Cholelithiasis has a complex pathogenesis,necessitating better therapeutic and preventive strategies.We recently read with interest Wang et al’s study on lysine acetyltransferase 2A(KAT2A)-mediated adenosine monophos...Cholelithiasis has a complex pathogenesis,necessitating better therapeutic and preventive strategies.We recently read with interest Wang et al’s study on lysine acetyltransferase 2A(KAT2A)-mediated adenosine monophosphate-activated protein kinase(AMPK)succinylation in cholelithiasis.Using mouse models and gallbladder mucosal epithelial cells,they found that KAT2A inhibits gallstones through AMPK K170 succinylation,thereby activating the AMPK/silent information regulator 1 pathway to reduce inflammation and pyroptosis.This study is the first to connect lysine succinylation with cholelithiasis,offering new insights and identifying succinylation as a potential therapeutic target.Future research should confirm these findings using patient samples,investigate other posttranslational modifications,and use structural biology to clarify succinylationinduced conformational changes,thereby bridging basic research to clinical applications.展开更多
Reader proteins that bind specific methyllysine are important to biological functions of lysine methylation,but readers of many methyllysine sites are still unknown.Therefore,development of covalent probes is importan...Reader proteins that bind specific methyllysine are important to biological functions of lysine methylation,but readers of many methyllysine sites are still unknown.Therefore,development of covalent probes is important to identify readers from cell samples so as to understand biological roles of lysine methylation.Generally,readers bind methyllysine via aromatic cages that contain tryptophan,tyrosine and phenylalanine,that offer a unique motif for selective crosslinking.We recently reported a site-selective tryptophan crosslinking strategy based on dimethylsulfonium that mimics dimethyllysine to crosslink tryptophan in aromatic cages of readers.Since tyrosine is a key residue for binding affinity to methyllysine,especially some readers that do not contain tryptophan residues in the binding pocket.Here we developed strategies of site-selective crosslinking to tyrosine.Ultraviolet(UV)source was applied to excite tyrosine at neutral pH or phenoxide at basic p H,and subsequent single-electron transfer(SET)from Tyr*to sulfonium inside the binding pocket enables selective crosslinking.In consequence,methyllysine readers with tyrosine-containing aromatic cages could be selectively crosslinked by site-specific sulfonium peptide probes.In addition,we expanded substrates from aromatic cages to tyrosine residues of proximate contact with sulfonium probes.The pair of LgBiT and SmBiT exhibited orthogonal crosslinking in complicated cell samples.As a result,we may expand sulfonium tools to target local tyrosine in future investigations.展开更多
Lysine-rich protein gene (lys) was cloned from Psophocarpus tetragonolobus (L.) DC. A plant expression plasmid was constructed and lys gene was under the control of maize ubiquitin promoter which is the highest effici...Lysine-rich protein gene (lys) was cloned from Psophocarpus tetragonolobus (L.) DC. A plant expression plasmid was constructed and lys gene was under the control of maize ubiquitin promoter which is the highest efficient monocotyledon promoter. The plasmid was introduced into rice embryogenic calli by microprojectile bombardment. The regenerated fertile plants were obtained by effective selection for hygromycin B resistance. Genomic PCR and Southern blotting analyses showed that the lys gene has been integrated into rice genome. Simultaneously, the results of GUS histochemical assay demonstrated that gus report gene is also expressed in leaves, stems and roots of the transgenic rice plants. Data analysis showed that lysine content in most of the 11 transgenic plants is differently improved, and in one of them increased by 16.04%.展开更多
Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttra...Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.展开更多
BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational mo...BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational modification,its role in cholelithiasis remains unexplored.AIM To investigate the functional role of succinylation in cholelithiasis and determine its underlying molecular mechanisms.METHODS A murine cholelithiasis model was established through high-fat diet feeding,followed by isolation of mouse gallbladder mucosal epithelial cells(GMECs)for in vitro analysis.Gallbladder tissues and serum samples were collected for subsequent analysis.Inflammatory cytokine production was quantified using enzyme-linked immunosorbent assay.Pyroptosis was analyzed by flow cytometry,while succinylation-and pyroptosis-related protein expression was detected via western blot.RESULTS Our findings demonstrated that lysine acetyltransferase 2A(KAT2A)-mediated succinylation regulated gallstone formation.KAT2A overexpression inhibited the pyroptosis,inflammatory responses,and promoted the activation of the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)sig-naling pathway in GMECs.Mechanistically,AMPK exhibited succinylation at lysine 170(K170).Notably,AMPK inhibition significantly increased pyroptosis rates,inflammatory responses,and pyroptosis-related protein ex-pression in GMECs.Furthermore,in vivo experiments revealed that KAT2A overexpression suppressed both inflammation and gallstone formation.CONCLUSION KAT2A-mediated succinylation of AMPK inhibited cholelithiasis progression by modulating the AMPK/SIRT1 signaling pathway,offering potential therapeutic strategies for this condition.展开更多
Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigene...Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.展开更多
Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD i...Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD is increasing,affecting up to 20%of the Western European population.This trend was particularly pronounced in high-risk occupational sectors,including healthcare,food services,metal and construction workers,and hairdressers[1].The skin sensitization adverse outcome pathway(AOP)comprises 11 elements,with four designated key events(KEs):formation of proteinhapten complexes(KE-1),inflammatory keratinocyte response(KE-2),dendritic cell(DC)activation(KE-3),and T-cell proliferation(KE-4)[2].As there is no cure for ACD,preventive strategies are of great relevance.In addition to avoiding exposure,preventive measures,such as the use of latex gloves,barrier creams,emollients,and moisturizers,often have limited effectiveness[3].展开更多
In this study, nine high-lysine maize kernels and two kernels of common maize hybrid were used as experiment materials, and quantitative determination of lysine contents in high-lysine maize kernels and common maize k...In this study, nine high-lysine maize kernels and two kernels of common maize hybrid were used as experiment materials, and quantitative determination of lysine contents in high-lysine maize kernels and common maize kernels was carried out using Hitachi L-8900 Automatic Amino-acid Analyzer, to know the effect of the Analyzer in distinguishing the lysine contents between common maize kernels and high-lysine maize kernels. The results showed that the lysine contents of high-lysine maize kernels were among 0.34%-0.42%, while of common maize kernels were a- mong 0.24%-0.25%, and the difference was significant. Compared with other tradi- tional methods, this method is rapid, simple, sensitive, highly reproductive and needs fewer maize kernels, thus it is applicable in maize breeding.展开更多
A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far.In the present work,the thermal degradation kinetics of lys...A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far.In the present work,the thermal degradation kinetics of lysine hydrochloride solutions for injection,the special solvent for ademetionine 1,4-butanedisulfonate(SAM)for injection,was investigated at selected temperatures and pH values.The main degradation product of lysine was separated,purified,and confirmed as lysine lactam.A reversed-phase high performance liquid chromatographic(RP-HPLC)method without derivation was developed for the simultaneous determination of lysine and lysine lactam.The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics.The degradation and generation rate constants increased with increasing temperatures and decreasing pH values.The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol,respectively.Meanwhile,a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy.Considering there could be other side effects,we established an upper limit of lysine lactam(500 mg/ml),as the acceptable criteria for stability to estimate the shelf life together with lysine,which made the prediction more accurate and credible.Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature.展开更多
Lysine-rich protein gene （lys） was cloned from winged bean （Psophocarpus tetragonolobus （L.） DC）, and cloned into prokaryotie expression vector pHT43, the recombinant plasmid pHT43/lys were constructed and then ...Lysine-rich protein gene （lys） was cloned from winged bean （Psophocarpus tetragonolobus （L.） DC）, and cloned into prokaryotie expression vector pHT43, the recombinant plasmid pHT43/lys were constructed and then transferred into Bacillus subtilis168, upon IPTG induction, the recombinant protein was expressed, and the content of lysine was detected by HPLC. The result showed that lysine content increased by 9.85%. It was suggested that introducing lys gene into Bacillus subtilis 168 was an effective way to improve its nutrition quality.展开更多
Two 3×3 factorial design trials with 1 080 of Yorkshire×Landrace×Duroc barrows were conducted to investigate the effects of dietary net energy （NE） density and standardized ileal digestible （SID） ly...Two 3×3 factorial design trials with 1 080 of Yorkshire×Landrace×Duroc barrows were conducted to investigate the effects of dietary net energy （NE） density and standardized ileal digestible （SID） lysine：NE ratio on the performance of growing- finishing pigs and carcass characteristic of finishing pigs fed low crude protein （CP） supplemented with crystalline amino acids （CAA） diets. Low CP corn-soybean meal basal diets （14% for Exp. 1 and 11% for Exp. 2） supplemented with crystalline lysine, methionine, threonine, and tryptophan were formulated. Nine treatments with increasing NE density and SID lysine：NE ratio were used in each trial （Exp. 1： 9.66, 9.87, and 10.08 MJ kg-1 NE, 0.89, 0.96, and 1.03 g MJ-1 SID lysine： NE; Exp. 2： 9.83, 10.04, and 10.25 MJ kg-1 NE, 0.69, 0.76, and 0.83 g MJ-1 SID lysine：NE）. In Exp. 1, we observed that the average daily gain （ADG） for barrows that received the diet containing 9.87 MJ kg-1 NE was significantly higher than that of barrows fed a 9.66 MJ kg-1 NE diet （P0.05）, but no difference was observed when compared with barrows that received a diet containing 10.08 MJ kg-1 NE （P0.05）. The ADG was affected both linearly （P0.05） and quadratically （P0.05） as the SID lysine：NE ratio increased. The NE density or SID lysine：NE ratio and their interaction had no effect on the average daily feed intake （ADFI） and serum urea nitrogen （SUN） （P0.05）. The feed to gain ratio （F：G） decreased （linearly, P0.05; quadratically, P0.05） as the NE density or SID lysine：NE ratio increased, but no interaction of NE density and SID lysine： NE ratio on the F：G. In Exp. 2, the dietary NE density both linearly （P0.05） and quadratically （P0.05） affected the ADG and F：G. Barrows that received a diet containing 10.04 MJ kg-1 NE had a greater ADG （P0.05） than barrows that received a 9.83 MJ kg-1 diet, but there was no difference （P0.05） as compared with barrows that received a diet containing 10.25 MJ kg-1 NE. F：G was significantly higher （P0.05） for barrows that received a 9.83 MJ kg-1 diet when compared with barrows that received the other two diets. The ADG was significantly decreased （P0.05） for pigs that received a diet containing 0.69 g MJ-1 SID lysine：NE ratio when compared with pigs fed a diet containing 0.76 or 0.83 g MJ-1 SID lysine：NE ratio. The NE density or SID lysine：NE ratio and their interaction had no effect on the average daily feed intake, SUN, and carcass characteristic for finishing barrows （P0.05）. The overall results of the two experiments indicated that barrows that received the diet with the dietary CP level reduced 4 percentage units compared the NRC （1998） recommendations. Maximized the best performance with NE density and SID lysine：NE ratio were 9.87 MJ kg-1, 1.03 g MJ-1 NE for 20-50 kg pigs, and 10.04 MJ kg-1, 0.76 g MJ-1 NE for 60-100 kg pigs, respectively.展开更多
The diffusion coefficients of l-lysine hydrochloride and I-arginine hydrochloride in their aqueous solutions at 25℃ were determined by the metallic diaphragm cell method which is characterized by accuracy, promptness...The diffusion coefficients of l-lysine hydrochloride and I-arginine hydrochloride in their aqueous solutions at 25℃ were determined by the metallic diaphragm cell method which is characterized by accuracy, promptness and convenience. Meanwhile, the densities and viscosities of the solutions were also determined. Based on all these data a semi-empirical model for correlating the diffusion coefficients of solid organic salts in their aqueous solutions at 25℃ was proposed. The fitting result of this model is comparatively satisfactory. Compared to a former model, Gordon Model, this model can avoid a number of difficulties and arduous work.展开更多
A total of 335 lactating sows （Landrace x Large White） were used in two experiments to determine the optimum ratio of standardized ileal digestible lysine （SID-Lys） to metabolizable energy （ME） for mixed parity ...A total of 335 lactating sows （Landrace x Large White） were used in two experiments to determine the optimum ratio of standardized ileal digestible lysine （SID-Lys） to metabolizable energy （ME） for mixed parity sows during lactation. In Exp. 1, 185 sows （weighing an average of 256.2 ± 6.5 kg and having an average parity of 3.4 ± 0.3） were allocated to one of six experimental diets in a completely randomized block design within parity groups （1, 2, and 3＋）. The experimental diets were formulated to contain 3.06, 3.16, 3.20, 3.25, 3.30 or 3.40 Mcal/kg of ME and each diet was fed to the sows throughout a 28 day lactation. All diets provided a similar SID-lysine level （0.86%）. As a result, the diets provided a SID-Lys：ME ratio of 2.81, 2.72, 2.69, 2.65, 2.61 or 2.53 g/Mcal ME. Sow feed intake was significantly （P 〈 0.01） affected by the energy content of the diet as well as by sow parity. Using regression analysis, feed intake was shown to be maximized at 3.25, 3.21, 3.21 and 3.21 Mcal/kg of ME for parity 1, 2, 3＋ sows and the entire cohort of sows respectively （quadratic; P 〈 0.01）. In addition, the result of feed intake can be expressed as 2.65, 2.69, 2.69 and 2.68 g/Mcal based on analysis of SID-Lys：ME ratio. Litter weight gain was affected by dietary treatment for parity 3＋ sows and the entire cohort （P 〈 0.01）. Based on regression analysis, litter weight gain was maximized at 3.25 and 3.24 Mcal/kg of ME for parity 3＋ （quadratic; P 〈 0.01） and the entire cohort （quadratic; P 〈 0.01）. Similarly, the result of litter weight gain could be expressed as 2.65 and 2.66 g/Mcal of SID- Lys：ME ratio. Therefore, 3.25 Mcal/kg of ME was selected for Exp. 2 in which 150 sows （weighing 254.6 ± 7.3 kg and having an average parity of 3.4 ± 0.4） were allocated to one of five treatments in a completely randomized block design within parity （1, 2, and 3＋）. The experimental diets were formulated to contain 2.1, 2.4, 2.7, 3.0 or 3.3 g/Mcal of SID-Lys：ME ratio with all diets providing 3.25 Mcal/kg of ME. The diets were fed to the sows throughout a 28 day lactation. Sow body weight loss was affected by dietary treatment （parity 3＋ sows, P = 0.02; entire cohort, P 〈 0.01） and by sow parity （P 〈 0.01）. Litter weight at weaning and litter weight gain were affected by dietary treatment for parity 1, 2, 3＋ sows and the entire cohort （P 〈 0.01） as well as by sow parity （P 〈 0.01）. Plasma urea nitrogen （P 〈 0.01）, creatinine （P 〈 0.01） and non-esterifide fatty acids （P = 0.04） were decreased as the SID-Lys：ME ratio of the diet increased. Insulin-like growth factor-1 （P = 0.02）, estradiol （P 〈 0.01） and luteinizing hormone （P = 0.02） were increased as the SID-Lys：ME ratio in diet increased. Based on a broken-line model, the estimated SID-Lys： ME ratio to maximize litter weight gain was estimated to be 3.05 g/Mcal.展开更多
AIM:To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1(LSD1) in hepatocellular carcinoma(HCC).METHODS:We examined LSD1 expression in 60 paired liver cancer tissues an...AIM:To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1(LSD1) in hepatocellular carcinoma(HCC).METHODS:We examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by quantitative real time polymerase chain reaction(qRT-PCR) and Western blotting.In addition,we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry.The relationship between LSD1 expression,clinicopathological features and patient survival was investigated.RESULTS:Immunohistochemistry,Western blotting,and qRT-PCR consistently confirmed LSD1 overexpression in HCC tissues compared to adjacent non-neoplastic tissues(P < 0.01).Additionally,immunostaining showed more LSD1-positive cells in the higher tumor stage(T3-4) and tumor grade(G3) than in the lower tumor stage(T1-2,P < 0.001) and tumor grade(G1-2,P < 0.001),respectively.Moreover,HCC patients with high LSD1 expression had significantly lower 5-year overall survival rates(P < 0.001) and lower 5-year disease-free survival rates(P < 0.001),respectively.A Cox proportional hazards model further demonstrated that LSD1 over-expression was an independent predictor of poor prognosis for both 5-year disease-free survival [hazards ratio(HR) = 1.426,95%CI:0.672-2.146,P < 0.001] and 5-year overall survival(HR = 2.456,95%CI:1.234-3.932,P < 0.001) in HCC.CONCLUSION:Our data suggest for the first time that the overexpression of LSD1 protein in HCC tissues indicates tumor progression and predicts poor prognosis.展开更多
Soybean meal （SBM） is commonly used for livestock feeds, but its application in diets for livestock is limited due to some antinutritional factors. The contents of methionine and lysine of soybean meal were promoted...Soybean meal （SBM） is commonly used for livestock feeds, but its application in diets for livestock is limited due to some antinutritional factors. The contents of methionine and lysine of soybean meal were promoted by Bacillus natto and Leuconostoc mesenteroides fermentation, benefial for the livestock feeds. It was crude protein （CP） 56.8%, methionine 43.56 mg · g^-1, and lysine 74.87 mg · g^-1, cows fed a diet with FSBM milk yield raised 14.2%, the change in the milk protein, the lactose and the dry matter content had also obvious increase. This convenient technique offers helpful exploration for industrialization of soybean meal fermentation.展开更多
A feed trial was conducted with a total of 1 134 Beijing ducklings to study the optimum level of dietary lysine （Lys） （0.95, 1.10, 1.25%）, methionine （Met） （0.26, 0.46, 0.66%） and tryptophan （Trp） （0.20, 0....A feed trial was conducted with a total of 1 134 Beijing ducklings to study the optimum level of dietary lysine （Lys） （0.95, 1.10, 1.25%）, methionine （Met） （0.26, 0.46, 0.66%） and tryptophan （Trp） （0.20, 0.30, 0.40%） for those ducklings during a phase of 0-2 weeks. Ducklings were randomly allotted to 27 groups according to a 3 × 3× 3 factorial arrangement and fed a basal corn-soybean-peanut meal diet containing 20.26% CP, 12.45 MJ kg^-1 ME. The results from this study indicate that Lys affected body weight （P〈0.01）, feed intake （0-14 d） （P〈0.01）, but had no effect on feed/gain （0-14 d） （P〉0.05）, uric acid concentration （P 〉 0.05）. Methionine influenced body weight （P 〈 0.01）, feed/gain （P 〈 0.05）, and feed intake （P 〈 0.01）. Tryphtophan had no effect on indices measured. The requirement of the Lys and Met for Beijing ducklings of 0-2 weeks of age were 1.10 and 0.46%. The requirement of Trp for Beijing ducklings of 0-2 weeks of age was not more than 0.20%.展开更多
[Objective] The paper was to study the effects on growth performance and feed digestibility of Hainan black pigs by adding lysine in low prntein diet. [Method] A tntal of 36 Hainan black pigs with the body weight of ...[Objective] The paper was to study the effects on growth performance and feed digestibility of Hainan black pigs by adding lysine in low prntein diet. [Method] A tntal of 36 Hainan black pigs with the body weight of （46.34±3.06） kg were randomly divided into three groups： con- trol group （protein level 15%, lysine level 0.83%）, experimental grnup 1 （protein level 13%, 0.83%）, and experimental group II （protein level 13%, lysine level 1.03）, each group had three replicates of four pigs. The trial lasted 35 d. [Result] The growth performance of Hainan black pig in grnup II had no significan! difference with that in contrail group （P〉0.05）. The apparent digestibility of chide protein and phosphorus of Hainan black pigs in Group II increased significantly （P〈0.05）, which were increased by 10.08% and 11.85% respectively compared to the control group; the apparent digestibility of calcium was increased, but the difference was not signifieant （P〉0.05）. [Conclusion] It will not reduce the growth performance of Hainan blaek pig when the protein level of diet is reduced by 2% and Ihe lysine level is increased to 1.03%. It is recommended that the diet can be used in the production of llainan black pig.展开更多
A total of 2,121 growing-finishing pigs （Duroc × Landrace ×Large White） were utilized in six experiments conducted to determine the effects of different ratios of standardized ileal digestible lysine （SID...A total of 2,121 growing-finishing pigs （Duroc × Landrace ×Large White） were utilized in six experiments conducted to determine the effects of different ratios of standardized ileal digestible lysine （SID-Lys） to metabolizable energy （ME） on the performance and carcass characteristics of growing-finishing pigs. Exps. 1 （30 to 50 kg）, 2 （52 to 70 kg） and 3 （81 to 104 kg） were conducted to find an optimum ME level and then this level was used in Exps. 4 （29 to 47 kg）, 5 （54 to 76 kg） and 6 （84 to 109 kg） to test the response of pigs to different ratios of SID-Lys：ME. In Exps.1 to 3, four treatments were used consisting of diets with a formulated ME content of 3.1, 3.2, 3.3 or 3.4 in Exps. I and 2 while Exp. 3 used 3.05, 3.1 S, 3.25 or 3.35 Mcal/kg. A constant SID-Lys：ME ratio of 2.6, 2.3 or 2.0 g/Mcal was used in Exps. 1, 2 and 3, respectively. Weight gain was significantly increased with increasing energy level in Exp.1 while weight gain was unaltered in Exps. 2 and 3. For all three experiments, feed intake was decreased （P 〈 0.05） and feed efficiency was improved （P 〈 0.05） with increasing energy level. Tenth rib back fat thickness linearly increased （P 〈 0.05） with increasing energy level, in Exps. 4 to 6, five treatments were used consisting of diets with a SID-Lys：ME ratio of 2.4, 2.6, 2.8, 3.0 or 3.2 in Exp. 1, 2.1, 2.3, 2.5, 2.7, 2.9 or 3.2 in Exp. 2 and 1.8, 2.0, 2.2, 2.4, or 2.6 in Exp. 3. A constant ME level 3.2, 3.2 and 3.05 Mcal/kg was used in Exps. 1, 2 and 3, respectively （selected based on the results of weight gain）. For all three experiments, weight gain increased （P 〈 0.05） and feed efficiency improved linearly （P 〈 0.05） as the SID-Lys：ME ratio increased. Tenth rib back fat thickness linearly decreased （P 〈 0.0,5） as the SID-Lys：ME ratio increased. Based on a straight broken-line model, the estimated SID-Lys：ME ratio to maximize weight gain was 3.0, 2.43 and 2.2 for 29 to 47, 54 to76 and 84 to 109 kg of pigs, respectively.展开更多
The effects of dietary lysine on production performance,serum concentrations of metabolites,growth hormone （GH）,insulin-like growth factor-I （IGF-I） and IGF-I mRNA expression in growing rabbits were examined.One h...The effects of dietary lysine on production performance,serum concentrations of metabolites,growth hormone （GH）,insulin-like growth factor-I （IGF-I） and IGF-I mRNA expression in growing rabbits were examined.One hundred weaned New Zealand rabbits were allocated to individual cages and randomly offered a diet containing 5.5 （L1）,6.5 （L2）,7.5 （L3）,8.5 （L4）,or 9.5 g （L5） lysine per kg diet.The results showed that the average daily gain （ADG） of the rabbits from L3,L4 or L5 was higher than those from L1 or L2 （P 〈 0.05）.The feed gain ratio （F/G） in the rabbits from L4 or L5 was lower than those from L1 or L2 （P 〈 0.05）.Dietary lysine did not affect serum concentrations of total protein （TP）,glucose,insulin （INS）,and growth hormone （GH） （P 〉 0.05）.The quadratic effects of lysine on the serum urea nitrogen （SUN） concentration was detected （P = 0.035）.Serum IGF-I concentrations had a trend to increase quadratically with the increasing dietary lysine （P = 0.07）.A significant correlation was found between serum IGF-I concentrations （x,ng mL-1） and ADG （y,g kg-1）： y = -0.017x2 ＋ 1.984x ＋ 20.87 （R2 = 0.8982,P = 0.003）.The relative abundance of hepatic and muscular IGF-I mRNA tended to increase with increasing dietary lysine levels （P = 0.053 and 0.082,respectively）.Providing the diets mainly consisted of corn,wheat bran and peanut vine,the most appropriate dietary lysine level for growing meat rabbits from weaning to 70 d old was found to be 8.5 g kg-1,and IGF-I may be an important factor controlling growth of weaned rabbits.展开更多
Lysine specific demethylase 1(LSD1),a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9,has become a potential therapeutic target for cancer therapy.LSD1 mediates many...Lysine specific demethylase 1(LSD1),a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9,has become a potential therapeutic target for cancer therapy.LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation,invasion,migration,and differentiation.Recent research has focused on the exploration of its pharmacological inhibitors.Natural products are a major source of compounds with abundant scaffold diversity and structural complexity,which have made a major contribution to drug discovery,particularly anticancer agents.In this review,we briefly highlight recent advances in natural LSD1 inhibitors over the past decade.We present a comprehensive review on their discovery and identification process,natural plant sources,chemical structures,anticancer effects,and structure-activity relationships,and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.展开更多
基金Supported by Wenzhou Science and Technology Bureau,No.Y20240207.
文摘Cholelithiasis has a complex pathogenesis,necessitating better therapeutic and preventive strategies.We recently read with interest Wang et al’s study on lysine acetyltransferase 2A(KAT2A)-mediated adenosine monophosphate-activated protein kinase(AMPK)succinylation in cholelithiasis.Using mouse models and gallbladder mucosal epithelial cells,they found that KAT2A inhibits gallstones through AMPK K170 succinylation,thereby activating the AMPK/silent information regulator 1 pathway to reduce inflammation and pyroptosis.This study is the first to connect lysine succinylation with cholelithiasis,offering new insights and identifying succinylation as a potential therapeutic target.Future research should confirm these findings using patient samples,investigate other posttranslational modifications,and use structural biology to clarify succinylationinduced conformational changes,thereby bridging basic research to clinical applications.
基金the support from National Natural Science Foundation of China(No.22161132006)Key R&D Program of Zhejiang(No.2024SSYS0036)Westlake University Startup。
文摘Reader proteins that bind specific methyllysine are important to biological functions of lysine methylation,but readers of many methyllysine sites are still unknown.Therefore,development of covalent probes is important to identify readers from cell samples so as to understand biological roles of lysine methylation.Generally,readers bind methyllysine via aromatic cages that contain tryptophan,tyrosine and phenylalanine,that offer a unique motif for selective crosslinking.We recently reported a site-selective tryptophan crosslinking strategy based on dimethylsulfonium that mimics dimethyllysine to crosslink tryptophan in aromatic cages of readers.Since tyrosine is a key residue for binding affinity to methyllysine,especially some readers that do not contain tryptophan residues in the binding pocket.Here we developed strategies of site-selective crosslinking to tyrosine.Ultraviolet(UV)source was applied to excite tyrosine at neutral pH or phenoxide at basic p H,and subsequent single-electron transfer(SET)from Tyr*to sulfonium inside the binding pocket enables selective crosslinking.In consequence,methyllysine readers with tyrosine-containing aromatic cages could be selectively crosslinked by site-specific sulfonium peptide probes.In addition,we expanded substrates from aromatic cages to tyrosine residues of proximate contact with sulfonium probes.The pair of LgBiT and SmBiT exhibited orthogonal crosslinking in complicated cell samples.As a result,we may expand sulfonium tools to target local tyrosine in future investigations.
文摘Lysine-rich protein gene (lys) was cloned from Psophocarpus tetragonolobus (L.) DC. A plant expression plasmid was constructed and lys gene was under the control of maize ubiquitin promoter which is the highest efficient monocotyledon promoter. The plasmid was introduced into rice embryogenic calli by microprojectile bombardment. The regenerated fertile plants were obtained by effective selection for hygromycin B resistance. Genomic PCR and Southern blotting analyses showed that the lys gene has been integrated into rice genome. Simultaneously, the results of GUS histochemical assay demonstrated that gus report gene is also expressed in leaves, stems and roots of the transgenic rice plants. Data analysis showed that lysine content in most of the 11 transgenic plants is differently improved, and in one of them increased by 16.04%.
基金the National Natural Science Foundation of China(Nos.82373722,22077144)Hunan Provincial Natural Science Foundation of China(No.2023JJ30527)+2 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515040006)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Key Research and Development Program of Guangdong Province(No.2020B1111110003).
文摘Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.
基金Supported by National Natural Science Foundation of China,No.82000579 and No.81870205Natural Science Foundation of Shandong Province,No.ZR2021QH061 and No.ZR2021QH186.
文摘BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational modification,its role in cholelithiasis remains unexplored.AIM To investigate the functional role of succinylation in cholelithiasis and determine its underlying molecular mechanisms.METHODS A murine cholelithiasis model was established through high-fat diet feeding,followed by isolation of mouse gallbladder mucosal epithelial cells(GMECs)for in vitro analysis.Gallbladder tissues and serum samples were collected for subsequent analysis.Inflammatory cytokine production was quantified using enzyme-linked immunosorbent assay.Pyroptosis was analyzed by flow cytometry,while succinylation-and pyroptosis-related protein expression was detected via western blot.RESULTS Our findings demonstrated that lysine acetyltransferase 2A(KAT2A)-mediated succinylation regulated gallstone formation.KAT2A overexpression inhibited the pyroptosis,inflammatory responses,and promoted the activation of the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)sig-naling pathway in GMECs.Mechanistically,AMPK exhibited succinylation at lysine 170(K170).Notably,AMPK inhibition significantly increased pyroptosis rates,inflammatory responses,and pyroptosis-related protein ex-pression in GMECs.Furthermore,in vivo experiments revealed that KAT2A overexpression suppressed both inflammation and gallstone formation.CONCLUSION KAT2A-mediated succinylation of AMPK inhibited cholelithiasis progression by modulating the AMPK/SIRT1 signaling pathway,offering potential therapeutic strategies for this condition.
基金NIH/NIDCR grant R01 DE031413 and CTSA pilot grant UL1TR001430 to Manish V.Bais.
文摘Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
基金support was provided by the European Regional Development Fund(ERDF),through the Centro 2020 Regional Operational Programme,Portugal(Project No.:CENTRO-01-0145-FEDER-000012(HealthyAging2020))through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation and Portuguese National Funds via Fundaçao para a Ciencia e a Tecnologia,Portugal(Project Nos.:POCI-01-0145-FEDER-029369 UIDB/04539/2020,iBiMED UIDB/04501/2020,DOI identifier https://doi.org/10.54499/UIDB/04501/2020 and project reference UIDP/04501/2020,DOI identifier https://doi.org/10.54499/UIDP/04501/2020,and LA/P/0058/2020)supported by Fundaçao para a Ciencia e a Tecnologia through the individual PhD fellowships,Portugal(Grant Nos.:PD/BDE/142926/2018 and SFRH/BD/110717/2015)。
文摘Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD is increasing,affecting up to 20%of the Western European population.This trend was particularly pronounced in high-risk occupational sectors,including healthcare,food services,metal and construction workers,and hairdressers[1].The skin sensitization adverse outcome pathway(AOP)comprises 11 elements,with four designated key events(KEs):formation of proteinhapten complexes(KE-1),inflammatory keratinocyte response(KE-2),dendritic cell(DC)activation(KE-3),and T-cell proliferation(KE-4)[2].As there is no cure for ACD,preventive strategies are of great relevance.In addition to avoiding exposure,preventive measures,such as the use of latex gloves,barrier creams,emollients,and moisturizers,often have limited effectiveness[3].
基金Supported by Henan Major Scientific and Technological Project(121100110300)Outstanding Youth Project of Henan Academy of Agricultural Sciences(2013YQ006)~~
文摘In this study, nine high-lysine maize kernels and two kernels of common maize hybrid were used as experiment materials, and quantitative determination of lysine contents in high-lysine maize kernels and common maize kernels was carried out using Hitachi L-8900 Automatic Amino-acid Analyzer, to know the effect of the Analyzer in distinguishing the lysine contents between common maize kernels and high-lysine maize kernels. The results showed that the lysine contents of high-lysine maize kernels were among 0.34%-0.42%, while of common maize kernels were a- mong 0.24%-0.25%, and the difference was significant. Compared with other tradi- tional methods, this method is rapid, simple, sensitive, highly reproductive and needs fewer maize kernels, thus it is applicable in maize breeding.
文摘A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far.In the present work,the thermal degradation kinetics of lysine hydrochloride solutions for injection,the special solvent for ademetionine 1,4-butanedisulfonate(SAM)for injection,was investigated at selected temperatures and pH values.The main degradation product of lysine was separated,purified,and confirmed as lysine lactam.A reversed-phase high performance liquid chromatographic(RP-HPLC)method without derivation was developed for the simultaneous determination of lysine and lysine lactam.The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics.The degradation and generation rate constants increased with increasing temperatures and decreasing pH values.The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol,respectively.Meanwhile,a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy.Considering there could be other side effects,we established an upper limit of lysine lactam(500 mg/ml),as the acceptable criteria for stability to estimate the shelf life together with lysine,which made the prediction more accurate and credible.Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature.
基金Supported by Funding of Heilongjiang Provincial Science Research Project (GB08B401-02)Innovation Team Project of Northeast Agricultural University (CXT005-1-2)
文摘Lysine-rich protein gene （lys） was cloned from winged bean （Psophocarpus tetragonolobus （L.） DC）, and cloned into prokaryotie expression vector pHT43, the recombinant plasmid pHT43/lys were constructed and then transferred into Bacillus subtilis168, upon IPTG induction, the recombinant protein was expressed, and the content of lysine was detected by HPLC. The result showed that lysine content increased by 9.85%. It was suggested that introducing lys gene into Bacillus subtilis 168 was an effective way to improve its nutrition quality.
基金supported by the National Key Tech-nology R&D Program of China (2006BAD12B02)
文摘Two 3×3 factorial design trials with 1 080 of Yorkshire×Landrace×Duroc barrows were conducted to investigate the effects of dietary net energy （NE） density and standardized ileal digestible （SID） lysine：NE ratio on the performance of growing- finishing pigs and carcass characteristic of finishing pigs fed low crude protein （CP） supplemented with crystalline amino acids （CAA） diets. Low CP corn-soybean meal basal diets （14% for Exp. 1 and 11% for Exp. 2） supplemented with crystalline lysine, methionine, threonine, and tryptophan were formulated. Nine treatments with increasing NE density and SID lysine：NE ratio were used in each trial （Exp. 1： 9.66, 9.87, and 10.08 MJ kg-1 NE, 0.89, 0.96, and 1.03 g MJ-1 SID lysine： NE; Exp. 2： 9.83, 10.04, and 10.25 MJ kg-1 NE, 0.69, 0.76, and 0.83 g MJ-1 SID lysine：NE）. In Exp. 1, we observed that the average daily gain （ADG） for barrows that received the diet containing 9.87 MJ kg-1 NE was significantly higher than that of barrows fed a 9.66 MJ kg-1 NE diet （P0.05）, but no difference was observed when compared with barrows that received a diet containing 10.08 MJ kg-1 NE （P0.05）. The ADG was affected both linearly （P0.05） and quadratically （P0.05） as the SID lysine：NE ratio increased. The NE density or SID lysine：NE ratio and their interaction had no effect on the average daily feed intake （ADFI） and serum urea nitrogen （SUN） （P0.05）. The feed to gain ratio （F：G） decreased （linearly, P0.05; quadratically, P0.05） as the NE density or SID lysine：NE ratio increased, but no interaction of NE density and SID lysine： NE ratio on the F：G. In Exp. 2, the dietary NE density both linearly （P0.05） and quadratically （P0.05） affected the ADG and F：G. Barrows that received a diet containing 10.04 MJ kg-1 NE had a greater ADG （P0.05） than barrows that received a 9.83 MJ kg-1 diet, but there was no difference （P0.05） as compared with barrows that received a diet containing 10.25 MJ kg-1 NE. F：G was significantly higher （P0.05） for barrows that received a 9.83 MJ kg-1 diet when compared with barrows that received the other two diets. The ADG was significantly decreased （P0.05） for pigs that received a diet containing 0.69 g MJ-1 SID lysine：NE ratio when compared with pigs fed a diet containing 0.76 or 0.83 g MJ-1 SID lysine：NE ratio. The NE density or SID lysine：NE ratio and their interaction had no effect on the average daily feed intake, SUN, and carcass characteristic for finishing barrows （P0.05）. The overall results of the two experiments indicated that barrows that received the diet with the dietary CP level reduced 4 percentage units compared the NRC （1998） recommendations. Maximized the best performance with NE density and SID lysine：NE ratio were 9.87 MJ kg-1, 1.03 g MJ-1 NE for 20-50 kg pigs, and 10.04 MJ kg-1, 0.76 g MJ-1 NE for 60-100 kg pigs, respectively.
文摘The diffusion coefficients of l-lysine hydrochloride and I-arginine hydrochloride in their aqueous solutions at 25℃ were determined by the metallic diaphragm cell method which is characterized by accuracy, promptness and convenience. Meanwhile, the densities and viscosities of the solutions were also determined. Based on all these data a semi-empirical model for correlating the diffusion coefficients of solid organic salts in their aqueous solutions at 25℃ was proposed. The fitting result of this model is comparatively satisfactory. Compared to a former model, Gordon Model, this model can avoid a number of difficulties and arduous work.
基金the Special Public Sector Fund in Agriculture(200903006)the State Key Laboratory of Animal Nutrition(2004DA125184-0810) of China+3 种基金National Natural Science Foundation of China(NSFC3080078931072040)Ministry of Science and Technology of the People's Republic of China(2006BAD12B05-102009IM03310005)
文摘A total of 335 lactating sows （Landrace x Large White） were used in two experiments to determine the optimum ratio of standardized ileal digestible lysine （SID-Lys） to metabolizable energy （ME） for mixed parity sows during lactation. In Exp. 1, 185 sows （weighing an average of 256.2 ± 6.5 kg and having an average parity of 3.4 ± 0.3） were allocated to one of six experimental diets in a completely randomized block design within parity groups （1, 2, and 3＋）. The experimental diets were formulated to contain 3.06, 3.16, 3.20, 3.25, 3.30 or 3.40 Mcal/kg of ME and each diet was fed to the sows throughout a 28 day lactation. All diets provided a similar SID-lysine level （0.86%）. As a result, the diets provided a SID-Lys：ME ratio of 2.81, 2.72, 2.69, 2.65, 2.61 or 2.53 g/Mcal ME. Sow feed intake was significantly （P 〈 0.01） affected by the energy content of the diet as well as by sow parity. Using regression analysis, feed intake was shown to be maximized at 3.25, 3.21, 3.21 and 3.21 Mcal/kg of ME for parity 1, 2, 3＋ sows and the entire cohort of sows respectively （quadratic; P 〈 0.01）. In addition, the result of feed intake can be expressed as 2.65, 2.69, 2.69 and 2.68 g/Mcal based on analysis of SID-Lys：ME ratio. Litter weight gain was affected by dietary treatment for parity 3＋ sows and the entire cohort （P 〈 0.01）. Based on regression analysis, litter weight gain was maximized at 3.25 and 3.24 Mcal/kg of ME for parity 3＋ （quadratic; P 〈 0.01） and the entire cohort （quadratic; P 〈 0.01）. Similarly, the result of litter weight gain could be expressed as 2.65 and 2.66 g/Mcal of SID- Lys：ME ratio. Therefore, 3.25 Mcal/kg of ME was selected for Exp. 2 in which 150 sows （weighing 254.6 ± 7.3 kg and having an average parity of 3.4 ± 0.4） were allocated to one of five treatments in a completely randomized block design within parity （1, 2, and 3＋）. The experimental diets were formulated to contain 2.1, 2.4, 2.7, 3.0 or 3.3 g/Mcal of SID-Lys：ME ratio with all diets providing 3.25 Mcal/kg of ME. The diets were fed to the sows throughout a 28 day lactation. Sow body weight loss was affected by dietary treatment （parity 3＋ sows, P = 0.02; entire cohort, P 〈 0.01） and by sow parity （P 〈 0.01）. Litter weight at weaning and litter weight gain were affected by dietary treatment for parity 1, 2, 3＋ sows and the entire cohort （P 〈 0.01） as well as by sow parity （P 〈 0.01）. Plasma urea nitrogen （P 〈 0.01）, creatinine （P 〈 0.01） and non-esterifide fatty acids （P = 0.04） were decreased as the SID-Lys：ME ratio of the diet increased. Insulin-like growth factor-1 （P = 0.02）, estradiol （P 〈 0.01） and luteinizing hormone （P = 0.02） were increased as the SID-Lys：ME ratio in diet increased. Based on a broken-line model, the estimated SID-Lys： ME ratio to maximize litter weight gain was estimated to be 3.05 g/Mcal.
文摘AIM:To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1(LSD1) in hepatocellular carcinoma(HCC).METHODS:We examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by quantitative real time polymerase chain reaction(qRT-PCR) and Western blotting.In addition,we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry.The relationship between LSD1 expression,clinicopathological features and patient survival was investigated.RESULTS:Immunohistochemistry,Western blotting,and qRT-PCR consistently confirmed LSD1 overexpression in HCC tissues compared to adjacent non-neoplastic tissues(P < 0.01).Additionally,immunostaining showed more LSD1-positive cells in the higher tumor stage(T3-4) and tumor grade(G3) than in the lower tumor stage(T1-2,P < 0.001) and tumor grade(G1-2,P < 0.001),respectively.Moreover,HCC patients with high LSD1 expression had significantly lower 5-year overall survival rates(P < 0.001) and lower 5-year disease-free survival rates(P < 0.001),respectively.A Cox proportional hazards model further demonstrated that LSD1 over-expression was an independent predictor of poor prognosis for both 5-year disease-free survival [hazards ratio(HR) = 1.426,95%CI:0.672-2.146,P < 0.001] and 5-year overall survival(HR = 2.456,95%CI:1.234-3.932,P < 0.001) in HCC.CONCLUSION:Our data suggest for the first time that the overexpression of LSD1 protein in HCC tissues indicates tumor progression and predicts poor prognosis.
基金Supported by Science and Technology Foundation (GB08B401-02)Science and Technology for Youth in Heilongjiang Province (QC07C35)
文摘Soybean meal （SBM） is commonly used for livestock feeds, but its application in diets for livestock is limited due to some antinutritional factors. The contents of methionine and lysine of soybean meal were promoted by Bacillus natto and Leuconostoc mesenteroides fermentation, benefial for the livestock feeds. It was crude protein （CP） 56.8%, methionine 43.56 mg · g^-1, and lysine 74.87 mg · g^-1, cows fed a diet with FSBM milk yield raised 14.2%, the change in the milk protein, the lactose and the dry matter content had also obvious increase. This convenient technique offers helpful exploration for industrialization of soybean meal fermentation.
文摘A feed trial was conducted with a total of 1 134 Beijing ducklings to study the optimum level of dietary lysine （Lys） （0.95, 1.10, 1.25%）, methionine （Met） （0.26, 0.46, 0.66%） and tryptophan （Trp） （0.20, 0.30, 0.40%） for those ducklings during a phase of 0-2 weeks. Ducklings were randomly allotted to 27 groups according to a 3 × 3× 3 factorial arrangement and fed a basal corn-soybean-peanut meal diet containing 20.26% CP, 12.45 MJ kg^-1 ME. The results from this study indicate that Lys affected body weight （P〈0.01）, feed intake （0-14 d） （P〈0.01）, but had no effect on feed/gain （0-14 d） （P〉0.05）, uric acid concentration （P 〉 0.05）. Methionine influenced body weight （P 〈 0.01）, feed/gain （P 〈 0.05）, and feed intake （P 〈 0.01）. Tryphtophan had no effect on indices measured. The requirement of the Lys and Met for Beijing ducklings of 0-2 weeks of age were 1.10 and 0.46%. The requirement of Trp for Beijing ducklings of 0-2 weeks of age was not more than 0.20%.
基金Supported by Technical Development Project of Provincial Scientific Research Institutes in Hainan(KYYS-2016-12)
文摘[Objective] The paper was to study the effects on growth performance and feed digestibility of Hainan black pigs by adding lysine in low prntein diet. [Method] A tntal of 36 Hainan black pigs with the body weight of （46.34±3.06） kg were randomly divided into three groups： con- trol group （protein level 15%, lysine level 0.83%）, experimental grnup 1 （protein level 13%, 0.83%）, and experimental group II （protein level 13%, lysine level 1.03）, each group had three replicates of four pigs. The trial lasted 35 d. [Result] The growth performance of Hainan black pig in grnup II had no significan! difference with that in contrail group （P〉0.05）. The apparent digestibility of chide protein and phosphorus of Hainan black pigs in Group II increased significantly （P〈0.05）, which were increased by 10.08% and 11.85% respectively compared to the control group; the apparent digestibility of calcium was increased, but the difference was not signifieant （P〉0.05）. [Conclusion] It will not reduce the growth performance of Hainan blaek pig when the protein level of diet is reduced by 2% and Ihe lysine level is increased to 1.03%. It is recommended that the diet can be used in the production of llainan black pig.
基金supported by the State Key Laboratory of Animal Nutrition (2004DA125184-0810) of ChinaNational Natural Science Foundation of China(31072040)+2 种基金Guangdong cooperation project between Industry-Academia-Research of China (2009B090300110)the Ministry of Science and Technology of the People's Republic of China(2006BAD12B05-10Nyhyzx07-34)
文摘A total of 2,121 growing-finishing pigs （Duroc × Landrace ×Large White） were utilized in six experiments conducted to determine the effects of different ratios of standardized ileal digestible lysine （SID-Lys） to metabolizable energy （ME） on the performance and carcass characteristics of growing-finishing pigs. Exps. 1 （30 to 50 kg）, 2 （52 to 70 kg） and 3 （81 to 104 kg） were conducted to find an optimum ME level and then this level was used in Exps. 4 （29 to 47 kg）, 5 （54 to 76 kg） and 6 （84 to 109 kg） to test the response of pigs to different ratios of SID-Lys：ME. In Exps.1 to 3, four treatments were used consisting of diets with a formulated ME content of 3.1, 3.2, 3.3 or 3.4 in Exps. I and 2 while Exp. 3 used 3.05, 3.1 S, 3.25 or 3.35 Mcal/kg. A constant SID-Lys：ME ratio of 2.6, 2.3 or 2.0 g/Mcal was used in Exps. 1, 2 and 3, respectively. Weight gain was significantly increased with increasing energy level in Exp.1 while weight gain was unaltered in Exps. 2 and 3. For all three experiments, feed intake was decreased （P 〈 0.05） and feed efficiency was improved （P 〈 0.05） with increasing energy level. Tenth rib back fat thickness linearly increased （P 〈 0.05） with increasing energy level, in Exps. 4 to 6, five treatments were used consisting of diets with a SID-Lys：ME ratio of 2.4, 2.6, 2.8, 3.0 or 3.2 in Exp. 1, 2.1, 2.3, 2.5, 2.7, 2.9 or 3.2 in Exp. 2 and 1.8, 2.0, 2.2, 2.4, or 2.6 in Exp. 3. A constant ME level 3.2, 3.2 and 3.05 Mcal/kg was used in Exps. 1, 2 and 3, respectively （selected based on the results of weight gain）. For all three experiments, weight gain increased （P 〈 0.05） and feed efficiency improved linearly （P 〈 0.05） as the SID-Lys：ME ratio increased. Tenth rib back fat thickness linearly decreased （P 〈 0.0,5） as the SID-Lys：ME ratio increased. Based on a straight broken-line model, the estimated SID-Lys：ME ratio to maximize weight gain was 3.0, 2.43 and 2.2 for 29 to 47, 54 to76 and 84 to 109 kg of pigs, respectively.
基金supported by the Agriculture Profession Item (3-52)by the earmarked fund for Modern Agro-Industry Technology Research System of the Ministry of Agriculture of the P.R.China (nycytx-44)
文摘The effects of dietary lysine on production performance,serum concentrations of metabolites,growth hormone （GH）,insulin-like growth factor-I （IGF-I） and IGF-I mRNA expression in growing rabbits were examined.One hundred weaned New Zealand rabbits were allocated to individual cages and randomly offered a diet containing 5.5 （L1）,6.5 （L2）,7.5 （L3）,8.5 （L4）,or 9.5 g （L5） lysine per kg diet.The results showed that the average daily gain （ADG） of the rabbits from L3,L4 or L5 was higher than those from L1 or L2 （P 〈 0.05）.The feed gain ratio （F/G） in the rabbits from L4 or L5 was lower than those from L1 or L2 （P 〈 0.05）.Dietary lysine did not affect serum concentrations of total protein （TP）,glucose,insulin （INS）,and growth hormone （GH） （P 〉 0.05）.The quadratic effects of lysine on the serum urea nitrogen （SUN） concentration was detected （P = 0.035）.Serum IGF-I concentrations had a trend to increase quadratically with the increasing dietary lysine （P = 0.07）.A significant correlation was found between serum IGF-I concentrations （x,ng mL-1） and ADG （y,g kg-1）： y = -0.017x2 ＋ 1.984x ＋ 20.87 （R2 = 0.8982,P = 0.003）.The relative abundance of hepatic and muscular IGF-I mRNA tended to increase with increasing dietary lysine levels （P = 0.053 and 0.082,respectively）.Providing the diets mainly consisted of corn,wheat bran and peanut vine,the most appropriate dietary lysine level for growing meat rabbits from weaning to 70 d old was found to be 8.5 g kg-1,and IGF-I may be an important factor controlling growth of weaned rabbits.
基金This work was co-supported by National Natural Science Foundation of China(Nos.81803695 and 82104359)the Natural Science Fund in Jiangsu Province(BK20180568)+2 种基金the China Postdoctoral Science Foundation(2021M691647)the Fundamental Research Funds for the Central Universities(2632021ZD24)the Open Project of State Key Laboratory of Natural Medicines(SKLNMKF202207).
文摘Lysine specific demethylase 1(LSD1),a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9,has become a potential therapeutic target for cancer therapy.LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation,invasion,migration,and differentiation.Recent research has focused on the exploration of its pharmacological inhibitors.Natural products are a major source of compounds with abundant scaffold diversity and structural complexity,which have made a major contribution to drug discovery,particularly anticancer agents.In this review,we briefly highlight recent advances in natural LSD1 inhibitors over the past decade.We present a comprehensive review on their discovery and identification process,natural plant sources,chemical structures,anticancer effects,and structure-activity relationships,and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.
