TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal...TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies wer...We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.展开更多
Integrative cultivation practices(ICPs)are essential for enhancing cereal yield and resource use efficiency.However,the effects of ICP on the rhizosphere environment and roots of paddy rice are still poorly understood...Integrative cultivation practices(ICPs)are essential for enhancing cereal yield and resource use efficiency.However,the effects of ICP on the rhizosphere environment and roots of paddy rice are still poorly understood.In this study,four rice varieties were produced in the field.Each variety was treated with six different cultivation techniques,including zero nitrogen application(0 N),local farmers’practice(LFP),nitrogen reduction(NR),and three progressive ICP techniques comprised of enhanced fertilizer N practice and increased plant density(ICP1),a treatment similar to ICP1 but with alternate wetting and moderate drying instead of continuous flooding(ICP2),and the same practices as ICP2 with the application of organic fertilizer(ICP3).The ICPs had greater grain production and nitrogen use efficiency than the other three methods.Root length,dry weight,root diameter,activity of root oxidation,root bleeding rate,zeatin and zeatin riboside compositions,and total organic acids in root exudates were elevated with the introduction of the successive cultivation practices.ICPs enhanced nitrate nitrogen,the activities of urease and invertase,and the diversity of microbes(bacteria)in rhizosphere and non-rhizosphere soil,while reducing the ammonium nitrogen content.The nutrient contents(ammonium nitrogen,total nitrogen,total potassium,total phosphorus,nitrate,and available phosphorus)and urease activity in rhizosphere soil were reduced in all treatments in comparison with the non-rhizosphere soil,but the invertase activity and bacterial diversity were greater.The main root morphology and physiology,and the ammonium nitrogen contents in rhizosphere soil at the primary stages were closely correlated with grain yield and internal nitrogen use efficiency.These findings suggest that the coordinated enhancement of the root system and the environment of the rhizosphere under integrative cultivation approaches may lead to higher rice production.展开更多
GTs(Glycosyltransferases)are important in plant growth and abiotic stresses.However,its role in maize heat response is far from clear.Here,we describe the constitutively expressed UDP-glycosyltransferase ZmUGT92A1,whi...GTs(Glycosyltransferases)are important in plant growth and abiotic stresses.However,its role in maize heat response is far from clear.Here,we describe the constitutively expressed UDP-glycosyltransferase ZmUGT92A1,which has a highly conserved PSPG box and is localized in chloroplasts,is induced under heat stress.Functional disruption of ZmUGT92A1 leads to heat sensitivity and reactive oxygen species accumulation in maize.Metabolomics analysis revealed that ZmUGT92A1 affected multiple metabolic pathways and altered the metabolic homeostasis of flavonoids under heat stress.In vitro assay showed ZmUGT92A1 exhibits glycosyltransferase activity on flavonoids and hormones.Additionally,we identified a rapidly heat-induced transcription factor,ZmHSF08,which can directly bind and repress the promoter region of ZmUGT92A1.The ZmHSF08 overexpression line exhibits heat sensitivity and reactive oxygen species accumulation.These findings reveal that the ZmHSF08-ZmUGT92A1 module plays a role in heat tolerance in maize and provide candidate strategies for the development of heat-tolerant varieties.展开更多
The aim of the present study was to evaluate the nutritional quality of green and purple eggplant, their antioxidant activity and their nutritional efficacy on Wistar rats. For nutritional quality, the parameters meas...The aim of the present study was to evaluate the nutritional quality of green and purple eggplant, their antioxidant activity and their nutritional efficacy on Wistar rats. For nutritional quality, the parameters measured are dry matter, protein, lipid, ash, carbohydrate, iron, phosphorus, calcium, magnesium and energy content. For antioxidant activity, the parameters measured are 50% DDPH free radical inhibition concentration and total polyphenol content. Nutritional efficacy was evaluated in rats fed the control diet and in rats fed the three treated diets containing eggplant meal obtained by replacing 5%, 10%, and 15% of the control diet. The parameters measured are the amount consumed, the weight of the animal and target organs, and hematologic parameters. The results of the nutritional analysis show the following values: 13.31% protein, 2.66% lipids, 0.84% calcium, 0.12% magnesium, 0.43% phosphorus for the Solanum aethiopicum L. species and 13.47% protein, 3.66% lipids, 0.36% calcium, 0.22% magnesium, 0.35% phosphorus for the Solanum melongena L. species. In terms of antioxidant activity, we obtained DDPH inhibition percentages of 40.28 mg/ml for Solanum aethiopicum L. and 12.42 mg/ml for Solanum melongena L., respectively. Finally, hematologic and anthropometric tests showed that for the different diets used, weight loss and an increase in hematologic parameters were observed in the rats tested. This study showed that eggplant has interesting nutritional characteristics and antioxidant activity, contributing to an increase in weight and anthropometric parameters.展开更多
Leontice L. is a perennial herbaceous plant belonging to the Berberidaceae family. Our research was conducted in Navoi region. The article presents an ecological analysis of Leontice L. species in the Navoi region. Th...Leontice L. is a perennial herbaceous plant belonging to the Berberidaceae family. Our research was conducted in Navoi region. The article presents an ecological analysis of Leontice L. species in the Navoi region. The genus Leontice grows mainly in mountainous areas and some are distributed in arid climates. According to the information that 2 species have been identified in Navoi region, these species are plants with flavanoids healing properties. Leontice species have been used in traditional medicine since ancient times in ethnobotany. The presence of this species was discovered during the research and Leontice has identified numerous unique compounds, such as alkaloids, flavonoids, and phenolic acids, with potential medicinal properties such as anti-inflammatory, antitumor, and antiviral effects. According to ecological analysis, the Leontice genus thrives on stony, gravelly, and fine-grained mountain slopes and ridges, foothills, mountains, rocks, colorful rock outcrops, rocky slopes, and sandy, clay, and gravel deserts.展开更多
Recently developed ‘super’ rice cultivars with greater yield potentials often suffer from the problem of poor grain filling, especially in inferior spikelets. Here, we studied the activities of enzymes related to st...Recently developed ‘super’ rice cultivars with greater yield potentials often suffer from the problem of poor grain filling, especially in inferior spikelets. Here, we studied the activities of enzymes related to starch metabolism in rice stems and grains, and the microstructures related to carbohydrate accumulation and transportation to investigate the effects of different water regimes on grain filling. Two ‘super’ rice cultivars were grown under two irrigation regimes of well-watered(WW) and alternate wetting and moderate soil drying(AWMD). Compared with the WW treatment,the activities of ADP glucose pyrophosphorylase(AGPase), starch synthase(StSase) and starch branching enzyme(SBE), and the accumulation of non-structural carbohydrates(NSCs) in the stems before heading were significantly improved, and more starch granules were stored in the stems in the AWMD treatment. After heading, the activities of α-amylase, β-amylase, sucrose phosphate synthase(SPS) and sucrose synthase in the synthetic direction(SSs)were increased in the stems to promote the remobilization of NSCs for grain filling under AWMD. During grain filling, the enzymatic activities of sucrose synthase in the cleavage direction(SSc), AGPase, StSase and SBE in the inferior spikelets were increased, which promoted grain filling, especially for the inferior spikelets under AWMD.However, there were no significant differences in vascular microstructures. The grain yield and grain weight could be improved by 13.1 and 7.5%, respectively, by optimizing of the irrigation regime. We concluded that the low activities of key enzymes in carbon metabolism is the key limitation for the poor grain filling, as opposed to the vascular microstructures, and AWMD can increase the amount of NSC accumulation in the stems before heading, improve the utilization rate of NSCs after heading, and increase the grain filling, especially in the inferior spikelets, by altering the activities of key enzymes in carbon metabolism.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
The purpose of this study is to investigate the physicochemical properties of some local varieties of onion (Allium cepa L.) and compare them with an imported variety, all collected in May 2021. Proteins, reducing sug...The purpose of this study is to investigate the physicochemical properties of some local varieties of onion (Allium cepa L.) and compare them with an imported variety, all collected in May 2021. Proteins, reducing sugars, lipids, and polyphenol content were estimated according to the AFNOR standardized methods. The determination of calcium, magnesium, iron, sodium, potassium and phosphorus was performed by atomic absorption spectrophotometer coupled with a CCD detector. The results highlighted an average acidity of 0.377% ± 0.002% lower than the value of the imported variety which is 0.520% ± 0.001%. Local varieties have a pH ranging from 6.35 ± 0.003 to 6.42 ± 0.004, while the variety has a pH of 6.36 ± 0.003. The ash and dry matter contents vary respectively from 4.788% ± 0.004% to 8.253% ± 0.003% and 7.945% ± 0.021% to 11.945% ± 0.007% for the local varieties. Moreover, the imported one has ash and dry matter contents of 5.175% ± 0.007% and 10.035% ± 0.021% respectively. The results show that the protein, reducing sugar and lipid contents in the local onion varieties vary respectively from 2.815 ± 0.000 to 15.634 ± 0.001 g·100 g<sup>-1</sup>;4.691 ± 0.001 to 12.596 ± 0.002 g·100 g<sup>-1</sup> and 0.006 ± 0.001 to 0.050 ± 0.057 g·100 g<sup>-1</sup>. Furthermore, the imported variety has a protein, reducing sugar and lipid content of 5.649 ± 0.002;8.565 ± 0.002 g·100 g<sup>-1</sup> and 0.011 ± 0.010 g·100 g<sup>-1</sup> respectively. The maximum levels of total polyphenols are obtained in the imported variety, Bellani and Gandiol, respectively 9.973 ± 0.001, 4.535 ± 0.002, and 3.425 ± 0.006 mg EAG/g of dry matter. The local varieties have a significant calorific intake of between 35.451 ± 0.001 and 112.980 ± 0.003 kcal·100 g<sup>-1</sup> compared to the imported one with an energy value of 56.953 ± 0.001 kcal·100 g<sup>-1</sup> of dry matter. The bulbs of different onion varieties studied have a fairly high content of mineral elements. The potassium content of local varieties is between 502.16 ± 0.06 mg·100 g<sup>-1</sup> and 582.77 ± 0.04 mg·100 g<sup>-1</sup> while the imported variety has a content of 536.62 ± 1.30 mg·100 g<sup>-1</sup>. They note that the local varieties have a better calcium content (249.75 ± 0.07 to 434.20 ± 0.57 mg·100 g<sup>-1</sup>) and magnesium (142.15 ± 0.07 to 162.60 ± 0.42 mg·100 g<sup>-1</sup>) than the imported variety (229.58 ± 0.04 mg·100 g<sup>-1</sup>) except for the varieties White Grano (228.29 ± 0.01 mg·100 g<sup>-1</sup>) and Rouge Amposta (117.00 ± 0.42 mg·100 g<sup>-1</sup>) respectively. These results reveal that Gandiol, Dayo and Orient F1 are nutritionally found better due to their higher antioxidant property, proteins, carbohydrates, and reducing sugar and should be included in diets to supplement our daily allowance needed by the body.展开更多
Motivated by recent advances made in the study of dividend control and risk management problems involving the U.S.bankruptcy code,in this paper we follow[44]to revisit the De Finetti dividend control problem under the...Motivated by recent advances made in the study of dividend control and risk management problems involving the U.S.bankruptcy code,in this paper we follow[44]to revisit the De Finetti dividend control problem under the reorganization process and the regulator's intervention documented in U.S.Chapter 11 bankruptcy.We do this by further accommodating the fixed transaction costs on dividends to imitate the real-world procedure of dividend payments.Incorporating the fixed transaction costs transforms the targeting optimal dividend problem into an impulse control problem rather than a singular control problem,and hence computations and proofs that are distinct from[44]are needed.To account for the financial stress that is due to the more subtle concept of Chapter 11 bankruptcy,the surplus process after dividends is driven by a piece-wise spectrally negative Lévy process with endogenous regime switching.Some explicit expressions of the expected net present values under a double barrier dividend strategy,new to the literature,are established in terms of scale functions.With the help of these expressions,we are able to characterize the optimal strategy among the set of admissible double barrier dividend strategies.When the tail of the Lévy measure is log-convex,this optimal double barrier dividend strategy is then verified as the optimal dividend strategy,solving our optimal impulse control problem.展开更多
The fruit of Morinda citrifolia L., commonly known as noni, has an extensive history of use as a food and traditional medicine around the world. Adding value to Morinda citrifolia L. products, particularly the fruit, ...The fruit of Morinda citrifolia L., commonly known as noni, has an extensive history of use as a food and traditional medicine around the world. Adding value to Morinda citrifolia L. products, particularly the fruit, could be one way of building resilience in vulnerable farming households. The aim of this study was to determine the secondary metabolite and mineral composition of noni juice obtained by fermenting the fruit of Morinda citrifolia L. Fruits were collected in August 2022 from the local field in Thiès region, West of Senegal. Extraction yields were determined and the secondary metabolites were determined using conventional analytical methods. Calcium, magnesium, iron, sodium and potassium were determined by atomic absorption spectrophotometer coupled with a CCD detector. The results show that an average fruit mass (503.2 ± 110.96 g) consists of 171.44 ± 50.01 g pulp and 34.06 ± 10.35 g seeds. The traditional extraction yield of noni juice is 16.46% after three weeks of fermentation. The contents of total polyphenols, flavonoids and tannins obtained in noni are 608.97 ± 4.53 mg EAG/100mL, 7.78 ± 0.01 mg EQ/100mL and 0.191 ± 0.01 mg EC/100mL respectively. The ethanol content of noni varies from 3.57 to 5.23 mL/100mL during extraction. Noni has a high calcium content with a concentration of 383.79 ± 33.23 mg/L. This is followed by a good concentration of magnesium, potassium and sodium, at 278.47 ± 26.30, 187.43 ± 10.7 and 155.95 ± 28.66 mg/L respectively. Noni also has an iron content of 202.15 ± 0.05 mg/L.展开更多
The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centere...The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.展开更多
基金supported by the Koeln Fortune Program/Faculty of Medicine,University of Cologne,the Alzheimer Forschung Initiative e.V.(grant#22039,to HZ)open-access funding from the DFG/GRC issued to the University of CologneAlzheimer Forschung Initiative e.V.for Open Access Publishing(a publication grant#P2401,to MAAK)。
文摘TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear cells.Most of the studies involved children and the study cohorts were largely males.Many of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA expression.Only five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to controls.The microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of adults.Several important limitations were identified in the studies reviewed,and need to be taken into account in future studies.Further studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.
基金supported by the National Key Research and Development Program of China (2022YFD2300304)the National Natural Science Foundation of China (32071944 and 32272197)+2 种基金the Hong Kong Research Grants Council, China (GRF 14177617, 12103219, 12103220, and AoE/M-403/16)the State Key Laboratory of Agrobiotechnology (Strategic Collaborative Projects) in The Chinese University of Hong Kong, China, the Six Talent Peaks Project in Jiangsu Province, China (SWYY151)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, China (PAPD).
文摘Integrative cultivation practices(ICPs)are essential for enhancing cereal yield and resource use efficiency.However,the effects of ICP on the rhizosphere environment and roots of paddy rice are still poorly understood.In this study,four rice varieties were produced in the field.Each variety was treated with six different cultivation techniques,including zero nitrogen application(0 N),local farmers’practice(LFP),nitrogen reduction(NR),and three progressive ICP techniques comprised of enhanced fertilizer N practice and increased plant density(ICP1),a treatment similar to ICP1 but with alternate wetting and moderate drying instead of continuous flooding(ICP2),and the same practices as ICP2 with the application of organic fertilizer(ICP3).The ICPs had greater grain production and nitrogen use efficiency than the other three methods.Root length,dry weight,root diameter,activity of root oxidation,root bleeding rate,zeatin and zeatin riboside compositions,and total organic acids in root exudates were elevated with the introduction of the successive cultivation practices.ICPs enhanced nitrate nitrogen,the activities of urease and invertase,and the diversity of microbes(bacteria)in rhizosphere and non-rhizosphere soil,while reducing the ammonium nitrogen content.The nutrient contents(ammonium nitrogen,total nitrogen,total potassium,total phosphorus,nitrate,and available phosphorus)and urease activity in rhizosphere soil were reduced in all treatments in comparison with the non-rhizosphere soil,but the invertase activity and bacterial diversity were greater.The main root morphology and physiology,and the ammonium nitrogen contents in rhizosphere soil at the primary stages were closely correlated with grain yield and internal nitrogen use efficiency.These findings suggest that the coordinated enhancement of the root system and the environment of the rhizosphere under integrative cultivation approaches may lead to higher rice production.
基金supported by the National Key Research and Development Program of China (2021YFF1000301)the National Natural Science Foundation of China (31771805)。
文摘GTs(Glycosyltransferases)are important in plant growth and abiotic stresses.However,its role in maize heat response is far from clear.Here,we describe the constitutively expressed UDP-glycosyltransferase ZmUGT92A1,which has a highly conserved PSPG box and is localized in chloroplasts,is induced under heat stress.Functional disruption of ZmUGT92A1 leads to heat sensitivity and reactive oxygen species accumulation in maize.Metabolomics analysis revealed that ZmUGT92A1 affected multiple metabolic pathways and altered the metabolic homeostasis of flavonoids under heat stress.In vitro assay showed ZmUGT92A1 exhibits glycosyltransferase activity on flavonoids and hormones.Additionally,we identified a rapidly heat-induced transcription factor,ZmHSF08,which can directly bind and repress the promoter region of ZmUGT92A1.The ZmHSF08 overexpression line exhibits heat sensitivity and reactive oxygen species accumulation.These findings reveal that the ZmHSF08-ZmUGT92A1 module plays a role in heat tolerance in maize and provide candidate strategies for the development of heat-tolerant varieties.
文摘The aim of the present study was to evaluate the nutritional quality of green and purple eggplant, their antioxidant activity and their nutritional efficacy on Wistar rats. For nutritional quality, the parameters measured are dry matter, protein, lipid, ash, carbohydrate, iron, phosphorus, calcium, magnesium and energy content. For antioxidant activity, the parameters measured are 50% DDPH free radical inhibition concentration and total polyphenol content. Nutritional efficacy was evaluated in rats fed the control diet and in rats fed the three treated diets containing eggplant meal obtained by replacing 5%, 10%, and 15% of the control diet. The parameters measured are the amount consumed, the weight of the animal and target organs, and hematologic parameters. The results of the nutritional analysis show the following values: 13.31% protein, 2.66% lipids, 0.84% calcium, 0.12% magnesium, 0.43% phosphorus for the Solanum aethiopicum L. species and 13.47% protein, 3.66% lipids, 0.36% calcium, 0.22% magnesium, 0.35% phosphorus for the Solanum melongena L. species. In terms of antioxidant activity, we obtained DDPH inhibition percentages of 40.28 mg/ml for Solanum aethiopicum L. and 12.42 mg/ml for Solanum melongena L., respectively. Finally, hematologic and anthropometric tests showed that for the different diets used, weight loss and an increase in hematologic parameters were observed in the rats tested. This study showed that eggplant has interesting nutritional characteristics and antioxidant activity, contributing to an increase in weight and anthropometric parameters.
文摘Leontice L. is a perennial herbaceous plant belonging to the Berberidaceae family. Our research was conducted in Navoi region. The article presents an ecological analysis of Leontice L. species in the Navoi region. The genus Leontice grows mainly in mountainous areas and some are distributed in arid climates. According to the information that 2 species have been identified in Navoi region, these species are plants with flavanoids healing properties. Leontice species have been used in traditional medicine since ancient times in ethnobotany. The presence of this species was discovered during the research and Leontice has identified numerous unique compounds, such as alkaloids, flavonoids, and phenolic acids, with potential medicinal properties such as anti-inflammatory, antitumor, and antiviral effects. According to ecological analysis, the Leontice genus thrives on stony, gravelly, and fine-grained mountain slopes and ridges, foothills, mountains, rocks, colorful rock outcrops, rocky slopes, and sandy, clay, and gravel deserts.
基金This project was finically supported by the R&D Foundation of Jiangsu Province,China(BE2022425)the National Key Research and Development Program of China(2022YFD2300304)the Priority Academic Program Development of Jiangsu Higher-Education Institutions,China(PAPD).
文摘Recently developed ‘super’ rice cultivars with greater yield potentials often suffer from the problem of poor grain filling, especially in inferior spikelets. Here, we studied the activities of enzymes related to starch metabolism in rice stems and grains, and the microstructures related to carbohydrate accumulation and transportation to investigate the effects of different water regimes on grain filling. Two ‘super’ rice cultivars were grown under two irrigation regimes of well-watered(WW) and alternate wetting and moderate soil drying(AWMD). Compared with the WW treatment,the activities of ADP glucose pyrophosphorylase(AGPase), starch synthase(StSase) and starch branching enzyme(SBE), and the accumulation of non-structural carbohydrates(NSCs) in the stems before heading were significantly improved, and more starch granules were stored in the stems in the AWMD treatment. After heading, the activities of α-amylase, β-amylase, sucrose phosphate synthase(SPS) and sucrose synthase in the synthetic direction(SSs)were increased in the stems to promote the remobilization of NSCs for grain filling under AWMD. During grain filling, the enzymatic activities of sucrose synthase in the cleavage direction(SSc), AGPase, StSase and SBE in the inferior spikelets were increased, which promoted grain filling, especially for the inferior spikelets under AWMD.However, there were no significant differences in vascular microstructures. The grain yield and grain weight could be improved by 13.1 and 7.5%, respectively, by optimizing of the irrigation regime. We concluded that the low activities of key enzymes in carbon metabolism is the key limitation for the poor grain filling, as opposed to the vascular microstructures, and AWMD can increase the amount of NSC accumulation in the stems before heading, improve the utilization rate of NSCs after heading, and increase the grain filling, especially in the inferior spikelets, by altering the activities of key enzymes in carbon metabolism.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
文摘The purpose of this study is to investigate the physicochemical properties of some local varieties of onion (Allium cepa L.) and compare them with an imported variety, all collected in May 2021. Proteins, reducing sugars, lipids, and polyphenol content were estimated according to the AFNOR standardized methods. The determination of calcium, magnesium, iron, sodium, potassium and phosphorus was performed by atomic absorption spectrophotometer coupled with a CCD detector. The results highlighted an average acidity of 0.377% ± 0.002% lower than the value of the imported variety which is 0.520% ± 0.001%. Local varieties have a pH ranging from 6.35 ± 0.003 to 6.42 ± 0.004, while the variety has a pH of 6.36 ± 0.003. The ash and dry matter contents vary respectively from 4.788% ± 0.004% to 8.253% ± 0.003% and 7.945% ± 0.021% to 11.945% ± 0.007% for the local varieties. Moreover, the imported one has ash and dry matter contents of 5.175% ± 0.007% and 10.035% ± 0.021% respectively. The results show that the protein, reducing sugar and lipid contents in the local onion varieties vary respectively from 2.815 ± 0.000 to 15.634 ± 0.001 g·100 g<sup>-1</sup>;4.691 ± 0.001 to 12.596 ± 0.002 g·100 g<sup>-1</sup> and 0.006 ± 0.001 to 0.050 ± 0.057 g·100 g<sup>-1</sup>. Furthermore, the imported variety has a protein, reducing sugar and lipid content of 5.649 ± 0.002;8.565 ± 0.002 g·100 g<sup>-1</sup> and 0.011 ± 0.010 g·100 g<sup>-1</sup> respectively. The maximum levels of total polyphenols are obtained in the imported variety, Bellani and Gandiol, respectively 9.973 ± 0.001, 4.535 ± 0.002, and 3.425 ± 0.006 mg EAG/g of dry matter. The local varieties have a significant calorific intake of between 35.451 ± 0.001 and 112.980 ± 0.003 kcal·100 g<sup>-1</sup> compared to the imported one with an energy value of 56.953 ± 0.001 kcal·100 g<sup>-1</sup> of dry matter. The bulbs of different onion varieties studied have a fairly high content of mineral elements. The potassium content of local varieties is between 502.16 ± 0.06 mg·100 g<sup>-1</sup> and 582.77 ± 0.04 mg·100 g<sup>-1</sup> while the imported variety has a content of 536.62 ± 1.30 mg·100 g<sup>-1</sup>. They note that the local varieties have a better calcium content (249.75 ± 0.07 to 434.20 ± 0.57 mg·100 g<sup>-1</sup>) and magnesium (142.15 ± 0.07 to 162.60 ± 0.42 mg·100 g<sup>-1</sup>) than the imported variety (229.58 ± 0.04 mg·100 g<sup>-1</sup>) except for the varieties White Grano (228.29 ± 0.01 mg·100 g<sup>-1</sup>) and Rouge Amposta (117.00 ± 0.42 mg·100 g<sup>-1</sup>) respectively. These results reveal that Gandiol, Dayo and Orient F1 are nutritionally found better due to their higher antioxidant property, proteins, carbohydrates, and reducing sugar and should be included in diets to supplement our daily allowance needed by the body.
基金the financial support from the National Natural Science Foundation of China(12171405 and 11661074)the Program for New Century Excellent Talents in Fujian Province University+2 种基金the financial support from the Characteristic&Preponderant Discipline of Key Construction Universities in Zhejiang Province(Zhejiang Gongshang University-Statistics)Collaborative Innovation Center of Statistical Data Engineering Technology&ApplicationDigital+Discipline Construction Project(SZJ2022B004)。
文摘Motivated by recent advances made in the study of dividend control and risk management problems involving the U.S.bankruptcy code,in this paper we follow[44]to revisit the De Finetti dividend control problem under the reorganization process and the regulator's intervention documented in U.S.Chapter 11 bankruptcy.We do this by further accommodating the fixed transaction costs on dividends to imitate the real-world procedure of dividend payments.Incorporating the fixed transaction costs transforms the targeting optimal dividend problem into an impulse control problem rather than a singular control problem,and hence computations and proofs that are distinct from[44]are needed.To account for the financial stress that is due to the more subtle concept of Chapter 11 bankruptcy,the surplus process after dividends is driven by a piece-wise spectrally negative Lévy process with endogenous regime switching.Some explicit expressions of the expected net present values under a double barrier dividend strategy,new to the literature,are established in terms of scale functions.With the help of these expressions,we are able to characterize the optimal strategy among the set of admissible double barrier dividend strategies.When the tail of the Lévy measure is log-convex,this optimal double barrier dividend strategy is then verified as the optimal dividend strategy,solving our optimal impulse control problem.
文摘The fruit of Morinda citrifolia L., commonly known as noni, has an extensive history of use as a food and traditional medicine around the world. Adding value to Morinda citrifolia L. products, particularly the fruit, could be one way of building resilience in vulnerable farming households. The aim of this study was to determine the secondary metabolite and mineral composition of noni juice obtained by fermenting the fruit of Morinda citrifolia L. Fruits were collected in August 2022 from the local field in Thiès region, West of Senegal. Extraction yields were determined and the secondary metabolites were determined using conventional analytical methods. Calcium, magnesium, iron, sodium and potassium were determined by atomic absorption spectrophotometer coupled with a CCD detector. The results show that an average fruit mass (503.2 ± 110.96 g) consists of 171.44 ± 50.01 g pulp and 34.06 ± 10.35 g seeds. The traditional extraction yield of noni juice is 16.46% after three weeks of fermentation. The contents of total polyphenols, flavonoids and tannins obtained in noni are 608.97 ± 4.53 mg EAG/100mL, 7.78 ± 0.01 mg EQ/100mL and 0.191 ± 0.01 mg EC/100mL respectively. The ethanol content of noni varies from 3.57 to 5.23 mL/100mL during extraction. Noni has a high calcium content with a concentration of 383.79 ± 33.23 mg/L. This is followed by a good concentration of magnesium, potassium and sodium, at 278.47 ± 26.30, 187.43 ± 10.7 and 155.95 ± 28.66 mg/L respectively. Noni also has an iron content of 202.15 ± 0.05 mg/L.
文摘The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.