM)to optimize the use of polymyxin B.It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use.We report a consensus on TDM guidelines for polymyxin B,as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society.The consensus panel was composed of clinicians,pharmacists,and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations,sample collection,reporting,and explanation of TDM results.The guidelines provide the first-ever consensus on conducting TDM of polymyxin B,and are intended to guide optimal clinical use.展开更多
B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 anti...B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody screening.Micro-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in vivo.Fu rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models.Micro-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid varied.The PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity.Interestingly,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor growth.Taken together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effective antitumor effects with an ideal safety profile.Therefore,we expect hu4G4 to be an excellent antibody for the development of GBM RIT.展开更多
A dual-amplification system is reported to apply in DNA sensing via the assembly of DNA and protein. In this process, the biotinylatedcapature DNA bounded with streptavidin（SA） through the biotinstreptavidin reactio...A dual-amplification system is reported to apply in DNA sensing via the assembly of DNA and protein. In this process, the biotinylatedcapature DNA bounded with streptavidin（SA） through the biotinstreptavidin reaction, and then the assembly of DNA and protein was triggered by the linker DNA after the target hybridized with biotinylatedcapature DNA. Sequentially, the 3,3＇,5,5＇-tetramethylbenzidine（TMB）was oxidized by H_2O_2 under the catalysis of horseradish peroxidase. Based on the variation of the color and the UV–vis absorbance intensities, qualitative and quantitative DNA analyses were realized. This proposed method could detect the target DNA as low as 1.75 pmol/L and discriminate perfectly matched target DNA from the mismatch DNA. What＇s more, it can be expanded to detect other molecules with a reasonable design of the corresponding DNA sequences.展开更多
Dear Editor,Through distributed machine learning,multi-UAV systems can achieve global optimization goals without a centralized server,such as optimal target tracking,by leveraging local calculation and communication w...Dear Editor,Through distributed machine learning,multi-UAV systems can achieve global optimization goals without a centralized server,such as optimal target tracking,by leveraging local calculation and communication with neighbors.In this work,we implement the stochastic gradient descent algorithm(SGD)distributedly to optimize tracking errors based on local state and aggregation of the neighbors'estimation.However,Byzantine agents can mislead neighbors,causing deviations from optimal tracking.We prove that the swarm achieves resilient convergence if aggregated results lie within the normal neighbors'convex hull,which can be guaranteed by the introduced centerpoint-based aggregation rule.In the given simulated scenarios,distributed learning using average,geometric median(GM),and coordinate-wise median(CM)based aggregation rules fail to track the target.Compared to solely using the centerpoint aggregation method,our approach,which combines a pre-filter with the centroid aggregation rule,significantly enhances resilience against Byzantine attacks,achieving faster convergence and smaller tracking errors.展开更多
The fundamental physics of anomalous and normal Doppler resonances between electrons and electromagnetic(EM)waves is analyzed using a quantum model that incorporates angular-momentum conservation.This work extends pri...The fundamental physics of anomalous and normal Doppler resonances between electrons and electromagnetic(EM)waves is analyzed using a quantum model that incorporates angular-momentum conservation.This work extends prior theory by explicitly linking the resonant integer m to the EM wave's angular-momentum quantum number.Numerical simulations based on the volume-preserving algorithm(VPA)further confirm this correspondence.Moreover,a direct comparison of the energy-transfer ratio from translational energy to gyrokinetic energy during resonance,between classical dynamics and quantum predictions,is presented and verified numerically.展开更多
Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically,especially among the young and people of reproductive age,which consequently leads to an increase in ...Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically,especially among the young and people of reproductive age,which consequently leads to an increase in antidepressant consumption.Antidepressants are associated with sexual dysfunction in both men and women;however,their role in male fertility has been scarcely studied.Fluoxetine and sertraline,two serotonin reuptake inhibitors(SSRIs),are among the most prescribed antidepressants worldwide.To determine their possible effects,human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment.Spermatozoa were incubated for up to 24 h at 37℃ and 5%CO_(2),and important functional parameters such as sperm motility,viability,mitochondrial membrane potential,cellular reactive oxygen species(ROS)production,chromatin/DNA integrity,acrosome status,and tyrosine phosphorylation were assessed.At low levels,fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation.Nevertheless,it did not affect viability,mitochondrial membrane potential,acrosome reaction nor chromatin/DNA integrity.Sertraline,on the other hand,had little to nonsignificant impact at low doses,but affected almost all tested parameters at supratherapeutic concentrations.Altogether,our results suggest that both antidepressants may impair sperm function,possibly through different mechanisms of action,but fluoxetine is the only exhibiting mild negative effects at doses found in vivo.展开更多
BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To stu...BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To study the effectiveness of in vitro chemosensitivity tests adenosine tripho-sphate-based tumour chemotherapy sensitivity test(ATP-TCA)for tailoring po-stoperative chemotherapy regimens for patients with CRC.METHODS Between January 2015 to December 2021,a total of 1549 CRC patients underwent surgery and in vitro chemosensitivity testing using ATP-TCA.A subset of 405 patients who met the survival assessment criteria were followed to collect data on overall survival(OS)and disease-free survival(DFS).Cox regression analysis revealed independent prognostic factors that affect OS and DFS for those re-ceiving oxaliplatin(L-OPH)and fluoropyrimidine-based regimens,aiding in the development of clinical predictive models.The relationships between the ATP-TCA results and clinical outcomes were analysed using the Kaplan-Meier method.RESULTS Tumour heterogeneity and resistance to multiple drugs were observed in 1549 patients.The sensitivity to 5-fluorouracil(5-FU)combined with L-OPH was tested among 1474 of these patients,yielding a sensitivity rate of 11.9%.ATP-TCA results were identified as an independent prognostic factor for DFS[P=0.002,hazard ratio(95%confidence interval):4.98(1.81-13.72)]in patients with resectable CRC.Compared with drug-resistant patients,sensitive CRC patients treated with 5-FU and L-OPH had significantly prolonged DFS(P=0.027).Further Kaplan-Meier analysis indicated that ATP-TCA sensitivity was significantly associated with improved OS(P=0.048)and DFS(P=0.003)in patients with stage III CRC.CONCLUSION The response of CRC patients to the combination regimen of 5-FU and L-OPH is heterogeneous.This study confirmed that the ATP-TCA is a valuable tool for predicting clinical outcomes,such as DFS,in patients with resectable CRC receiving chemotherapy.Although further validation with multicentre data is still necessary,these findings support that the ATP-TCA may function as a guiding tool for personalized chemotherapy administration,thereby optimizing treatment opportunities for patients.展开更多
In this investigation,we meticulously annotated a corpus of 21,174 auroral images captured by the THEMIS All-Sky Imager across diverse temporal instances.These images were categorized using an array of descriptors suc...In this investigation,we meticulously annotated a corpus of 21,174 auroral images captured by the THEMIS All-Sky Imager across diverse temporal instances.These images were categorized using an array of descriptors such as'arc','ab'(aurora but bright),'cloudy','diffuse','discrete',and'clear'.Subsequently,we utilized a state-of-the-art convolutional neural network,ConvNeXt(Convolutional Neural Network Next),deploying deep learning techniques to train the model on a dataset classified into six distinct categories.Remarkably,on the test set our methodology attained an accuracy of 99.4%,a performance metric closely mirroring human visual observation,thereby underscoring the classifier’s competence in paralleling human perceptual accuracy.Building upon this foundation,we embarked on the identification of large-scale auroral optical data,meticulously quantifying the monthly occurrence and Magnetic Local Time(MLT)variations of auroras from stations at different latitudes:RANK(high-latitude),FSMI(mid-latitude),and ATHA(low-latitude),under different solar wind conditions.This study paves the way for future explorations into the temporal variations of auroral phenomena in diverse geomagnetic contexts.展开更多
The way sporadic Parkinson's disease(PD)is perceived has undergone drastic changes in recent decades.For a long time,PD was considered a brain disease characterized by motor disturbances;however,the identification...The way sporadic Parkinson's disease(PD)is perceived has undergone drastic changes in recent decades.For a long time,PD was considered a brain disease characterized by motor disturbances;however,the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light.Today,after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution,there is a greater understanding of the involvement of other organ systems.For this reason,PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.展开更多
Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain....Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential.展开更多
In turbomachinery,strong secondary flow can produce significant losses of total pressure near the endwall and reduce the efficiency of the considered turbomachine.In this study,splitters located at different positions...In turbomachinery,strong secondary flow can produce significant losses of total pressure near the endwall and reduce the efficiency of the considered turbomachine.In this study,splitters located at different positions with respect to the main blade have been used to reduce such losses and improve the efficiency of the outlet guide vane(OGV).Three different relative positions have been considered assuming a NACA 65-010 profile for both the main blade and the splitter.The numerical results indicate that splitters can effectively reduce the total pressure loss by suppressing the secondary flow around the main blade,but the splitters themselves also produce flow losses,which are caused by flow separation effects.展开更多
SnO2 nanotube arrays have been synthesized by means of a simple and low-cost method. The ZnO nanorod arrays prepared by aqueous chemical growth method were used as templates. By liquid phase deposition, SnO2 nanotubes...SnO2 nanotube arrays have been synthesized by means of a simple and low-cost method. The ZnO nanorod arrays prepared by aqueous chemical growth method were used as templates. By liquid phase deposition, SnO2 nanotubes were obtained with proper deposition time. Scanning electron microscopy, transmission electron microscopy and X-ray diffraction were used to characterize the morphologies and structures of the products, and the formation mechanism was discussed according to the experimental results.展开更多
Brain plasticity is heterogeneous in mammals：Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and oth...Brain plasticity is heterogeneous in mammals：Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and other age-related problems affecting the central nervous system（CNS）do represent a heavy health and social burden.Efficacious re-generative processes are not＂ a natural property of the mammalian CNS, rather, due to evolutionary constraints they seem substantially reduced （if compared to those occurring in non-mammalian vertebrates） and hardly inducible by therapeutic approaches （reviewed in Martino et al., 2011）.展开更多
TiO2 -Au aerogels containing different amounts of gold nanoparticles of different sizes (5 and 16 nm) were successfully synthesized using a sol-gel procedure, and were tested for salicylic acid photodegradation under ...TiO2 -Au aerogels containing different amounts of gold nanoparticles of different sizes (5 and 16 nm) were successfully synthesized using a sol-gel procedure, and were tested for salicylic acid photodegradation under UV irradiation. The structure and morphology of the obtained materials were investigated using X-ray diffraction, transmission electron microscopy, and N2 adsorption-desorption measurements. UV-Vis spectroscopy was used to study the optical properties. The effects of the gold nanoparticles on the TiO2 crystallization process were twofold, as follows: (i) the number of crystallized zones was strongly related to the concentration of the gold nanoparticles, and (ii) the smaller gold particles increased the time taken for the crystallization of the samples. It was found that the noble metal-doped samples exhibited higher degradation rates compared with bare titania. It was found that the most active photocatalyst in each studied system was the sample with the highest concentration of gold nanoparticles. Additionally, the highest degradation rate value was obtained with the smallest Au nanoparticles (46.4 10-3 μmol/(L·s).展开更多
Due to their ecological disadvantages, many mountain regions have experienced land-use abandonment and shrub encroachment on former grassland at higher altitudinal zones--especially during recent decades of urbanizati...Due to their ecological disadvantages, many mountain regions have experienced land-use abandonment and shrub encroachment on former grassland at higher altitudinal zones--especially during recent decades of urbanization. But does this trend also apply to the hinterland of urban settlements？ By using the Southern Colombian example of Popay^n, a medium-sized city located in the Northern Andes, we can show that the landscape changes observed between 1989 and 2010 can hardly be related to agricultural abandonment. Hypsometric variations of land-cover change indicate that, until 2001, woods or shrubland expanded faster at the lower altitudinal range adjacent to the city than at the more remote higher zones. In contrast, after 2001 grassland areas increased on former woods or shrnbland at all altitudinal belts. Both periods thus present developments that can be interpreted as the result of land-use expansion below 2000 m asl and land-use persistence in the tierrafrla of the mountain city＇s hinterland.展开更多
Under the influence of concentrated and extended urbanization,Andean cities and the different altitudinal zones of their“hinterlands”are experiencing profound changes in land cover—from the central plazas up to the...Under the influence of concentrated and extended urbanization,Andean cities and the different altitudinal zones of their“hinterlands”are experiencing profound changes in land cover—from the central plazas up to the highest peaks.The complex regional-geographic characteristics of these socioecological systems,such as the vertical complementarity of land use,require a montological perspective on verticality and urbanization:it transcends disciplinary approaches and can be crucial to properly interpret the trajectories of land cover change and formulate hypotheses for future practiceoriented research.Which trajectories of land cover change characterized altitudinal zones of Andean cities and their surroundings over the last three decades?Are there similarities that allow for the formulation of more general hypotheses?Using the Peruvian cases of Cusco and Huaraz,and combining a traditional altitudinal zonation model of land use in Peru with direct field observations and GIS-based analyses of remotely sensed data from 1991,2001,2011,and 2021,this study identifies the main trajectories of land cover change in the Quechua(>2300–3500 m),Suni(>3500–4000 m),and Puna(>4000–4800 m)regions—and finds insightful similarities between Cusco and Huaraz:(1)an impressive area of built-up land substitutes grassland in the Quechua,which,following regional altitudinal zonation models,is characterized by irrigated and rain-fed cropland;(2)an unexpected expansion of irrigated cropland takes place in the Suni,which,in theory,often lacks irrigation infrastructure and is mostly used for rain-fed tuber cultivation;and(3)a clear change from“other land”to grassland occurs in the Puna—where grassland is thought to predominate,anyway,since pre-Hispanic times.Hypothesizing that these changes reflect the interplay between speculative fallow,agricultural intensification,and ecological restoration,the results can be read as vertically complementary,local manifestations of concentrated and extended urbanization in a formerly peripheral mountain region of the Global South—and they underscore the need to overcome mental city-mountain dichotomies for a socially inclusive and ecologically balanced Andean development between plaza and peak.展开更多
The influence of the width of the circular ring of a car cooling fan on the aerodynamic noise is investigated numerically through the determination of the overall sound pressure level(OASPL).The results demonstrate th...The influence of the width of the circular ring of a car cooling fan on the aerodynamic noise is investigated numerically through the determination of the overall sound pressure level(OASPL).The results demonstrate that when the circular rings cover near 2/3 of the width of the blade tips of the rotor in the axis direction,the rotor has the lowest OASPL and the related total pressure efficiency and flow mass rate are better than the corresponding values obtained for a reference rotor without a circular ring.With increasing the width of the circular ring in the axis direction,the tip vortex around the trailing edge of the blade tip becomes smaller and finally disappears.Meanwhile,a separated flow field arises gradually and then grows in size around the middle of the junction of the blade tips with the ring.When the circular rings cover nearly 2/3 s of the width of the blade tips of the fan in the axis direction,the extension of the separated flow around the blade’s tip attains a minimum.展开更多
Discerning electromagnetically induced transparency(EIT) from Autler–Townes splitting(ATS) is a significant issue in quantum optics and has attracted wide attention in various three-level configurations. Here we pres...Discerning electromagnetically induced transparency(EIT) from Autler–Townes splitting(ATS) is a significant issue in quantum optics and has attracted wide attention in various three-level configurations. Here we present a detailed study of EIT and ATS in a five-level atomic system considered to be composed of a four-level Y-type subsystem and a three-level Λ-type subsystem. In our theoretical calculations with standard density matrix formalism and steadystate approximation, we obtain the general analytical expression of the first-order matrix element responsible for the probe-field absorption. In light of the well-known three-level EIT and ATS criteria, we numerically show an intersection of EIT with ATS for the Y-type subsystem. Furthermore, we show that an EIT dip is sandwiched between two ATS dips(i.e., multi-dip mixture of EIT and ATS) in the absorption line for the five-level system, which can be explained by the dressed-state theory and Fano interference.展开更多
基金funding by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy within the Cluster of Excellence PhoenixD(EXC 2122,Project ID 390833453).
文摘Traditional inverse neural network(INN)approaches for inverse design typically require auxiliary feedforward networks,leading to increased computational complexity and architectural dependencies.This study introduces a standalone INN methodology that eliminates the need for feedforward networks while maintaining high reconstruction accuracy.The approach integrates Principal Component Analysis(PCA)and Partial Least Squares(PLS)for optimized feature space learning,enabling the standalone INN to effectively capture bidirectionalmappings between geometric parameters and mechanical properties.Validation using established numerical datasets demonstrates that the standalone INN architecture achieves reconstruction accuracy equal or better than traditional tandem approaches while completely eliminating the workload and training time required for Feedforward Neural Networks(FNN).These findings contribute to AI methodology development by proving that standalone invertible architectures can achieve comparable performance to complex hybrid systems with significantly improved computational efficiency.
基金Financial support of this study from CNRS is gratefully acknowledged
文摘Diisobutylaluminium hydride （DIBAL-H） promotes secondary rim regioselective bis-de-O-methylation of permethylated β- cyclodextrin （β-CD） to give diol 2. To gain an insight into the mechanism of this remarkable regioselective behavior, two corresponding permethylated β-CDs with an alcohol function at either 2- or 3-position were synthesized in our previous study. As a step further to this work, the two compounds were subjected to deoxygenation reaction with tributyltin hydride in the present of 2,2＇- azobisisobutyronitrile affording the corresponding 2- and 3-deoxy permethylated β-CD derivatives （19 and 16）. The structures of these two compounds were characterized by 1D and 2D NMR and HRMS. Compounds 16 and 19 were unable to react with DIBAL- H which suggests that O-2A and O-3B are necessary for DIBAL-H promoted bis-de-O-methylation reaction of permethylated β-CD.
基金the Shanghai Leading Talents Award,Shanghai Municipal Health Commission(No.LJ2016-01)the Clinical Research Plan of Shanghai Hospital Development Center(No.SHDC2022CRW004)。
文摘Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk toxicity,treatment failure,and emergence of resistance,there is an urgent clinical need to perform therapeutic drug monitoring(TDM)to optimize the use of polymyxin B.It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use.We report a consensus on TDM guidelines for polymyxin B,as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society.The consensus panel was composed of clinicians,pharmacists,and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations,sample collection,reporting,and explanation of TDM results.The guidelines provide the first-ever consensus on conducting TDM of polymyxin B,and are intended to guide optimal clinical use.
基金funded by the National Natural Science Foundation of China(31320103918 and 82104318)Key Research and Development Program of Jiangsu Province(BE2021644)+4 种基金the Jiangsu Innovative and Entrepreneurial Talent Programme(JSSCBS20211568)the Science and Technology Plan of Suzhou(SKJYD2021161 and SKY2022046)Key Project of Jiangsu Provincial Health Commission(zd2021050)the Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University(GZK1202203)support of Jiangsu Institute of Nuclear Medicine for the ^(89)Zr-PET imaging in this study。
文摘B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody screening.Micro-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in vivo.Fu rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models.Micro-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid varied.The PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity.Interestingly,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor growth.Taken together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effective antitumor effects with an ideal safety profile.Therefore,we expect hu4G4 to be an excellent antibody for the development of GBM RIT.
基金supported by the National Science Foundation of China (No. 21205089)
文摘A dual-amplification system is reported to apply in DNA sensing via the assembly of DNA and protein. In this process, the biotinylatedcapature DNA bounded with streptavidin（SA） through the biotinstreptavidin reaction, and then the assembly of DNA and protein was triggered by the linker DNA after the target hybridized with biotinylatedcapature DNA. Sequentially, the 3,3＇,5,5＇-tetramethylbenzidine（TMB）was oxidized by H_2O_2 under the catalysis of horseradish peroxidase. Based on the variation of the color and the UV–vis absorbance intensities, qualitative and quantitative DNA analyses were realized. This proposed method could detect the target DNA as low as 1.75 pmol/L and discriminate perfectly matched target DNA from the mismatch DNA. What＇s more, it can be expanded to detect other molecules with a reasonable design of the corresponding DNA sequences.
基金supported By Guangdong Major Project of Basic and Applied Basic Research(2023B0303000009)Guangdong Basic and Applied Basic Research Foundation(2024A1515030153,2025A1515011587)+1 种基金Project of Department of Education of Guangdong Province(2023ZDZX4046)Shen-zhen Natural Science Fund(Stable Support Plan Program 20231122121608001),Ningbo Municipal Science and Technology Bureau(ZX2024000604).
文摘Dear Editor,Through distributed machine learning,multi-UAV systems can achieve global optimization goals without a centralized server,such as optimal target tracking,by leveraging local calculation and communication with neighbors.In this work,we implement the stochastic gradient descent algorithm(SGD)distributedly to optimize tracking errors based on local state and aggregation of the neighbors'estimation.However,Byzantine agents can mislead neighbors,causing deviations from optimal tracking.We prove that the swarm achieves resilient convergence if aggregated results lie within the normal neighbors'convex hull,which can be guaranteed by the introduced centerpoint-based aggregation rule.In the given simulated scenarios,distributed learning using average,geometric median(GM),and coordinate-wise median(CM)based aggregation rules fail to track the target.Compared to solely using the centerpoint aggregation method,our approach,which combines a pre-filter with the centroid aggregation rule,significantly enhances resilience against Byzantine attacks,achieving faster convergence and smaller tracking errors.
基金supported by the National Magnetic Confinement Fusion Energy Program of China(Grant No.2019YFE03020001)。
文摘The fundamental physics of anomalous and normal Doppler resonances between electrons and electromagnetic(EM)waves is analyzed using a quantum model that incorporates angular-momentum conservation.This work extends prior theory by explicitly linking the resonant integer m to the EM wave's angular-momentum quantum number.Numerical simulations based on the volume-preserving algorithm(VPA)further confirm this correspondence.Moreover,a direct comparison of the energy-transfer ratio from translational energy to gyrokinetic energy during resonance,between classical dynamics and quantum predictions,is presented and verified numerically.
文摘Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically,especially among the young and people of reproductive age,which consequently leads to an increase in antidepressant consumption.Antidepressants are associated with sexual dysfunction in both men and women;however,their role in male fertility has been scarcely studied.Fluoxetine and sertraline,two serotonin reuptake inhibitors(SSRIs),are among the most prescribed antidepressants worldwide.To determine their possible effects,human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment.Spermatozoa were incubated for up to 24 h at 37℃ and 5%CO_(2),and important functional parameters such as sperm motility,viability,mitochondrial membrane potential,cellular reactive oxygen species(ROS)production,chromatin/DNA integrity,acrosome status,and tyrosine phosphorylation were assessed.At low levels,fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation.Nevertheless,it did not affect viability,mitochondrial membrane potential,acrosome reaction nor chromatin/DNA integrity.Sertraline,on the other hand,had little to nonsignificant impact at low doses,but affected almost all tested parameters at supratherapeutic concentrations.Altogether,our results suggest that both antidepressants may impair sperm function,possibly through different mechanisms of action,but fluoxetine is the only exhibiting mild negative effects at doses found in vivo.
基金Supported by the National Natural Science Foundation of China,No.U24A20765 and No.T2321005Jiangsu Provincial Science and Technology Plan Special Fund,No.BM2023003+5 种基金Jiangsu Provincial Medical Key Discipline,No.ZDXK202247the Priority Academic Program Development of the Jiangsu Higher Education InstitutesJiangsu Engineering Research Center on Drug Evaluation and Translation of Organoids/Organ Chip(2024)the Science and Technology Plan of Suzhou,No.SKYD2023183the Research Project Established by Chinese Pharmaceutical Association Hospital Pharmacy Department,No.CPA-Z05-ZC-2023002Gusu Health Talent Research Project,No.GSWS2022015.
文摘BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To study the effectiveness of in vitro chemosensitivity tests adenosine tripho-sphate-based tumour chemotherapy sensitivity test(ATP-TCA)for tailoring po-stoperative chemotherapy regimens for patients with CRC.METHODS Between January 2015 to December 2021,a total of 1549 CRC patients underwent surgery and in vitro chemosensitivity testing using ATP-TCA.A subset of 405 patients who met the survival assessment criteria were followed to collect data on overall survival(OS)and disease-free survival(DFS).Cox regression analysis revealed independent prognostic factors that affect OS and DFS for those re-ceiving oxaliplatin(L-OPH)and fluoropyrimidine-based regimens,aiding in the development of clinical predictive models.The relationships between the ATP-TCA results and clinical outcomes were analysed using the Kaplan-Meier method.RESULTS Tumour heterogeneity and resistance to multiple drugs were observed in 1549 patients.The sensitivity to 5-fluorouracil(5-FU)combined with L-OPH was tested among 1474 of these patients,yielding a sensitivity rate of 11.9%.ATP-TCA results were identified as an independent prognostic factor for DFS[P=0.002,hazard ratio(95%confidence interval):4.98(1.81-13.72)]in patients with resectable CRC.Compared with drug-resistant patients,sensitive CRC patients treated with 5-FU and L-OPH had significantly prolonged DFS(P=0.027).Further Kaplan-Meier analysis indicated that ATP-TCA sensitivity was significantly associated with improved OS(P=0.048)and DFS(P=0.003)in patients with stage III CRC.CONCLUSION The response of CRC patients to the combination regimen of 5-FU and L-OPH is heterogeneous.This study confirmed that the ATP-TCA is a valuable tool for predicting clinical outcomes,such as DFS,in patients with resectable CRC receiving chemotherapy.Although further validation with multicentre data is still necessary,these findings support that the ATP-TCA may function as a guiding tool for personalized chemotherapy administration,thereby optimizing treatment opportunities for patients.
基金supported by the General Program of the National Natural Science Foundation of China(Grant No.42374212)the National Magnetic Confinement Fusion Energy Research and Development Program of China(Grant No.2024YFE03020004).
文摘In this investigation,we meticulously annotated a corpus of 21,174 auroral images captured by the THEMIS All-Sky Imager across diverse temporal instances.These images were categorized using an array of descriptors such as'arc','ab'(aurora but bright),'cloudy','diffuse','discrete',and'clear'.Subsequently,we utilized a state-of-the-art convolutional neural network,ConvNeXt(Convolutional Neural Network Next),deploying deep learning techniques to train the model on a dataset classified into six distinct categories.Remarkably,on the test set our methodology attained an accuracy of 99.4%,a performance metric closely mirroring human visual observation,thereby underscoring the classifier’s competence in paralleling human perceptual accuracy.Building upon this foundation,we embarked on the identification of large-scale auroral optical data,meticulously quantifying the monthly occurrence and Magnetic Local Time(MLT)variations of auroras from stations at different latitudes:RANK(high-latitude),FSMI(mid-latitude),and ATHA(low-latitude),under different solar wind conditions.This study paves the way for future explorations into the temporal variations of auroral phenomena in diverse geomagnetic contexts.
基金supported by Santa Casa da Misericórdia de Lisboa,Portugal,through the Mantero Belard Neurosciences Prize 2016(MB-40-2016)the FMUC-PEPITA(2018)the European Regional Development Fund(ERDF),through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization and Portuguese National Funds via Fundação para a Ciência e a Tecnologia projects UIDB/04539/2020,LA/P/0058/2020,POCI-01-0145-FEDER-030712,and PTDC/MED-NEU/3644/2020.
文摘The way sporadic Parkinson's disease(PD)is perceived has undergone drastic changes in recent decades.For a long time,PD was considered a brain disease characterized by motor disturbances;however,the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light.Today,after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution,there is a greater understanding of the involvement of other organ systems.For this reason,PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.
基金Supported by FEDER(Programa Operacional Factores de Competitividade-COMPETE)Portuguese funds via Portuguese Science Foundation(FCT)(Projects:PTDC/SAUNMC/110990/2009,PTDC/SAU-TOX/117481/2010 and Pest/SAU/LA0001/2011fellowships:SFRH/BD/90036/2012,PTDC/SAU-TOX/117481/2010,SFRH/BPD/95770/2013,SFRH/BPD/84163/2012,QREN Do IT,"DIAMARKER PROJECT",n.o 13853,SFRH/BD/73388/2010,SFRH/BPD/84473/2012)
文摘Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential.
基金the Natural Science Foundation from Hubei Province of China[Grant No.2019CFC866]the Guiding Project of Scientific Research Plan of Hubei Education Department of China[Grant No.B2020227]+2 种基金the Collaborative Innovation Team of Discipline Characteristics of Jianghan University[Grant No.03100061]the Research Start-up Funds of Jianghan University[Grant No.101906320001]and the Research Start-up Funds of Jianghan University[101906270002].
文摘In turbomachinery,strong secondary flow can produce significant losses of total pressure near the endwall and reduce the efficiency of the considered turbomachine.In this study,splitters located at different positions with respect to the main blade have been used to reduce such losses and improve the efficiency of the outlet guide vane(OGV).Three different relative positions have been considered assuming a NACA 65-010 profile for both the main blade and the splitter.The numerical results indicate that splitters can effectively reduce the total pressure loss by suppressing the secondary flow around the main blade,but the splitters themselves also produce flow losses,which are caused by flow separation effects.
基金supported by the Scientific Research Foundation of Jianghan University(No.2009008)the Science&Technology Program of Wuhan City(No.201150699189-19)+2 种基金the Youth Science Foundation of Wuhan Institute of Technology(No.Q201006)the Scientific Research Foundation of Wuhan Institute of Technology(No.11105021)the National Natural Science Foundation of China(No.61240056)
文摘SnO2 nanotube arrays have been synthesized by means of a simple and low-cost method. The ZnO nanorod arrays prepared by aqueous chemical growth method were used as templates. By liquid phase deposition, SnO2 nanotubes were obtained with proper deposition time. Scanning electron microscopy, transmission electron microscopy and X-ray diffraction were used to characterize the morphologies and structures of the products, and the formation mechanism was discussed according to the experimental results.
基金supported by MIUR-PRIN2015(grant 2015Y5W9YP)University of Turin(Ricerca locale 2016)
文摘Brain plasticity is heterogeneous in mammals：Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and other age-related problems affecting the central nervous system（CNS）do represent a heavy health and social burden.Efficacious re-generative processes are not＂ a natural property of the mammalian CNS, rather, due to evolutionary constraints they seem substantially reduced （if compared to those occurring in non-mammalian vertebrates） and hardly inducible by therapeutic approaches （reviewed in Martino et al., 2011）.
文摘TiO2 -Au aerogels containing different amounts of gold nanoparticles of different sizes (5 and 16 nm) were successfully synthesized using a sol-gel procedure, and were tested for salicylic acid photodegradation under UV irradiation. The structure and morphology of the obtained materials were investigated using X-ray diffraction, transmission electron microscopy, and N2 adsorption-desorption measurements. UV-Vis spectroscopy was used to study the optical properties. The effects of the gold nanoparticles on the TiO2 crystallization process were twofold, as follows: (i) the number of crystallized zones was strongly related to the concentration of the gold nanoparticles, and (ii) the smaller gold particles increased the time taken for the crystallization of the samples. It was found that the noble metal-doped samples exhibited higher degradation rates compared with bare titania. It was found that the most active photocatalyst in each studied system was the sample with the highest concentration of gold nanoparticles. Additionally, the highest degradation rate value was obtained with the smallest Au nanoparticles (46.4 10-3 μmol/(L·s).
基金funded by the Austrian Science Fund (FWF) [Project No. P24692]
文摘Due to their ecological disadvantages, many mountain regions have experienced land-use abandonment and shrub encroachment on former grassland at higher altitudinal zones--especially during recent decades of urbanization. But does this trend also apply to the hinterland of urban settlements？ By using the Southern Colombian example of Popay^n, a medium-sized city located in the Northern Andes, we can show that the landscape changes observed between 1989 and 2010 can hardly be related to agricultural abandonment. Hypsometric variations of land-cover change indicate that, until 2001, woods or shrubland expanded faster at the lower altitudinal range adjacent to the city than at the more remote higher zones. In contrast, after 2001 grassland areas increased on former woods or shrnbland at all altitudinal belts. Both periods thus present developments that can be interpreted as the result of land-use expansion below 2000 m asl and land-use persistence in the tierrafrla of the mountain city＇s hinterland.
基金funded in whole,or in part,by the Austrian Science Fund(FWF)(P 31855-G)。
文摘Under the influence of concentrated and extended urbanization,Andean cities and the different altitudinal zones of their“hinterlands”are experiencing profound changes in land cover—from the central plazas up to the highest peaks.The complex regional-geographic characteristics of these socioecological systems,such as the vertical complementarity of land use,require a montological perspective on verticality and urbanization:it transcends disciplinary approaches and can be crucial to properly interpret the trajectories of land cover change and formulate hypotheses for future practiceoriented research.Which trajectories of land cover change characterized altitudinal zones of Andean cities and their surroundings over the last three decades?Are there similarities that allow for the formulation of more general hypotheses?Using the Peruvian cases of Cusco and Huaraz,and combining a traditional altitudinal zonation model of land use in Peru with direct field observations and GIS-based analyses of remotely sensed data from 1991,2001,2011,and 2021,this study identifies the main trajectories of land cover change in the Quechua(>2300–3500 m),Suni(>3500–4000 m),and Puna(>4000–4800 m)regions—and finds insightful similarities between Cusco and Huaraz:(1)an impressive area of built-up land substitutes grassland in the Quechua,which,following regional altitudinal zonation models,is characterized by irrigated and rain-fed cropland;(2)an unexpected expansion of irrigated cropland takes place in the Suni,which,in theory,often lacks irrigation infrastructure and is mostly used for rain-fed tuber cultivation;and(3)a clear change from“other land”to grassland occurs in the Puna—where grassland is thought to predominate,anyway,since pre-Hispanic times.Hypothesizing that these changes reflect the interplay between speculative fallow,agricultural intensification,and ecological restoration,the results can be read as vertically complementary,local manifestations of concentrated and extended urbanization in a formerly peripheral mountain region of the Global South—and they underscore the need to overcome mental city-mountain dichotomies for a socially inclusive and ecologically balanced Andean development between plaza and peak.
基金supported by the Guiding Project of Scientific Research Plan of Hubei Education Department of China[Grant No.B2020227].
文摘The influence of the width of the circular ring of a car cooling fan on the aerodynamic noise is investigated numerically through the determination of the overall sound pressure level(OASPL).The results demonstrate that when the circular rings cover near 2/3 of the width of the blade tips of the rotor in the axis direction,the rotor has the lowest OASPL and the related total pressure efficiency and flow mass rate are better than the corresponding values obtained for a reference rotor without a circular ring.With increasing the width of the circular ring in the axis direction,the tip vortex around the trailing edge of the blade tip becomes smaller and finally disappears.Meanwhile,a separated flow field arises gradually and then grows in size around the middle of the junction of the blade tips with the ring.When the circular rings cover nearly 2/3 s of the width of the blade tips of the fan in the axis direction,the extension of the separated flow around the blade’s tip attains a minimum.
基金Supported by the National Natural Science Foundation of China under Grant Nos.11274132,11547208the Science Foundation of China Three Gorges University
文摘Discerning electromagnetically induced transparency(EIT) from Autler–Townes splitting(ATS) is a significant issue in quantum optics and has attracted wide attention in various three-level configurations. Here we present a detailed study of EIT and ATS in a five-level atomic system considered to be composed of a four-level Y-type subsystem and a three-level Λ-type subsystem. In our theoretical calculations with standard density matrix formalism and steadystate approximation, we obtain the general analytical expression of the first-order matrix element responsible for the probe-field absorption. In light of the well-known three-level EIT and ATS criteria, we numerically show an intersection of EIT with ATS for the Y-type subsystem. Furthermore, we show that an EIT dip is sandwiched between two ATS dips(i.e., multi-dip mixture of EIT and ATS) in the absorption line for the five-level system, which can be explained by the dressed-state theory and Fano interference.
