Oxidative stress is one of the main ways to cause alcohol-induced liver injury,and alcoholic liver disease(ALD)has been a common health problem worldwide.Lactic acid bacteria(LAB)is also considered as a potential trea...Oxidative stress is one of the main ways to cause alcohol-induced liver injury,and alcoholic liver disease(ALD)has been a common health problem worldwide.Lactic acid bacteria(LAB)is also considered as a potential treatment to alleviate alcohol-induced liver injury.Lactobacillus plantarum J26 is a LAB isolated from Chinese traditional fermented dairy products with excellent probiotic effects.This study aimed to establish a mice model of alcoholic liver injury through acute-on-chronic alcohol feeding and to study the alleviating effect of pre-intake of L.plantarum J26 on alcohol-induced oxidative liver injury and focus on its potential mechanism of alleviating effect.The results showed that pre-intake of L.plantarum J26 could improve liver pathological changes,reduce lipid accumulation,increase mitochondrial ATP and mitochondrial(mtDNA)levels,and alleviate liver injury.In addition,pre-intake L.plantarum J26 can improve the level of short-chain fatty acids(SCFAs)in the intestines in mice,short chain fatty acids can be used as a signaling molecule activation of nuclear factor E2-related factor 2(Nrf2)signaling pathway to alleviate liver oxidative stress,and maintain mitochondrial homeostasis by regulating the expression of genes related to mitochondrial dynamics and autophagy,thereby reducing cell apoptosis to alleviate alcohol-induced oxidative liver injury.展开更多
A combination method of optimization of the back-ground value and optimization of the initial item is proposed. The sequences of the unbiased exponential distribution are simulated and predicted through the optimizati...A combination method of optimization of the back-ground value and optimization of the initial item is proposed. The sequences of the unbiased exponential distribution are simulated and predicted through the optimization of the background value in grey differential equations. The principle of the new information priority in the grey system theory and the rationality of the initial item in the original GM（1,1） model are ful y expressed through the improvement of the initial item in the proposed time response function. A numerical example is employed to il ustrate that the proposed method is able to simulate and predict sequences of raw data with the unbiased exponential distribution and has better simulation performance and prediction precision than the original GM（1,1） model relatively.展开更多
A new method to improve prediction precision of GM（1,1） model with unequal time interval is presented.The grey derivative is multiplied by a parameter to guarantee the time response function satisfying approximately...A new method to improve prediction precision of GM（1,1） model with unequal time interval is presented.The grey derivative is multiplied by a parameter to guarantee the time response function satisfying approximately exponential function distribution.To simplify the process of parametric estimation,an approximate value is taken for the multiplied parameter.Then the estimators of coefficient of development and grey action quantity can be derived.At the same time,the principle of the new information priority is also considered.We take the last item of the first-order accumulated generation operator（1-AGO） on raw data sequence as the initial condition in the time response function.Then the new information can be taken full advantage of through the improved initial condition.Some properties of this new model are also discussed.The presented method is actually a combination of improvement of grey derivative and improvement of the initial condition.The results of an example indicate that the proposed method can improve prediction precision prominently.展开更多
BACKGROUND： α-asarone and acrous gramineus have been shown to play a necessary function in enhancing the reactivity and convulsant threshold to electric stimulation of immature rats. They have also been shown to eff...BACKGROUND： α-asarone and acrous gramineus have been shown to play a necessary function in enhancing the reactivity and convulsant threshold to electric stimulation of immature rats. They have also been shown to effectively suppress epileptic seizures induced by pentylenetetrazol in young rats. However, the mechanisms for these roles have been still unclear. OBJECTIVE： To observe the effects in immature rats of acrous gramineus and α -asarone on apoptosis of hippocampal neurons after epileptic seizure at the protein level, and to analyze the mechanism for these effects. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Pediatrics, First Hospital of Jilin University; Department of Histology and Embryology, Norman Bethune Medical School of Jilin University; Department of Internal Medicine, Children＇s Hospital of Changchun City; Department of Neurology, First Clinical Hospital affiliated to Harbin Medical University. MATERIALS： Fifty 3-week old Wistar rats, 34-40 g, irrespective of gender, were provided by Gaoxin Research Center of Medical Animal Experiment, Changchun. The animals were treated according to the animal ethical standards. The following chemicals were used for this study： acrous gramineus powders or infusion （Batch No, 0307113, Tianjiang Medicine Company Limited, Jiangyin）, α-asarone tablets （Batch No. 030219, Tianwei Pharmaceutical Factory, Shenyang）, and phenobarbital sodium tablets （Batch No. 020608, Xinya Medicine Company Limited, Shanghai）. The animals were divided into five groups randomly. First, ten rats were chosen as the normal controls. The remaining rats were treated with i.p. injections of pentylenetetrazol to stimulate an epileptic model. METHODS： The experiments were performed at the Neurological Laboratory of the First Hospital of Jilin University between October and December 2004. The rats were treated with i.p. injections of pentylenetetrazol （60 mg/kg） to establish an epileptic model. According to Racine＇ s standard, animals that reached stage 4 and 5 were chosen and randomly divided into 4 groups： model group, phenobarbital sodium, acrous gramineus, and a-asarone group. The normal control group was treated with an i.p. injection of physiological saline （0.5 mL）. After modeling, the model groups were intragastrically administrated 0.5 mL saline. The phenobarbital sodium, acrous gramineus, and α-asarone groups were intragastrically administrated 18 mg/kg/d phenobarbital sodium, 2 350 mg/kg/d acrous gramineus and 29 mg/kg/d α-asarone, respectively. The course of treatment was twice a day for 7 days. The normal group received intragastric administration of 0.5 mL saline at the same time. The rats were sacrificed and brain sections were prepared for light microscopy and electron microscopy. MAIN OUTCOME MEASURES： （1） Pathological changes of CA1 and CA3 hippocampal region neurons were observed by light microscopy and electronic microscopy. （2） Neuronal apoptosis in the CA1 and CA3 region was measured by TUNEL staining. （3） Bcl-2 and Bax expression in CA1 and CA3 region neurons was detected by immunohistochemistry and a ratio of Bcl-2/Bax was calculated. RESULTS： All 50 immature rats were included in the final analysis. （1） Pathological changes of CA1 and CA3 region hippocampal neurons： there were different pathological changes in all groups other than the normal control group. The number of damaged neurons in the model group was highest. The phenobarbital sodium, acrous gramineus, and α -asarone group exhibited different degrees of improvement. （2） Neuronal apoptosis in the CA1 and CA3 regions： there were less TUNEL-positive cells in the CA1 and CA3 regions in the normal control group. One week after PTZ-induced seizure, numerous TUNEL-positive cells were detected in the CA1 and CA3 regions in the remaining four groups. There was a significant difference between the normal control group and the remaining four groups （t = 12.089-19.162, P 〈 0.0 1）. The number of TUNEL-positive cells was less in the phenobarbital sodium, acrous gramineus, and α-asarone groups compared to the model group （t = 4.707-5.268, P 〈 0.01）. （3）Bcl-2 and Bax expression of neurons in the CA1 and CA3 regions： The number of Bcl-2- and Bax-positive cells was less in the normal control group. The Bax-positive cells exhibited a normal shape and had large round nuclei that were predominant. One week after PTZ-induced epilepsy, the number of Bcl-2- and Bax-positive cells in the CA1 and CA2 regions was significantly increased in the remaining four groups compared to the normal control group （t = 11.606-27.042, P 〈 0.01）. The Bax-positive cells exhibited a reduced size and nuclear pyknosis was predominant. However, there was no significant difference among the four groups （P 〉 0.05）. The number of Bcl-2-positive cells in the phenobarbital sodium, acrous gramineus, and a-asarone groups were significantly increased compared to the model group （t = 4.051-6.404, P 〈 0.01）. However, the number of Bax-positive cells was not significantly different among the four groups. The ratio of Bcl-2 to Bax expression was approximately 6.0 in the normal controls, 0.7 in the model group, and 1.0 in the remaining three groups. CONCLUSION： Acrous gramineus and a-asarone increased Bcl-2 expression and decreased Bax expression, and also reduced the number of apoptotic hippocampal neurons during PTZ-induced epileptic seizures in immature rats.展开更多
Heterografting has long been used to enhance the chilling tolerance of temperature-sensitive crops,including watermelon,whose mechanism is known to involve bidirectional long-distance mRNA movements.Despite several st...Heterografting has long been used to enhance the chilling tolerance of temperature-sensitive crops,including watermelon,whose mechanism is known to involve bidirectional long-distance mRNA movements.Despite several studies reporting on mobile mRNA(mb-mRNA)profiles in plants,accurate identification of mb-mRNAs is challenging owing to an array of technical problems.Here,we developed a bioinformatical pipeline that took most of the known technical concerns into consideration and is considered to be a universal tool for mb-mRNA detection in heterografts.By applying this pipeline to a commercial watermelon–bottle gourd heterografting system,we detected 130 and 1144 mb-mRNAs upwardly and 167 and 1051 mb-mRNAs downwardly transmitted under normal and chilling-stress conditions,respectively.Quantitative real-time PCR indicated a high accuracy rate(88.2%)of mb-mRNA prediction with our pipeline.We further revealed that the mobility of mRNAs was not associated with their abundance.Functional annotation and classification implied that scions may convey the stress signal to the rootstock,subsequently triggering energy metabolism reprogramming and abscisic acid-mediated stress responses by upward movement of effective mRNAs,ultimately leading to enhanced chilling tolerance.This study provides a universal tool for mb-mRNA detection in plant heterografting systems and novel insights into heterografting advantages under chilling stress.展开更多
Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by ...Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by multiple complex and interacting genetic,psychological,social,and environmental factors,which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety.The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology,and the development of new drugs.Therefore,a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease.This review summarizes animal models and the pathogenesis of anxiety disorders,and discusses the current research status to provide insights for further study of anxiety disorders.展开更多
BACKGROUND： The traditional Chinese medicine acrous gramimeus is the dry rhizome of Acrous gramimeus Soland, a kind of Araceae familial perennial herb, which has a sedation action, anticonvulsant and antiepileptic ef...BACKGROUND： The traditional Chinese medicine acrous gramimeus is the dry rhizome of Acrous gramimeus Soland, a kind of Araceae familial perennial herb, which has a sedation action, anticonvulsant and antiepileptic effect. Its effective component has not been known yet, and α-asarone, the major component of the volatile oil extracted from acrous gramineus, has been supposed to play a necessary role in it. OBJECTIVE： To explore the effects of acrous gramimeu and α-asarone on the reactivity and convulsive threshold to electric stimulation in immature rats, furthermore, attempt to definitize the anticonvulsant effect of α-asarone. DESIGN： A randomized controlled study.SETTINGS： Department of Pediatrics, First Hospital of Jilin University; Department of Histology and Embryology, School of Basic Medical Sciences of Jilin University; Department of Neurology, First Clinical Hospital affiliated to Harbin Medical University; Department of Internal Medicine, Children＇s Hospital of Changchun City. MATERIALS ： Seventy 3-week immature Wistar rats （either males or females） of 34-40 g were used. Acrous gramimeu （1 g/bag, the content of α-oasarone was 0.046 26%-0.070 16%） with the batch number of 0307113 was provided by Tianjiang Medicine Company Limited, Jiangyin City. α-asarone tablet （60 mg per tablet） with the batch number of 030219 was provided by Tianwei Pharmaceutical Factory, Shenyang City. α-asarone injectable preparation （2 mL per piece） with the batch number of 030105 was provided by Shuanghe Medicine Limited Company, Beijing City. METHODS ： The experiments were carried out in the Neurological Laboratory of the First Hospital of Jilin University between August and October in 2004.① The 70 rats were randomly divided into intragastric subset and intraperitoneal subset. The intragastric subset included four groups of control, phenobarbital sodium, acrous gramimeu and α-asarone; the intraperitoneal subset included three groups of control, phenobarbital sodium and α-asarone. There were 10 rats per group. ② In the intragastric subset, different group was treated with saline （1 mL for each time, phenobarbital sodium （18 mg/kg per day）, acrous gramineu （2 350 mg/kg per day） and α-asarone （29 mg/kg per day） respectively twice every day for 5 days. In the intraperitoneal subset, different group was treated with saline （0.5 mL）, phenobarbital sodium （29 mg/kg） and α-asarone （2.9 mg/kg） respectively. ③ Before and after administration for 5 days in the intragastric subset as well as before and after administration for about 1 hour in the intraperitoneal subset respectively, the rats were given electric stimulation with the NIHOM KOMDEM multifunctional electrophysiological recorder, and the reactivity and convulsive threshold to electric stimulation of the rats were recorded. MAIN OUTCOME MEASURES： The reactivity and convulsive threshold to electric stimulation in immature rats were compared. RESULTS： All the rats were involved in the analysis of results. ① Results for intragastric administration： Before intragastric administration, there were no obvious differences in the reactivity and convulsive threshold to electric stimulation among the groups （P 〉 0.05）. After intragastric administration for 5 days, the reactivity and convulsive threshold to the electric stimulation had no obvious changes in the control group, but those were significantly higher than before administration in the drug administration groups （t=-3.317-7.401, P 〈 0.01）, which were also obviously higher than those in the control group （t=3.027-8.941, P 〈 0.01）, and those in the acrous gramimeu group and α-asarone group were not markedly different from those in the phenobarbital sodium group. ② Results for intraperitoneal injection： Before intraperitoneal injection, the reactivity and convulsive threshold to the electric stimulation had no obvious differences among the groups. After the intraperitoneal injection for 1 hour, the reactivity and convulsive threshold to the electric stimulation had no obvious change in the control group, but those were significantly higher than before administration in the drug administration groups （P 〈 0.01）, which were also obviously higher than those in the control group （t=6.211-7.237, P 〈 0.01; t=4.085-5.633, P 〈 0.05）, and there was no marked difference between α-asarone group and phenobarbital sodium group （P 〉 0.05）.CONCLUSION ： ① As effective anticonvulsants, both acrous gramineu and α-asarone can enhance the reactivity and convulsive threshold of immature rats to electric stimulation. ② As one of the major effective components against convulsion of acrous gramineu, α-asarone is equivalent to phenobarbital sodium.展开更多
Allelopathic autotoxicity occurs when a plant releases toxic chemical substances into the environment which inhibits development and growth of the same plant species.Rehmannia glutinosa L.( R.glutinosa ) is one of the...Allelopathic autotoxicity occurs when a plant releases toxic chemical substances into the environment which inhibits development and growth of the same plant species.Rehmannia glutinosa L.( R.glutinosa ) is one of the most common traditional Chinese medicines,whose productivity and quality,however,are seriously impacted by consecutive monoculture obstacle.Allelopathic autotoxicity is one reason for consecutive monoculture obstacle.In this paper,we reviewed the categories of allelochemicals,the methods of allelochemicals identification,and the mechanisms of allelopathic autotoxicity,which provides clues for further study of the molecular mechanisms of allelopathic autotoxicity and consecutive monoculture obstacle.展开更多
Fatigue performance evaluation on asphalt mixture provides an essential reference for asphalt mixture design and pavement structure design.Laboratory fatigue test has been widely used by researchers and engineers to a...Fatigue performance evaluation on asphalt mixture provides an essential reference for asphalt mixture design and pavement structure design.Laboratory fatigue test has been widely used by researchers and engineers to assess the fatigue performance of asphalt mixture,due to its low cost,high efficiency,and strong operability.To ensure performance assessment reliability,fatigue test operated in the laboratory needs to simulate the loading and environmental conditions occurring in the field asphalt layer.As a result,loading setups in laboratory fatigue tests,including loading mode,loading frequency,loading waveform,temperature,and the controlled mode,have been carefully devised by researchers.This paper reviews the above common setups in fatigue tests,which aims to illustrate the classical and latest considerations as well as ideas proposed by researchers for improving fatigue test procedures.As fatigue response data of asphalt mixture is measured from fatigue test,an analysis method is required to process the data and identify fatigue behaviors of the material.Presently,the frequently-used fatigue data analysis methods include the fatigue life model,stiffness-modulus-based method,energy-based method,and viscoelastic continuum damage(VECD)method.This paper also provides a review survey on the main concepts,indicators,and models included in those methods to facilitate their applications.Meanwhile,the latest research progress and outputs related to the four methods are also introduced and discussed to reveal the state-of-the-art developments in this research area.展开更多
Rehmannia glutinosa L.is one of the important medicinal crops in China.Continuous cropping obstacle severely restricts the yield and quality of R.glutinosa,but its molecular mechanism is still unclear.In this study,wi...Rehmannia glutinosa L.is one of the important medicinal crops in China.Continuous cropping obstacle severely restricts the yield and quality of R.glutinosa,but its molecular mechanism is still unclear.In this study,with widely-planted "Wen 85-5" as an experiment material,based on the digital gene expression profiling (DGE) data of previous five stress treatments (continuous cropping,phenolic acid,salt,drought and waterlogging) and the first cropping and continuous cropping treatments of R.glutinosa in five different periods (seedling period,elongation period,early expanding period,middle expanding period and later expanding period),80 candidate genes (|log 2 ratio|≥1,FDR <0.001) specifically responding to continuous cropping obstacle in R.glutinosa were screened.Functional analysis revealed that the differentially expressed genes were involved in the secretion and endocytosis of root cells,which may suggest that the recognition and absorption of allelopathic autotoxins by the roots of R.glutinosa is an important factor that restricts the development of roots in continuous cropping of R.glutinosa.In order to accurately lock genes specifically responding to continuous cropping obstacle in R.glutinosa,continuous cropping soil extract and ferulic acid and p-hydroxybenzonic acid were used to treat aseptic plantlets of R.glutinosa,respectively,and it was confirmed through qRT-PCR that the expression levels of some genes under phenolic acid treatment changed more severely than that under the continuous cropping soil extract treatment,and four key genes involved in the response of R.glutinosa to continuous cropping were finally locked.This study lays a foundation for further exploration of the molecular mechanism of continuous cropping obstacle.展开更多
After the publication of this article1,the authors became aware that there was an error in Fig.2b that“Ref2-M”(below“Bowtie2”)on the right panel was mistakenly written as“Ref1-M”.The correct version is shown below.
In order to improve the utilization of the residential electricity consumption data which contains the information on the user’s electricity consumption habits, a residential electricity consumption behaviors mining ...In order to improve the utilization of the residential electricity consumption data which contains the information on the user’s electricity consumption habits, a residential electricity consumption behaviors mining algorithm model is constructed. Firstly, according to the attribute, the collected data can be divided into the global data and the phase data, then the appropriate global variables are selected to mine the user’s electricity consumption patterns in the near future on the system clustering algorithm. Based on the theory of grey relational analysis, combing phase data with the power modes to analyze the potential characteristics of residential electricity consumption behaviors deeply that verify the ability of latest power mode to predict household electricity consumption situation in the coming few days and the effect of dominant phase variables on the peak load shifting. Finally, from the actual data of a certain family, the proposed data mining algorithm is testified that it can effectively explore the electricity consumption behavior habits and characteristics of the family.展开更多
Apigenin (4’, 5, 7-trihydroxyflavone, AP), a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. In the present study, in order to explore the potential mechanis...Apigenin (4’, 5, 7-trihydroxyflavone, AP), a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. In the present study, in order to explore the potential mechanism and provide the references for further studies, we investigated the effect of apigenin at various dosages on the hepatic oxidative stress of male rats. Totally 48 SD male rats were randomly divided into control group (saline, 1 ml/100g·bw), low-dose group (AP, 234 mg/kg·bw), middle-dose group (AP, 468 mg/kg·bw) and high-dose group (AP, 936 mg/kg·bw). The rats were administered with apigenin or saline via intragastriation once a day, 6 days per week, and 5 consecutive weeks. Rats were sacrificed and the livers were harvested and then immediately preserved at ﹣20°C. Liver homogenate was prepared before detection. Hepatic malondialdehyde (MDA), nitric oxide syntheses (NOS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and glutathione (GSH) were determined by colorimetric methods according to the provided procedures. The weights of liver and spleen in apigenin treatment groups did not reveal statistically significant difference when compared with that in the control group (P > 0.05). Total protein (TP), albumin (ALB) and globulin (GLO) in apigenin treatment groups were significantly lower than those in the control group (P < 0.05). SOD in the middle-dose group (AP, 468 mg/kg·bw) and high-dose group (AP, 936 mg/kg·bw) were significantly higher than that in the control group (P < 0.05). T-AOC, CAT and GSH-Px in apigenin treatment groups were significantly lower than those in the control group (P < 0.05). In high-dose AP group (AP, 936 mg/kg·bw), apigenin can result in the reduction of T-AOC, thus leading to the oxidative damage of liver tissues. In contrast, in middle-dose AP group (AP, 468 mg/kg·bw), apegenin can reduce the elimination capacity of oxygen free radicals.展开更多
Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to...Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to now, multiple approaches are being sought to overcome these limitations to obtaining “super curcumin”, and many analogues of curcumin have been designed and synthesized. In all of those analogues, a series of mono-carbonyl curcumin analogues deleting the β-diketone draw our attention. Since the seven-carbon β-diketone linker in curcumin may be responsible for its instability, the series of mono-carbonyl curcumin analogues deleting the β-diketone may be potential prodrug with improved pharmacokinetic and pharmacodynamic properties. This review just focuses on these more stable mono-carbonyl analogues of curcumin, and shows the new class of active structure by introducing the synthesis and anticancer activity of them.展开更多
This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology a...This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology and experimental validation techniques.Active constituents of Astragali Radix and their corresponding targets were identified using the TCMSP database,while therapeutic targets associated with hypoxia-induced pulmonary hypertension were sourced from the GeneCards database.The Venn online tool facilitated the identification of overlapping targets between the active constituents of Astragali Radix and hypoxia-induced pulmonary hypertension.Interaction network diagrams depicting the relationship between Astragali Radix’s active constituents and their targets were constructed using Cytoscape software,with core targets and sub-networks identified using the CytoHubba plug-in.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using the DAVID database.Additionally,the FerrDb database was consulted to analyze genes implicated in regulating ferroptosis.The investigation revealed 18 active constituents selected from Astragali Radix,with quercetin emerging as the key component.A total of 35 potential targets associated with Astragali Radix in regulating ferroptosis and addressing hypoxia-induced pulmonary hypertension were predicted.Experimental validation demonstrated that quercetin could inhibit the MAPK signaling pathway,resulting in reduced Fe2+and lipid peroxide levels,increased GPX4 expression,and the reversal of ferroptosis.In summary,this study elucidated the fundamental constituents and pivotal signaling pathways through which Astragali Radix modulated ferroptosis and mitigated hypoxia-induced pulmonary hypertension.Specifically,quercetin,a core constituent of Astragali Radix,was observed to inhibit ferroptosis in pulmonary arterial smooth muscle cells via the MAPK pathway and alleviate hypoxia-induced pulmonary hypertension.展开更多
Cotton(Gossypium)stands as a crucial economic crop,serving as the primary source of naturalfiber for the textile sector.However,the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolv...Cotton(Gossypium)stands as a crucial economic crop,serving as the primary source of naturalfiber for the textile sector.However,the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolved.In this investigation,we leveraged 25 Gossypium genomes and introduced four novel assem-blies—G.harknessii,G.gossypioides,G.trilobum,and G.klotzschianum(Gklo)—to delve into the speciation history of this genus.Notably,we encountered intricate phylogenies potentially stemming from introgres-sion.These complexities are further compounded by incomplete lineage sorting(ILS),a factor likely to have been instrumental in shaping the swift diversification of cotton.Our focus subsequently shifted to the rapid radiation episode during a concise period in Gossypium evolution.For a recently diverged lineage comprising G.davidsonii,Gklo,and G.raimondii,we constructed afinely detailed ILS map.Intriguingly,this analysis revealed the non-random distribution of ILS regions across the reference Gklo genome.Moreover,we identified signs of robust natural selection influencing specific ILS regions.Noteworthy variations per-taining to speciation emerged between the closely related sister species Gklo and G.davidsonii.Approxi-mately 15.74%of speciation structural variation genes and 12.04%of speciation-associated genes were esti-mated to intersect with ILS signatures.Thesefindings enrich our understanding of the role of ILS in adaptive radiation,shedding fresh light on the intricate speciation history of the Gossypium genus.展开更多
The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive corr...The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis.Subsequently,an oxygen generator loaded with copper ions(Cu/APH-M)has been constructed,which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment.Importantly,Cu/APH-M-mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA-sequencing analysis,but also effec-tively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy,creating a robust immune memory effect.Our work reveals the ben-eficial effects of enhanced cuproptosis in radio-immunotherapy and elucidates its underlying mechanisms,which provides a novel approach for the synergistic inte-gration of cuproptosis with immunotherapy and radiotherapy,broadening the scope of cuproptosis-mediated tumor therapy.展开更多
基金supported by the National Key R&D Program of China(2021YFD2100701).
文摘Oxidative stress is one of the main ways to cause alcohol-induced liver injury,and alcoholic liver disease(ALD)has been a common health problem worldwide.Lactic acid bacteria(LAB)is also considered as a potential treatment to alleviate alcohol-induced liver injury.Lactobacillus plantarum J26 is a LAB isolated from Chinese traditional fermented dairy products with excellent probiotic effects.This study aimed to establish a mice model of alcoholic liver injury through acute-on-chronic alcohol feeding and to study the alleviating effect of pre-intake of L.plantarum J26 on alcohol-induced oxidative liver injury and focus on its potential mechanism of alleviating effect.The results showed that pre-intake of L.plantarum J26 could improve liver pathological changes,reduce lipid accumulation,increase mitochondrial ATP and mitochondrial(mtDNA)levels,and alleviate liver injury.In addition,pre-intake L.plantarum J26 can improve the level of short-chain fatty acids(SCFAs)in the intestines in mice,short chain fatty acids can be used as a signaling molecule activation of nuclear factor E2-related factor 2(Nrf2)signaling pathway to alleviate liver oxidative stress,and maintain mitochondrial homeostasis by regulating the expression of genes related to mitochondrial dynamics and autophagy,thereby reducing cell apoptosis to alleviate alcohol-induced oxidative liver injury.
基金supported by the Key Project of National Social Science Foundation(12AZD111)the National Project for Education Science Planning(EFA110351)+2 种基金the Humanities and Social Science Foundation of Ministry of Education of China(12YJCZH207)the Key Project for Jiangsu Province Social Science Foundation(12DDA011)the Jiangsu College of Humanities and Social Sciences outside Campus Research Base:Chinese Development of Strategic Research Base for Internet of Things
文摘A combination method of optimization of the back-ground value and optimization of the initial item is proposed. The sequences of the unbiased exponential distribution are simulated and predicted through the optimization of the background value in grey differential equations. The principle of the new information priority in the grey system theory and the rationality of the initial item in the original GM（1,1） model are ful y expressed through the improvement of the initial item in the proposed time response function. A numerical example is employed to il ustrate that the proposed method is able to simulate and predict sequences of raw data with the unbiased exponential distribution and has better simulation performance and prediction precision than the original GM（1,1） model relatively.
基金supported by the National Natural Science Foundation of China (7090103471071077)+2 种基金the National Educational Sciences Planning Key Project of Ministry of Education (DFA090215)the Fundamental Research Funds for the Central Universities (JUSRP21146JUSRP31107)
文摘A new method to improve prediction precision of GM（1,1） model with unequal time interval is presented.The grey derivative is multiplied by a parameter to guarantee the time response function satisfying approximately exponential function distribution.To simplify the process of parametric estimation,an approximate value is taken for the multiplied parameter.Then the estimators of coefficient of development and grey action quantity can be derived.At the same time,the principle of the new information priority is also considered.We take the last item of the first-order accumulated generation operator（1-AGO） on raw data sequence as the initial condition in the time response function.Then the new information can be taken full advantage of through the improved initial condition.Some properties of this new model are also discussed.The presented method is actually a combination of improvement of grey derivative and improvement of the initial condition.The results of an example indicate that the proposed method can improve prediction precision prominently.
基金grants from Jilin Bureau of Science and Technology(No. 20030430)Traditional Chinese Medicine and Drug Adminsitration of Jilin Provinece(No. 2004079)
文摘BACKGROUND： α-asarone and acrous gramineus have been shown to play a necessary function in enhancing the reactivity and convulsant threshold to electric stimulation of immature rats. They have also been shown to effectively suppress epileptic seizures induced by pentylenetetrazol in young rats. However, the mechanisms for these roles have been still unclear. OBJECTIVE： To observe the effects in immature rats of acrous gramineus and α -asarone on apoptosis of hippocampal neurons after epileptic seizure at the protein level, and to analyze the mechanism for these effects. DESIGN： A randomized controlled animal experiment. SETTINGS： Department of Pediatrics, First Hospital of Jilin University; Department of Histology and Embryology, Norman Bethune Medical School of Jilin University; Department of Internal Medicine, Children＇s Hospital of Changchun City; Department of Neurology, First Clinical Hospital affiliated to Harbin Medical University. MATERIALS： Fifty 3-week old Wistar rats, 34-40 g, irrespective of gender, were provided by Gaoxin Research Center of Medical Animal Experiment, Changchun. The animals were treated according to the animal ethical standards. The following chemicals were used for this study： acrous gramineus powders or infusion （Batch No, 0307113, Tianjiang Medicine Company Limited, Jiangyin）, α-asarone tablets （Batch No. 030219, Tianwei Pharmaceutical Factory, Shenyang）, and phenobarbital sodium tablets （Batch No. 020608, Xinya Medicine Company Limited, Shanghai）. The animals were divided into five groups randomly. First, ten rats were chosen as the normal controls. The remaining rats were treated with i.p. injections of pentylenetetrazol to stimulate an epileptic model. METHODS： The experiments were performed at the Neurological Laboratory of the First Hospital of Jilin University between October and December 2004. The rats were treated with i.p. injections of pentylenetetrazol （60 mg/kg） to establish an epileptic model. According to Racine＇ s standard, animals that reached stage 4 and 5 were chosen and randomly divided into 4 groups： model group, phenobarbital sodium, acrous gramineus, and a-asarone group. The normal control group was treated with an i.p. injection of physiological saline （0.5 mL）. After modeling, the model groups were intragastrically administrated 0.5 mL saline. The phenobarbital sodium, acrous gramineus, and α-asarone groups were intragastrically administrated 18 mg/kg/d phenobarbital sodium, 2 350 mg/kg/d acrous gramineus and 29 mg/kg/d α-asarone, respectively. The course of treatment was twice a day for 7 days. The normal group received intragastric administration of 0.5 mL saline at the same time. The rats were sacrificed and brain sections were prepared for light microscopy and electron microscopy. MAIN OUTCOME MEASURES： （1） Pathological changes of CA1 and CA3 hippocampal region neurons were observed by light microscopy and electronic microscopy. （2） Neuronal apoptosis in the CA1 and CA3 region was measured by TUNEL staining. （3） Bcl-2 and Bax expression in CA1 and CA3 region neurons was detected by immunohistochemistry and a ratio of Bcl-2/Bax was calculated. RESULTS： All 50 immature rats were included in the final analysis. （1） Pathological changes of CA1 and CA3 region hippocampal neurons： there were different pathological changes in all groups other than the normal control group. The number of damaged neurons in the model group was highest. The phenobarbital sodium, acrous gramineus, and α -asarone group exhibited different degrees of improvement. （2） Neuronal apoptosis in the CA1 and CA3 regions： there were less TUNEL-positive cells in the CA1 and CA3 regions in the normal control group. One week after PTZ-induced seizure, numerous TUNEL-positive cells were detected in the CA1 and CA3 regions in the remaining four groups. There was a significant difference between the normal control group and the remaining four groups （t = 12.089-19.162, P 〈 0.0 1）. The number of TUNEL-positive cells was less in the phenobarbital sodium, acrous gramineus, and α-asarone groups compared to the model group （t = 4.707-5.268, P 〈 0.01）. （3）Bcl-2 and Bax expression of neurons in the CA1 and CA3 regions： The number of Bcl-2- and Bax-positive cells was less in the normal control group. The Bax-positive cells exhibited a normal shape and had large round nuclei that were predominant. One week after PTZ-induced epilepsy, the number of Bcl-2- and Bax-positive cells in the CA1 and CA2 regions was significantly increased in the remaining four groups compared to the normal control group （t = 11.606-27.042, P 〈 0.01）. The Bax-positive cells exhibited a reduced size and nuclear pyknosis was predominant. However, there was no significant difference among the four groups （P 〉 0.05）. The number of Bcl-2-positive cells in the phenobarbital sodium, acrous gramineus, and a-asarone groups were significantly increased compared to the model group （t = 4.051-6.404, P 〈 0.01）. However, the number of Bax-positive cells was not significantly different among the four groups. The ratio of Bcl-2 to Bax expression was approximately 6.0 in the normal controls, 0.7 in the model group, and 1.0 in the remaining three groups. CONCLUSION： Acrous gramineus and a-asarone increased Bcl-2 expression and decreased Bax expression, and also reduced the number of apoptotic hippocampal neurons during PTZ-induced epileptic seizures in immature rats.
基金supported by the National Natural Science Foundation of China(31772291)the Key Science Project of Plant Breeding in Zhejiang(2016C02051)+1 种基金the Cucurbitaceae Rootstock Breeding Innovation Team of Ningbo(2015C110028)the National Program for Support of Top-notch Young Professionals(to P.X.)。
文摘Heterografting has long been used to enhance the chilling tolerance of temperature-sensitive crops,including watermelon,whose mechanism is known to involve bidirectional long-distance mRNA movements.Despite several studies reporting on mobile mRNA(mb-mRNA)profiles in plants,accurate identification of mb-mRNAs is challenging owing to an array of technical problems.Here,we developed a bioinformatical pipeline that took most of the known technical concerns into consideration and is considered to be a universal tool for mb-mRNA detection in heterografts.By applying this pipeline to a commercial watermelon–bottle gourd heterografting system,we detected 130 and 1144 mb-mRNAs upwardly and 167 and 1051 mb-mRNAs downwardly transmitted under normal and chilling-stress conditions,respectively.Quantitative real-time PCR indicated a high accuracy rate(88.2%)of mb-mRNA prediction with our pipeline.We further revealed that the mobility of mRNAs was not associated with their abundance.Functional annotation and classification implied that scions may convey the stress signal to the rootstock,subsequently triggering energy metabolism reprogramming and abscisic acid-mediated stress responses by upward movement of effective mRNAs,ultimately leading to enhanced chilling tolerance.This study provides a universal tool for mb-mRNA detection in plant heterografting systems and novel insights into heterografting advantages under chilling stress.
基金National Natural Science Foundation of ChinaGrant/Award Number:82104793 and 82104836+5 种基金Natural Science Foundation of Hunan ProvinceGrant/Award Number:2023JJ60482Openof TCM First-class Disciplines in HNUCMGrant/Award Number:2022ZYX18Science and Technology talent promotion Project of Hunan ProvinceGrant/Award Number:2023TJ-N22。
文摘Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by multiple complex and interacting genetic,psychological,social,and environmental factors,which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety.The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology,and the development of new drugs.Therefore,a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease.This review summarizes animal models and the pathogenesis of anxiety disorders,and discusses the current research status to provide insights for further study of anxiety disorders.
基金grants from Changchun Bureau of Science and Technology, No. 20030430 Traditional Chinese Medicine and Drug Administration of Jilin Province, No. 2004079
文摘BACKGROUND： The traditional Chinese medicine acrous gramimeus is the dry rhizome of Acrous gramimeus Soland, a kind of Araceae familial perennial herb, which has a sedation action, anticonvulsant and antiepileptic effect. Its effective component has not been known yet, and α-asarone, the major component of the volatile oil extracted from acrous gramineus, has been supposed to play a necessary role in it. OBJECTIVE： To explore the effects of acrous gramimeu and α-asarone on the reactivity and convulsive threshold to electric stimulation in immature rats, furthermore, attempt to definitize the anticonvulsant effect of α-asarone. DESIGN： A randomized controlled study.SETTINGS： Department of Pediatrics, First Hospital of Jilin University; Department of Histology and Embryology, School of Basic Medical Sciences of Jilin University; Department of Neurology, First Clinical Hospital affiliated to Harbin Medical University; Department of Internal Medicine, Children＇s Hospital of Changchun City. MATERIALS ： Seventy 3-week immature Wistar rats （either males or females） of 34-40 g were used. Acrous gramimeu （1 g/bag, the content of α-oasarone was 0.046 26%-0.070 16%） with the batch number of 0307113 was provided by Tianjiang Medicine Company Limited, Jiangyin City. α-asarone tablet （60 mg per tablet） with the batch number of 030219 was provided by Tianwei Pharmaceutical Factory, Shenyang City. α-asarone injectable preparation （2 mL per piece） with the batch number of 030105 was provided by Shuanghe Medicine Limited Company, Beijing City. METHODS ： The experiments were carried out in the Neurological Laboratory of the First Hospital of Jilin University between August and October in 2004.① The 70 rats were randomly divided into intragastric subset and intraperitoneal subset. The intragastric subset included four groups of control, phenobarbital sodium, acrous gramimeu and α-asarone; the intraperitoneal subset included three groups of control, phenobarbital sodium and α-asarone. There were 10 rats per group. ② In the intragastric subset, different group was treated with saline （1 mL for each time, phenobarbital sodium （18 mg/kg per day）, acrous gramineu （2 350 mg/kg per day） and α-asarone （29 mg/kg per day） respectively twice every day for 5 days. In the intraperitoneal subset, different group was treated with saline （0.5 mL）, phenobarbital sodium （29 mg/kg） and α-asarone （2.9 mg/kg） respectively. ③ Before and after administration for 5 days in the intragastric subset as well as before and after administration for about 1 hour in the intraperitoneal subset respectively, the rats were given electric stimulation with the NIHOM KOMDEM multifunctional electrophysiological recorder, and the reactivity and convulsive threshold to electric stimulation of the rats were recorded. MAIN OUTCOME MEASURES： The reactivity and convulsive threshold to electric stimulation in immature rats were compared. RESULTS： All the rats were involved in the analysis of results. ① Results for intragastric administration： Before intragastric administration, there were no obvious differences in the reactivity and convulsive threshold to electric stimulation among the groups （P 〉 0.05）. After intragastric administration for 5 days, the reactivity and convulsive threshold to the electric stimulation had no obvious changes in the control group, but those were significantly higher than before administration in the drug administration groups （t=-3.317-7.401, P 〈 0.01）, which were also obviously higher than those in the control group （t=3.027-8.941, P 〈 0.01）, and those in the acrous gramimeu group and α-asarone group were not markedly different from those in the phenobarbital sodium group. ② Results for intraperitoneal injection： Before intraperitoneal injection, the reactivity and convulsive threshold to the electric stimulation had no obvious differences among the groups. After the intraperitoneal injection for 1 hour, the reactivity and convulsive threshold to the electric stimulation had no obvious change in the control group, but those were significantly higher than before administration in the drug administration groups （P 〈 0.01）, which were also obviously higher than those in the control group （t=6.211-7.237, P 〈 0.01; t=4.085-5.633, P 〈 0.05）, and there was no marked difference between α-asarone group and phenobarbital sodium group （P 〉 0.05）.CONCLUSION ： ① As effective anticonvulsants, both acrous gramineu and α-asarone can enhance the reactivity and convulsive threshold of immature rats to electric stimulation. ② As one of the major effective components against convulsion of acrous gramineu, α-asarone is equivalent to phenobarbital sodium.
基金Supported by National Natural Science Foundation of China(31271674)Key Research Project of Colleges and Universities in Henan Province(17A180024)
文摘Allelopathic autotoxicity occurs when a plant releases toxic chemical substances into the environment which inhibits development and growth of the same plant species.Rehmannia glutinosa L.( R.glutinosa ) is one of the most common traditional Chinese medicines,whose productivity and quality,however,are seriously impacted by consecutive monoculture obstacle.Allelopathic autotoxicity is one reason for consecutive monoculture obstacle.In this paper,we reviewed the categories of allelochemicals,the methods of allelochemicals identification,and the mechanisms of allelopathic autotoxicity,which provides clues for further study of the molecular mechanisms of allelopathic autotoxicity and consecutive monoculture obstacle.
基金The study is supported by the National Natural Science Foundation of China(Grant No.52108412)the Postdoctoral Science Foundation of China(Grant Nos.BX2021216,2021M702479).
文摘Fatigue performance evaluation on asphalt mixture provides an essential reference for asphalt mixture design and pavement structure design.Laboratory fatigue test has been widely used by researchers and engineers to assess the fatigue performance of asphalt mixture,due to its low cost,high efficiency,and strong operability.To ensure performance assessment reliability,fatigue test operated in the laboratory needs to simulate the loading and environmental conditions occurring in the field asphalt layer.As a result,loading setups in laboratory fatigue tests,including loading mode,loading frequency,loading waveform,temperature,and the controlled mode,have been carefully devised by researchers.This paper reviews the above common setups in fatigue tests,which aims to illustrate the classical and latest considerations as well as ideas proposed by researchers for improving fatigue test procedures.As fatigue response data of asphalt mixture is measured from fatigue test,an analysis method is required to process the data and identify fatigue behaviors of the material.Presently,the frequently-used fatigue data analysis methods include the fatigue life model,stiffness-modulus-based method,energy-based method,and viscoelastic continuum damage(VECD)method.This paper also provides a review survey on the main concepts,indicators,and models included in those methods to facilitate their applications.Meanwhile,the latest research progress and outputs related to the four methods are also introduced and discussed to reveal the state-of-the-art developments in this research area.
基金Supported by National Natural Science Foundation of China(31271674)Key Research Project of Colleges and Universities in Henan Province(17A180024)
文摘Rehmannia glutinosa L.is one of the important medicinal crops in China.Continuous cropping obstacle severely restricts the yield and quality of R.glutinosa,but its molecular mechanism is still unclear.In this study,with widely-planted "Wen 85-5" as an experiment material,based on the digital gene expression profiling (DGE) data of previous five stress treatments (continuous cropping,phenolic acid,salt,drought and waterlogging) and the first cropping and continuous cropping treatments of R.glutinosa in five different periods (seedling period,elongation period,early expanding period,middle expanding period and later expanding period),80 candidate genes (|log 2 ratio|≥1,FDR <0.001) specifically responding to continuous cropping obstacle in R.glutinosa were screened.Functional analysis revealed that the differentially expressed genes were involved in the secretion and endocytosis of root cells,which may suggest that the recognition and absorption of allelopathic autotoxins by the roots of R.glutinosa is an important factor that restricts the development of roots in continuous cropping of R.glutinosa.In order to accurately lock genes specifically responding to continuous cropping obstacle in R.glutinosa,continuous cropping soil extract and ferulic acid and p-hydroxybenzonic acid were used to treat aseptic plantlets of R.glutinosa,respectively,and it was confirmed through qRT-PCR that the expression levels of some genes under phenolic acid treatment changed more severely than that under the continuous cropping soil extract treatment,and four key genes involved in the response of R.glutinosa to continuous cropping were finally locked.This study lays a foundation for further exploration of the molecular mechanism of continuous cropping obstacle.
文摘After the publication of this article1,the authors became aware that there was an error in Fig.2b that“Ref2-M”(below“Bowtie2”)on the right panel was mistakenly written as“Ref1-M”.The correct version is shown below.
文摘In order to improve the utilization of the residential electricity consumption data which contains the information on the user’s electricity consumption habits, a residential electricity consumption behaviors mining algorithm model is constructed. Firstly, according to the attribute, the collected data can be divided into the global data and the phase data, then the appropriate global variables are selected to mine the user’s electricity consumption patterns in the near future on the system clustering algorithm. Based on the theory of grey relational analysis, combing phase data with the power modes to analyze the potential characteristics of residential electricity consumption behaviors deeply that verify the ability of latest power mode to predict household electricity consumption situation in the coming few days and the effect of dominant phase variables on the peak load shifting. Finally, from the actual data of a certain family, the proposed data mining algorithm is testified that it can effectively explore the electricity consumption behavior habits and characteristics of the family.
文摘Apigenin (4’, 5, 7-trihydroxyflavone, AP), a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. In the present study, in order to explore the potential mechanism and provide the references for further studies, we investigated the effect of apigenin at various dosages on the hepatic oxidative stress of male rats. Totally 48 SD male rats were randomly divided into control group (saline, 1 ml/100g·bw), low-dose group (AP, 234 mg/kg·bw), middle-dose group (AP, 468 mg/kg·bw) and high-dose group (AP, 936 mg/kg·bw). The rats were administered with apigenin or saline via intragastriation once a day, 6 days per week, and 5 consecutive weeks. Rats were sacrificed and the livers were harvested and then immediately preserved at ﹣20°C. Liver homogenate was prepared before detection. Hepatic malondialdehyde (MDA), nitric oxide syntheses (NOS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and glutathione (GSH) were determined by colorimetric methods according to the provided procedures. The weights of liver and spleen in apigenin treatment groups did not reveal statistically significant difference when compared with that in the control group (P > 0.05). Total protein (TP), albumin (ALB) and globulin (GLO) in apigenin treatment groups were significantly lower than those in the control group (P < 0.05). SOD in the middle-dose group (AP, 468 mg/kg·bw) and high-dose group (AP, 936 mg/kg·bw) were significantly higher than that in the control group (P < 0.05). T-AOC, CAT and GSH-Px in apigenin treatment groups were significantly lower than those in the control group (P < 0.05). In high-dose AP group (AP, 936 mg/kg·bw), apigenin can result in the reduction of T-AOC, thus leading to the oxidative damage of liver tissues. In contrast, in middle-dose AP group (AP, 468 mg/kg·bw), apegenin can reduce the elimination capacity of oxygen free radicals.
文摘Curcumin has been reported to possess multifunctional bioactivities with low toxicity. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Up to now, multiple approaches are being sought to overcome these limitations to obtaining “super curcumin”, and many analogues of curcumin have been designed and synthesized. In all of those analogues, a series of mono-carbonyl curcumin analogues deleting the β-diketone draw our attention. Since the seven-carbon β-diketone linker in curcumin may be responsible for its instability, the series of mono-carbonyl curcumin analogues deleting the β-diketone may be potential prodrug with improved pharmacokinetic and pharmacodynamic properties. This review just focuses on these more stable mono-carbonyl analogues of curcumin, and shows the new class of active structure by introducing the synthesis and anticancer activity of them.
基金National Natural Science Foundation of China(Grant No.82305214)Hunan Province’s Natural Science Fund(Grant No.2023JJ40401)+2 种基金Hunan Administration of Traditional Chinese Medicine(Grant No.B2023024)Hunan Provincial Department of Education Outstanding Youth Project(Grant No.22B0394)State Key Laboratory Project of Chinese Medicine Powder and Innovative Drugs Project(Grant No.21PTKF1002).
文摘This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology and experimental validation techniques.Active constituents of Astragali Radix and their corresponding targets were identified using the TCMSP database,while therapeutic targets associated with hypoxia-induced pulmonary hypertension were sourced from the GeneCards database.The Venn online tool facilitated the identification of overlapping targets between the active constituents of Astragali Radix and hypoxia-induced pulmonary hypertension.Interaction network diagrams depicting the relationship between Astragali Radix’s active constituents and their targets were constructed using Cytoscape software,with core targets and sub-networks identified using the CytoHubba plug-in.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using the DAVID database.Additionally,the FerrDb database was consulted to analyze genes implicated in regulating ferroptosis.The investigation revealed 18 active constituents selected from Astragali Radix,with quercetin emerging as the key component.A total of 35 potential targets associated with Astragali Radix in regulating ferroptosis and addressing hypoxia-induced pulmonary hypertension were predicted.Experimental validation demonstrated that quercetin could inhibit the MAPK signaling pathway,resulting in reduced Fe2+and lipid peroxide levels,increased GPX4 expression,and the reversal of ferroptosis.In summary,this study elucidated the fundamental constituents and pivotal signaling pathways through which Astragali Radix modulated ferroptosis and mitigated hypoxia-induced pulmonary hypertension.Specifically,quercetin,a core constituent of Astragali Radix,was observed to inhibit ferroptosis in pulmonary arterial smooth muscle cells via the MAPK pathway and alleviate hypoxia-induced pulmonary hypertension.
基金the National Natural Science Foundation of China (32272090,32171994,and 32072023)the Central Plains Science and Technology Innovation Leader Project (214200510029 and 2022C01NY001)+1 种基金the Project of Sanya Yazhou Bay Science and Technology City (SCKY-JYRC-2022-88)the National Key R&D Program of China (2021YFE0101200)for financial support.
文摘Cotton(Gossypium)stands as a crucial economic crop,serving as the primary source of naturalfiber for the textile sector.However,the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolved.In this investigation,we leveraged 25 Gossypium genomes and introduced four novel assem-blies—G.harknessii,G.gossypioides,G.trilobum,and G.klotzschianum(Gklo)—to delve into the speciation history of this genus.Notably,we encountered intricate phylogenies potentially stemming from introgres-sion.These complexities are further compounded by incomplete lineage sorting(ILS),a factor likely to have been instrumental in shaping the swift diversification of cotton.Our focus subsequently shifted to the rapid radiation episode during a concise period in Gossypium evolution.For a recently diverged lineage comprising G.davidsonii,Gklo,and G.raimondii,we constructed afinely detailed ILS map.Intriguingly,this analysis revealed the non-random distribution of ILS regions across the reference Gklo genome.Moreover,we identified signs of robust natural selection influencing specific ILS regions.Noteworthy variations per-taining to speciation emerged between the closely related sister species Gklo and G.davidsonii.Approxi-mately 15.74%of speciation structural variation genes and 12.04%of speciation-associated genes were esti-mated to intersect with ILS signatures.Thesefindings enrich our understanding of the role of ILS in adaptive radiation,shedding fresh light on the intricate speciation history of the Gossypium genus.
基金Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20190946Gusu Leading Talent Program for Innovation and Entrepreneurship,Grant/Award Number:ZXL2021441+5 种基金Suzhou health youth backbone talent“national tutorial system”training project,Grant/Award Number:Qngg2023005Key Research and Development Program of Social Development of Jiangsu Province,Grant/Award Number:BE2022725Natural Science Foundation of Anhui Province,Grant/Award Number:2308085QH281Beijing Sisko Clinical Oncology Research Foundation,Grant/Award Number:Y-tongshu2021/qn-0366Key Scientific Research Project of Colleges and Universities of Anhui Province of China,Grant/Award Number:2022AH050683National Natural Science Foundation of China,Grant/Award Numbers:12275003,32171382,32301169,U1932208。
文摘The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis.Subsequently,an oxygen generator loaded with copper ions(Cu/APH-M)has been constructed,which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment.Importantly,Cu/APH-M-mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA-sequencing analysis,but also effec-tively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy,creating a robust immune memory effect.Our work reveals the ben-eficial effects of enhanced cuproptosis in radio-immunotherapy and elucidates its underlying mechanisms,which provides a novel approach for the synergistic inte-gration of cuproptosis with immunotherapy and radiotherapy,broadening the scope of cuproptosis-mediated tumor therapy.
