With the large-scale development and utilization of renewable energy,industrial flexible loads,as a kind of loadside resource with strong regulation ability,provide new opportunities for the research on renewable ener...With the large-scale development and utilization of renewable energy,industrial flexible loads,as a kind of loadside resource with strong regulation ability,provide new opportunities for the research on renewable energy consumption problem in power systems.This paper proposes a two-layer active power optimization model based on industrial flexible loads for power grid partitioning,aiming at improving the line over-limit problem caused by renewable energy consumption in power grids with high proportion of renewable energy,and achieving the safe,stable and economical operation of power grids.Firstly,according to the evaluation index of renewable energy consumption characteristics of line active power,the power grid is divided into several partitions,and the interzone tie lines are taken as the optimization objects.Then,on the basis of partitioning,a two-layer active power optimization model considering the power constraints of industrial flexible loads is established.The upper-layer model optimizes the planned power of the inter-zone tie lines under the constraint of the minimum peak-valley difference within a day;the lower-layer model optimizes the regional source-load dispatching plan of each resource in each partition under the constraint of theminimumoperation cost of the partition,so as to reduce the line overlimit phenomenon caused by renewable energy consumption and save the electricity cost of industrial flexible loads.Finally,through simulation experiments,it is verified that the proposed model can effectively mobilize industrial flexible loads to participate in power grid operation and improve the economic stability of power grid.展开更多
Objective: The “six-step teaching method” is a teaching method, which is summarized based on practical experience. This study aimed to explore the effect of “six-step teaching method” in clinical teaching of ...Objective: The “six-step teaching method” is a teaching method, which is summarized based on practical experience. This study aimed to explore the effect of “six-step teaching method” in clinical teaching of obstetrics. Methods: A quasi-experimental study design was used, 30 nursing students who entered obstetrics practice from March 2022 to July 2022 were selected as the control group according to the order of time, and traditional teaching methods were adopted. From August to December 2022, 30 interns were selected as the experimental group, and the “six-step teaching method” was adopted. After 8 weeks of clinical practice, the assessment results and teaching effect satisfaction of the two groups were compared. Results: The scores of obstetrical specialty in the experimental group were higher than those in the control group, and the difference was statistically significant (P < 0.05);The evaluation of teaching methods, teaching quality, classroom atmosphere and individual observation ability, clinical thinking ability and nurse-patient communication ability of the experimental group were higher than those of the control group, and the differences were statistically significant (P Conclusion: “six-step teaching method” can effectively master the professional knowledge of obstetrics, stimulate the clinical thinking ability of interns, and improve the teaching effect and satisfaction. .展开更多
The Yadu-Ziyun-Luodian aulacogen(YZLA) developed into being NW-trending in the Late Paleozoic,and was considered as an important passive continental margin aulacogen in Guizhou Province, South China. This tectonic zon...The Yadu-Ziyun-Luodian aulacogen(YZLA) developed into being NW-trending in the Late Paleozoic,and was considered as an important passive continental margin aulacogen in Guizhou Province, South China. This tectonic zone is considered a large intracontinental thrust-slip tectonic unit, which has undergone a long period of development. It was ultimately determined in the Yanshanian, where the typical Upper Paleozoic marine shales were deposited. In 2021, Well QSD-1 was deployed in the Liupanshui area at the northwest margin of the aulacogen, and obtained a daily shale gas flow of 11011 m3in the Carboniferous Dawuba Formation. It thus achieved a breakthrough in the invesgation of shale gas in the Lower Carboniferous in South China, revealing relatively good gas-bearing properties and broad exploration prospects of the aulacogen. Being different from the Lower Paleozoic strata in the Sichuan Basin and the Yichang area of the Middle Yangtze, the development of the Carboniferous Dawuba Formation in the aulacogen exhibits the following characteristics:(1) The Lower Carboniferous shale is thick and widely distributed, with interbedded shale and marlstone of virous thickness;(2) The total organic carbon(TOC) content of the shale in the Dawuba Formation ranges from 1% to 5%, with an average of 2%, and the thermal maturity of organic matter(Ro) varies from 1% to 4%, with an average of2.5%, indicating good hydrocarbon generation capacity;(3) The main shale in the aulacogen was formed during the fault subsidence stage from the Middle Devonian to the Early Permian. Although the strong compression and deformation during the late Indosinian-Himalayan played a certain role in destroying the formed shale gas reservoirs, comparative analysis suggests that the area covered by the current Triassic strata has a low degree of destruction. It therefore provides good conditions for shale gas preservation,which can be regarded as a favorable area for the next exploration.展开更多
Thermal metamaterials offer a promising avenue for creating artificial materials with unconventional physical properties,such as thermal cloak,concentrator,rotator,and illusion.However,designs and fabrication of therm...Thermal metamaterials offer a promising avenue for creating artificial materials with unconventional physical properties,such as thermal cloak,concentrator,rotator,and illusion.However,designs and fabrication of thermal metamaterials are of challenge due to the limitations of existing methods on anisotropic material properties.We propose an evolutionary framework for designing thermal metamaterials using genetic algorithm optimization.Our approach encodes unit cells with different thermal conductivities and performs global optimization using the evolution-inspired operators.We further fabricate the thermal functional cells using 3D printing and verify their thermal illusion functionality experimentally.Our study introduces a new design paradigm for advanced thermal metamaterials that can manipulate heat flows robustly and realize functional thermal metadevices without anisotropic thermal conductivity.Our approach can be easily applied to fabrications in various fields such as thermal management and thermal sensing.展开更多
Black spot disease in poplar is a disease of the leaf caused by fungus. The major pathogen is Marssonina brunnea f. sp. multigermtubi. To date, little is known about the molecular mechanism of poplar (M. brunnea) in...Black spot disease in poplar is a disease of the leaf caused by fungus. The major pathogen is Marssonina brunnea f. sp. multigermtubi. To date, little is known about the molecular mechanism of poplar (M. brunnea) interaction. In order to identify the proteins related to disease resistance and understand its molecular basis, the clone "NL895" (P. euramericana CL"NL895"), which is highly resistant to M. brunnea f. sp. multigermtubi, was used in this study. We used two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) to identify the proteins in poplar leaves that were differentially expressed in response to black spot disease pathogen, M. brunnea f. sp. multigermtubi. Proteins extracted from poplar leaves at 0, 12, 24, 48, and 72 h after pathogen-inoculation were separated by 2-DE, About 500 reproducible protein spots were detected, of which 40 protein spots displayed differential expression in levels and were subjected to Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) followed by database searching. According to the function, the identified proteins were sorted into five categories, that is, protein synthesis, metabolism, defense response and unclassified proteins.展开更多
Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve t...Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.展开更多
The water gas shift reaction is of vital significance for the generation and transition of energy due to the application in hydrogen production and industries such as ammonia synthesis and fuel cells.The influence of ...The water gas shift reaction is of vital significance for the generation and transition of energy due to the application in hydrogen production and industries such as ammonia synthesis and fuel cells.The influence of support doping and bimetallic alloying on the catalytic performance of Pt/Ce O_(2)-based nanocatalysts in water gas shift reaction was reported in this work.Various lanthanide ions and 3d transition metals were respectively introduced into the Ce O_(2)support or Pt to form Pt/Ce O_(2):Ln(Ln=La,Nd,Gd,Tb,Yb)and Pt M/Ce O_(2)(M=Fe,Co,Ni)nanocatalysts.The sample of Pt/Ce O_(2):Tb showed the highest activity(TOF at 200℃=0.051 s^(-1))among the Pt/Ce O_(2):Ln and the undoped Pt/Ce O_(2)catalysts.Besides,the sample of Pt Fe/Ce O_(2)exhibited the highest activity(TOF at 200℃=0.12 s^(-1))among Pt M/Ce O_(2)catalysts.The results of the multiple characterizations indicated that the catalytic activity of Pt/Ce O_(2):Ln catalysts was closely correlated with the amount of oxygen vacancies in doped ceria support.However,the different activity of Pt M/Ce O_(2)bimetallic catalysts was owing to the various Pt oxidation states of the bimetals dispersed on ceria.The study of the reaction pathway indicated that both the samples of Pt/Ce O_(2)and Pt/Ce O_(2):Tb catalyzed the reaction through the formate pathway,and the enhanced activity of the latter derived from the increased concentration of oxygen vacancies along with promoted water dissociation.As for the sample of Pt Fe/Ce O_(2),its catalytic mechanism was the carboxyl route with a higher reaction rate due to the moderate valence of Pt along with improved CO activation.展开更多
The mevalonate diphosphate deearboxylase (MVD) is an essential enzyme in mevalonate (MVA) pathway that catalyzes the irreversible Mg2+ -ATP de- pendent decarboxylation of 6-carben compound mevalonate-5-diphospha...The mevalonate diphosphate deearboxylase (MVD) is an essential enzyme in mevalonate (MVA) pathway that catalyzes the irreversible Mg2+ -ATP de- pendent decarboxylation of 6-carben compound mevalonate-5-diphosphate (MVAPP) into 5-carbon isopentenyl diphosphate ( IPP), the building block of sterol and isoprenoid biosynthesis. In this study, based on the published geanme sequences and ESTs, a genome-wide search was carried out for the first time to identify MVD gene family in four genome-sequenced Euphorbiaceae plants, i.e. castor bean ( Ricinus communis), physic nut ( Jatropha curcas), cassava (Manihot esculenta) and rubber tree (Hevea brasiliensis), and to analyze the gene structure and phylogenetic characteristics. According to the experimental results, 1, 1,2 and 2 MVD genes, which all contain 9 introns, were identh'ied from castor bean, physic nut, cassava and rubber tree, respectively. Homology analysis indicates that MVD genes are widely distributed in eukaryotes, some archaea and eubacteria, which suggests an early origin of this gerte family. Although MVD genes were identified in most green plants, no homologous genes were found in unicellular green algae. In most genome-sequenced plants including castor bean and physic nut, a single copy of MVD gene was found; however, in cassava and rubber tree, two copies were identified just like that in moss, maize, Arabidopsis and poplar. "In castor bean, digital expression profiling suggests that in five examined tissues, i.e. leaf, flower, II/III stage endosperm, V/VI stage endosperm and seed, RcPMK was expressed strongly in flower and II/III stage endosperm, moderately in V/VI stage endosperm and leaf, and weakly in seed.展开更多
In order to figure out the redox conditions and paleo-sedimentary environment of the Middle Devonian shales in the northwest of Guizhong Depression,the trace element analysis was conducted on the Middle Devonian cores...In order to figure out the redox conditions and paleo-sedimentary environment of the Middle Devonian shales in the northwest of Guizhong Depression,the trace element analysis was conducted on the Middle Devonian cores(320.35–938.50 m)of the typical shale gas investigation well(GY-1)at a 1.50 m sampling interval through X-ray fluorescence spectroscopy(XRF)and inductively coupled plasma mass spectrometry(ICP-MS).According to the test result,the average values of V/(V+Ni),V/Cr and Ni/Co in Nabiao formation(Fm.)are larger than 0.67,4.65 and 7.71 respectively,and Nabiao Fm.is rich in biological assemblages such as tabasheer,ammonite,etc.These evidences indicate the rising sea level rose relatively in the sedimentation period of Nabiao Fm.and a deepwater shelf environment,which was favorable for the preservation of organic matters.The V/(V+Ni),V/Cr and Ni/Co in Luofu Fm.and Tangting Fm.are 0.38–0.65,0.73–4.10 and 3.70–6.72 respectively,indicating that the sea level dropped relatively in their sedimentation period,during which the water bodies became shallow,and the sedimentary environment was a weak oxidizing shallow water shelf environment.In addition,the variation of TOC has a high correlation with the enrichment degree of Ba element,indicating the favorable conditions for the enrichment and preservation of organic matters under an oxygen-deficient environment.Moreover,according to the identification of trace element indexes,the northwest of Guizhong Depression experienced the sedimentary cycle of relative rise to relative fall of sea level from bottom to top in the Middle Devonian sedimentation period.The relative sea level rose to the highest in the sedimentation period of Nabiao Fm.,in which the organic-rich shales with stable thickness and high organic content were deposited.Hence,the Nabiao Fm.could be regarded as the favorable exploration target interval in this area.展开更多
1.Objective The Qinglong area is located in the Eastern Yunnan- Western Guizhou uplift tectonic belt, west of the Zishui fault zone and north of the Youjiang basin. There are many sets of organic-rich shale in Longtan...1.Objective The Qinglong area is located in the Eastern Yunnan- Western Guizhou uplift tectonic belt, west of the Zishui fault zone and north of the Youjiang basin. There are many sets of organic-rich shale in Longtan Formation in Qinglong area. Many predecessors did a great deal of research on the geological features of Permian coal fields in Western Guizhou (Mei MX et al., 2004;Dou XZ et al., 2012), but lack of the research on sedimentary background and distribution characteristics of organic-rich shale in Longtan Formation. Therefore, this study focuses on the analysis of the sedimentary environment of the Upper Permian Longtan Formation in Qinglong area.展开更多
Using an isotig encoding a putative polypeptide with high similarity to Arabidopsis LEA14 as a query, a 613 bp long cDNA was in silico cloned from the transeriptome data of rubber tree. The sequence nominated as HbLEA...Using an isotig encoding a putative polypeptide with high similarity to Arabidopsis LEA14 as a query, a 613 bp long cDNA was in silico cloned from the transeriptome data of rubber tree. The sequence nominated as HbLEA14L2 contains an ORF of 456 bp with 3 bp 5' UTR and 154 bp 3' UTR. Subsequently, a 464 bp eDNA and an 834 bp genome sequence containing this ORF was amplified and sequenced. Sequence analysis suggested that HbLEA14L2 has one intron and encodes 151 amino acids with a theoretical molecular weight of 16.55 kDa, isoleetric point of 4.93 and GRAVY value of -0.022, indicating a cytoplasmle localization pattern; HbLEA14L2 protein contains a conserved LEA_2 domain and belongs to LEA_2 subfamily, sharing 91%, 76%, 75%, 72% and 63% similarity with the homologous proteins in castor bean, leafy spurge, poplar, cotton, and Arabidopsis, respectively. Swiss-Model indicated that the tertiary structure of HbLEA14L2 is consisted of one α-helix and seven β-sheets, which was proposed to serve as a regulatory protein to prevent cellular desiccation.展开更多
The change of vocal flinction after vocal fold dehydration due to dryness was discussed along with the treatment eHect of different atomizing agents.Forty-eight staffs from The Central Hospital of Wuhan were recniited...The change of vocal flinction after vocal fold dehydration due to dryness was discussed along with the treatment eHect of different atomizing agents.Forty-eight staffs from The Central Hospital of Wuhan were recniited.All volunteers breathed dry air for vocal fold dehydration.After dry air inhalation,the subjects were randomly divided into four groups,with 12 cases each.Three groups were treatment groups,receiving 0.9%nonnal saline(IS),5%hypertonic saline(HS)and double-distilled water(SW)atomizing inhalation therapy,respectively,and the last group was the control group without treatment.Voice data were collected for all subjects before and immediately after dry air inhalation using the Multi-Dimensional Voice Program(MDVP)system.Atomizing inhalation therapy was given 10 min after dry air inhalation,and voice data were collected using MDVP system at the following time points after atomizing inhalation treatment:5 min,20 min,35 min,50 min,65 min,80 min,95 min,110 min.In the control group,voice data were collected at the same time points and compared with those of treatment groups.The vocal function parameters collected before and after dry air inhalation as well as after treatment were subjected to test using SPSS 16.0 software.In the four groups,jitter(fundamental frequency perturbation),shimmer(amplitude perturbation),and amplitude perturbation quotient(APQ)were significantly increased after dry air inhalation(P<0.05).In IS,HS and SW groups,after atomizing inhalation treatment,there was an obvious reduction in jitter,shimmer and APQ,showing significant differences as compared with those after dry air inhalation(P<0.05).Moreover,these parameters were significantly lower than those in the control group(P<0.05).The jitter,shimmer and APQ in the IS group were significantly lower than those in the HS and SW groups(P<0.05).We are led to a con elusion:Vocal fold dehydration induced by dryness can reduce the stability of voice;such decreased voice stability can be improved by atomizing inhalation therapy;without proper treatment,voice stability caused by vocal fold dehydration cannot heal spontaneously;of three atomizing agents namely,IS,HS and SW,IS had the best treatment effect for decreased voice stability caused by vocal fold dehydration.展开更多
Objective This study aimed to assess the feasibility and usefulness of transabdominal color Doppler flow imaging(CDFI)technology and the high-definition flow imaging(HDFI)technique in detecting fetal pulmonary veins(P...Objective This study aimed to assess the feasibility and usefulness of transabdominal color Doppler flow imaging(CDFI)technology and the high-definition flow imaging(HDFI)technique in detecting fetal pulmonary veins(PVs)in the first trimester(11–13^(+6)weeks).Methods From December 2018 to October 2019,328 pregnant women with 328 normal singleton fetuses(crown-rump length:45–84 mm)who had undergone CDFI and HDFI scans for fetal heart and vessel examination were enrolled in this study.The cases were divided into three groups according to the gestational age:group A,11^(+0)−11^(+6)weeks;group B,12^(+0)−12^(+6)weeks;and group C,13^(+0)−13^(+6)weeks.Baseline sonograms and CDFI and HDFI images were analyzed by two senior radiologists independently and blindly.The abilities of CDFI and HDFI to display PVs were compared.Results Successful PV display rates via CDFI and HDFI were 2.3%and 68.2%(P<0.01),22.4%and 82.4%(P<0.01),41.5%and 91.2%(P<0.01)for group A,group B,and group C,respectively.The total successful display rates for the two methods were 28.9%(CDFI)and 84.8%(HDFI)(P<0.01).Conclusions The HDFI technique is more valuable than CDFI for detecting PVs in early pregnancy(11–13^(+6)weeks).HDFI can detect at least one PV in all cases and may be used to detect pulmonary venous anomalies early.展开更多
As one of the widely used upgrading way in road engineering, the widening embankment(WE) has suffered evident differential deformation, which is even severer for highway in permafrost regions due to the temperature se...As one of the widely used upgrading way in road engineering, the widening embankment(WE) has suffered evident differential deformation, which is even severer for highway in permafrost regions due to the temperature sensitivity of frozen soil and the heat absorption effect of the asphalt pavement. Given this issue, a full-scale experimental highway of WE was performed along the Qinghai-Tibet Highway(QTH) to investigate the differential deformation features and its developing law. The continuous three years' monitoring data taken from the experimental site, including the ground temperature and the layered deformation of WE and original embankment(OE), were used to analyze the thermal-deformation process. The results indicate that the widening part presented the remarkable thermal disturbance to the existing embankment(EE). The underlying permafrost was in a noteworthy degradation state, embodying the apparent decrease of the permafrost table and the increase of the ground temperature. Correspondingly, the heat disruption induced by widening led to a much higher deformation at the widening side compared to the original embankment, showing a periodic stepwise curve. Specifically, the deformation mainly occurred in the junction of the EE and the widening part, most of which was caused by the thawing consolidation near the original permafrost table. In contrast, the deformation of EE mainly attributed to the compression of the active layer. Furthermore, it was the deformation origination differences that resulted in the differential deformation of WE developed gradually during the monitoring period, the maximum of which reached up to 64 mm.展开更多
Delay Tolerant Networks (DTNs) is a dynamic topology network, in which connection durations of each link are variable and paths between two nodes are intermittent. Most of protocols which are widely used in traditiona...Delay Tolerant Networks (DTNs) is a dynamic topology network, in which connection durations of each link are variable and paths between two nodes are intermittent. Most of protocols which are widely used in traditional wireless network are not suitable for DTNs. DTN adopts store-and-forward mechanism to cope with the problem of intermittent path. With limited storage of each node, it is a challenge for scheduling nodes’ transmission to avoid overflow of nodes’ buffers. In this paper we propose an optimal transmission scheduling algorithm for DTN with nodes’ buffer constraints. The object of the optimal algorithm is to get maximum throughput. We also present an algorithm for obtaining suboptimal transmission schedules. Our solution is certified through simulation, and it is observed that our solution can improve network performance in the aspects of avoiding overflow and increasing network throughput.展开更多
Phosphorus is an essential macronutrient for plant development and metabolism,and plants have evolved ingenious mechanisms to overcome phosphate(Pi)starvation.However,the molecular mechanisms underlying the regulation...Phosphorus is an essential macronutrient for plant development and metabolism,and plants have evolved ingenious mechanisms to overcome phosphate(Pi)starvation.However,the molecular mechanisms underlying the regulation of shoot and root architecture by low phosphorus conditions and the coordinated utilization of Pi and nitrogen remain largely unclear.Here,we show that Nodulation Signaling Pathway 1(NSP1)and NSP2 regulate rice tiller number by promoting the biosynthesis of strigolactones(SLs),a class of phytohormones with fundamental effects on plant architecture and environmental responses.We found that NSP1 and NSP2 are induced by Oryza sativa PHOSPHATE STARVATION RESPONSE2(OsPHR2)in response to low-Pi stress and form a complex to directly bind the promoters of SL biosynthesis genes,thus markedly increasing SL biosynthesis in rice.Interestingly,the NSP1/2–SL signaling module represses the expression of CROWN ROOTLESS 1(CRL1),a newly identified early SL-responsive gene in roots,to restrain lateral root density under Pi deficiency.We also demonstrated that GR24^(4DO) treatment under normal conditions inhibits the expression of OsNRTs and OsAMTs to suppress nitrogen absorption but enhances the expression of OsPTs to promote Pi absorption,thus facilitating the balance between nitrogen and phosphorus uptake in rice.Importantly,we found that NSP1p:NSP1 and NSP2p:NSP2 transgenic plants show improved agronomic traits and grain yield under low-and medium-phosphorus conditions.Taken together,these results revealed a novel regulatory mechanism of SL biosynthesis and signaling in response to Pi starvation,providing genetic resources for improving plant architecture and nutrient-use efficiency in low-Pi environments.展开更多
Cast-in-place pile foundations are widely used in permafrost regions to support buildings.The stability of cast-in-place pile foundations is highly sensitive to permafrost thermal regime changes.Permafrost degradation...Cast-in-place pile foundations are widely used in permafrost regions to support buildings.The stability of cast-in-place pile foundations is highly sensitive to permafrost thermal regime changes.Permafrost degradation caused by climate change is increasing the disaster risk of castin-place pile foundations.However,proactive cooling methods for cast-in-place pile foundations are seldom reported.The cold energy produced by two-phase closed thermosyphons(TPCTs)can efficiently prevent the permafrost thermal regime from being disturbed by engineering activities and climate change.TPCTs were installed in a concrete pile forming a thermal pile.Then,a model experiment was conducted to explore the thermal regime,influence scope,dissipation process of cold energy,and freezing strength of the thermal pile.The results indicated that the thermal pile may significantly cool the foundation soil.Most of cold energy produced by the thermal pile dissipated during the warm period,and the cooling scope of the thermal pile can cover the area within a 40 cm(twice the pile diameter)radius around the pile.Additionally,the TPCTs can significantly improve freezing strength between the thermal pile and frozen soil.The lesson learned from this study can provide a new approach to control the thermal regime of cast-in-place pile foundation in permafrost,which was of valuable to the construction of pile foundations in cold regions.展开更多
MEK is a canonical effector of mutant KRAS;however,MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers.Here,we identified mitochondrial oxidative phosphorylation(OXPHOS)induction as a pr...MEK is a canonical effector of mutant KRAS;however,MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers.Here,we identified mitochondrial oxidative phosphorylation(OXPHOS)induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer(NSCLC)resistance to the clinical MEK inhibitor trametinib.Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment,satisfying their energy demand and protecting them from apoptosis.As molecular events in this process,the pyruvate dehydrogenase complex(PDHc)and carnitine palmitoyl transferase IA(CPTIA),two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation.Importantly,the co-administration of trametinib and IACS-010759,a clinical mitochondrial complex I inhibitor that blocks OXPHOS,significantly impeded tumor growth and prolonged mouse survival.Overall,our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.展开更多
基金supported by State Grid Corporation of China Project“Research and Application of Key Technologies for Active Power Control in Regional Power Grid with High Penetration of Distributed Renewable Generation”(5108-202316044A-1-1-ZN).
文摘With the large-scale development and utilization of renewable energy,industrial flexible loads,as a kind of loadside resource with strong regulation ability,provide new opportunities for the research on renewable energy consumption problem in power systems.This paper proposes a two-layer active power optimization model based on industrial flexible loads for power grid partitioning,aiming at improving the line over-limit problem caused by renewable energy consumption in power grids with high proportion of renewable energy,and achieving the safe,stable and economical operation of power grids.Firstly,according to the evaluation index of renewable energy consumption characteristics of line active power,the power grid is divided into several partitions,and the interzone tie lines are taken as the optimization objects.Then,on the basis of partitioning,a two-layer active power optimization model considering the power constraints of industrial flexible loads is established.The upper-layer model optimizes the planned power of the inter-zone tie lines under the constraint of the minimum peak-valley difference within a day;the lower-layer model optimizes the regional source-load dispatching plan of each resource in each partition under the constraint of theminimumoperation cost of the partition,so as to reduce the line overlimit phenomenon caused by renewable energy consumption and save the electricity cost of industrial flexible loads.Finally,through simulation experiments,it is verified that the proposed model can effectively mobilize industrial flexible loads to participate in power grid operation and improve the economic stability of power grid.
文摘Objective: The “six-step teaching method” is a teaching method, which is summarized based on practical experience. This study aimed to explore the effect of “six-step teaching method” in clinical teaching of obstetrics. Methods: A quasi-experimental study design was used, 30 nursing students who entered obstetrics practice from March 2022 to July 2022 were selected as the control group according to the order of time, and traditional teaching methods were adopted. From August to December 2022, 30 interns were selected as the experimental group, and the “six-step teaching method” was adopted. After 8 weeks of clinical practice, the assessment results and teaching effect satisfaction of the two groups were compared. Results: The scores of obstetrical specialty in the experimental group were higher than those in the control group, and the difference was statistically significant (P < 0.05);The evaluation of teaching methods, teaching quality, classroom atmosphere and individual observation ability, clinical thinking ability and nurse-patient communication ability of the experimental group were higher than those of the control group, and the differences were statistically significant (P Conclusion: “six-step teaching method” can effectively master the professional knowledge of obstetrics, stimulate the clinical thinking ability of interns, and improve the teaching effect and satisfaction. .
基金supported by the China Geological Survey Projects of Shale Gas Survey in the GuizhongNanpanjiang Area (DD20190088)Investigation and evaluation of Paleozoic shale gas in Yunnan-Guizhou-Guangxi region (DD20230264)+1 种基金Investigation and Evaluation of Carboniferous Shale Gas in Southern Guizhou-Central Guangxi (ZDDYR2023018)Reservoir Characteristics and Gas Accumulation of Trough-platform Shale: A Case Study of Early Carboniferous Shale in Yaziluo Rift Trough (YKC2023-YC08)。
文摘The Yadu-Ziyun-Luodian aulacogen(YZLA) developed into being NW-trending in the Late Paleozoic,and was considered as an important passive continental margin aulacogen in Guizhou Province, South China. This tectonic zone is considered a large intracontinental thrust-slip tectonic unit, which has undergone a long period of development. It was ultimately determined in the Yanshanian, where the typical Upper Paleozoic marine shales were deposited. In 2021, Well QSD-1 was deployed in the Liupanshui area at the northwest margin of the aulacogen, and obtained a daily shale gas flow of 11011 m3in the Carboniferous Dawuba Formation. It thus achieved a breakthrough in the invesgation of shale gas in the Lower Carboniferous in South China, revealing relatively good gas-bearing properties and broad exploration prospects of the aulacogen. Being different from the Lower Paleozoic strata in the Sichuan Basin and the Yichang area of the Middle Yangtze, the development of the Carboniferous Dawuba Formation in the aulacogen exhibits the following characteristics:(1) The Lower Carboniferous shale is thick and widely distributed, with interbedded shale and marlstone of virous thickness;(2) The total organic carbon(TOC) content of the shale in the Dawuba Formation ranges from 1% to 5%, with an average of 2%, and the thermal maturity of organic matter(Ro) varies from 1% to 4%, with an average of2.5%, indicating good hydrocarbon generation capacity;(3) The main shale in the aulacogen was formed during the fault subsidence stage from the Middle Devonian to the Early Permian. Although the strong compression and deformation during the late Indosinian-Himalayan played a certain role in destroying the formed shale gas reservoirs, comparative analysis suggests that the area covered by the current Triassic strata has a low degree of destruction. It therefore provides good conditions for shale gas preservation,which can be regarded as a favorable area for the next exploration.
基金supported by the National Natural Science Foundation of China(Grant No.11875047)。
文摘Thermal metamaterials offer a promising avenue for creating artificial materials with unconventional physical properties,such as thermal cloak,concentrator,rotator,and illusion.However,designs and fabrication of thermal metamaterials are of challenge due to the limitations of existing methods on anisotropic material properties.We propose an evolutionary framework for designing thermal metamaterials using genetic algorithm optimization.Our approach encodes unit cells with different thermal conductivities and performs global optimization using the evolution-inspired operators.We further fabricate the thermal functional cells using 3D printing and verify their thermal illusion functionality experimentally.Our study introduces a new design paradigm for advanced thermal metamaterials that can manipulate heat flows robustly and realize functional thermal metadevices without anisotropic thermal conductivity.Our approach can be easily applied to fabrications in various fields such as thermal management and thermal sensing.
基金This work was supported by the National Natural Science Foundation of China (No. 30230300).
文摘Black spot disease in poplar is a disease of the leaf caused by fungus. The major pathogen is Marssonina brunnea f. sp. multigermtubi. To date, little is known about the molecular mechanism of poplar (M. brunnea) interaction. In order to identify the proteins related to disease resistance and understand its molecular basis, the clone "NL895" (P. euramericana CL"NL895"), which is highly resistant to M. brunnea f. sp. multigermtubi, was used in this study. We used two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) to identify the proteins in poplar leaves that were differentially expressed in response to black spot disease pathogen, M. brunnea f. sp. multigermtubi. Proteins extracted from poplar leaves at 0, 12, 24, 48, and 72 h after pathogen-inoculation were separated by 2-DE, About 500 reproducible protein spots were detected, of which 40 protein spots displayed differential expression in levels and were subjected to Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) followed by database searching. According to the function, the identified proteins were sorted into five categories, that is, protein synthesis, metabolism, defense response and unclassified proteins.
基金special construction projects fund which belongs to“Taishan Scholar-Pharmacy Specially Recruited Experts”.
文摘Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.
基金financial support from the National Natural Science Foundation of China(21832001 and 21771009)the Beijing National Laboratory for Molecular Sciences(BNLMSCXXM-202104)。
文摘The water gas shift reaction is of vital significance for the generation and transition of energy due to the application in hydrogen production and industries such as ammonia synthesis and fuel cells.The influence of support doping and bimetallic alloying on the catalytic performance of Pt/Ce O_(2)-based nanocatalysts in water gas shift reaction was reported in this work.Various lanthanide ions and 3d transition metals were respectively introduced into the Ce O_(2)support or Pt to form Pt/Ce O_(2):Ln(Ln=La,Nd,Gd,Tb,Yb)and Pt M/Ce O_(2)(M=Fe,Co,Ni)nanocatalysts.The sample of Pt/Ce O_(2):Tb showed the highest activity(TOF at 200℃=0.051 s^(-1))among the Pt/Ce O_(2):Ln and the undoped Pt/Ce O_(2)catalysts.Besides,the sample of Pt Fe/Ce O_(2)exhibited the highest activity(TOF at 200℃=0.12 s^(-1))among Pt M/Ce O_(2)catalysts.The results of the multiple characterizations indicated that the catalytic activity of Pt/Ce O_(2):Ln catalysts was closely correlated with the amount of oxygen vacancies in doped ceria support.However,the different activity of Pt M/Ce O_(2)bimetallic catalysts was owing to the various Pt oxidation states of the bimetals dispersed on ceria.The study of the reaction pathway indicated that both the samples of Pt/Ce O_(2)and Pt/Ce O_(2):Tb catalyzed the reaction through the formate pathway,and the enhanced activity of the latter derived from the increased concentration of oxygen vacancies along with promoted water dissociation.As for the sample of Pt Fe/Ce O_(2),its catalytic mechanism was the carboxyl route with a higher reaction rate due to the moderate valence of Pt along with improved CO activation.
基金Supported by National Natural Science Foundation of China(31100460)Natural Science Foundation of Hainan Province(312026)Fundamental Research Fund for the Rubber Research Institute in Chinese Academy of Tropical Agricultural Sciences(1630022011014)
文摘The mevalonate diphosphate deearboxylase (MVD) is an essential enzyme in mevalonate (MVA) pathway that catalyzes the irreversible Mg2+ -ATP de- pendent decarboxylation of 6-carben compound mevalonate-5-diphosphate (MVAPP) into 5-carbon isopentenyl diphosphate ( IPP), the building block of sterol and isoprenoid biosynthesis. In this study, based on the published geanme sequences and ESTs, a genome-wide search was carried out for the first time to identify MVD gene family in four genome-sequenced Euphorbiaceae plants, i.e. castor bean ( Ricinus communis), physic nut ( Jatropha curcas), cassava (Manihot esculenta) and rubber tree (Hevea brasiliensis), and to analyze the gene structure and phylogenetic characteristics. According to the experimental results, 1, 1,2 and 2 MVD genes, which all contain 9 introns, were identh'ied from castor bean, physic nut, cassava and rubber tree, respectively. Homology analysis indicates that MVD genes are widely distributed in eukaryotes, some archaea and eubacteria, which suggests an early origin of this gerte family. Although MVD genes were identified in most green plants, no homologous genes were found in unicellular green algae. In most genome-sequenced plants including castor bean and physic nut, a single copy of MVD gene was found; however, in cassava and rubber tree, two copies were identified just like that in moss, maize, Arabidopsis and poplar. "In castor bean, digital expression profiling suggests that in five examined tissues, i.e. leaf, flower, II/III stage endosperm, V/VI stage endosperm and seed, RcPMK was expressed strongly in flower and II/III stage endosperm, moderately in V/VI stage endosperm and leaf, and weakly in seed.
基金This article was supported by project of China Geological Survey“Guizhong-Nanpanjiang Depression shale gas geological survey”(DD20190088).
文摘In order to figure out the redox conditions and paleo-sedimentary environment of the Middle Devonian shales in the northwest of Guizhong Depression,the trace element analysis was conducted on the Middle Devonian cores(320.35–938.50 m)of the typical shale gas investigation well(GY-1)at a 1.50 m sampling interval through X-ray fluorescence spectroscopy(XRF)and inductively coupled plasma mass spectrometry(ICP-MS).According to the test result,the average values of V/(V+Ni),V/Cr and Ni/Co in Nabiao formation(Fm.)are larger than 0.67,4.65 and 7.71 respectively,and Nabiao Fm.is rich in biological assemblages such as tabasheer,ammonite,etc.These evidences indicate the rising sea level rose relatively in the sedimentation period of Nabiao Fm.and a deepwater shelf environment,which was favorable for the preservation of organic matters.The V/(V+Ni),V/Cr and Ni/Co in Luofu Fm.and Tangting Fm.are 0.38–0.65,0.73–4.10 and 3.70–6.72 respectively,indicating that the sea level dropped relatively in their sedimentation period,during which the water bodies became shallow,and the sedimentary environment was a weak oxidizing shallow water shelf environment.In addition,the variation of TOC has a high correlation with the enrichment degree of Ba element,indicating the favorable conditions for the enrichment and preservation of organic matters under an oxygen-deficient environment.Moreover,according to the identification of trace element indexes,the northwest of Guizhong Depression experienced the sedimentary cycle of relative rise to relative fall of sea level from bottom to top in the Middle Devonian sedimentation period.The relative sea level rose to the highest in the sedimentation period of Nabiao Fm.,in which the organic-rich shales with stable thickness and high organic content were deposited.Hence,the Nabiao Fm.could be regarded as the favorable exploration target interval in this area.
文摘1.Objective The Qinglong area is located in the Eastern Yunnan- Western Guizhou uplift tectonic belt, west of the Zishui fault zone and north of the Youjiang basin. There are many sets of organic-rich shale in Longtan Formation in Qinglong area. Many predecessors did a great deal of research on the geological features of Permian coal fields in Western Guizhou (Mei MX et al., 2004;Dou XZ et al., 2012), but lack of the research on sedimentary background and distribution characteristics of organic-rich shale in Longtan Formation. Therefore, this study focuses on the analysis of the sedimentary environment of the Upper Permian Longtan Formation in Qinglong area.
基金Supported by National Natural Science Foundation of China(31100460)Key Science and Technology Project of Hainan Province(90107)+1 种基金Natural Science Foundation of Hainan Province(312026)Fundamental Research Fund for the Rubber Research Institute in Chinese Academy of Tropical Agricultural Sciences(1630022011014)
文摘Using an isotig encoding a putative polypeptide with high similarity to Arabidopsis LEA14 as a query, a 613 bp long cDNA was in silico cloned from the transeriptome data of rubber tree. The sequence nominated as HbLEA14L2 contains an ORF of 456 bp with 3 bp 5' UTR and 154 bp 3' UTR. Subsequently, a 464 bp eDNA and an 834 bp genome sequence containing this ORF was amplified and sequenced. Sequence analysis suggested that HbLEA14L2 has one intron and encodes 151 amino acids with a theoretical molecular weight of 16.55 kDa, isoleetric point of 4.93 and GRAVY value of -0.022, indicating a cytoplasmle localization pattern; HbLEA14L2 protein contains a conserved LEA_2 domain and belongs to LEA_2 subfamily, sharing 91%, 76%, 75%, 72% and 63% similarity with the homologous proteins in castor bean, leafy spurge, poplar, cotton, and Arabidopsis, respectively. Swiss-Model indicated that the tertiary structure of HbLEA14L2 is consisted of one α-helix and seven β-sheets, which was proposed to serve as a regulatory protein to prevent cellular desiccation.
文摘The change of vocal flinction after vocal fold dehydration due to dryness was discussed along with the treatment eHect of different atomizing agents.Forty-eight staffs from The Central Hospital of Wuhan were recniited.All volunteers breathed dry air for vocal fold dehydration.After dry air inhalation,the subjects were randomly divided into four groups,with 12 cases each.Three groups were treatment groups,receiving 0.9%nonnal saline(IS),5%hypertonic saline(HS)and double-distilled water(SW)atomizing inhalation therapy,respectively,and the last group was the control group without treatment.Voice data were collected for all subjects before and immediately after dry air inhalation using the Multi-Dimensional Voice Program(MDVP)system.Atomizing inhalation therapy was given 10 min after dry air inhalation,and voice data were collected using MDVP system at the following time points after atomizing inhalation treatment:5 min,20 min,35 min,50 min,65 min,80 min,95 min,110 min.In the control group,voice data were collected at the same time points and compared with those of treatment groups.The vocal function parameters collected before and after dry air inhalation as well as after treatment were subjected to test using SPSS 16.0 software.In the four groups,jitter(fundamental frequency perturbation),shimmer(amplitude perturbation),and amplitude perturbation quotient(APQ)were significantly increased after dry air inhalation(P<0.05).In IS,HS and SW groups,after atomizing inhalation treatment,there was an obvious reduction in jitter,shimmer and APQ,showing significant differences as compared with those after dry air inhalation(P<0.05).Moreover,these parameters were significantly lower than those in the control group(P<0.05).The jitter,shimmer and APQ in the IS group were significantly lower than those in the HS and SW groups(P<0.05).We are led to a con elusion:Vocal fold dehydration induced by dryness can reduce the stability of voice;such decreased voice stability can be improved by atomizing inhalation therapy;without proper treatment,voice stability caused by vocal fold dehydration cannot heal spontaneously;of three atomizing agents namely,IS,HS and SW,IS had the best treatment effect for decreased voice stability caused by vocal fold dehydration.
基金the Clinical Research Foundation of the Seventh Affiliated Hospital of Sun Yat-sen University(No.ZSQYLCKYJJ202010)the General Program of Science and Technology Project of Shenzhen(No.JCYJ20190814170205768)the Foundation of the Key Program of Social Science and Technology Development Project of Dongguan(No.202050715041216).
文摘Objective This study aimed to assess the feasibility and usefulness of transabdominal color Doppler flow imaging(CDFI)technology and the high-definition flow imaging(HDFI)technique in detecting fetal pulmonary veins(PVs)in the first trimester(11–13^(+6)weeks).Methods From December 2018 to October 2019,328 pregnant women with 328 normal singleton fetuses(crown-rump length:45–84 mm)who had undergone CDFI and HDFI scans for fetal heart and vessel examination were enrolled in this study.The cases were divided into three groups according to the gestational age:group A,11^(+0)−11^(+6)weeks;group B,12^(+0)−12^(+6)weeks;and group C,13^(+0)−13^(+6)weeks.Baseline sonograms and CDFI and HDFI images were analyzed by two senior radiologists independently and blindly.The abilities of CDFI and HDFI to display PVs were compared.Results Successful PV display rates via CDFI and HDFI were 2.3%and 68.2%(P<0.01),22.4%and 82.4%(P<0.01),41.5%and 91.2%(P<0.01)for group A,group B,and group C,respectively.The total successful display rates for the two methods were 28.9%(CDFI)and 84.8%(HDFI)(P<0.01).Conclusions The HDFI technique is more valuable than CDFI for detecting PVs in early pregnancy(11–13^(+6)weeks).HDFI can detect at least one PV in all cases and may be used to detect pulmonary venous anomalies early.
文摘As one of the widely used upgrading way in road engineering, the widening embankment(WE) has suffered evident differential deformation, which is even severer for highway in permafrost regions due to the temperature sensitivity of frozen soil and the heat absorption effect of the asphalt pavement. Given this issue, a full-scale experimental highway of WE was performed along the Qinghai-Tibet Highway(QTH) to investigate the differential deformation features and its developing law. The continuous three years' monitoring data taken from the experimental site, including the ground temperature and the layered deformation of WE and original embankment(OE), were used to analyze the thermal-deformation process. The results indicate that the widening part presented the remarkable thermal disturbance to the existing embankment(EE). The underlying permafrost was in a noteworthy degradation state, embodying the apparent decrease of the permafrost table and the increase of the ground temperature. Correspondingly, the heat disruption induced by widening led to a much higher deformation at the widening side compared to the original embankment, showing a periodic stepwise curve. Specifically, the deformation mainly occurred in the junction of the EE and the widening part, most of which was caused by the thawing consolidation near the original permafrost table. In contrast, the deformation of EE mainly attributed to the compression of the active layer. Furthermore, it was the deformation origination differences that resulted in the differential deformation of WE developed gradually during the monitoring period, the maximum of which reached up to 64 mm.
文摘Delay Tolerant Networks (DTNs) is a dynamic topology network, in which connection durations of each link are variable and paths between two nodes are intermittent. Most of protocols which are widely used in traditional wireless network are not suitable for DTNs. DTN adopts store-and-forward mechanism to cope with the problem of intermittent path. With limited storage of each node, it is a challenge for scheduling nodes’ transmission to avoid overflow of nodes’ buffers. In this paper we propose an optimal transmission scheduling algorithm for DTN with nodes’ buffer constraints. The object of the optimal algorithm is to get maximum throughput. We also present an algorithm for obtaining suboptimal transmission schedules. Our solution is certified through simulation, and it is observed that our solution can improve network performance in the aspects of avoiding overflow and increasing network throughput.
基金was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA28030202)the National Key Research and Development of China(2022YFF1002901)+1 种基金the National Natural Science Foundation of China(32122012,32270327)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2019099).
文摘Phosphorus is an essential macronutrient for plant development and metabolism,and plants have evolved ingenious mechanisms to overcome phosphate(Pi)starvation.However,the molecular mechanisms underlying the regulation of shoot and root architecture by low phosphorus conditions and the coordinated utilization of Pi and nitrogen remain largely unclear.Here,we show that Nodulation Signaling Pathway 1(NSP1)and NSP2 regulate rice tiller number by promoting the biosynthesis of strigolactones(SLs),a class of phytohormones with fundamental effects on plant architecture and environmental responses.We found that NSP1 and NSP2 are induced by Oryza sativa PHOSPHATE STARVATION RESPONSE2(OsPHR2)in response to low-Pi stress and form a complex to directly bind the promoters of SL biosynthesis genes,thus markedly increasing SL biosynthesis in rice.Interestingly,the NSP1/2–SL signaling module represses the expression of CROWN ROOTLESS 1(CRL1),a newly identified early SL-responsive gene in roots,to restrain lateral root density under Pi deficiency.We also demonstrated that GR24^(4DO) treatment under normal conditions inhibits the expression of OsNRTs and OsAMTs to suppress nitrogen absorption but enhances the expression of OsPTs to promote Pi absorption,thus facilitating the balance between nitrogen and phosphorus uptake in rice.Importantly,we found that NSP1p:NSP1 and NSP2p:NSP2 transgenic plants show improved agronomic traits and grain yield under low-and medium-phosphorus conditions.Taken together,these results revealed a novel regulatory mechanism of SL biosynthesis and signaling in response to Pi starvation,providing genetic resources for improving plant architecture and nutrient-use efficiency in low-Pi environments.
基金the Second Tibetan Plateau Scientific Expedition and Research(STEP)program(2019QZKK0905)the National Natural Science Foundation of China(42001063,41961011)+1 种基金the Open Fund of State Key Laboratory of Road Engineering Safety and Health in Cold and High-Altitude Regions(YGY2020KYPT-04)CCCC Scientific and Technological Research Program(2020-ZJKJPTJS04).
文摘Cast-in-place pile foundations are widely used in permafrost regions to support buildings.The stability of cast-in-place pile foundations is highly sensitive to permafrost thermal regime changes.Permafrost degradation caused by climate change is increasing the disaster risk of castin-place pile foundations.However,proactive cooling methods for cast-in-place pile foundations are seldom reported.The cold energy produced by two-phase closed thermosyphons(TPCTs)can efficiently prevent the permafrost thermal regime from being disturbed by engineering activities and climate change.TPCTs were installed in a concrete pile forming a thermal pile.Then,a model experiment was conducted to explore the thermal regime,influence scope,dissipation process of cold energy,and freezing strength of the thermal pile.The results indicated that the thermal pile may significantly cool the foundation soil.Most of cold energy produced by the thermal pile dissipated during the warm period,and the cooling scope of the thermal pile can cover the area within a 40 cm(twice the pile diameter)radius around the pile.Additionally,the TPCTs can significantly improve freezing strength between the thermal pile and frozen soil.The lesson learned from this study can provide a new approach to control the thermal regime of cast-in-place pile foundation in permafrost,which was of valuable to the construction of pile foundations in cold regions.
基金sponsored by the National Natural Science Foundation of China(82122045,82073073,81874207,and 81872418)Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20210802,China)+4 种基金MOE Key Laboratory of Biosystems Homeostasis&Protection(Zhejiang University,China)Science and Technology Commission of Shanghai Municipality(21S11902000,China)Jointed PI Program from Shanghai Changning Maternity and Infant Health Hospital(11300-412311-20033,China)ECNU Construction Fund of Innovation and Entrepreneurship Laboratory(44400-20201-532300/021,China)the ECNU multifunctional platform for innovation(011 and 004,China).
文摘MEK is a canonical effector of mutant KRAS;however,MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers.Here,we identified mitochondrial oxidative phosphorylation(OXPHOS)induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer(NSCLC)resistance to the clinical MEK inhibitor trametinib.Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment,satisfying their energy demand and protecting them from apoptosis.As molecular events in this process,the pyruvate dehydrogenase complex(PDHc)and carnitine palmitoyl transferase IA(CPTIA),two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation.Importantly,the co-administration of trametinib and IACS-010759,a clinical mitochondrial complex I inhibitor that blocks OXPHOS,significantly impeded tumor growth and prolonged mouse survival.Overall,our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.