Amino acids are the building blocks of proteins and play vital roles in both biological systems and drug development.In recent years,increasing attention has been given to the functionalization of amino acid derivativ...Amino acids are the building blocks of proteins and play vital roles in both biological systems and drug development.In recent years,increasing attention has been given to the functionalization of amino acid derivatives.Since the introduction of therapeutic insulin in the early 20th century,the conjugation of drug molecules with amino acids and peptides has been pivotal in driving advancements in drug discovery and become an integral part of modern medical practice.Currently,over a hundred peptide-drug conjugates have received global approval and are widely used to treat diseases such as diabetes,cancer,chronic pain,and multiple sclerosis.Key technologies for conjugating peptides with bioactive molecules include antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),and proteolysis targeting chimeras(PROTACs).Significant efforts have been dedicated to developing strategies for the modification of amino acids and peptides,with particular focus on site-selective C-H alkylation/arylation reactions.These reactions are crucial for synthesizing bioactive molecules,as they enable the precise introduction of functional groups at specific positions,thereby improving the pharmacological properties of the resulting compounds.展开更多
The objective of this study was to predict,screen,synthesize,and investigate cocrystals of poorly soluble flavonoids that are commonly found in dietary supplements with bipolar compound picolinic acid(PA).To improve t...The objective of this study was to predict,screen,synthesize,and investigate cocrystals of poorly soluble flavonoids that are commonly found in dietary supplements with bipolar compound picolinic acid(PA).To improve the efficiency and success rate of experimental screening,two virtual tools based on hydrogen bond propensity(HBP)and modified molecular electrostatic potential(MEP)maps were used.The prediction accuracy of HBP and MEP is 58.82%and 94.11%,respectively,presenting that the MEP model is very powerful in the discovery of pharmaceutical cocrystals.Among the 12 successfully obtained cocrystals,4 single crystals of PA with luteolin(LUT),genistein(GEN),taxifolin(TAX),dihydromyricetin(DHM)were obtained for the first time.Charged-assisted O-H…O and N-H…O hydrogen bonds appear as main hydrogen bonding synthons,and PA adopts a zwitterionic form after cocrystallization.GEN-PA,TAX-PA,and DHM-PA showed higher DPPH'radical-scavenging capacities;LUT-PA and DHM-PA showed higher ABTS^(+)radical-scavenging capacities;GEN-PA and DHM-PA possessed better protective effects on H9c2 cells from hypoxic injury caused by CoCl_(2)than corresponding pure flavonoids.展开更多
Objective To optimize the ultrasonic extraction process for benzoic acid as a harmful substance in Paeonia lactiflora Pall.(P.lactiflora Pall.).Methods Methanol and ethanol solutions at different concentration gradien...Objective To optimize the ultrasonic extraction process for benzoic acid as a harmful substance in Paeonia lactiflora Pall.(P.lactiflora Pall.).Methods Methanol and ethanol solutions at different concentration gradients(25,50,75%)were prepared to investigate the effects of extraction solvents on the extraction efficiency of benzoic acid.The influences of ultrasonic frequency(35,50 Hz),ultrasonic power(40,60,80,100 W),ultrasonic time(10,20,30,40,50,60 minutes),and ultrasonic temperature(20,30,40,50℃)on the extraction efficiency were examined.Orthogonal experiments were conducted to analyze the effects of temperature,time,and ultrasonic power on the extraction efficiency and to screen the optimal ultrasonic extraction process.Results Various influencing factors had certain effects on the extraction efficiency of benzoic acid from P.lactiflora Pall.Single-factor analysis revealed that 25%methanol,ultrasonic frequency of 50 Hz,ultrasonic power of 40 W,ultrasonic time of 10minutes,and ultrasonic temperature of 30℃yielded the highest extraction efficiency for benzoic acid.The order of influence of different factors on the extraction efficiency was temperature>time>power.The optimal conditions obtained from orthogonal experiments were:extraction solvent of 25%methanol,ultrasonic frequency of 50 Hz,ultrasonic time of 20 minutes,ultrasonic power of 40 W,and ultrasonic temperature of 30℃.Conclusion Under the conditions of 25%methanol as the extraction solvent,ultrasonic frequency of 50 Hz,ultrasonic time of 20 minutes,ultrasonic power of 40 W,and ultrasonic temperature of 30℃,the extraction efficiency of benzoic acid from P.lactiflora Pall.was the highest.This method offers advantages such as simple operation,small sample size requirement,and low solvent consumption,providing a reliable analytical approach for quality control and safety evaluation of P.lactiflora Pall.展开更多
Three copper(Ⅱ),nickel and cadmium(Ⅱ)complexes,namely[Cu_(2)(μ-H2dbda)2(phen)2]·2H_(2)O(1),[Ni(μ-H2dbda)(μ-bpb)(H_(2)O)2]n(2),and[Cd(μ-H2dbda)(μ-bpa)]n(3),have been constructed hydrothermally using H4dbda(...Three copper(Ⅱ),nickel and cadmium(Ⅱ)complexes,namely[Cu_(2)(μ-H2dbda)2(phen)2]·2H_(2)O(1),[Ni(μ-H2dbda)(μ-bpb)(H_(2)O)2]n(2),and[Cd(μ-H2dbda)(μ-bpa)]n(3),have been constructed hydrothermally using H4dbda(4,4'-dihydroxy-[1,1'-biphenyl]-3,3'-dicarboxylic acid),phen(1,10-phenanthroline),bpb(1,4-bis(pyrid-4-yl)benzene),bpa(bis(4-pyridyl)amine),and copper,nickel and cadmium chlorides at 160℃.The products were isolated as stable crystalline solids and were characterized by IR spectra,elemental analyses,thermogravimetric analyses,and singlecrystal X-ray diffraction analyses.Single-crystal X-ray diffraction analyses revealed that three complexes crystallize in the monoclinic P21/n,tetragonal I42d,and orthorhombic P21212 space groups.The complexes exhibit molecular dimers(1)or 2D metal-organic networks(2 and 3).The catalytic performances in the Knoevenagel reaction of these complexes were investigated.Complex 1 exhibits an effective catalytic activity and excellent reusability as a heterogeneous catalyst in the Knoevenagel reaction at room temperature.CCDC:2463800,1;2463801,2;2463802,3.展开更多
Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,includi...Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).展开更多
Investigating structural and hydroxyl group effects in electrooxidation of alcohols to value-added products by solid-acid electrocatalysts is essential for upgrading biomass alcohols.Herein,we report efficient electro...Investigating structural and hydroxyl group effects in electrooxidation of alcohols to value-added products by solid-acid electrocatalysts is essential for upgrading biomass alcohols.Herein,we report efficient electrocatalytic oxidations of saturated alcohols(C_(1)-C_(6))to selectively form formate using Ni Co hydroxide(Ni Co-OH)derived Ni Co_(2)O_(4)solid-acid electrocatalysts with balanced Lewis acid(LASs)and Brønsted acid sites(BASs).Thermal treatment transforms BASs-rich(89.6%)Ni Co-OH into Ni Co_(2)O_(4)with nearly equal distribution of LASs(53.1%)and BASs(46.9%)which synergistically promote adsorption and activation of OH-and alcohol molecules for enhanced oxidation activity.In contrast,BASs-enriched Ni Co-OH facilitates formation of higher valence metal sites,beneficial for water oxidation.The combined experimental studies and theoretical calculation imply the oxidation ability of C1-C6alcohols increases as increased number of hydroxyl groups and decreased HOMO-LUMO gaps:methanol(C_(1))<ethylene glycol(C_(2))<glycerol(C3)<meso-erythritol(C4)<xylitol(C5)<sorbitol(C6),while the formate selectivity shows the opposite trend from 100 to 80%.This study unveils synergistic roles of LASs and BASs,as well as hydroxyl group effect in electro-upgrading of alcohols using solid-acid electrocatalysts.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism ...Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism in osteosarcoma.Methods:We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments(TARGET)database and single-cell RNA sequencing.Least Absolute Shrinkage and Selection Operator(LASSO)regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma.Tumor-associated macrophages(TAMs)and their interactions with immune cells were examined through single-cell analysis and co-culture experiments.Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6(LPAR6)inhibitors.Results:Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3)and aldehyde dehydrogenase 7 family member A1(ALDH7A1)were identified as key prognostic genes in osteosarcoma,with high AGPAT3 expression correlating with improved survival.Single-cell analysis revealed that AGPAT3 expression is associated with tumor immune microenvironment,particularly with TAMs.Knockdown of AGPAT3 in osteosarcoma cells resulted in elevated lysophosphatidic acid(LPA)levels,which regulated the immune environment,inhibiting cytotoxic T cell function through TAMs’LPAR6 signaling.LPAR6 signaling in TAMs mediates immune regulation through cytokine secretion,including interleukin-6(IL-6)and interleukin-10(IL-10).Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6.Conclusion:AGPAT3 is an important gene related to the prognosis of osteosarcoma.Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment,particularly in immunotherapy contexts.展开更多
Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and tr...Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
ObjectiveThis study aimed to investigate the effect of fulvic acid on the growth and yield components of direct seeding rice （Nanjing 44）. MethodThe rice seeds were soaked in 0 （water as a control）, 1, 2, 4 and 6 ...ObjectiveThis study aimed to investigate the effect of fulvic acid on the growth and yield components of direct seeding rice （Nanjing 44）. MethodThe rice seeds were soaked in 0 （water as a control）, 1, 2, 4 and 6 g/L fulvic acid （FA） before sowed. Then, the rice morphological indices, leaf chlorophyll content, photosynthesis parameters, root activity and chlorophyll fluorescence parameters were measured in the following field studies. ResultCompared with the control, the leaf area index, chlorophyll content, net photosynthetic rate, stomatal conductance and dry matter weight and some fluorescence parameters such as the maximum photochemical efficiency of photosystem II （PSII） （Fv/Fm）, excitation energy capture efficiency of opened PSII reaction center （Fv’/Fm’） and efficiency of the open reaction centre （ΦPS II） increased by different levels at both jointing stage and heading stage of direct seeding rice, whose seeds were soaked by FA with different concentrations. High FA concentration （4-6 g/L） significantly increased the cultivated rice leaf area index, chlorophyll content, net photosynthetic rate, stomatal conductance, transpiration rate and dry matter weight by 10.32% -22.88% , 5.88% -13.11% , 12.16% -26.84% , 11.43% -88.46% , 10.63% -21.63% , 18.49% -19.68% , respectively, thereby improving the physiological function and light energy transform efficiency of rice at the growth stage. With FA concentration increasing, the yield, effective panicles, grain number per panicle and seed setting rate were increased significantly compared with the control by 17.52%-18.71%, 3.46%-3.85%, 6.30%- 6.51% and 7.82%-8.69% respectively. ConclusionSoaking rice seed with FA could be considered as an effective way to improve the rice competitiveness at early growth stage.展开更多
In this review, the carcass, meat quality, internal organs, basic nutrition component, amino acids （AAs）, fatty acids, inosine monophosphate （IMP） and mus- cle fiber of Tibetan swine were summarized for the first ...In this review, the carcass, meat quality, internal organs, basic nutrition component, amino acids （AAs）, fatty acids, inosine monophosphate （IMP） and mus- cle fiber of Tibetan swine were summarized for the first time. The formation mecha- nism of excellent features was analyzed from the aspects of physiological traits, ge- ographical environments and constraint reasons. Thereby, the outstanding features of Tibetan swine could be extended continuously, and the poor characteristics should be improved in the future.展开更多
The effects of soil solid components on soil sensitivity to acid deposition by sequential extraction method were studied. A multiple regression equation of soil sensitivity was set up on the basis of stepwise regressi...The effects of soil solid components on soil sensitivity to acid deposition by sequential extraction method were studied. A multiple regression equation of soil sensitivity was set up on the basis of stepwise regression analysis. The results showed that organic matter expressed dual effects that were decided by soil original pH value and exchangeable cation composition on acid buffering reactions. The hydrolysis of activated oxides was a very important proton buffering reaction when in low pH situation. The crystalline oxides also played a role in the buffering reactions, but the role was restricted by the rate of activation of oxides. Meanwhile, the results by stepwise analysis showed that factors that had significant effect on soil acid buffering capacity were content of montmorillite, soil original pH value, Al 0, Mn 0 and CEC in decreasing order. Finally, sixteen soils were classified into four types of sensitive with single index cluster and multiple fuzzy cluster analysis respectively.展开更多
Global warming causes the exacerbation of rice growing environment, which seriously affects rice growth and reproduction, and finally results in the decrease of rice yield and quality. We investigated the activities o...Global warming causes the exacerbation of rice growing environment, which seriously affects rice growth and reproduction, and finally results in the decrease of rice yield and quality. We investigated the activities of aspartate metabolism enzymes in grains, and the contents of Aspartate-family amino acids and protein components to further understand the effects of high temperature （HT） on rice nutritional quality during rice grain filling. Under HT, the average activities of aspartate aminotransferase （AAT） and aspartokinase （AK） in grains significantly increased, the amino acid contents of aspartate （Asp）, lysine （Lys）, threonine （Thr）, methionine （Met） and isoleucine （lie） and the protein contents of albumin, globulin, prolamin and glutelin also significantly increased. The results indicated that HT enhanced Asp metabolism during rice grain filling and the enhancement of Asp metabolism might play an important role in the increase of Asp-family amino acids and protein components in grains. In case of the partial appraisal of the change of Asp-family amino acids and protein components under HT, we introduced eight indicators （amino acid or protein content, ratio of amino acid or protein, amino acid or protein content per grain and amino acid or protein content per panicle） to estimate the effects of HT. It is suggested that HT during rice grain filling was benefit for the accumulation of Asp-family amino acids and protein components. Combined with the improvement of Asp-family amino acid ratio in grains under HT, it is suggested that HT during grain filling may improve the rice nutritional quality. However, the yields of parts of Asp-family amino acids and protein components were decreased under HT during rice grain filling.展开更多
Humic acid(HA) is a readily available and low-cost material that is used to enhance crop production and reduce nitrogen(N) loss. However, there is little consensus on the efficacy of different HA components. In the cu...Humic acid(HA) is a readily available and low-cost material that is used to enhance crop production and reduce nitrogen(N) loss. However, there is little consensus on the efficacy of different HA components. In the current study, a soil column experiment was conducted using the ^(15)N tracer technique in Dezhou City, Shandong Province, China, to compare the effects of urea with and without the addition of weathered coal-derived HA components on maize yield and the fate of fertilizerderived N(fertilizer N). The HA components were incorporated into urea by blending different HA components into molten urea to obtain the three different types of HA-enhanced urea(HAU). At harvest, the aboveground dry biomass of plants grown with HAU was enhanced by 11.50–21.33% when compared to that of plants grown with U. More significantly, the grain yields under the HAU treatments were 5.58–18.67% higher than the yield under the urea treatment. These higher yields were due to an increase in the number of kernels per plant rather than the weight of individual kernels. The uptake of fertilizer N under the HAU treatments was also higher than that under the urea treatment by 11.49–29.46%, while the unaccounted N loss decreased by 12.37–30.05%. More fertilizer-derived N was retained in the 0–30 cm soil layer under the HAU treatments than that under the urea treatment, while less N was retained in the 30–90 cm soil layer. The total residual amount of fertilizer N in the soil column, however, did not differ significantly between the treatments. Of the three HAU treatments investigated, the one with an HA fraction derived from extraction with pH values ranging from 6 to 7, resulted in the best improvement in all assessment targets. This is likely due to the abundance of the COO/C–N=O group in this HA component.展开更多
An efficient green protocol is described for the preparation of highly functionalized piperidines via a one-pot five-component reaction between aromatic aldehydes,anilines andβ-ketoesters in the presence of oxalic ac...An efficient green protocol is described for the preparation of highly functionalized piperidines via a one-pot five-component reaction between aromatic aldehydes,anilines andβ-ketoesters in the presence of oxalic acid dihydrate as catalyst in ethanol at ambient temperature.The structure as well as the relative stereochemistry of these compounds was confirmed by single X-ray crystallographic analysis.展开更多
An efficient protocol was developed for the synthesis of 3-aminoalkylated indoles using 3- chlorophenylboronic acid as a catalyst under ambient temperature conditions.The three-component reaction of indoles,aromatic a...An efficient protocol was developed for the synthesis of 3-aminoalkylated indoles using 3- chlorophenylboronic acid as a catalyst under ambient temperature conditions.The three-component reaction of indoles,aromatic aldehydes and N-methyl aniline offered corresponding 3-aminoalkylated indoles in excellent yields.This protocol presents some remarkable features such as mild reaction conditions,simple workup procedure and excellent yields.展开更多
A simple,efficient,and general method has been developed for the synthesis ofα-amino nitriles.Oxalic acid as a BrФnsted acid promotes the addition of TMSCN to various imines（generated in situ）.
文摘Amino acids are the building blocks of proteins and play vital roles in both biological systems and drug development.In recent years,increasing attention has been given to the functionalization of amino acid derivatives.Since the introduction of therapeutic insulin in the early 20th century,the conjugation of drug molecules with amino acids and peptides has been pivotal in driving advancements in drug discovery and become an integral part of modern medical practice.Currently,over a hundred peptide-drug conjugates have received global approval and are widely used to treat diseases such as diabetes,cancer,chronic pain,and multiple sclerosis.Key technologies for conjugating peptides with bioactive molecules include antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),and proteolysis targeting chimeras(PROTACs).Significant efforts have been dedicated to developing strategies for the modification of amino acids and peptides,with particular focus on site-selective C-H alkylation/arylation reactions.These reactions are crucial for synthesizing bioactive molecules,as they enable the precise introduction of functional groups at specific positions,thereby improving the pharmacological properties of the resulting compounds.
基金supported by the Beijing Natural Science Foundation(No.7222261)CAMS Innovation Fund for Medical Sciences(No.2022-I2M-1-015)。
文摘The objective of this study was to predict,screen,synthesize,and investigate cocrystals of poorly soluble flavonoids that are commonly found in dietary supplements with bipolar compound picolinic acid(PA).To improve the efficiency and success rate of experimental screening,two virtual tools based on hydrogen bond propensity(HBP)and modified molecular electrostatic potential(MEP)maps were used.The prediction accuracy of HBP and MEP is 58.82%and 94.11%,respectively,presenting that the MEP model is very powerful in the discovery of pharmaceutical cocrystals.Among the 12 successfully obtained cocrystals,4 single crystals of PA with luteolin(LUT),genistein(GEN),taxifolin(TAX),dihydromyricetin(DHM)were obtained for the first time.Charged-assisted O-H…O and N-H…O hydrogen bonds appear as main hydrogen bonding synthons,and PA adopts a zwitterionic form after cocrystallization.GEN-PA,TAX-PA,and DHM-PA showed higher DPPH'radical-scavenging capacities;LUT-PA and DHM-PA showed higher ABTS^(+)radical-scavenging capacities;GEN-PA and DHM-PA possessed better protective effects on H9c2 cells from hypoxic injury caused by CoCl_(2)than corresponding pure flavonoids.
基金supported by the Heilongjiang Provincial Administration of Traditional Chinese Medicine Project(ZHY18-153).
文摘Objective To optimize the ultrasonic extraction process for benzoic acid as a harmful substance in Paeonia lactiflora Pall.(P.lactiflora Pall.).Methods Methanol and ethanol solutions at different concentration gradients(25,50,75%)were prepared to investigate the effects of extraction solvents on the extraction efficiency of benzoic acid.The influences of ultrasonic frequency(35,50 Hz),ultrasonic power(40,60,80,100 W),ultrasonic time(10,20,30,40,50,60 minutes),and ultrasonic temperature(20,30,40,50℃)on the extraction efficiency were examined.Orthogonal experiments were conducted to analyze the effects of temperature,time,and ultrasonic power on the extraction efficiency and to screen the optimal ultrasonic extraction process.Results Various influencing factors had certain effects on the extraction efficiency of benzoic acid from P.lactiflora Pall.Single-factor analysis revealed that 25%methanol,ultrasonic frequency of 50 Hz,ultrasonic power of 40 W,ultrasonic time of 10minutes,and ultrasonic temperature of 30℃yielded the highest extraction efficiency for benzoic acid.The order of influence of different factors on the extraction efficiency was temperature>time>power.The optimal conditions obtained from orthogonal experiments were:extraction solvent of 25%methanol,ultrasonic frequency of 50 Hz,ultrasonic time of 20 minutes,ultrasonic power of 40 W,and ultrasonic temperature of 30℃.Conclusion Under the conditions of 25%methanol as the extraction solvent,ultrasonic frequency of 50 Hz,ultrasonic time of 20 minutes,ultrasonic power of 40 W,and ultrasonic temperature of 30℃,the extraction efficiency of benzoic acid from P.lactiflora Pall.was the highest.This method offers advantages such as simple operation,small sample size requirement,and low solvent consumption,providing a reliable analytical approach for quality control and safety evaluation of P.lactiflora Pall.
文摘Three copper(Ⅱ),nickel and cadmium(Ⅱ)complexes,namely[Cu_(2)(μ-H2dbda)2(phen)2]·2H_(2)O(1),[Ni(μ-H2dbda)(μ-bpb)(H_(2)O)2]n(2),and[Cd(μ-H2dbda)(μ-bpa)]n(3),have been constructed hydrothermally using H4dbda(4,4'-dihydroxy-[1,1'-biphenyl]-3,3'-dicarboxylic acid),phen(1,10-phenanthroline),bpb(1,4-bis(pyrid-4-yl)benzene),bpa(bis(4-pyridyl)amine),and copper,nickel and cadmium chlorides at 160℃.The products were isolated as stable crystalline solids and were characterized by IR spectra,elemental analyses,thermogravimetric analyses,and singlecrystal X-ray diffraction analyses.Single-crystal X-ray diffraction analyses revealed that three complexes crystallize in the monoclinic P21/n,tetragonal I42d,and orthorhombic P21212 space groups.The complexes exhibit molecular dimers(1)or 2D metal-organic networks(2 and 3).The catalytic performances in the Knoevenagel reaction of these complexes were investigated.Complex 1 exhibits an effective catalytic activity and excellent reusability as a heterogeneous catalyst in the Knoevenagel reaction at room temperature.CCDC:2463800,1;2463801,2;2463802,3.
基金supported by the Hellenic Foundation for Research and Innovation,HFRI,“2nd Call for HFRI Research Projects to support Faculty Members&Researchers”Project 02667 to GL.
文摘Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).
基金the financial support from the National Natural Science Foundation of China(52172110,52472231,52311530113)Shanghai"Science and Technology Innovation Action Plan"intergovernmental international science and technology cooperation project(23520710600)+1 种基金Science and Technology Commission of Shanghai Municipality(22DZ1205600)the Central Guidance on Science and Technology Development Fund of Zhejiang Province(2024ZY01011)。
文摘Investigating structural and hydroxyl group effects in electrooxidation of alcohols to value-added products by solid-acid electrocatalysts is essential for upgrading biomass alcohols.Herein,we report efficient electrocatalytic oxidations of saturated alcohols(C_(1)-C_(6))to selectively form formate using Ni Co hydroxide(Ni Co-OH)derived Ni Co_(2)O_(4)solid-acid electrocatalysts with balanced Lewis acid(LASs)and Brønsted acid sites(BASs).Thermal treatment transforms BASs-rich(89.6%)Ni Co-OH into Ni Co_(2)O_(4)with nearly equal distribution of LASs(53.1%)and BASs(46.9%)which synergistically promote adsorption and activation of OH-and alcohol molecules for enhanced oxidation activity.In contrast,BASs-enriched Ni Co-OH facilitates formation of higher valence metal sites,beneficial for water oxidation.The combined experimental studies and theoretical calculation imply the oxidation ability of C1-C6alcohols increases as increased number of hydroxyl groups and decreased HOMO-LUMO gaps:methanol(C_(1))<ethylene glycol(C_(2))<glycerol(C3)<meso-erythritol(C4)<xylitol(C5)<sorbitol(C6),while the formate selectivity shows the opposite trend from 100 to 80%.This study unveils synergistic roles of LASs and BASs,as well as hydroxyl group effect in electro-upgrading of alcohols using solid-acid electrocatalysts.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
基金supported by the National Natural Science Foundation of China(grant number 82460425)Jiangxi Provincial Health Technology Project(grant number 202510141).
文摘Background:Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors,however,its function in osteosarcoma is unclear.This study aimed to explore the role of glycerolipid metabolism in osteosarcoma.Methods:We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments(TARGET)database and single-cell RNA sequencing.Least Absolute Shrinkage and Selection Operator(LASSO)regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma.Tumor-associated macrophages(TAMs)and their interactions with immune cells were examined through single-cell analysis and co-culture experiments.Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6(LPAR6)inhibitors.Results:Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3)and aldehyde dehydrogenase 7 family member A1(ALDH7A1)were identified as key prognostic genes in osteosarcoma,with high AGPAT3 expression correlating with improved survival.Single-cell analysis revealed that AGPAT3 expression is associated with tumor immune microenvironment,particularly with TAMs.Knockdown of AGPAT3 in osteosarcoma cells resulted in elevated lysophosphatidic acid(LPA)levels,which regulated the immune environment,inhibiting cytotoxic T cell function through TAMs’LPAR6 signaling.LPAR6 signaling in TAMs mediates immune regulation through cytokine secretion,including interleukin-6(IL-6)and interleukin-10(IL-10).Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6.Conclusion:AGPAT3 is an important gene related to the prognosis of osteosarcoma.Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment,particularly in immunotherapy contexts.
文摘Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
基金Supported by Special Fund for Agro-scientific Research in the Public Interest(201303022)National Key Technology Research and Development Program during the 12th Five-Year Plan Period(2012BAD19B02)~~
文摘ObjectiveThis study aimed to investigate the effect of fulvic acid on the growth and yield components of direct seeding rice （Nanjing 44）. MethodThe rice seeds were soaked in 0 （water as a control）, 1, 2, 4 and 6 g/L fulvic acid （FA） before sowed. Then, the rice morphological indices, leaf chlorophyll content, photosynthesis parameters, root activity and chlorophyll fluorescence parameters were measured in the following field studies. ResultCompared with the control, the leaf area index, chlorophyll content, net photosynthetic rate, stomatal conductance and dry matter weight and some fluorescence parameters such as the maximum photochemical efficiency of photosystem II （PSII） （Fv/Fm）, excitation energy capture efficiency of opened PSII reaction center （Fv’/Fm’） and efficiency of the open reaction centre （ΦPS II） increased by different levels at both jointing stage and heading stage of direct seeding rice, whose seeds were soaked by FA with different concentrations. High FA concentration （4-6 g/L） significantly increased the cultivated rice leaf area index, chlorophyll content, net photosynthetic rate, stomatal conductance, transpiration rate and dry matter weight by 10.32% -22.88% , 5.88% -13.11% , 12.16% -26.84% , 11.43% -88.46% , 10.63% -21.63% , 18.49% -19.68% , respectively, thereby improving the physiological function and light energy transform efficiency of rice at the growth stage. With FA concentration increasing, the yield, effective panicles, grain number per panicle and seed setting rate were increased significantly compared with the control by 17.52%-18.71%, 3.46%-3.85%, 6.30%- 6.51% and 7.82%-8.69% respectively. ConclusionSoaking rice seed with FA could be considered as an effective way to improve the rice competitiveness at early growth stage.
基金Supported by National Science and Technology Support Program"Integration and Demonstration of Security Technology for Production-Ecosystem-Life in Key Pastoral Areas"(2012BAD13B00)National Science and Technology Support Program"In-tegration and Demonstration of Optimized Security Technology for Production-Ecosystem-Life in the Pastoral Area of Northwest Sichuan"(2012BAD13B06)~~
文摘In this review, the carcass, meat quality, internal organs, basic nutrition component, amino acids （AAs）, fatty acids, inosine monophosphate （IMP） and mus- cle fiber of Tibetan swine were summarized for the first time. The formation mecha- nism of excellent features was analyzed from the aspects of physiological traits, ge- ographical environments and constraint reasons. Thereby, the outstanding features of Tibetan swine could be extended continuously, and the poor characteristics should be improved in the future.
文摘The effects of soil solid components on soil sensitivity to acid deposition by sequential extraction method were studied. A multiple regression equation of soil sensitivity was set up on the basis of stepwise regression analysis. The results showed that organic matter expressed dual effects that were decided by soil original pH value and exchangeable cation composition on acid buffering reactions. The hydrolysis of activated oxides was a very important proton buffering reaction when in low pH situation. The crystalline oxides also played a role in the buffering reactions, but the role was restricted by the rate of activation of oxides. Meanwhile, the results by stepwise analysis showed that factors that had significant effect on soil acid buffering capacity were content of montmorillite, soil original pH value, Al 0, Mn 0 and CEC in decreasing order. Finally, sixteen soils were classified into four types of sensitive with single index cluster and multiple fuzzy cluster analysis respectively.
基金financed by the International Technological Cooperation Program of Science and Technology DepartmentSichuan Province+1 种基金China(Grant No.2010HH0015)greatly thank for the State Scholarship Fund financed by China Scholarship Council(Grant No.201206910010)
文摘Global warming causes the exacerbation of rice growing environment, which seriously affects rice growth and reproduction, and finally results in the decrease of rice yield and quality. We investigated the activities of aspartate metabolism enzymes in grains, and the contents of Aspartate-family amino acids and protein components to further understand the effects of high temperature （HT） on rice nutritional quality during rice grain filling. Under HT, the average activities of aspartate aminotransferase （AAT） and aspartokinase （AK） in grains significantly increased, the amino acid contents of aspartate （Asp）, lysine （Lys）, threonine （Thr）, methionine （Met） and isoleucine （lie） and the protein contents of albumin, globulin, prolamin and glutelin also significantly increased. The results indicated that HT enhanced Asp metabolism during rice grain filling and the enhancement of Asp metabolism might play an important role in the increase of Asp-family amino acids and protein components in grains. In case of the partial appraisal of the change of Asp-family amino acids and protein components under HT, we introduced eight indicators （amino acid or protein content, ratio of amino acid or protein, amino acid or protein content per grain and amino acid or protein content per panicle） to estimate the effects of HT. It is suggested that HT during rice grain filling was benefit for the accumulation of Asp-family amino acids and protein components. Combined with the improvement of Asp-family amino acid ratio in grains under HT, it is suggested that HT during grain filling may improve the rice nutritional quality. However, the yields of parts of Asp-family amino acids and protein components were decreased under HT during rice grain filling.
基金supported by the National Natural Science Foundation of China (31601827)the National Key Research and Development Program of China (2016YFD0200402)
文摘Humic acid(HA) is a readily available and low-cost material that is used to enhance crop production and reduce nitrogen(N) loss. However, there is little consensus on the efficacy of different HA components. In the current study, a soil column experiment was conducted using the ^(15)N tracer technique in Dezhou City, Shandong Province, China, to compare the effects of urea with and without the addition of weathered coal-derived HA components on maize yield and the fate of fertilizerderived N(fertilizer N). The HA components were incorporated into urea by blending different HA components into molten urea to obtain the three different types of HA-enhanced urea(HAU). At harvest, the aboveground dry biomass of plants grown with HAU was enhanced by 11.50–21.33% when compared to that of plants grown with U. More significantly, the grain yields under the HAU treatments were 5.58–18.67% higher than the yield under the urea treatment. These higher yields were due to an increase in the number of kernels per plant rather than the weight of individual kernels. The uptake of fertilizer N under the HAU treatments was also higher than that under the urea treatment by 11.49–29.46%, while the unaccounted N loss decreased by 12.37–30.05%. More fertilizer-derived N was retained in the 0–30 cm soil layer under the HAU treatments than that under the urea treatment, while less N was retained in the 30–90 cm soil layer. The total residual amount of fertilizer N in the soil column, however, did not differ significantly between the treatments. Of the three HAU treatments investigated, the one with an HA fraction derived from extraction with pH values ranging from 6 to 7, resulted in the best improvement in all assessment targets. This is likely due to the abundance of the COO/C–N=O group in this HA component.
基金support from the Research Council of the University of Sistan and Baluchestanthe Australian National University
文摘An efficient green protocol is described for the preparation of highly functionalized piperidines via a one-pot five-component reaction between aromatic aldehydes,anilines andβ-ketoesters in the presence of oxalic acid dihydrate as catalyst in ethanol at ambient temperature.The structure as well as the relative stereochemistry of these compounds was confirmed by single X-ray crystallographic analysis.
基金Dr.P.L.More and Dr.W.N.Jadhav,Dnyanopasak College,Parbhani for providing necessary facilities and Financial support for this work by DST-SERC,New Delhi(SR/FT/CS- 023/2008) is highly appreciated
文摘An efficient protocol was developed for the synthesis of 3-aminoalkylated indoles using 3- chlorophenylboronic acid as a catalyst under ambient temperature conditions.The three-component reaction of indoles,aromatic aldehydes and N-methyl aniline offered corresponding 3-aminoalkylated indoles in excellent yields.This protocol presents some remarkable features such as mild reaction conditions,simple workup procedure and excellent yields.
基金supported by the Islamic Azad University,Ayatollah Amoli Branch
文摘A simple,efficient,and general method has been developed for the synthesis ofα-amino nitriles.Oxalic acid as a BrФnsted acid promotes the addition of TMSCN to various imines（generated in situ）.
