Background Ochratoxin A(OTA)is a toxin widely found in aquafeed ingredients,and hypoxia is a common prob-lem in fish farming.In practice,aquatic animals tend to be more sensitive to hypoxia while feeds are contaminate...Background Ochratoxin A(OTA)is a toxin widely found in aquafeed ingredients,and hypoxia is a common prob-lem in fish farming.In practice,aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA,but no studies exist in this area.This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin(CUR).Methods A total of 720 healthy juvenile grass carp(11.06±0.05 g)were selected and assigned randomly to 4 experi-mental groups:control group(without OTA and CUR),1.2 mg/kg OTA group,400 mg/kg CUR group,and 1.2 mg/kg OTA+400 mg/kg CUR group with three replicates each for 60 d.Subsequently,32 fish were selected,divided into nor-moxia(18 fish)and hypoxia(18 fish)groups,and subjected to hypoxia stress for 96 h.Results CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacu-olation and nuclear excursion.The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3,8,9,Bax,and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2,and attenuation of endoplasmic reticulum stress(ERS)by reducing Grp78 expression and chop levels.This may be attributed to the fact that the addi-tion of CUR increased the levels of catalase(CAT)and glutathione reductase(GSH),increased antioxidant capacity,and ensured the proper functioning of respiratory chain complexes I and II,which in turn reduced the high produc-tion of reactive oxygen species(ROS),thus alleviating apoptosis and ERS.Conclusions In conclusion,our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia.This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.展开更多
Background Ochratoxin A(OTA),a globally abundant and extremely hazardous pollutant,is a significant source of contamination in aquafeeds and is responsible for severe food pollution.The developmental toxicity of OTA a...Background Ochratoxin A(OTA),a globally abundant and extremely hazardous pollutant,is a significant source of contamination in aquafeeds and is responsible for severe food pollution.The developmental toxicity of OTA and the potential relieving strategy of natural products remain unclear.This study screened the substance curcumin(Cur),which had the best effect in alleviating OTA inhibition of myoblast proliferation,from 96 natural products and investigated its effect and mechanism in reducing OTA myotoxicity in vivo and in vitro.Methods A total of 720 healthy juvenile grass carp,with an initial average body weight of 11.06±0.05 g,were randomly assigned into 4 groups:the control group(without OTA and Cur),1.2 mg/kg OTA group,400 mg/kg Cur group,and 1.2 mg/kg OTA+400 mg/kg Cur group.Each treatment consisted of 3 replicates(180 fish)for 60 d.Results Firstly,we cultured,purified,and identified myoblasts using the tissue block culture method.Through preliminary screening and re-screening of 96 substances,we examined cell proliferation-related indicators such as cell viability and ultimately found that Cur had the best effect.Secondly,Cur could alleviate OTA-inhibited myoblast differentiation and myofibrillar development-related proteins(Myo G and MYHC)in vivo and in vitro and improve the growth performance of grass carp.Then,Cur could also promote the expression of OTA-inhibited protein synthesis-related proteins(S6K1 and TOR),which was related to the activation of the AKT/TOR signaling pathway.Finally,Cur could downregulate the expression of OTA-enhanced protein degradation-related genes(murf1,foxo3a,and ub),which was related to the inhibition of the Fox O3a signaling pathway.Conclusions In summary,our data demonstrated the effectiveness of Cur in alleviating OTA myotoxicity in vivo and in vitro.This study confirms the rapidity,feasibility,and effectiveness of establishing a natural product screening method targeting myoblasts to alleviate fungal toxin toxicity.展开更多
The formation of new and functional cardiomyocytes requires a 3-step process:dedifferentiation,proliferation,and redifferentiation,but the critical genes required for efficient dedifferentiation,proliferation,and redi...The formation of new and functional cardiomyocytes requires a 3-step process:dedifferentiation,proliferation,and redifferentiation,but the critical genes required for efficient dedifferentiation,proliferation,and redifferentiation remain unknown.In our study,a circular trajectory using single-nucleus RNA sequencing of the pericentriolar material 1 positive(PCM1^(+))cardiomyocyte nuclei from hearts 1 and 3 days after surgery-induced myocardial infarction(MI)on postnatal Day 1 was reconstructed and demonstrated that actin remodeling contributed to the dedifferentiation,proliferation,and redifferentiation of cardiomyocytes after injury.We identified four top actin-remodeling regulators,namely Tmsb4x,Tmsb10,Dmd,and Ctnna3,which we collectively referred to as 2D2P.Transiently expressed changes of 2D2P,using a polycistronic non-integrating lentivirus driven by Tnnt2(cardiac-specific troponin T)promoters(Tnnt2-2D2P-NIL),efficiently induced transiently proliferative activation and actin remodeling in postnatal Day 7 cardiomyocytes and adult hearts.Furthermore,the intramyocardial delivery of Tnnt2-2D2P-NIL resulted in a sustained improvement in cardiac function without ventricular dilatation,thickened septum,or fatal arrhythmia for at least 4 months.In conclusion,this study highlights the importance of actin remodeling in cardiac regeneration and provides a foundation for new gene-cocktail-therapy approaches to improve cardiac repair and treat heart failure using a novel transient and cardiomyocyte-specific viral construct.展开更多
Background Muscle represents a unique and complex system with many components and comprises the major edible part of animals.Vitamin D is a critical nutrient for animals and is known to enhance calcium absorption and ...Background Muscle represents a unique and complex system with many components and comprises the major edible part of animals.Vitamin D is a critical nutrient for animals and is known to enhance calcium absorption and immune response.In recent years,dietary vitamin D supplementation in livestock has received increased attention due to biological responses including improving shear force in mammalian meat.However,the vitamin D acquisition and myofiber development processes in fish differ from those in mammals,and the effect of vitamin D on fish flesh quality is poorly understood.Here,the influence of dietary vitamin D on fillet quality,antioxidant ability,and myofiber development was examined in grass carp(Ctenopharyngodon idella).Methods A total of 540 healthy grass carp,with an initial average body weight of 257.24±0.63 g,were allotted in 6 experimental groups with 3 replicates each,and respectively fed corresponding diets with 15.2,364.3,782.5,1,167.9,1,573.8,and 1,980.1 IU/kg vitamin D for 70 d.Results Supplementation with 1,167.9 IU/kg vitamin D significantly improved nutritional value and sensory quality of fillets,enhancing crude protein,free amino acid,lipid,and collagen contents;maintaining an ideal pH;and reduc-ing lactate content,shear force,and cooking loss relative to respective values in the control(15.2 IU/kg)group.Average myofiber diameter and the frequency of myofibers>50μm in diameter increased under supplementation with 782.5–1,167.9 IU/kg vitamin D.Levels of oxidative damage biomarkers decreased,and the expression of antioxi-dant enzymes and nuclear factor erythroid 2-related factor 2 signaling molecules was upregulated in the 1,167.9 IU/kg vitamin D treatment compared to respective values in the control group.Furthermore,vitamin D supplementation activated cell differentiation by enhancing the expression of myogenic regulatory factors and myocyte enhancer factors compared to that in the control group.In addition,supplementation with 1,167.9 IU/kg vitamin D improved protein deposition associated with protein synthesis molecule(target of rapamycin)signaling and vitamin D receptor paralogs,along with inhibition of protein degradation(forkhead box protein 1)signaling.Conclusions Overall,the results demonstrated that vitamin D strengthened antioxidant ability and myofiber devel-opment,thereby enhancing nutritional value and sensory quality of fish flesh.These findings suggest that dietary vitamin D supplementation is conducive to the production of nutrient-rich,high quality aquaculture products.展开更多
Objective:Dopamine,via its receptors,plays a vital role in the maintenance of blood pressure by modulating renal sodium transport.However,the role of the D_(4)dopamine receptor(D_(4)receptor)in renal proximal tubules(...Objective:Dopamine,via its receptors,plays a vital role in the maintenance of blood pressure by modulating renal sodium transport.However,the role of the D_(4)dopamine receptor(D_(4)receptor)in renal proximal tubules(PRTs)is still unclear.This study aimed to verify the hypothesis that activation of D_(4)receptor directly inhibits the activity of the Na+-K+-ATPase(NKA)in RPT cells.Methods:NKA activity,nitric oxide(NO)and cyclic guanosine monophosphate(cGMP)levels were measured in RPT cells treated with the D_(4)receptor agonist PD168077 and/or the D_(4)receptor antagonist L745870,the NO synthase inhibitor NG-nitro-L-arginine-methyl ester(L-NAME)or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one(ODQ).Total D_(4)receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHRs).Results:Activation of D_(4)receptors with PD168077,inhibited NKA activity in RPT cells from WKY rats in a concentration-and time-dependent manner.The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D_(4)receptor antagonist L745870,which by itself had no effect.The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ,which by themselves had no effect on NKA activity,eliminated the inhibitory effect of PD168077 on NKA activity.Activation of D_(4)receptors also increased NO levels in the culture medium and cGMP levels in RPT cells.However,the inhibitory effect of D_(4)receptors on NKA activity was absent in RPT cells from SHRs,which could be related to decreased plasma membrane expression of D_(4)receptors in SHR RPT cells.Conclusions:Activation of D_(4)receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs.Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.展开更多
D-mannose,essential for protein glycosylation,has been reported to have immunomodulatory effects and to maintain intestinal flora homeostasis.In addition to evaluating growth performance,we examined the impact of D-ma...D-mannose,essential for protein glycosylation,has been reported to have immunomodulatory effects and to maintain intestinal flora homeostasis.In addition to evaluating growth performance,we examined the impact of D-mannose on the structure of epithelial cells and apical junction complexes in the animal intestine.All 1800 grass carp(16.20±0.01 g)were randomly divided into six treatments with six replicates of 50 fish each and fed with six different levels of D-mannose(0.52,1.75,3.02,4.28,5.50 and 6.78 g/kg diet)for 70 d.The study revealed that D-mannose increased feed intake(P 0.05).D-mannose supplementation at 1.75 g/kg increased crude protein content in fish and lipid production value(P<0.05).D-mannose supplementation at 4.28 g/kg increased intestinal length,intestinal weight and fold height of grass carp compared to the control group(P<0.05).This improvement may be attributed to the phosphomannose isomerase(PMI)-mediated enhancement of glycolysis.This study found that D-mannose supplementation at 4.28 or 3.02 g/kg reduced serum diamine oxidase activity or D-lactate content(P<0.05)and improved cellular and intercellular structures for the first time.The improvement of cellular redox homeostasis involves alleviating endoplasmic reticulum(ER)stress through the inositol-requiring enzyme 1(IRE1),RNA-dependent protein kinase-like ER kinase(PERK),and activating transcription factor 6(ATF6)signaling pathways.The alleviation of ER stress may be linked to the phosphomannomutase(PMM)-mediated enhancement of protein glycosylation.In addition,ubiquitin-dependent[PTEN-induced putative kinase 1(PINK1)/Parkin]and ubiquitin-independent[BCL2-interacting protein 3-like(BNIP3L),BCL2-interacting protein 3(BNIP3),and FUN14 domain containing 1(FUNDC1)]mitophagy may play a role in maintaining cellular redox homeostasis.The enhancement of intercellular structures includes enhancing tight junction and adherent junction structures,which may be closely associated with the small Rho GTPase protein(RhoA)/the Rho-associated protein kinase(ROCK)signaling pathway.In conclusion,D-mannose improved intestinal cellular redox homeostasis associated with ER stress and mitophagy pathways,and enhanced intercellular structures related to tight junctions and adherent junctions.Furthermore,quadratic regression analysis of the PWG and intestinal reactive oxygen species content indicated that the optimal addition level of D-mannose for juvenile grass carp was 4.61 and 4.59 g/kg,respectively.展开更多
Background Methionine(Met)is the only sulfur-containing amino acid among animal essential amino acids,and methionine deficiency(MD)causes tissue damage and cell death in animals.The common modes of cell death include ...Background Methionine(Met)is the only sulfur-containing amino acid among animal essential amino acids,and methionine deficiency(MD)causes tissue damage and cell death in animals.The common modes of cell death include apoptosis,autophagy,pyroptosis,necroptosis.Howeve r,the studies about the major modes of cell death caused by MD have not been reported,which worth further study.Methods Primary hepatocytes from grass carp were isolated and treated with different doses of Met(0,0.5,1,1.5,2,2.5 mmol/L)to examine the expression of apoptosis,pyroptosis,autophagy and necroptosis-related proteins.Based on this,we subsequently modeled pyroptosis using lipopolysaccharides and nigericin sodium salt,then autophagy inhibitors chloroquine(CQ),AMP-activated protein kinase(AMPK)inhibitors compound C(CC)and reactive oxygen species(ROS)scavengers N-acetyl-L-cysteine(NAC)were further used to examine the expression of proteins related to pyroptosis,autophagy and AMPK pathway in MD-treated cells respectively.Results MD up-regulated B-cell lymphoma protein 2(Bax),microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ),and down-regulated the protein expression levels of B-cell lymphoma-2(Bcl-2),sequestosome 1(p62),cleavedcaspase-1,cleaved-interleukin(IL)-1βand receptor-interacting protein kinase(RIP)1 in hepatocytes,while it did not significantly affect RIPS.In addition,MD significantly increased the protein expression of liver kinase B1(LKB1),p-AMPK,and Unc-51-like kinase 1(ULK1)without significant effect on p-target of rapamycin.Subsequently,the use of CQ increased the protein expression of NOD-like receptor thermal protein domain associated protein 3(NLRP3),cleaved-caspase-1,and cleaved-IL-1βinhibited by MD;the use of CC significantly decreased the protein expression of MD-induced LC3Ⅱand increased the protein expression of MD-suppressed p62;then the use of NAC decreased the MD-induced p-AMPK protein expression.Conclusion MD promoted autophagy and apoptosis,but inhibited pyroptosis and necroptosis.MD inhibited pyroptosis may be related regarding the promotion of autophagy.MD activated AMPK by inducing ROS production which in turn promoted autophagy.These results could provide partial theoretical basis for the possible mechanisms of Met in ensuring the normal structure and function of animal organs.Furthermore,ferroptosis is closely related to redox states,it is worth investigating whether MD affects ferroptosis in hepatocytes.展开更多
Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear...Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.展开更多
Arecoline is an alkaloid with important pharmacological effects in the plant areca nut,which has been demonstrated to be an agonist of muscarinic receptors(M receptor).This study explored the influences of dietary are...Arecoline is an alkaloid with important pharmacological effects in the plant areca nut,which has been demonstrated to be an agonist of muscarinic receptors(M receptor).This study explored the influences of dietary arecoline on growth performance,intestinal digestion and absorption abilities,antioxidant capacity,and the apical junction complex(AJC)of adult grass carp(Ctenopharyngodon idella).Adult grass carp(608to 1512 g)were fed at 6 graded levels of dietary arecoline(0,0.5,1.0,1.5,2.0,and 2.5 mg/kg diet)for 9weeks.The results suggested that appropriate dietary supplementation of arecoline(1.0 mg/kg)increased growth parameters and intestinal growth in adult grass carp(P<0.05),enhanced digestion and absorption capacities(P<0.05),up-regulated muscarinic receptor 3(M3)mRNA level(P<0.05),increased the content of neuropeptide fish substance P(P<0.05),improved antioxidant capacity by activating the Keap1a/Nrf2signaling pathway(P<0.05),reduced intestinal mucosal permeability(P<0.05),and increased m RNA levels of tight junction(TJ)and adherent junction AJ-related proteins in fish by inhibiting the RhoA/ROCK signaling pathway(RhoA/ROCK/MLCK/NMII)(P<0.05).In addition,the appropriate arecoline supplementation for adult grass carp was determined to be 1.20,1.21,1.07,and 1.19 mg/kg based on percentage weight gain,lipase activity,serum diamine oxidase,and protein carbonyl,respectively.Overall,to the best of our knowledge,we investigated for the first time the effects and possible mechanisms of dietary arecoline on intestinal digestive and absorptive capacities and structural integrity in fish and evaluated the appropriate level of supplementation.展开更多
For carbonate reservoirs,gas-water and oil-gas relative permeability curve are of importance for parameters calculation in oil-field development,dynamic analysis and numerical reservoir simulation.The oil-gas/gas-wate...For carbonate reservoirs,gas-water and oil-gas relative permeability curve are of importance for parameters calculation in oil-field development,dynamic analysis and numerical reservoir simulation.The oil-gas/gas-water relative permeability curves were measured with unstable method under normal temperature and low pressure,using fifteen artificial fractured cores.The shape and change characteristics of gas/water and oil/gas relative permeability curve were mainly analyzed.The results showed that for the relative permeability curve of water driving gas.The saturation of equal permeability point,the saturation range of two-phase flow region and the displacement efficiency has a good power-function relation with core permeability.In addition,the saturation of equal permeability point,the saturation range of two-phase flow region and the displacement efficiency will decrease with the increasing of core permeability.However,for oil-gas relative permeability curves,the saturation of equal permeability point,the saturation range of two-phase flow region and the displacement efficiency will increase with the increasing of core permeability.It should be noted that the gas relative permeability presents a straight line in the normalized relative permeability curve,which indicates that the main flow is dominated by fracture with low displacement efficiency.The research results provide theory basis for fracture-vuggy carbonate reservoir development and new research idea for the further study of this kind of reservoir.展开更多
Long-term stereoscopic observations of aerosol,NO2,and HCHO were carried out at the Yangmeikeng(YMK)site in Shenzhen.Aerosol optical depths and NO2 vertical column concentration(NO2 VCD)derived from MAX-DOAS were foun...Long-term stereoscopic observations of aerosol,NO2,and HCHO were carried out at the Yangmeikeng(YMK)site in Shenzhen.Aerosol optical depths and NO2 vertical column concentration(NO2 VCD)derived from MAX-DOAS were found to be consistent with other datasets.The total NO2 VCD values of the site remained low,varying from 2×10^(15)to 8×10^(15)mol/cm^(2),while the HCHO VCD was higher than NO2 VCD,varying from 7×10^(15)to 11×10^(15)mol/cm^(2).HCHO VCD was higher from September to early November than that was from mid-late November to December and during February 2021,in contrast,NO2 VCD did not change much during the same period.In January,NO2 VCD and HCHO VCD were both fluctuating drastically.High temperature and HCHO level in the YMK site is not only driving the ozone production up but alsomay be driving up the ozone concentration as well,and the O_(3)production regime in the YMK site tends to be NOx-limited.At various altitudes,backward trajectory clustering analysis and Potential Source Contribution Function(PSCF)were utilized to identify possible NO2 and HCHO source locations.The results suggested that the Huizhou-Shanwei border and the Daya Bay Sea area were the key potential source locations in the lower(200 m)and middle(500 m)atmosphere(WPSCF>0.6).The WPSCF valuewas high at the 1000maltitude whichwas closer to the YMKsite than the near ground,indicating that the pollution transport capability in the upper atmosphere was limited.展开更多
Atmospheric aerosols have effects on atmospheric radiation assessments,global climate change,local air quality and visibility.In particular,aerosols are more likely transformed and accumulated in winter.In this paper,...Atmospheric aerosols have effects on atmospheric radiation assessments,global climate change,local air quality and visibility.In particular,aerosols are more likely transformed and accumulated in winter.In this paper,we used the Multi-Axis Differential Optical Absorption Spectroscopy(MAX-DOAS)instrument to study the characteristics of aerosol type and contributions of PM_(2.5) chemical components to aerosol extinction(AE),vertical distribution of aerosols,and source.From December 30,2018 to January 27,2019,we conducted MAX-DOAS observations on Sanmenxia.The proportion of PM_(2.5) to PM10 was 69.48%-95.39%,indicating that the aerosol particles were mainly fine particles.By analyzing the ion data and modifying Interagency Monitoring of Protected Visual Environments(IMPROVE)method,we found that nitrate was the largest contributor to AE,accounting for 31.51%,28.98%,and 27.95%of AE on heavily polluted,polluted,and clean days,respectively.NH4+,OC,and SO42-were also major contributors to AE.The near-surface aerosol extinction retrieved from MAX-DOAS measurement the PM_(2.5) and PM10 concentrations measured by an Unmanned Aerial Vehicle(UAV)have the same trend in vertical distribution.AE increased about 3 times from surface to 500 m.With the backward trajectory of the air mass during the haze,we also found that the continuous heavy pollution was mainly caused by transport of polluted air from the northeast,then followed by local industrial emissions and other sources of emissions under continuous and steady weather conditions.展开更多
The neonatal mammalian heart has a remarkable regenerative capacity,while the adult heart has difficulty to regenerate.A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of ca...The neonatal mammalian heart has a remarkable regenerative capacity,while the adult heart has difficulty to regenerate.A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth.In this study,we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation.Reversing metabolic reprogramming by carnitine palmitoyltransferase 1(CPT1)inhibition,using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction.The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir,a CPT1 inhibitor.CPT1 inhibition,by decreasing poly(ADP-ribose)polymerase 1 expression,reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes,leading to decreased p38 MAPK phosphorylation,and stimulation of cardiomyocyte proliferation.Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation.CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.展开更多
Studying the spatiotemporal distribution and transboundary transport of aerosols,NO_(2),SO_(2),and HCHO in typical regions is crucial for understanding regional pollution causes.In a 2-year study using multi-axis diff...Studying the spatiotemporal distribution and transboundary transport of aerosols,NO_(2),SO_(2),and HCHO in typical regions is crucial for understanding regional pollution causes.In a 2-year study using multi-axis differential optical absorption spectroscopy in Qingdao,Shanghai,Xi’an,and Kunming,we investigated pollutant distribution and transport across Eastern China-Ocean,Tibetan Plateau-Central and Eastern China,and China-Southeast Asia interfaces.First,pollutant distributionwas analyzed.Kunming,frequently clouded and misty,exhibited consistently high aerosol optical depth throughout the year.In Qingdao and Shanghai,NO_(2)and SO_(2),as well as SO_(2)in Xi’an,increased in winter.Elevated HCHO in summer in Shanghai and Xi’an,especially Xi’an,suggests potential ozone pollution issues.Subsequently,pollutant transportation across interfaces was studied.At the Eastern China-Ocean interface,the gas transport flux was the largest among other interfaces,with the outflux exceeding the influx,especially in winter and spring.The input of pollutants from the Tibetan Plateau to central-eastern Chinawas larger than the output in winter and spring,with SO_(2)having the highest transport flux in winter.The pollution input from Southeast Asia to China significantly exceeded the output,with spring and winter inputs being 3.22 and 3.03 times the output,respectively.Lastly,the transportation characteristics of a pollution event at Kunming were studied.During this period,pollutants were transported from west to east,with themaximum SO_(2)transport flux at an altitude of 2.87 km equaling 27.74μg/(m^(2)·s).It is speculated that this pollution was caused by the transport from Southeast Asian countries to Kunming.展开更多
Aflatoxin B1(AFB1),an important fungal toxin,exists mainly in plant feed ingredients and animals consuming feed contaminated with AFB1 will have reduced growth and impaired health condition mainly due to oxidative str...Aflatoxin B1(AFB1),an important fungal toxin,exists mainly in plant feed ingredients and animals consuming feed contaminated with AFB1 will have reduced growth and impaired health condition mainly due to oxidative stress and reduced immunity.Our previous study found that AFB1 caused oxidative damage and inhibited muscle development of zebrafish.4-Methylesculetin(4-ME),a coumarin derivative,is now used in biochemistry and medicine widely because of its antioxidant function.Whether 4-ME could alleviate the inhibition of muscle development in grass carp induced by AFB1 has not been reported.In this experiment,720 healthy grass carp(11.40±0.01 g)were randomly divided into 4 groups with 3 replicates of 60 fish each,including control group,AFB1 group(60 mg/kg diet AFB1),4-ME group(10 mg/kg diet 4-ME),and AFB1+4-ME group(60 mg/kg diet AFB1+10 mg/kg 4-ME diet),for a 60-d growth experiment.In vitro,we also set up 4 treatment groups for grass carp primary myoblast,including control group,AFB1 group(15 mmol/L AFB1),4-ME group(0.5 mmol/L 4-ME)and AFB1+4-ME group(15 mmol/L AFB1+0.5 mmol/L 4-ME).The results showed that dietary AFB1 decreased growth performance of grass carp,damaged the ultrastructure and induced oxidative damage in grass carp muscle,and significantly decreased the mRNA and protein expression levels of myogenin(MyoG),myogenic differentiation(MyoD),myosin heavy chain(MYHC),as well as the protein expression levels of lamininβ1,fibronectin and collagen I(P<0.05),significantly activated the protein expression levels of urokinase-type plasminogen activator(uPA),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9)and phosphorylate-38 mitogen-activated protein kinase(p38 MAPK)both in grass carp muscle and grass carp primary myoblast(P<0.05).Supplementation of AFB1 with 4-ME significantly improved the growth performance inhibition and alleviated the muscle fiber development inhibition and extracellular matrix(ECM)degradation in grass carp induced by AFB1(P<0.05).The present results revealed that supplementation of AFB1 contaminated feed with 4-ME reduced the inhibition of growth and muscle development by alleviating AFB1-induced ECM degradation in grass carp,which might be related to the p38 MAPK/uPA/MMP/ECM pathway.The results implied that 4-ME could be used as a valuable mycotoxin scavenger in animal feed.展开更多
基金This research was financially supported by the earmarked fund for CARS(CARS-45)National Natural Science Foundation of China(32273144,32072985)National Key R&D Program of China(2019YFD0900200).
文摘Background Ochratoxin A(OTA)is a toxin widely found in aquafeed ingredients,and hypoxia is a common prob-lem in fish farming.In practice,aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA,but no studies exist in this area.This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin(CUR).Methods A total of 720 healthy juvenile grass carp(11.06±0.05 g)were selected and assigned randomly to 4 experi-mental groups:control group(without OTA and CUR),1.2 mg/kg OTA group,400 mg/kg CUR group,and 1.2 mg/kg OTA+400 mg/kg CUR group with three replicates each for 60 d.Subsequently,32 fish were selected,divided into nor-moxia(18 fish)and hypoxia(18 fish)groups,and subjected to hypoxia stress for 96 h.Results CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacu-olation and nuclear excursion.The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3,8,9,Bax,and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2,and attenuation of endoplasmic reticulum stress(ERS)by reducing Grp78 expression and chop levels.This may be attributed to the fact that the addi-tion of CUR increased the levels of catalase(CAT)and glutathione reductase(GSH),increased antioxidant capacity,and ensured the proper functioning of respiratory chain complexes I and II,which in turn reduced the high produc-tion of reactive oxygen species(ROS),thus alleviating apoptosis and ERS.Conclusions In conclusion,our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia.This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.
基金financially supported by the earmarked fund for CARS(CARS-45)National Natural Science Foundation of China for Outstanding Youth Science Foundation(31922086)+1 种基金the Young Top-Notch Talent Support Programthe 111 project(D17015)。
文摘Background Ochratoxin A(OTA),a globally abundant and extremely hazardous pollutant,is a significant source of contamination in aquafeeds and is responsible for severe food pollution.The developmental toxicity of OTA and the potential relieving strategy of natural products remain unclear.This study screened the substance curcumin(Cur),which had the best effect in alleviating OTA inhibition of myoblast proliferation,from 96 natural products and investigated its effect and mechanism in reducing OTA myotoxicity in vivo and in vitro.Methods A total of 720 healthy juvenile grass carp,with an initial average body weight of 11.06±0.05 g,were randomly assigned into 4 groups:the control group(without OTA and Cur),1.2 mg/kg OTA group,400 mg/kg Cur group,and 1.2 mg/kg OTA+400 mg/kg Cur group.Each treatment consisted of 3 replicates(180 fish)for 60 d.Results Firstly,we cultured,purified,and identified myoblasts using the tissue block culture method.Through preliminary screening and re-screening of 96 substances,we examined cell proliferation-related indicators such as cell viability and ultimately found that Cur had the best effect.Secondly,Cur could alleviate OTA-inhibited myoblast differentiation and myofibrillar development-related proteins(Myo G and MYHC)in vivo and in vitro and improve the growth performance of grass carp.Then,Cur could also promote the expression of OTA-inhibited protein synthesis-related proteins(S6K1 and TOR),which was related to the activation of the AKT/TOR signaling pathway.Finally,Cur could downregulate the expression of OTA-enhanced protein degradation-related genes(murf1,foxo3a,and ub),which was related to the inhibition of the Fox O3a signaling pathway.Conclusions In summary,our data demonstrated the effectiveness of Cur in alleviating OTA myotoxicity in vivo and in vitro.This study confirms the rapidity,feasibility,and effectiveness of establishing a natural product screening method targeting myoblasts to alleviate fungal toxin toxicity.
基金supported by the grant to Chunyu Zeng from the National Key R&D Program of China(2022YFA1104500)the National Natural Science Foundation of China(82200307)the grant to Chunyu Zeng from the National Natural Science Foundation of China(81930008).
文摘The formation of new and functional cardiomyocytes requires a 3-step process:dedifferentiation,proliferation,and redifferentiation,but the critical genes required for efficient dedifferentiation,proliferation,and redifferentiation remain unknown.In our study,a circular trajectory using single-nucleus RNA sequencing of the pericentriolar material 1 positive(PCM1^(+))cardiomyocyte nuclei from hearts 1 and 3 days after surgery-induced myocardial infarction(MI)on postnatal Day 1 was reconstructed and demonstrated that actin remodeling contributed to the dedifferentiation,proliferation,and redifferentiation of cardiomyocytes after injury.We identified four top actin-remodeling regulators,namely Tmsb4x,Tmsb10,Dmd,and Ctnna3,which we collectively referred to as 2D2P.Transiently expressed changes of 2D2P,using a polycistronic non-integrating lentivirus driven by Tnnt2(cardiac-specific troponin T)promoters(Tnnt2-2D2P-NIL),efficiently induced transiently proliferative activation and actin remodeling in postnatal Day 7 cardiomyocytes and adult hearts.Furthermore,the intramyocardial delivery of Tnnt2-2D2P-NIL resulted in a sustained improvement in cardiac function without ventricular dilatation,thickened septum,or fatal arrhythmia for at least 4 months.In conclusion,this study highlights the importance of actin remodeling in cardiac regeneration and provides a foundation for new gene-cocktail-therapy approaches to improve cardiac repair and treat heart failure using a novel transient and cardiomyocyte-specific viral construct.
基金National Key R&D Program of China(2018YFD0900400 and 2019YFD0900200)National Natural Science Foundation of China for Outstanding Youth Science Foundation(31922086)+1 种基金the earmarked fund for CARS(CARS-45)Sichuan Science and Technology Program(2019YFN0036).
文摘Background Muscle represents a unique and complex system with many components and comprises the major edible part of animals.Vitamin D is a critical nutrient for animals and is known to enhance calcium absorption and immune response.In recent years,dietary vitamin D supplementation in livestock has received increased attention due to biological responses including improving shear force in mammalian meat.However,the vitamin D acquisition and myofiber development processes in fish differ from those in mammals,and the effect of vitamin D on fish flesh quality is poorly understood.Here,the influence of dietary vitamin D on fillet quality,antioxidant ability,and myofiber development was examined in grass carp(Ctenopharyngodon idella).Methods A total of 540 healthy grass carp,with an initial average body weight of 257.24±0.63 g,were allotted in 6 experimental groups with 3 replicates each,and respectively fed corresponding diets with 15.2,364.3,782.5,1,167.9,1,573.8,and 1,980.1 IU/kg vitamin D for 70 d.Results Supplementation with 1,167.9 IU/kg vitamin D significantly improved nutritional value and sensory quality of fillets,enhancing crude protein,free amino acid,lipid,and collagen contents;maintaining an ideal pH;and reduc-ing lactate content,shear force,and cooking loss relative to respective values in the control(15.2 IU/kg)group.Average myofiber diameter and the frequency of myofibers>50μm in diameter increased under supplementation with 782.5–1,167.9 IU/kg vitamin D.Levels of oxidative damage biomarkers decreased,and the expression of antioxi-dant enzymes and nuclear factor erythroid 2-related factor 2 signaling molecules was upregulated in the 1,167.9 IU/kg vitamin D treatment compared to respective values in the control group.Furthermore,vitamin D supplementation activated cell differentiation by enhancing the expression of myogenic regulatory factors and myocyte enhancer factors compared to that in the control group.In addition,supplementation with 1,167.9 IU/kg vitamin D improved protein deposition associated with protein synthesis molecule(target of rapamycin)signaling and vitamin D receptor paralogs,along with inhibition of protein degradation(forkhead box protein 1)signaling.Conclusions Overall,the results demonstrated that vitamin D strengthened antioxidant ability and myofiber devel-opment,thereby enhancing nutritional value and sensory quality of fish flesh.These findings suggest that dietary vitamin D supplementation is conducive to the production of nutrient-rich,high quality aquaculture products.
基金the National Key R&D Program of China(2018YFC1312700)the National Naturai Science Foundation of China(831730043)+4 种基金the Program of Innovative Research Team of the National Natural Science Foundation(81721001)Program for Changjiang Scholars and Innovative Research Team in University(IRT1216)Key Research and Development Projects of Science and Technology Innovation of Social and People's Livelihood in Chongqing City,(cstc2018jscx-mszdX0024)Clinical Medical Research Talent Training Program from The Third Military Medical University(2018XLCi012)National Institutes of Health,USA(P01HL074940,DK039308,and DK119652).
文摘Objective:Dopamine,via its receptors,plays a vital role in the maintenance of blood pressure by modulating renal sodium transport.However,the role of the D_(4)dopamine receptor(D_(4)receptor)in renal proximal tubules(PRTs)is still unclear.This study aimed to verify the hypothesis that activation of D_(4)receptor directly inhibits the activity of the Na+-K+-ATPase(NKA)in RPT cells.Methods:NKA activity,nitric oxide(NO)and cyclic guanosine monophosphate(cGMP)levels were measured in RPT cells treated with the D_(4)receptor agonist PD168077 and/or the D_(4)receptor antagonist L745870,the NO synthase inhibitor NG-nitro-L-arginine-methyl ester(L-NAME)or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one(ODQ).Total D_(4)receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHRs).Results:Activation of D_(4)receptors with PD168077,inhibited NKA activity in RPT cells from WKY rats in a concentration-and time-dependent manner.The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D_(4)receptor antagonist L745870,which by itself had no effect.The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ,which by themselves had no effect on NKA activity,eliminated the inhibitory effect of PD168077 on NKA activity.Activation of D_(4)receptors also increased NO levels in the culture medium and cGMP levels in RPT cells.However,the inhibitory effect of D_(4)receptors on NKA activity was absent in RPT cells from SHRs,which could be related to decreased plasma membrane expression of D_(4)receptors in SHR RPT cells.Conclusions:Activation of D_(4)receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs.Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.
基金supported by the earmarked fund for CARS (CARS-45),and the National Key R&D Program of China (2019YFD0900200).
文摘D-mannose,essential for protein glycosylation,has been reported to have immunomodulatory effects and to maintain intestinal flora homeostasis.In addition to evaluating growth performance,we examined the impact of D-mannose on the structure of epithelial cells and apical junction complexes in the animal intestine.All 1800 grass carp(16.20±0.01 g)were randomly divided into six treatments with six replicates of 50 fish each and fed with six different levels of D-mannose(0.52,1.75,3.02,4.28,5.50 and 6.78 g/kg diet)for 70 d.The study revealed that D-mannose increased feed intake(P 0.05).D-mannose supplementation at 1.75 g/kg increased crude protein content in fish and lipid production value(P<0.05).D-mannose supplementation at 4.28 g/kg increased intestinal length,intestinal weight and fold height of grass carp compared to the control group(P<0.05).This improvement may be attributed to the phosphomannose isomerase(PMI)-mediated enhancement of glycolysis.This study found that D-mannose supplementation at 4.28 or 3.02 g/kg reduced serum diamine oxidase activity or D-lactate content(P<0.05)and improved cellular and intercellular structures for the first time.The improvement of cellular redox homeostasis involves alleviating endoplasmic reticulum(ER)stress through the inositol-requiring enzyme 1(IRE1),RNA-dependent protein kinase-like ER kinase(PERK),and activating transcription factor 6(ATF6)signaling pathways.The alleviation of ER stress may be linked to the phosphomannomutase(PMM)-mediated enhancement of protein glycosylation.In addition,ubiquitin-dependent[PTEN-induced putative kinase 1(PINK1)/Parkin]and ubiquitin-independent[BCL2-interacting protein 3-like(BNIP3L),BCL2-interacting protein 3(BNIP3),and FUN14 domain containing 1(FUNDC1)]mitophagy may play a role in maintaining cellular redox homeostasis.The enhancement of intercellular structures includes enhancing tight junction and adherent junction structures,which may be closely associated with the small Rho GTPase protein(RhoA)/the Rho-associated protein kinase(ROCK)signaling pathway.In conclusion,D-mannose improved intestinal cellular redox homeostasis associated with ER stress and mitophagy pathways,and enhanced intercellular structures related to tight junctions and adherent junctions.Furthermore,quadratic regression analysis of the PWG and intestinal reactive oxygen species content indicated that the optimal addition level of D-mannose for juvenile grass carp was 4.61 and 4.59 g/kg,respectively.
基金financially supported by National Natural Science Foundation of China(32072985,32273144)the earmarked fund for CARS(CARS-45)National Key R&D Program of China(2019YFD0900200)。
文摘Background Methionine(Met)is the only sulfur-containing amino acid among animal essential amino acids,and methionine deficiency(MD)causes tissue damage and cell death in animals.The common modes of cell death include apoptosis,autophagy,pyroptosis,necroptosis.Howeve r,the studies about the major modes of cell death caused by MD have not been reported,which worth further study.Methods Primary hepatocytes from grass carp were isolated and treated with different doses of Met(0,0.5,1,1.5,2,2.5 mmol/L)to examine the expression of apoptosis,pyroptosis,autophagy and necroptosis-related proteins.Based on this,we subsequently modeled pyroptosis using lipopolysaccharides and nigericin sodium salt,then autophagy inhibitors chloroquine(CQ),AMP-activated protein kinase(AMPK)inhibitors compound C(CC)and reactive oxygen species(ROS)scavengers N-acetyl-L-cysteine(NAC)were further used to examine the expression of proteins related to pyroptosis,autophagy and AMPK pathway in MD-treated cells respectively.Results MD up-regulated B-cell lymphoma protein 2(Bax),microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ),and down-regulated the protein expression levels of B-cell lymphoma-2(Bcl-2),sequestosome 1(p62),cleavedcaspase-1,cleaved-interleukin(IL)-1βand receptor-interacting protein kinase(RIP)1 in hepatocytes,while it did not significantly affect RIPS.In addition,MD significantly increased the protein expression of liver kinase B1(LKB1),p-AMPK,and Unc-51-like kinase 1(ULK1)without significant effect on p-target of rapamycin.Subsequently,the use of CQ increased the protein expression of NOD-like receptor thermal protein domain associated protein 3(NLRP3),cleaved-caspase-1,and cleaved-IL-1βinhibited by MD;the use of CC significantly decreased the protein expression of MD-induced LC3Ⅱand increased the protein expression of MD-suppressed p62;then the use of NAC decreased the MD-induced p-AMPK protein expression.Conclusion MD promoted autophagy and apoptosis,but inhibited pyroptosis and necroptosis.MD inhibited pyroptosis may be related regarding the promotion of autophagy.MD activated AMPK by inducing ROS production which in turn promoted autophagy.These results could provide partial theoretical basis for the possible mechanisms of Met in ensuring the normal structure and function of animal organs.Furthermore,ferroptosis is closely related to redox states,it is worth investigating whether MD affects ferroptosis in hepatocytes.
基金supported by grants to Chunyu Zeng from the Program of Innovative Research Team by National Natural Science Foundation(81721001,China)National Natural Science Foundation of China(31430043,31730043)+5 种基金Program for Changjiang Scholars,and Innovative Research Team in University(IRT1216,China)the National Key R&D Program of China(2018YFC1312700)by grant to Jingwen Guo from the National Natural Science Foundation of China(82000476)by grant to Yijie Hu from the Excellent Talents Project of Third Military Medical University(B-3232,China)by grant to Hongyong Wang from the Clinical Technology Innovation and Cultivation Program of AMU(CX2019JS220,China)by grant to Xinyue Li from Chongqing Natural Science Foundation(CSTB2022NSCQ-BHX0025,China)。
文摘Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.
基金This research was financially supported by the National Key R&D Program of China(2019YFD0900200,2018YFD0900400)National Natural Science Foundation of China for Outstanding Youth Science Foundation(31922086)supported by the earmarked fund for CARS(CARS-45).
文摘Arecoline is an alkaloid with important pharmacological effects in the plant areca nut,which has been demonstrated to be an agonist of muscarinic receptors(M receptor).This study explored the influences of dietary arecoline on growth performance,intestinal digestion and absorption abilities,antioxidant capacity,and the apical junction complex(AJC)of adult grass carp(Ctenopharyngodon idella).Adult grass carp(608to 1512 g)were fed at 6 graded levels of dietary arecoline(0,0.5,1.0,1.5,2.0,and 2.5 mg/kg diet)for 9weeks.The results suggested that appropriate dietary supplementation of arecoline(1.0 mg/kg)increased growth parameters and intestinal growth in adult grass carp(P<0.05),enhanced digestion and absorption capacities(P<0.05),up-regulated muscarinic receptor 3(M3)mRNA level(P<0.05),increased the content of neuropeptide fish substance P(P<0.05),improved antioxidant capacity by activating the Keap1a/Nrf2signaling pathway(P<0.05),reduced intestinal mucosal permeability(P<0.05),and increased m RNA levels of tight junction(TJ)and adherent junction AJ-related proteins in fish by inhibiting the RhoA/ROCK signaling pathway(RhoA/ROCK/MLCK/NMII)(P<0.05).In addition,the appropriate arecoline supplementation for adult grass carp was determined to be 1.20,1.21,1.07,and 1.19 mg/kg based on percentage weight gain,lipase activity,serum diamine oxidase,and protein carbonyl,respectively.Overall,to the best of our knowledge,we investigated for the first time the effects and possible mechanisms of dietary arecoline on intestinal digestive and absorptive capacities and structural integrity in fish and evaluated the appropriate level of supplementation.
基金Supported by PetroChina Major Science and Technology Project(2014E-35-05).
文摘For carbonate reservoirs,gas-water and oil-gas relative permeability curve are of importance for parameters calculation in oil-field development,dynamic analysis and numerical reservoir simulation.The oil-gas/gas-water relative permeability curves were measured with unstable method under normal temperature and low pressure,using fifteen artificial fractured cores.The shape and change characteristics of gas/water and oil/gas relative permeability curve were mainly analyzed.The results showed that for the relative permeability curve of water driving gas.The saturation of equal permeability point,the saturation range of two-phase flow region and the displacement efficiency has a good power-function relation with core permeability.In addition,the saturation of equal permeability point,the saturation range of two-phase flow region and the displacement efficiency will decrease with the increasing of core permeability.However,for oil-gas relative permeability curves,the saturation of equal permeability point,the saturation range of two-phase flow region and the displacement efficiency will increase with the increasing of core permeability.It should be noted that the gas relative permeability presents a straight line in the normalized relative permeability curve,which indicates that the main flow is dominated by fracture with low displacement efficiency.The research results provide theory basis for fracture-vuggy carbonate reservoir development and new research idea for the further study of this kind of reservoir.
基金supported by the National Natural Science Foundation of China(No.41775029)the National Key Research and Development Project of China(No.2018YFC0213201)the Science and Technology Commission of Shanghai Municipality(No.17DZ1203102).
文摘Long-term stereoscopic observations of aerosol,NO2,and HCHO were carried out at the Yangmeikeng(YMK)site in Shenzhen.Aerosol optical depths and NO2 vertical column concentration(NO2 VCD)derived from MAX-DOAS were found to be consistent with other datasets.The total NO2 VCD values of the site remained low,varying from 2×10^(15)to 8×10^(15)mol/cm^(2),while the HCHO VCD was higher than NO2 VCD,varying from 7×10^(15)to 11×10^(15)mol/cm^(2).HCHO VCD was higher from September to early November than that was from mid-late November to December and during February 2021,in contrast,NO2 VCD did not change much during the same period.In January,NO2 VCD and HCHO VCD were both fluctuating drastically.High temperature and HCHO level in the YMK site is not only driving the ozone production up but alsomay be driving up the ozone concentration as well,and the O_(3)production regime in the YMK site tends to be NOx-limited.At various altitudes,backward trajectory clustering analysis and Potential Source Contribution Function(PSCF)were utilized to identify possible NO2 and HCHO source locations.The results suggested that the Huizhou-Shanwei border and the Daya Bay Sea area were the key potential source locations in the lower(200 m)and middle(500 m)atmosphere(WPSCF>0.6).The WPSCF valuewas high at the 1000maltitude whichwas closer to the YMKsite than the near ground,indicating that the pollution transport capability in the upper atmosphere was limited.
基金supported by the National Natural Science Foundation of China (Nos.41530644, 41775029, 41975037)the National Key Research and Development Plan of China (Nos.2018YFC0213201, 2017YFC0209902, 2018YFC0213801)。
文摘Atmospheric aerosols have effects on atmospheric radiation assessments,global climate change,local air quality and visibility.In particular,aerosols are more likely transformed and accumulated in winter.In this paper,we used the Multi-Axis Differential Optical Absorption Spectroscopy(MAX-DOAS)instrument to study the characteristics of aerosol type and contributions of PM_(2.5) chemical components to aerosol extinction(AE),vertical distribution of aerosols,and source.From December 30,2018 to January 27,2019,we conducted MAX-DOAS observations on Sanmenxia.The proportion of PM_(2.5) to PM10 was 69.48%-95.39%,indicating that the aerosol particles were mainly fine particles.By analyzing the ion data and modifying Interagency Monitoring of Protected Visual Environments(IMPROVE)method,we found that nitrate was the largest contributor to AE,accounting for 31.51%,28.98%,and 27.95%of AE on heavily polluted,polluted,and clean days,respectively.NH4+,OC,and SO42-were also major contributors to AE.The near-surface aerosol extinction retrieved from MAX-DOAS measurement the PM_(2.5) and PM10 concentrations measured by an Unmanned Aerial Vehicle(UAV)have the same trend in vertical distribution.AE increased about 3 times from surface to 500 m.With the backward trajectory of the air mass during the haze,we also found that the continuous heavy pollution was mainly caused by transport of polluted air from the northeast,then followed by local industrial emissions and other sources of emissions under continuous and steady weather conditions.
基金supported by grants from the National Key Research and Development Program of China(No.2022YFA1104500)National Natural Science Foundation of China(No.81930008)+1 种基金Natural Science Foundation of Sichuan Province(No.2023NSFSC1651,China)the National Institutes of Health(No.DK134574 and No.DK119652,US).
文摘The neonatal mammalian heart has a remarkable regenerative capacity,while the adult heart has difficulty to regenerate.A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth.In this study,we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation.Reversing metabolic reprogramming by carnitine palmitoyltransferase 1(CPT1)inhibition,using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction.The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir,a CPT1 inhibitor.CPT1 inhibition,by decreasing poly(ADP-ribose)polymerase 1 expression,reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes,leading to decreased p38 MAPK phosphorylation,and stimulation of cardiomyocyte proliferation.Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation.CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.
基金supported by the National Key Research and Development Project of China(Nos.2022YFC3703502 and 2018YFC0213201)the National Natural Science Foundation of China(No.42105133)the Local Service Project of Hefei(No.2020BFFFD01804).
文摘Studying the spatiotemporal distribution and transboundary transport of aerosols,NO_(2),SO_(2),and HCHO in typical regions is crucial for understanding regional pollution causes.In a 2-year study using multi-axis differential optical absorption spectroscopy in Qingdao,Shanghai,Xi’an,and Kunming,we investigated pollutant distribution and transport across Eastern China-Ocean,Tibetan Plateau-Central and Eastern China,and China-Southeast Asia interfaces.First,pollutant distributionwas analyzed.Kunming,frequently clouded and misty,exhibited consistently high aerosol optical depth throughout the year.In Qingdao and Shanghai,NO_(2)and SO_(2),as well as SO_(2)in Xi’an,increased in winter.Elevated HCHO in summer in Shanghai and Xi’an,especially Xi’an,suggests potential ozone pollution issues.Subsequently,pollutant transportation across interfaces was studied.At the Eastern China-Ocean interface,the gas transport flux was the largest among other interfaces,with the outflux exceeding the influx,especially in winter and spring.The input of pollutants from the Tibetan Plateau to central-eastern Chinawas larger than the output in winter and spring,with SO_(2)having the highest transport flux in winter.The pollution input from Southeast Asia to China significantly exceeded the output,with spring and winter inputs being 3.22 and 3.03 times the output,respectively.Lastly,the transportation characteristics of a pollution event at Kunming were studied.During this period,pollutants were transported from west to east,with themaximum SO_(2)transport flux at an altitude of 2.87 km equaling 27.74μg/(m^(2)·s).It is speculated that this pollution was caused by the transport from Southeast Asian countries to Kunming.
基金financially supported by the National Natural Science Foundation of China(U23A20250)the earmarked fund for CARS(CARS-45)the National Key R&D Program of China(2019YFD0900200)。
文摘Aflatoxin B1(AFB1),an important fungal toxin,exists mainly in plant feed ingredients and animals consuming feed contaminated with AFB1 will have reduced growth and impaired health condition mainly due to oxidative stress and reduced immunity.Our previous study found that AFB1 caused oxidative damage and inhibited muscle development of zebrafish.4-Methylesculetin(4-ME),a coumarin derivative,is now used in biochemistry and medicine widely because of its antioxidant function.Whether 4-ME could alleviate the inhibition of muscle development in grass carp induced by AFB1 has not been reported.In this experiment,720 healthy grass carp(11.40±0.01 g)were randomly divided into 4 groups with 3 replicates of 60 fish each,including control group,AFB1 group(60 mg/kg diet AFB1),4-ME group(10 mg/kg diet 4-ME),and AFB1+4-ME group(60 mg/kg diet AFB1+10 mg/kg 4-ME diet),for a 60-d growth experiment.In vitro,we also set up 4 treatment groups for grass carp primary myoblast,including control group,AFB1 group(15 mmol/L AFB1),4-ME group(0.5 mmol/L 4-ME)and AFB1+4-ME group(15 mmol/L AFB1+0.5 mmol/L 4-ME).The results showed that dietary AFB1 decreased growth performance of grass carp,damaged the ultrastructure and induced oxidative damage in grass carp muscle,and significantly decreased the mRNA and protein expression levels of myogenin(MyoG),myogenic differentiation(MyoD),myosin heavy chain(MYHC),as well as the protein expression levels of lamininβ1,fibronectin and collagen I(P<0.05),significantly activated the protein expression levels of urokinase-type plasminogen activator(uPA),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9)and phosphorylate-38 mitogen-activated protein kinase(p38 MAPK)both in grass carp muscle and grass carp primary myoblast(P<0.05).Supplementation of AFB1 with 4-ME significantly improved the growth performance inhibition and alleviated the muscle fiber development inhibition and extracellular matrix(ECM)degradation in grass carp induced by AFB1(P<0.05).The present results revealed that supplementation of AFB1 contaminated feed with 4-ME reduced the inhibition of growth and muscle development by alleviating AFB1-induced ECM degradation in grass carp,which might be related to the p38 MAPK/uPA/MMP/ECM pathway.The results implied that 4-ME could be used as a valuable mycotoxin scavenger in animal feed.
