Objective The expression of HERG in common bone tumors is scarcely reported and there is a lack of dedicated studies.This study aimed to investigated the expression of HERG in several common musculoskeletal tumors.Met...Objective The expression of HERG in common bone tumors is scarcely reported and there is a lack of dedicated studies.This study aimed to investigated the expression of HERG in several common musculoskeletal tumors.Methods Immunohistochemical staining,RT-PCR,and Western blotting were used to observe HERG expression differences in various tissues and cell lines.Results HERG was differentially expressed in different malignant tumors,both at a differential protein level and localization within tumors.HERG was not expressed in normal bone tissue.The HERG inhibitor E-4031 markedly inhibited the proliferation of osteosarcoma cell lines.Conclusion HERG was highly expressed in malignant tumors.Blocking of HERG can effectively inhibit the proliferation of bone tumors.展开更多
We have designed,assembled,and tested a 4-MA,60-ns fast linear transformer driver(LTD),which is the first operating generator featuring multiple LTD modules connected in parallel.The LTD-based accelerator comprises si...We have designed,assembled,and tested a 4-MA,60-ns fast linear transformer driver(LTD),which is the first operating generator featuring multiple LTD modules connected in parallel.The LTD-based accelerator comprises six modules in parallel,each of which has ten-stage cavities stacked in series.The six LTD modules are connected to a water tank of diameter 6 m via a 3-m-long impedance-matched deionized waterinsulated coaxial transmission line.In the water tank,the electrical pulses are transmitted down by six horizontal tri-plate transmission lines.A 2.1-m-diameter two-level vacuum insulator stack is utilized to separate the deionized water region from the vacuum region.In the vacuum,the currents are further transported downstream by a two-level magnetically insulated transmission-line and then converged through four post-hole convolutes.Plasma radiation loads or bremsstrahlung electron beam diodes serve as loads that are expected to generate intense soft X rays or warm X rays.The machine is 3.2 m in height and 22 m in outer diameter,including support systems such as a high-voltage charge supply,magnetic core reset system,trigger system,and support platform for inner stalk installation and maintenance.A total of 1440 individual±100-kV multi-gap spark switches and 2880 individual 100-kV capacitors are employed in the accelerator.A total of 12 fiberoptic laser-controlled trigger generators combining photoconductive and traditional gas spark switch technologies are used to realize the synchronous discharge of the more than 1000 gas switches.At an LTD charge voltage of±85 kV,the accelerator stores an initial energy of about 300 kJ and is expected to deliver a current of 3–5 MA into various loads.To date,the LTD facility has shot into a thick-walled aluminum liner load and a reflex triode load.With a thick-walled aluminum liner of inductance 1.81 nH,a current with peak up to 4.1 MA and rise time(10%–90%)of about 60 ns has been achieved.The current transport efficiency from the insulator stack to the liner load approaches 100%during peak times.The LTD accelerator has been used to drive reflex triode loads generating warm X rays with high energy fluence and large radiation area.It has been demonstrated that this LTD is a promising and high-efficiency prime pulsed power source suitable for use in constructing the next generation of large-scale accelerators with currents of tens of megaamperes.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the th...The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.展开更多
Background: Bringing free-living animals into captivity subjects them to the stress of both capture and captivity, leading to the alteration of normal physiological processes and behaviors through activation of the hy...Background: Bringing free-living animals into captivity subjects them to the stress of both capture and captivity, leading to the alteration of normal physiological processes and behaviors through activation of the hypothalamic– pituitary–adrenal axis. In free-living birds, although elevated plasma corticosterone (CORT) is an important adaptation regulating physiological and behavioral responses during the process of capture and captivity stress, little information is currently available on the effects of such stress on plasma metabolite levels. Methods: We examined the effects of immediate capture and 24-h captivity on body mass, body condition, plasma CORT, and metabolite levels including glucose (Glu), triglyceride (TG), total cholesterol (TC), uric acid (UA), in breeding Eurasian Tree Sparrows (Passer montanus). Results: CORT and Glu levels were increased significantly by the stress of capture, whereas TC and UA levels decreased. Body mass, body condition declined notably after 24 h in captivity, but CORT, Glu, and UA levels increased. Furthermore, male sparrows had lower TG levels after both capture and captivity than those of females. The relationships between plasma CORT and metabolite levels varied between sexes. Conclusions: Our results revealed that the metabolic status of Eurasian Tree Sparrows could be dramatically altered by capture and captivity. Monitoring the dynamic effects of both capture and captivity on plasma CORT, metabolite levels in a free-living bird contributes to a better understanding of the stress-induced pathways involved in sexdependent energy mobilization.展开更多
Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor n...Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the disease.Although there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron degeneration.Thus,there is still a lack of effective treatment for this debilitating neurodegenerative disorder.Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons.Stem cell therapies may also be able to re-establish the motor control of voluntary muscles.Here,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis.We focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem cells.In our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord.Furthermore,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety of stem cell derivatives,including induced pluripotent stem cells,are being considered for clinical trials for various diseases.展开更多
Background: Geographic variation in body size is assumed to reflect adaptation to local environmental conditions. Although Bergmann's rule is usually sufficient to explain such variation in homeotherms, some excep...Background: Geographic variation in body size is assumed to reflect adaptation to local environmental conditions. Although Bergmann's rule is usually sufficient to explain such variation in homeotherms, some exceptions have been documented. The relationship between altitude, latitude and body size, has been well documented for some vertebrate taxa during the past decades. However, relatively little information is available on the effects of climate variables on body size in birds.Methods: We collected the data of 267 adult Eurasian Tree Sparrow(Passer montanus) specimens sampled at 48 localities in China's mainland, and further investigated the relationships between two response variables, body mass and wing length, as well as a suit of explanatory variables, i.e. altitude, latitude, mean annual temperature(MAT), annual precipitation(PRC), annual sunshine hours(SUN), average annual wind speed(WS), air pressure(AP) and relative humidity(RH).Results: Our study showed that(1) although the sexes did not differ significantly in body mass, males had longer wings than females;(2) body mass and wing length were positively correlated with altitude but not with latitude;(3) body mass and wing length were negatively correlated with AP and RH, but not significantly correlated with WS. Body mass was positively correlated with SUN and inversely correlated with MAT. Wing length was not correlated with MAT in either sex, but was positively correlated with SUN and negatively correlated with PRC in male sparrows;(4) variation in body mass could be best explained by AP and SUN, whereas variation in wing length could be explained by RH and AP in both sexes. In addition, variation in male sparrows can be explained by SUN, WS and PRC but not in females.Conclusions: Two different proxies of body size, body mass and wing length, correlated with same geographic factors and different climate factors. These differences may reflect selection for heat conservation in the case of body mass, and for efficient flight in the case of wing length.展开更多
Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water sh...Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water shortages and the overuse of fertilizers.The field experiment had twelve treatments and a control(CK)trial including two irrigation amounts(I1,100%ETm;I2,60%ETm;where ETm is the maximum evapotranspiration),two nitrogen applications(N1,360 kg ha^(−1);N2,120 kg ha^(−1))and three biochar application levels(B1,60 t ha^(−1);B_(2),30 t ha^(−1)and B3,0 t ha^(−1)).A multi-objective synergistic irrigation-nitrogen-biochar application system for improving tomato yield,quality,water and nitrogen use efficiency,and greenhouse emissions was developed by integrating the techniques of experimentation and optimization.First,a coupled irrigation-nitrogen-biochar plot experiment was arranged.Then,tomato yield and fruit quality parameters were determined experimentally to establish the response relationships between irrigation-nitrogen-biochar dosage and yield,comprehensive quality of tomatoes(TCQ),irrigation water use efficiency(IWUE),partial factor productivity of nitrogen(PFPN),and net greenhouse gas emissions(NGE).Finally,a multi-objective dynamic optimization regulation model of irrigation-nitrogen-biochar resource allocation at different growth stages of tomato was constructed which was solved by the fuzzy programming method.The results showed that the application of irrigation and nitrogen to biochar promoted increase in yield,IWUE and PFPN,while it had an inhibitory effect on NGE.In addition,the optimal allocation amounts of water and fertilizer were different under different scenarios.The yield of the S1 scenario increased by 8.31%compared to the B_(1)I_(1)N_(2) treatment;TCQ of the S2 scenario increased by 5.14%compared to the B_(2)I_(2)N_(1) treatment;IWUE of the S3 scenario increased by 10.01%compared to the B1I2N2 treatment;PFPN of the S4 scenario increased by 9.35%compared to the B_(1)I_(1)N_(2) treatment;and NGE of the S5 scenario decreased by 11.23%compared to the B_(2)I1N1 treatment.The optimization model showed that the coordination of multiple objectives considering yield,TCQ,IWUE,PFPN,and NGE increased on average from 4.44 to 69.02%compared to each treatment when the irrigation-nitrogen-biochar dosage was 205.18 mm,186 kg ha^(−1)and 43.31 t ha^(−1),respectively.This study provides a guiding basis for the sustainable management of water and fertilizer in greenhouse tomato production under drip irrigation fertilization conditions.展开更多
High entropy alloys(HEAs)with superb mechanical properties have been traditionally produced by solid-ification and subsequent heat treatment,In this paper,we demonstrate a new route via one-step process using sub-rapi...High entropy alloys(HEAs)with superb mechanical properties have been traditionally produced by solid-ification and subsequent heat treatment,In this paper,we demonstrate a new route via one-step process using sub-rapid cooling.Under proper cooling rates,the CrFeCoNiAl^(0.6) HEA could form ultrafineFCC+BCC dual-phase structure.By varying cooling rate,we can control the fraction of the BCC phaseand refinement of FCC microstructures that have tunable mechanical properties in yield strength and hardness ranging from~580 to~1460 MPa and~260 to~550 Hv.We show that the structure-property-processing relation originates from the sideplate microstructures formed during fast cooling that havespecific crystallographic orientation relationship between the FCC and BCC phases and chemical segrega tion.This work provides a new setting for better understanding of the solid-state phase transformation in HEAs under sub-rapid solidification conditions as well as a novel method for development of high-performance HEAs.展开更多
The hypothalamic-pituitary-gonadal(HPG)axis ubiquitously regulates seasonal reproduction,following the rhythmicity of a suite of environmental cues.Birds display prominent seasonal variations in gonad size regulated b...The hypothalamic-pituitary-gonadal(HPG)axis ubiquitously regulates seasonal reproduction,following the rhythmicity of a suite of environmental cues.Birds display prominent seasonal variations in gonad size regulated by two hypothalamic peptides,gonadotropin-releasing hormone-1(GnRH-I)and gonadotropin-inhibiting hormone(GnIH).How multi-brooded avian species adjust GnRH-I and GnIH to regulate gonadal morphology seasonally remains largely unknown.Here,we studied the variations in the hypothalamic immunoreactivity(ir)of GnRH-I and GnIH,gonadal proliferation,and apoptosis in a typical multi-brooded species,the Eurasian Tree Sparrow(Passer montanus),across the pre-breeding(PB),first breeding(FB),second breeding(SB),pre-basic molt(PM),and wintering stages(WS).Our results showed that both sexes had higher preoptic area(POA)-GnRH-I-ir but lower paraventricular nucleus(PVN)-GnIH-ir neurons during the breeding stages(FB and SB)relative to other life-history stages,with no significant differences between two broods.The testes and ovaries were significantly larger during the breeding stages.Testicular volume increased during the two broods due to anincreased diameter of seminiferous tubules.Furthermore,there were more testicular apoptotic cells in PB and WS stages than in breeding stages,and in PB stage than in PM stage.Males had higher POA-GnRH-I expression than females during the breeding stages,but both sexes had comparable PVN-GnIH expression throughout the annual cycle.Both sexes of the sparrows may undergo a similar pattern of life-history stage-dependent variation in the hypothalamic GnRH-I,GnIH,and gonadal morphology,except that during breeding stages,males may display higher expression of POA-GnRH-I relative to females.The higher expression of POA-GnRH-I-ir in breeding male sparrows may be critical for male-dependent parental care.展开更多
Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The sta...Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.展开更多
In this work, we study the influence of carrier gas H2flow rate on the quality of p-type GaN grown and annealed at lower temperatures. It is found that the concentration of H atoms in Mg-doped GaN epilayer can effecti...In this work, we study the influence of carrier gas H2flow rate on the quality of p-type GaN grown and annealed at lower temperatures. It is found that the concentration of H atoms in Mg-doped GaN epilayer can effectively decrease with appropriately reducing the carrier gas H2flow rate, and a high-quality p-type GaN layer could be obtained at a comparatively low annealing temperature by reducing the carrier gas H2flow rate. Meanwhile, it is found that the intensity and wavelength of DAP peak are changed as the annealing temperature varies, which shows that the thermal annealing has a remarkable effect not only on the activation of acceptors but also on the compensation donors.展开更多
The relation between catalytic reactivities and metal/metal oxide ratios,as well as the functions of the metal and the metal oxides were investigated in the CO_(2)hydrogenation reaction over highly active Co_x(CoO)_(1...The relation between catalytic reactivities and metal/metal oxide ratios,as well as the functions of the metal and the metal oxides were investigated in the CO_(2)hydrogenation reaction over highly active Co_x(CoO)_(1–x)catalysts in operando.The catalytic reactivity of the samples in the CO_(2)methanation improves with the increased Co O concentration.Strikingly,the sample with the highest concentration of CoO,i.e.,Co_(0.2)(CoO)_(0.8),shows activity at temperatures lower than 200°C where the other samples with less CoO are inactive.The origins of this improvement are the increased amount and moderate binding of adsorbed CO_(2)on CoO sites.The derivative adsorption species are found to be intermediates of the CH4 formation.The metallic Co functions as the electronically catalytic site which provides electrons for the hydrogenation steps.As a result,an abundant amount of CoO combined with Co is the optimal composition of the catalyst for achieving the highest reactivity for CO_(2)hydrogenation.展开更多
The solid-liquid interfacial free energy and its anisotropy are crucial quantities in determining the microstructure and mechanical properties of materials. However, most researches mainly concerned the solidliquid co...The solid-liquid interfacial free energy and its anisotropy are crucial quantities in determining the microstructure and mechanical properties of materials. However, most researches mainly concerned the solidliquid coexistence at melting point. In this work, two methods, the critical nucleus method （CNM） and the capillary fluctuation method （CFM）, were combined to get these quantities in undercooled system by molecular dynamics （MD） simulations. The melting point, Tolman length, interfacial free energy and its anisotropy were calculated, and good consistent results from these two methods are obtained. The results of interfacial free energy obtained by CNM and CFM are 103.79 and 102.13 mJ·m^-2, respectively, with the error 〈2%. Meanwhile, both of the methods provide the rank of interfacial free energy by γ7100〉 γ7120 〉 γ 7110 〉 γ112 〉 γ111. The results of the present study are also in good agreement with experimental data and computational data in the literature.展开更多
Four blue-violet light emitting InGaN/GaN multiple quantum well（MQW） structures with different well widths are grown by metal–organic chemical vapor deposition. The carrier localization effect in these samples is i...Four blue-violet light emitting InGaN/GaN multiple quantum well（MQW） structures with different well widths are grown by metal–organic chemical vapor deposition. The carrier localization effect in these samples is investigated mainly by temperature-dependent photoluminescence measurements. It is found that the localization effect is enhanced as the well width increases from 1.8 nm to 3.6 nm in our experiments. The temperature induced PL peak blueshift and linewidth variation increase with increasing well width, implying that a greater amplitude of potential fluctuation as well as more localization states exist in wider wells. In addition, it is noted that the broadening of the PL spectra always occurs mainly on the low-energy side of the PL spectra due to the temperature-induced band-gap shrinkage, while in the case of the widest well, a large extension of the spectral curve also occurs in the high energy sides due to the existence of more shallow localized centers.展开更多
基金Suppported by a grant from the Key Research and Development Program of Shaanxi Province Project(No.2018YBXM-SF-12-2)
文摘Objective The expression of HERG in common bone tumors is scarcely reported and there is a lack of dedicated studies.This study aimed to investigated the expression of HERG in several common musculoskeletal tumors.Methods Immunohistochemical staining,RT-PCR,and Western blotting were used to observe HERG expression differences in various tissues and cell lines.Results HERG was differentially expressed in different malignant tumors,both at a differential protein level and localization within tumors.HERG was not expressed in normal bone tissue.The HERG inhibitor E-4031 markedly inhibited the proliferation of osteosarcoma cell lines.Conclusion HERG was highly expressed in malignant tumors.Blocking of HERG can effectively inhibit the proliferation of bone tumors.
基金supported by the National Natural Science Foundation of China(Grant Nos.12027811 and 51790524).
文摘We have designed,assembled,and tested a 4-MA,60-ns fast linear transformer driver(LTD),which is the first operating generator featuring multiple LTD modules connected in parallel.The LTD-based accelerator comprises six modules in parallel,each of which has ten-stage cavities stacked in series.The six LTD modules are connected to a water tank of diameter 6 m via a 3-m-long impedance-matched deionized waterinsulated coaxial transmission line.In the water tank,the electrical pulses are transmitted down by six horizontal tri-plate transmission lines.A 2.1-m-diameter two-level vacuum insulator stack is utilized to separate the deionized water region from the vacuum region.In the vacuum,the currents are further transported downstream by a two-level magnetically insulated transmission-line and then converged through four post-hole convolutes.Plasma radiation loads or bremsstrahlung electron beam diodes serve as loads that are expected to generate intense soft X rays or warm X rays.The machine is 3.2 m in height and 22 m in outer diameter,including support systems such as a high-voltage charge supply,magnetic core reset system,trigger system,and support platform for inner stalk installation and maintenance.A total of 1440 individual±100-kV multi-gap spark switches and 2880 individual 100-kV capacitors are employed in the accelerator.A total of 12 fiberoptic laser-controlled trigger generators combining photoconductive and traditional gas spark switch technologies are used to realize the synchronous discharge of the more than 1000 gas switches.At an LTD charge voltage of±85 kV,the accelerator stores an initial energy of about 300 kJ and is expected to deliver a current of 3–5 MA into various loads.To date,the LTD facility has shot into a thick-walled aluminum liner load and a reflex triode load.With a thick-walled aluminum liner of inductance 1.81 nH,a current with peak up to 4.1 MA and rise time(10%–90%)of about 60 ns has been achieved.The current transport efficiency from the insulator stack to the liner load approaches 100%during peak times.The LTD accelerator has been used to drive reflex triode loads generating warm X rays with high energy fluence and large radiation area.It has been demonstrated that this LTD is a promising and high-efficiency prime pulsed power source suitable for use in constructing the next generation of large-scale accelerators with currents of tens of megaamperes.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金supported by the National Natural Science Foundation of China (Grant No.81622035, 81672610, and 81521002)
文摘The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.
基金supported by the National Natural Science Foundation of China(NSFC,31672292)the Natural Science Foundation of Hebei Province(C2017205059)+1 种基金the foundation of China Scholarship Council(201408130068) to D.Lithe NSFC(31770445)to Y.Wu,the NSFC(31372201)to X.Gao
文摘Background: Bringing free-living animals into captivity subjects them to the stress of both capture and captivity, leading to the alteration of normal physiological processes and behaviors through activation of the hypothalamic– pituitary–adrenal axis. In free-living birds, although elevated plasma corticosterone (CORT) is an important adaptation regulating physiological and behavioral responses during the process of capture and captivity stress, little information is currently available on the effects of such stress on plasma metabolite levels. Methods: We examined the effects of immediate capture and 24-h captivity on body mass, body condition, plasma CORT, and metabolite levels including glucose (Glu), triglyceride (TG), total cholesterol (TC), uric acid (UA), in breeding Eurasian Tree Sparrows (Passer montanus). Results: CORT and Glu levels were increased significantly by the stress of capture, whereas TC and UA levels decreased. Body mass, body condition declined notably after 24 h in captivity, but CORT, Glu, and UA levels increased. Furthermore, male sparrows had lower TG levels after both capture and captivity than those of females. The relationships between plasma CORT and metabolite levels varied between sexes. Conclusions: Our results revealed that the metabolic status of Eurasian Tree Sparrows could be dramatically altered by capture and captivity. Monitoring the dynamic effects of both capture and captivity on plasma CORT, metabolite levels in a free-living bird contributes to a better understanding of the stress-induced pathways involved in sexdependent energy mobilization.
基金supported by the Stem Cell and Translation National Key Project(No.2016YFA0101403,to ZC)the National Natural Science Foundation of China(Nos.81973351,81661130160,81422014,81561138004,all to ZC)+7 种基金the Beijing Municipal Natural Science Foundation(No.5142005,to ZC)Beijing Talents Foundation(No.2017000021223TD03,to ZC)the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-Year Plan(No.CIT&TCD20180333,to ZC)the Beijing Medical System High Level Talent Award(No.2015-3-063,to ZC)Beijing Municipal Health Commission Fund(No.PXM2020_026283_000005)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund(No.2018A03,to ZC)the Royal Society-Newton Advanced Fellowship(No.NA150482,to ZC)the USA Veterans Administration(No.I01 RX002264-01A2,to PL).
文摘Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the disease.Although there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron degeneration.Thus,there is still a lack of effective treatment for this debilitating neurodegenerative disorder.Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons.Stem cell therapies may also be able to re-establish the motor control of voluntary muscles.Here,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis.We focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem cells.In our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord.Furthermore,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety of stem cell derivatives,including induced pluripotent stem cells,are being considered for clinical trials for various diseases.
基金supported by grants from the National Natural Science Foundation of China (NSFC, 31330073, 31672292)the Natural Science Foundation of the Department of Education, Hebei Province (YQ2014024)
文摘Background: Geographic variation in body size is assumed to reflect adaptation to local environmental conditions. Although Bergmann's rule is usually sufficient to explain such variation in homeotherms, some exceptions have been documented. The relationship between altitude, latitude and body size, has been well documented for some vertebrate taxa during the past decades. However, relatively little information is available on the effects of climate variables on body size in birds.Methods: We collected the data of 267 adult Eurasian Tree Sparrow(Passer montanus) specimens sampled at 48 localities in China's mainland, and further investigated the relationships between two response variables, body mass and wing length, as well as a suit of explanatory variables, i.e. altitude, latitude, mean annual temperature(MAT), annual precipitation(PRC), annual sunshine hours(SUN), average annual wind speed(WS), air pressure(AP) and relative humidity(RH).Results: Our study showed that(1) although the sexes did not differ significantly in body mass, males had longer wings than females;(2) body mass and wing length were positively correlated with altitude but not with latitude;(3) body mass and wing length were negatively correlated with AP and RH, but not significantly correlated with WS. Body mass was positively correlated with SUN and inversely correlated with MAT. Wing length was not correlated with MAT in either sex, but was positively correlated with SUN and negatively correlated with PRC in male sparrows;(4) variation in body mass could be best explained by AP and SUN, whereas variation in wing length could be explained by RH and AP in both sexes. In addition, variation in male sparrows can be explained by SUN, WS and PRC but not in females.Conclusions: Two different proxies of body size, body mass and wing length, correlated with same geographic factors and different climate factors. These differences may reflect selection for heat conservation in the case of body mass, and for efficient flight in the case of wing length.
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
基金supported by the National Natural Science Foundation of China(52222902 and 52079029)。
文摘Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water shortages and the overuse of fertilizers.The field experiment had twelve treatments and a control(CK)trial including two irrigation amounts(I1,100%ETm;I2,60%ETm;where ETm is the maximum evapotranspiration),two nitrogen applications(N1,360 kg ha^(−1);N2,120 kg ha^(−1))and three biochar application levels(B1,60 t ha^(−1);B_(2),30 t ha^(−1)and B3,0 t ha^(−1)).A multi-objective synergistic irrigation-nitrogen-biochar application system for improving tomato yield,quality,water and nitrogen use efficiency,and greenhouse emissions was developed by integrating the techniques of experimentation and optimization.First,a coupled irrigation-nitrogen-biochar plot experiment was arranged.Then,tomato yield and fruit quality parameters were determined experimentally to establish the response relationships between irrigation-nitrogen-biochar dosage and yield,comprehensive quality of tomatoes(TCQ),irrigation water use efficiency(IWUE),partial factor productivity of nitrogen(PFPN),and net greenhouse gas emissions(NGE).Finally,a multi-objective dynamic optimization regulation model of irrigation-nitrogen-biochar resource allocation at different growth stages of tomato was constructed which was solved by the fuzzy programming method.The results showed that the application of irrigation and nitrogen to biochar promoted increase in yield,IWUE and PFPN,while it had an inhibitory effect on NGE.In addition,the optimal allocation amounts of water and fertilizer were different under different scenarios.The yield of the S1 scenario increased by 8.31%compared to the B_(1)I_(1)N_(2) treatment;TCQ of the S2 scenario increased by 5.14%compared to the B_(2)I_(2)N_(1) treatment;IWUE of the S3 scenario increased by 10.01%compared to the B1I2N2 treatment;PFPN of the S4 scenario increased by 9.35%compared to the B_(1)I_(1)N_(2) treatment;and NGE of the S5 scenario decreased by 11.23%compared to the B_(2)I1N1 treatment.The optimization model showed that the coordination of multiple objectives considering yield,TCQ,IWUE,PFPN,and NGE increased on average from 4.44 to 69.02%compared to each treatment when the irrigation-nitrogen-biochar dosage was 205.18 mm,186 kg ha^(−1)and 43.31 t ha^(−1),respectively.This study provides a guiding basis for the sustainable management of water and fertilizer in greenhouse tomato production under drip irrigation fertilization conditions.
基金supported by National Natural Science Foundation of China [grant nos. 51701183, U1704159]China Postdoctoral Science Foundation funded project [grant no. 2017M622368,2018M630834]
文摘High entropy alloys(HEAs)with superb mechanical properties have been traditionally produced by solid-ification and subsequent heat treatment,In this paper,we demonstrate a new route via one-step process using sub-rapid cooling.Under proper cooling rates,the CrFeCoNiAl^(0.6) HEA could form ultrafineFCC+BCC dual-phase structure.By varying cooling rate,we can control the fraction of the BCC phaseand refinement of FCC microstructures that have tunable mechanical properties in yield strength and hardness ranging from~580 to~1460 MPa and~260 to~550 Hv.We show that the structure-property-processing relation originates from the sideplate microstructures formed during fast cooling that havespecific crystallographic orientation relationship between the FCC and BCC phases and chemical segrega tion.This work provides a new setting for better understanding of the solid-state phase transformation in HEAs under sub-rapid solidification conditions as well as a novel method for development of high-performance HEAs.
基金supported by the National Natural Science Foundation of China(NSFC,31971413)to DL and NSFC(31770445)to YWthe Natural Science Foundation of Hebei Province,China(NSFHB,C2020205038)to DL and NSFHB(C2020205005)the Postdoctoral Research Foundation of China(PRFC,2020M670685)to LW。
文摘The hypothalamic-pituitary-gonadal(HPG)axis ubiquitously regulates seasonal reproduction,following the rhythmicity of a suite of environmental cues.Birds display prominent seasonal variations in gonad size regulated by two hypothalamic peptides,gonadotropin-releasing hormone-1(GnRH-I)and gonadotropin-inhibiting hormone(GnIH).How multi-brooded avian species adjust GnRH-I and GnIH to regulate gonadal morphology seasonally remains largely unknown.Here,we studied the variations in the hypothalamic immunoreactivity(ir)of GnRH-I and GnIH,gonadal proliferation,and apoptosis in a typical multi-brooded species,the Eurasian Tree Sparrow(Passer montanus),across the pre-breeding(PB),first breeding(FB),second breeding(SB),pre-basic molt(PM),and wintering stages(WS).Our results showed that both sexes had higher preoptic area(POA)-GnRH-I-ir but lower paraventricular nucleus(PVN)-GnIH-ir neurons during the breeding stages(FB and SB)relative to other life-history stages,with no significant differences between two broods.The testes and ovaries were significantly larger during the breeding stages.Testicular volume increased during the two broods due to anincreased diameter of seminiferous tubules.Furthermore,there were more testicular apoptotic cells in PB and WS stages than in breeding stages,and in PB stage than in PM stage.Males had higher POA-GnRH-I expression than females during the breeding stages,but both sexes had comparable PVN-GnIH expression throughout the annual cycle.Both sexes of the sparrows may undergo a similar pattern of life-history stage-dependent variation in the hypothalamic GnRH-I,GnIH,and gonadal morphology,except that during breeding stages,males may display higher expression of POA-GnRH-I relative to females.The higher expression of POA-GnRH-I-ir in breeding male sparrows may be critical for male-dependent parental care.
基金by the National Natural Science Foundation of China(No.82173765)the Science Foundation for Outstanding Youth of Liaoning Province(2021-YQ-08)+5 种基金Ningxia Key Research and Invention Program(No.2021BEG02039)Basic Research Projects of Liaoning Provincial Department of Education(2020LFW01)the Career Development Program for Young Teachers in Shenyang Pharmaceutical University(ZQN2019003)the Outstanding Youth Lifting Program in Shenyang Pharmaceutical University(YQ202115)the Natural Science Foundation of Liaoning Province(2020-MS-074)Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization(Dalian Minzu University),Ministry of Education(KF2022005),China.
文摘Nanocrystals(NCs),a colloidal dispersion system formulated with stabilizers,have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs.The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs.However,how stabilizers affect the bioavailability of NCs remains unknown.In this study,F68,F127,HPMC,and PVP were each used as a stabilizer to formulate naringenin NCs.The NCs formulated with PVP exhibited excellent release behaviors,cellular uptake,permeability,oral bioavailability,and anti-inflammatory effects.The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer,which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved.This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.
基金Project supported by the the Science Challenge Project of China(Grant No.TZ2016003)the National Natural Science Foundation of China(Grant Nos.61674138,61674139,61604145,61574135,61574134,61474142,and 61474110)Beijing Municipal Science and Technology Project(Grant No.Z161100002116037)
文摘In this work, we study the influence of carrier gas H2flow rate on the quality of p-type GaN grown and annealed at lower temperatures. It is found that the concentration of H atoms in Mg-doped GaN epilayer can effectively decrease with appropriately reducing the carrier gas H2flow rate, and a high-quality p-type GaN layer could be obtained at a comparatively low annealing temperature by reducing the carrier gas H2flow rate. Meanwhile, it is found that the intensity and wavelength of DAP peak are changed as the annealing temperature varies, which shows that the thermal annealing has a remarkable effect not only on the activation of acceptors but also on the compensation donors.
基金financially supported by Innosuisse,the Swiss Innovation Agency,is gratefully acknowledgedThe NAPXPS system is funded by the SNSF R’EQUIP project(No.170736)+1 种基金the financial support from SNSF(Ambizione Project PZ00P2_179989)the China Scholarship Council for the PhD grant(Grant No.201506060156)。
文摘The relation between catalytic reactivities and metal/metal oxide ratios,as well as the functions of the metal and the metal oxides were investigated in the CO_(2)hydrogenation reaction over highly active Co_x(CoO)_(1–x)catalysts in operando.The catalytic reactivity of the samples in the CO_(2)methanation improves with the increased Co O concentration.Strikingly,the sample with the highest concentration of CoO,i.e.,Co_(0.2)(CoO)_(0.8),shows activity at temperatures lower than 200°C where the other samples with less CoO are inactive.The origins of this improvement are the increased amount and moderate binding of adsorbed CO_(2)on CoO sites.The derivative adsorption species are found to be intermediates of the CH4 formation.The metallic Co functions as the electronically catalytic site which provides electrons for the hydrogenation steps.As a result,an abundant amount of CoO combined with Co is the optimal composition of the catalyst for achieving the highest reactivity for CO_(2)hydrogenation.
文摘The solid-liquid interfacial free energy and its anisotropy are crucial quantities in determining the microstructure and mechanical properties of materials. However, most researches mainly concerned the solidliquid coexistence at melting point. In this work, two methods, the critical nucleus method （CNM） and the capillary fluctuation method （CFM）, were combined to get these quantities in undercooled system by molecular dynamics （MD） simulations. The melting point, Tolman length, interfacial free energy and its anisotropy were calculated, and good consistent results from these two methods are obtained. The results of interfacial free energy obtained by CNM and CFM are 103.79 and 102.13 mJ·m^-2, respectively, with the error 〈2%. Meanwhile, both of the methods provide the rank of interfacial free energy by γ7100〉 γ7120 〉 γ 7110 〉 γ112 〉 γ111. The results of the present study are also in good agreement with experimental data and computational data in the literature.
基金supported by the National Key Research and Development Program of China(Grant No.2016YFB0401801)the National Natural Science Foundation of China(Grant Nos.61674138,61674139,61604145,61574135,61574134,61474142,61474110,61377020,and 61376089)+1 种基金Science Challenge Project,China(Grant No.JCKY2016212A503)One Hundred Person Project of the Chinese Academy of Sciences
文摘Four blue-violet light emitting InGaN/GaN multiple quantum well（MQW） structures with different well widths are grown by metal–organic chemical vapor deposition. The carrier localization effect in these samples is investigated mainly by temperature-dependent photoluminescence measurements. It is found that the localization effect is enhanced as the well width increases from 1.8 nm to 3.6 nm in our experiments. The temperature induced PL peak blueshift and linewidth variation increase with increasing well width, implying that a greater amplitude of potential fluctuation as well as more localization states exist in wider wells. In addition, it is noted that the broadening of the PL spectra always occurs mainly on the low-energy side of the PL spectra due to the temperature-induced band-gap shrinkage, while in the case of the widest well, a large extension of the spectral curve also occurs in the high energy sides due to the existence of more shallow localized centers.
