Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locall...Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.展开更多
As a data-driven approach, Deep Learning(DL)-based fault diagnosis methods need to collect the relatively comprehensive data on machine fault types to achieve satisfactory performance. A mechanical system may include ...As a data-driven approach, Deep Learning(DL)-based fault diagnosis methods need to collect the relatively comprehensive data on machine fault types to achieve satisfactory performance. A mechanical system may include multiple submachines in the real-world. During condition monitoring of a mechanical system, fault data are distributed in a continuous flow of constantly generated information and new faults will inevitably occur in unconsidered submachines, which are also called machine increments. Therefore, adequately collecting fault data in advance is difficult. Limited by the characteristics of DL, training existing models directly with new fault data of new submachines leads to catastrophic forgetting of old tasks, while the cost of collecting all known data to retrain the models is excessively high. DL-based fault diagnosis methods cannot learn continually and adaptively in dynamic environments. A new Continual Learning Fault Diagnosis method(CLFD) is proposed in this paper to solve a series of fault diagnosis tasks with machine increments. The stability–plasticity dilemma is an intrinsic issue in continual learning. The core of CLFD is the proposed Dual-branch Adaptive Aggregation Residual Network(DAARN).Two types of residual blocks are created in each block layer of DAARN: steady and dynamic blocks. The stability–plasticity dilemma is solved by assigning them with adaptive aggregation weights to balance stability and plasticity, and a bi-level optimization program is used to optimize adaptive aggregation weights and model parameters. In addition, a feature-level knowledge distillation loss function is proposed to further overcome catastrophic forgetting. CLFD is then applied to the fault diagnosis case with machine increments. Results demonstrate that CLFD outperforms other continual learning methods and has satisfactory robustness.展开更多
This paper studies the division of labor and economic development under global value chains in North South trade by mainly investigating the changes of production hours and cost per unit along with more and more outpu...This paper studies the division of labor and economic development under global value chains in North South trade by mainly investigating the changes of production hours and cost per unit along with more and more output and increasing trade value in several industries in the U.S., because the U. S. is at the leading position in the division of labor by global value chains. The empirical evidence reveals that more international outsourcing, there will be more detailed division of labor, and the industry unit production time and production cost will show more declining trend year by year. This is consistent with that the global value chains and the outsourcing play more and more important roles in the international division of labor and economic growth in both developed and developing countries, and helps explain the integration of workforce across countries in the global value chains.展开更多
Background: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these ...Background: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy. Methods and design: Patients with newly diagnosed malignant gliomas will have their tumor tissue samples submitted for the analysis of the status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. In Phase I, the patients will undergo an induction carbon ion radiotherapy (CIRT) boost followed by 60 GyE of proton irradiation with concurrent temozolomide (TMZ) at 75 mg/m2. To determine the maximal dose of safe induction boost, the tolerance, and acute toxicity rates in a dose-escalation manner from 9 to 18 GyE in three fractions will be used. In Phase III, GBM-only patients will be randomized to receive either 60 GyE (2 GyE per fraction) of proton irradia-tion with concurrent TMZ (control arm) or a CIRT boost (dose determined in Phase I of this trial) followed by 60 GyE of proton irradiation with concurrent TMZ. The primary endpoints are overall survival (OS) and toxicity rates (acute and long-term). Secondary endpoints are progression-free survival (PFS), and tumor response (based upon assess-ment with C-methionine/fluoro-ethyl-tyrosine positron emission tomography [MET/FET PET] or magnetic resonance imaging [MRI] and detection of serologic immune markers). We hypothesize that the induction CIRT boost will result in a greater initial tumor-killing ability and prime the tumor microenvironment for enhanced immunologic tumor clearance, resulting in an expected 33% improvement in OS rates. Discussion: The prognosis of GBM remains grim. The mechanism underpinning the poor prognosis of this malig-nancy is its chronic state of tumor hypoxia, which promotes both immunosuppression/immunologic evasion and radio-resistance. The unique physical and biological properties of CIRT are expected to overcome these microenviron-mental limitations to confer an improved tumor-killing ability and anti-tumor immune response, which could result in an improvement in OS with minimal toxicity. Trial registration number This trial has been registered with the China Clinical Trials Registry, and was allocated the number ChiCTR-OID-17013702.展开更多
Insect lytic polysaccharide monooxygenases(LPMO15s)are newly discovered copper-dependent enzymes that promote chitin degradation in insect through oxidative cleavage of glycosidic bonds.They are potential pesticide ta...Insect lytic polysaccharide monooxygenases(LPMO15s)are newly discovered copper-dependent enzymes that promote chitin degradation in insect through oxidative cleavage of glycosidic bonds.They are potential pesticide targets due to their critical role for chitin turnover in the integument,trachea,and peritrophic matrix of the midgut during insect molting.However,the knowledge about whether and how LPMO15s participate in chitin turnover in other tissues is still insufficient.Here,using the orthopteran pest Locusta migratoria as a model,a novel alternative splicing site of LmLPMO15-1 was discovered and it produces 2 variants,LmLPMO15-1a and LmLPMO15-1b.The transcripts of LmLPMO15-1a and LmLPMO15-1b were specifically expressed in the trachea and foregut,respectively.RNA interference targeting LmLPMO15-1(a common fragment shared by both LmLPMO15-1a and LmLPMO15-1b),a specific region of LmLPMO15-1a or LmLPMO15-1b all significantly reduced survival rate of nymphs and induced lethal phenotypes with developmental stasis or molt failure.Ultrastructure analysis demonstrated that LmLPMO15-1b was specifically involved in foregut old cuticle degradation,while LmLPMO15-1a was exclusively responsible for the degradation of the tracheal old cuticle.This study revealed LmLPMO15-1 achieved tissue-specific functional differentiation through alternative splicing,and proved the significance of the spliced variants during insect growth and development.It provides new strategies for pest control targeting LPMO15-1.展开更多
Background and Objectives:Previous studies on the risk factors for prolonged pleural effusion(PPE)have pri marily focused on surgical-related risk factors,with little research exploring the influence of nutritional fa...Background and Objectives:Previous studies on the risk factors for prolonged pleural effusion(PPE)have pri marily focused on surgical-related risk factors,with little research exploring the influence of nutritional factors on this delay.This study aimed to identify the nutritional risk factors for PPE in Chinese infants following congenital heart disease(CHD)surgery.Methods and Study Design:We retrospectively reviewed the medical records of patients under 3 years old with chylothorax following CHD surgery from 2016 to 2020.PPE was defined as pleu ral effusion lasting over 14 days.Logistical regression analysis was conducted to identify the risk factors.Results:Of 136 patients,42 patients developed PPE(30.9%).The PPE group had lower Height-for-Age Z-scores(HAZ)compared to the non-PPE group,while other demographic factors were not significantly different.Univariate analysis revealed that patients in PPE group exhibited delayed onset of chylothorax,prolonged duration of me chanical ventilation,increased chest effusion volume on the first postoperative day,and a reduced proportion of energy intake from enteral nutrition(EN)during the stable phase.Variables with p-value of<0.1 in univariate lo gistic regression analysis were included in the multivariate logistic regression analysis.A delayed onset of chylo thorax,extended periods of mechanical ventilation,a lower HAZ and a reduced proportion of energy intake from EN during the recovery phase.Conclusions:A delayed onset of chylothorax,extended periods of mechanical ventilation,a lower HAZ,and a reduced proportion of energy intake from EN during the recovery phase predict a higher risk of PPE.展开更多
Advanced glycation end products(AGEs),a group of complex compounds generated by nonenzymatic interactions between amino acids,proteins and reducing sugars or lipids,accumulate in vivo and activate various signaling pa...Advanced glycation end products(AGEs),a group of complex compounds generated by nonenzymatic interactions between amino acids,proteins and reducing sugars or lipids,accumulate in vivo and activate various signaling pathways closely related to the occurrence of various chronic metabolic diseases.This study aims to explore the structure-activity relationship between phenolic acids with different structure and affecting the AGEs generation,and to provide data support for AGEs control.Phenolic acids(4-hydroxybenzoic,protocatechuic,gallic,p-coumaric,caffeic,ferulic and sinapic acids)were employed to indicate the AGEs formation condition in Maillard reaction performed in the glucose-lysine model system.Three 1,2-dicarbonyl compounds were reacted with phenolic acids and then tested by liquid chromatography-mass spectrometry.The results showed that N^(ε)-carboxy-methyl-lysine(CML),N^(ε)-carboxy-ethyl-lysine(CEL),and pyrraline formation inhibited by phenolic acids varied from(8.7±2.5)%to(33.2±2.5)%,(10.5±0.8)%to(57.1±3.2)%and(1.3±0.3)%to(23.3±0.8)%,respectively.The p-coumaric acid has no inhibitory effect on CML and CEL formation.Gallic acid shows the best inhibitory effect on CML formation due to its strong antioxidant activity.Sinapic acid showed the best glyoxal(GO)trapping rate and thus had the stronger inhibitory effect on CML formation.Ferulic acid can react with mono-,di-,and tri-methylglyoxal(MGO)to form adduct products,showing the best MGO scavenging rate and a good inhibitory effect on CEL formation.The main role of phenolic acid is an antioxidant agent to inhibit pyrraline formation.The glucose itself or ammonia-induced degradation and Amadori rearrangement products oxidation were lowered by protocatechuic,gallic and caffeic acids due to their antioxidant activities to form AGEs,while AGEs inhibited by ferulic and sinapic acids were mainly dependent on their trapping ability on 1,2-dicarbonyl compounds.展开更多
Observations play a leading role in any branches of astronomy, including solar physics. In order to solve fundamental problems, such as solar dynamo [1], coronal heating [2] and the triggering of major solar eruptions...Observations play a leading role in any branches of astronomy, including solar physics. In order to solve fundamental problems, such as solar dynamo [1], coronal heating [2] and the triggering of major solar eruptions [3], solar observations with spatial resolution better than 0.1 arcsec are required. Such a goal cannot be achieved without the help of adaptive optics （AO）, which eliminates the wavefront distortion caused by atmosphere turbulence [4,5]. However, solar observations are performed over an extended field of view （FoV）. Flare trigger mechanisms operate rapidly and on the smallest spatial scales and their location within the FoV is difficult to predict.展开更多
Large-aperture solar telescopes play an important role in solar observations and research,and require high temporal and spatial resolution[1].To solve some fundamental problems such as the solar dynamo,coronal heating...Large-aperture solar telescopes play an important role in solar observations and research,and require high temporal and spatial resolution[1].To solve some fundamental problems such as the solar dynamo,coronal heating,and the triggering of major solar eruptions,the spatial resolution for solar-atmosphere observation should reach at least 0.1 arcsec[2].展开更多
Lytic polysaccharide monooxygenases(LPMOs)are important enzymes that boost the hydrolysis of recalcitrant polysaccharides,such as chitin.They are found extensively in different insect species and are classified as aux...Lytic polysaccharide monooxygenases(LPMOs)are important enzymes that boost the hydrolysis of recalcitrant polysaccharides,such as chitin.They are found extensively in different insect species and are classified as auxiliary activities family 15(AA15)LPMOs(LPMO15).Some of them were identified from the insect midgut and proven to act on chitin.However,knowledge about their physiological roles during insect growth and development remains limited.Here,we found that midgut-specific LPMO15s are widely distributed in different insect orders,such as the orthopteran Locusta migratoria and the lepidopteran Bombyx mori.Using L.migratoria as a model insect,the function of midgut-specific LmLPMO15-3 during development was investigated.Double-stranded RNA-mediated downregulation of LmLPMO15-3 expression at the 4th or 5th instar nymph stage severely decreased the survival rate and resulted in lethal phenotypes.Hematoxylin and eosin staining results indicated that the deficient individuals exhibited incompletely digested peritrophic matrix(PM),which suggested that LmLPMO15-3 is essential for the deconstruction of the PM during molting.This study provides direct evidence of the physiological importance of a midgut-specific LPMO15 during insect development.As L.migratoria is one of the most destructive agricultural pests,LmLPMO15-3 is a potential target for pest management.展开更多
Comprehensive Summary Currently,solid-state fluorescent carbonized polymer dots(CPDs)have attracted attention increasingly due to their applications for optoelectronic display.However,designing CPDs possessing solid-s...Comprehensive Summary Currently,solid-state fluorescent carbonized polymer dots(CPDs)have attracted attention increasingly due to their applications for optoelectronic display.However,designing CPDs possessing solid-state fluorescence and clarifying the fluorescence mechanism remain challenging.Herein,we initially synthesized a novel type of polythiophene derivatives CPDs,poly-4,4’-(thiophene-3,4-diyl)dibenzoic acid carbonized polymer dots(PDBA-CPDs)with solid-state fluorescence.Subsequently,the structural and optical characterization revealed that the solid-state fluorescence originated from the aggregation induced emission of the CPDs.In brief,in aggregation state,the remaining polymer structure groups on the surface of the CPDs overlapped and weakened the non-radiative transition,enhancing solid-state fluorescence emission.Thirdly,three polythiophene-derived CPDs were designed to further demonstrate the aggregation induced solid-state fluorescence mechanism.Finally,owing to their unique properties of solid-state fluorescence,the white LEDs(light emitting diodes)were fabricated with high color rendering index(CRI)of 82.7 and CIE coordinates of(0.37,0.39)using commercial 460 nm chip.展开更多
Efficient strategies for transforming Bacillus subtilis vegetative cells into spores(BtS transformation)are still limited,although they show promise for the treatment of inflammatory bowel disease(IBD).A novel,simple,an...Efficient strategies for transforming Bacillus subtilis vegetative cells into spores(BtS transformation)are still limited,although they show promise for the treatment of inflammatory bowel disease(IBD).A novel,simple,and rapid photo-induced BtS transformation mechanism is now presented that utilizes a novel aggregation-induced emission luminogen(AIEgen)photosensitizer,triphenylamine-benzothiadiazole-pyridine-p-tolylboronic acid bromine salt(TBPBB),that generates reactive oxygen species(ROS)when exposed to light.The ROS selectively target and damage the membranes of Bacillus subtilis and trigger their transformation into spores.These spores demonstrate considerable promise for the effective treatment of IBD in a mouse disease model.Furthermore,thefluorescence signal generated by TBPBB can be used to directly visualize the recovery of damaged intestinal tis-sue.This is a valuable tool for monitoring the healing process and gaining insights into therapeutic efficacy.This study highlights the remarkable practical value of AIEgen-induced BtS transformation for identifying,localizing,and visualizing the therapeutic outcomes of IBD treatments.展开更多
基金Shanghai Hospital Development Center(Joint Breakthrough Project for New Frontier Technologies.Project No.SHDC 12015118)Science and Technology Commission of Shanghai Municipality(Project No.15411950102&15411950106)Natural Science Foundation of Shanghai(Project No.14ZR1407100)
文摘Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.
基金supported by the National Natural Science Foundation of China(Nos.52272440,51875375)the China Postdoctoral Science Foundation Funded Project(No.2021M701503).
文摘As a data-driven approach, Deep Learning(DL)-based fault diagnosis methods need to collect the relatively comprehensive data on machine fault types to achieve satisfactory performance. A mechanical system may include multiple submachines in the real-world. During condition monitoring of a mechanical system, fault data are distributed in a continuous flow of constantly generated information and new faults will inevitably occur in unconsidered submachines, which are also called machine increments. Therefore, adequately collecting fault data in advance is difficult. Limited by the characteristics of DL, training existing models directly with new fault data of new submachines leads to catastrophic forgetting of old tasks, while the cost of collecting all known data to retrain the models is excessively high. DL-based fault diagnosis methods cannot learn continually and adaptively in dynamic environments. A new Continual Learning Fault Diagnosis method(CLFD) is proposed in this paper to solve a series of fault diagnosis tasks with machine increments. The stability–plasticity dilemma is an intrinsic issue in continual learning. The core of CLFD is the proposed Dual-branch Adaptive Aggregation Residual Network(DAARN).Two types of residual blocks are created in each block layer of DAARN: steady and dynamic blocks. The stability–plasticity dilemma is solved by assigning them with adaptive aggregation weights to balance stability and plasticity, and a bi-level optimization program is used to optimize adaptive aggregation weights and model parameters. In addition, a feature-level knowledge distillation loss function is proposed to further overcome catastrophic forgetting. CLFD is then applied to the fault diagnosis case with machine increments. Results demonstrate that CLFD outperforms other continual learning methods and has satisfactory robustness.
文摘This paper studies the division of labor and economic development under global value chains in North South trade by mainly investigating the changes of production hours and cost per unit along with more and more output and increasing trade value in several industries in the U.S., because the U. S. is at the leading position in the division of labor by global value chains. The empirical evidence reveals that more international outsourcing, there will be more detailed division of labor, and the industry unit production time and production cost will show more declining trend year by year. This is consistent with that the global value chains and the outsourcing play more and more important roles in the international division of labor and economic growth in both developed and developing countries, and helps explain the integration of workforce across countries in the global value chains.
基金The National Key Research and Development Program of China(Project No.2017YFC0108603)Shanghai Hospital Development Center(Joint Breakthrough Project for New Frontier Technologies.Project No.SHDC12016120)+1 种基金Science and Technology Development Fund of Shanghai Pudong New Area(Project Nos.PKJ2017-Y49 and No.PKJ2018-Y51)The authors would like to thank Dr.Fei Liang(from the Fudan University Shanghai Cancer Center)for his support in statistical analysis and advice towards the design of this protocol.
文摘Background: Glioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy. Methods and design: Patients with newly diagnosed malignant gliomas will have their tumor tissue samples submitted for the analysis of the status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. In Phase I, the patients will undergo an induction carbon ion radiotherapy (CIRT) boost followed by 60 GyE of proton irradiation with concurrent temozolomide (TMZ) at 75 mg/m2. To determine the maximal dose of safe induction boost, the tolerance, and acute toxicity rates in a dose-escalation manner from 9 to 18 GyE in three fractions will be used. In Phase III, GBM-only patients will be randomized to receive either 60 GyE (2 GyE per fraction) of proton irradia-tion with concurrent TMZ (control arm) or a CIRT boost (dose determined in Phase I of this trial) followed by 60 GyE of proton irradiation with concurrent TMZ. The primary endpoints are overall survival (OS) and toxicity rates (acute and long-term). Secondary endpoints are progression-free survival (PFS), and tumor response (based upon assess-ment with C-methionine/fluoro-ethyl-tyrosine positron emission tomography [MET/FET PET] or magnetic resonance imaging [MRI] and detection of serologic immune markers). We hypothesize that the induction CIRT boost will result in a greater initial tumor-killing ability and prime the tumor microenvironment for enhanced immunologic tumor clearance, resulting in an expected 33% improvement in OS rates. Discussion: The prognosis of GBM remains grim. The mechanism underpinning the poor prognosis of this malig-nancy is its chronic state of tumor hypoxia, which promotes both immunosuppression/immunologic evasion and radio-resistance. The unique physical and biological properties of CIRT are expected to overcome these microenviron-mental limitations to confer an improved tumor-killing ability and anti-tumor immune response, which could result in an improvement in OS with minimal toxicity. Trial registration number This trial has been registered with the China Clinical Trials Registry, and was allocated the number ChiCTR-OID-17013702.
基金supported by the National Key R&D Program of China(2022YFD1700204)the National Natural Science Foundation of China(31872972 and 32170501).
文摘Insect lytic polysaccharide monooxygenases(LPMO15s)are newly discovered copper-dependent enzymes that promote chitin degradation in insect through oxidative cleavage of glycosidic bonds.They are potential pesticide targets due to their critical role for chitin turnover in the integument,trachea,and peritrophic matrix of the midgut during insect molting.However,the knowledge about whether and how LPMO15s participate in chitin turnover in other tissues is still insufficient.Here,using the orthopteran pest Locusta migratoria as a model,a novel alternative splicing site of LmLPMO15-1 was discovered and it produces 2 variants,LmLPMO15-1a and LmLPMO15-1b.The transcripts of LmLPMO15-1a and LmLPMO15-1b were specifically expressed in the trachea and foregut,respectively.RNA interference targeting LmLPMO15-1(a common fragment shared by both LmLPMO15-1a and LmLPMO15-1b),a specific region of LmLPMO15-1a or LmLPMO15-1b all significantly reduced survival rate of nymphs and induced lethal phenotypes with developmental stasis or molt failure.Ultrastructure analysis demonstrated that LmLPMO15-1b was specifically involved in foregut old cuticle degradation,while LmLPMO15-1a was exclusively responsible for the degradation of the tracheal old cuticle.This study revealed LmLPMO15-1 achieved tissue-specific functional differentiation through alternative splicing,and proved the significance of the spliced variants during insect growth and development.It provides new strategies for pest control targeting LPMO15-1.
文摘Background and Objectives:Previous studies on the risk factors for prolonged pleural effusion(PPE)have pri marily focused on surgical-related risk factors,with little research exploring the influence of nutritional factors on this delay.This study aimed to identify the nutritional risk factors for PPE in Chinese infants following congenital heart disease(CHD)surgery.Methods and Study Design:We retrospectively reviewed the medical records of patients under 3 years old with chylothorax following CHD surgery from 2016 to 2020.PPE was defined as pleu ral effusion lasting over 14 days.Logistical regression analysis was conducted to identify the risk factors.Results:Of 136 patients,42 patients developed PPE(30.9%).The PPE group had lower Height-for-Age Z-scores(HAZ)compared to the non-PPE group,while other demographic factors were not significantly different.Univariate analysis revealed that patients in PPE group exhibited delayed onset of chylothorax,prolonged duration of me chanical ventilation,increased chest effusion volume on the first postoperative day,and a reduced proportion of energy intake from enteral nutrition(EN)during the stable phase.Variables with p-value of<0.1 in univariate lo gistic regression analysis were included in the multivariate logistic regression analysis.A delayed onset of chylo thorax,extended periods of mechanical ventilation,a lower HAZ and a reduced proportion of energy intake from EN during the recovery phase.Conclusions:A delayed onset of chylothorax,extended periods of mechanical ventilation,a lower HAZ,and a reduced proportion of energy intake from EN during the recovery phase predict a higher risk of PPE.
基金supported by the National Natural Science Foundation of China(32472468 and 32001817)the Fundamental Research Program of Shanxi Province(202303021221123)+1 种基金the Youth Project of the Shanxi Fundamental Research Program(202203021222032)theStart-up Funds forScientific Research atNorth University of China(304-1101285714).
文摘Advanced glycation end products(AGEs),a group of complex compounds generated by nonenzymatic interactions between amino acids,proteins and reducing sugars or lipids,accumulate in vivo and activate various signaling pathways closely related to the occurrence of various chronic metabolic diseases.This study aims to explore the structure-activity relationship between phenolic acids with different structure and affecting the AGEs generation,and to provide data support for AGEs control.Phenolic acids(4-hydroxybenzoic,protocatechuic,gallic,p-coumaric,caffeic,ferulic and sinapic acids)were employed to indicate the AGEs formation condition in Maillard reaction performed in the glucose-lysine model system.Three 1,2-dicarbonyl compounds were reacted with phenolic acids and then tested by liquid chromatography-mass spectrometry.The results showed that N^(ε)-carboxy-methyl-lysine(CML),N^(ε)-carboxy-ethyl-lysine(CEL),and pyrraline formation inhibited by phenolic acids varied from(8.7±2.5)%to(33.2±2.5)%,(10.5±0.8)%to(57.1±3.2)%and(1.3±0.3)%to(23.3±0.8)%,respectively.The p-coumaric acid has no inhibitory effect on CML and CEL formation.Gallic acid shows the best inhibitory effect on CML formation due to its strong antioxidant activity.Sinapic acid showed the best glyoxal(GO)trapping rate and thus had the stronger inhibitory effect on CML formation.Ferulic acid can react with mono-,di-,and tri-methylglyoxal(MGO)to form adduct products,showing the best MGO scavenging rate and a good inhibitory effect on CEL formation.The main role of phenolic acid is an antioxidant agent to inhibit pyrraline formation.The glucose itself or ammonia-induced degradation and Amadori rearrangement products oxidation were lowered by protocatechuic,gallic and caffeic acids due to their antioxidant activities to form AGEs,while AGEs inhibited by ferulic and sinapic acids were mainly dependent on their trapping ability on 1,2-dicarbonyl compounds.
基金supported by the National Natural Science Foundation of China (Grant Nos. 11178004, and 11727805)
文摘Observations play a leading role in any branches of astronomy, including solar physics. In order to solve fundamental problems, such as solar dynamo [1], coronal heating [2] and the triggering of major solar eruptions [3], solar observations with spatial resolution better than 0.1 arcsec are required. Such a goal cannot be achieved without the help of adaptive optics （AO）, which eliminates the wavefront distortion caused by atmosphere turbulence [4,5]. However, solar observations are performed over an extended field of view （FoV）. Flare trigger mechanisms operate rapidly and on the smallest spatial scales and their location within the FoV is difficult to predict.
基金supported by the National Natural Science Foundation of China(Grant No.11727805)the Youth Innovation Promotion Association,Chinese Academy of Sciences(Grant No.2018412)。
文摘Large-aperture solar telescopes play an important role in solar observations and research,and require high temporal and spatial resolution[1].To solve some fundamental problems such as the solar dynamo,coronal heating,and the triggering of major solar eruptions,the spatial resolution for solar-atmosphere observation should reach at least 0.1 arcsec[2].
基金supported by the National Natural Science Foundation of China(31872972,31830076)the Shenzhen Science and Technology Program(KQTD20180411143628272).
文摘Lytic polysaccharide monooxygenases(LPMOs)are important enzymes that boost the hydrolysis of recalcitrant polysaccharides,such as chitin.They are found extensively in different insect species and are classified as auxiliary activities family 15(AA15)LPMOs(LPMO15).Some of them were identified from the insect midgut and proven to act on chitin.However,knowledge about their physiological roles during insect growth and development remains limited.Here,we found that midgut-specific LPMO15s are widely distributed in different insect orders,such as the orthopteran Locusta migratoria and the lepidopteran Bombyx mori.Using L.migratoria as a model insect,the function of midgut-specific LmLPMO15-3 during development was investigated.Double-stranded RNA-mediated downregulation of LmLPMO15-3 expression at the 4th or 5th instar nymph stage severely decreased the survival rate and resulted in lethal phenotypes.Hematoxylin and eosin staining results indicated that the deficient individuals exhibited incompletely digested peritrophic matrix(PM),which suggested that LmLPMO15-3 is essential for the deconstruction of the PM during molting.This study provides direct evidence of the physiological importance of a midgut-specific LPMO15 during insect development.As L.migratoria is one of the most destructive agricultural pests,LmLPMO15-3 is a potential target for pest management.
基金the National Natural Science Foundation of China(Grant Nos.52272052,51972315,21873110,and 61720106014).
文摘Comprehensive Summary Currently,solid-state fluorescent carbonized polymer dots(CPDs)have attracted attention increasingly due to their applications for optoelectronic display.However,designing CPDs possessing solid-state fluorescence and clarifying the fluorescence mechanism remain challenging.Herein,we initially synthesized a novel type of polythiophene derivatives CPDs,poly-4,4’-(thiophene-3,4-diyl)dibenzoic acid carbonized polymer dots(PDBA-CPDs)with solid-state fluorescence.Subsequently,the structural and optical characterization revealed that the solid-state fluorescence originated from the aggregation induced emission of the CPDs.In brief,in aggregation state,the remaining polymer structure groups on the surface of the CPDs overlapped and weakened the non-radiative transition,enhancing solid-state fluorescence emission.Thirdly,three polythiophene-derived CPDs were designed to further demonstrate the aggregation induced solid-state fluorescence mechanism.Finally,owing to their unique properties of solid-state fluorescence,the white LEDs(light emitting diodes)were fabricated with high color rendering index(CRI)of 82.7 and CIE coordinates of(0.37,0.39)using commercial 460 nm chip.
基金National Science Foundation of China,Grant/Award Numbers:52003228,52273197Shenzhen Key Laboratory of Functional Aggregate Materials,Grant/Award Number:DSYS20211021111400001Science Technology Innovation Commission of Shenzhen Municipality,Grant/Award Numbers:KQTD20210811090142053,JCYJ20220818103007014,JSGG20220606141800001。
文摘Efficient strategies for transforming Bacillus subtilis vegetative cells into spores(BtS transformation)are still limited,although they show promise for the treatment of inflammatory bowel disease(IBD).A novel,simple,and rapid photo-induced BtS transformation mechanism is now presented that utilizes a novel aggregation-induced emission luminogen(AIEgen)photosensitizer,triphenylamine-benzothiadiazole-pyridine-p-tolylboronic acid bromine salt(TBPBB),that generates reactive oxygen species(ROS)when exposed to light.The ROS selectively target and damage the membranes of Bacillus subtilis and trigger their transformation into spores.These spores demonstrate considerable promise for the effective treatment of IBD in a mouse disease model.Furthermore,thefluorescence signal generated by TBPBB can be used to directly visualize the recovery of damaged intestinal tis-sue.This is a valuable tool for monitoring the healing process and gaining insights into therapeutic efficacy.This study highlights the remarkable practical value of AIEgen-induced BtS transformation for identifying,localizing,and visualizing the therapeutic outcomes of IBD treatments.
