Enabling tools are essential for facilitating the methanol bioconversion in Pichia pastoris.However,there is still a relative lack of promoters that can stably express high levels without being affected by the carbon ...Enabling tools are essential for facilitating the methanol bioconversion in Pichia pastoris.However,there is still a relative lack of promoters that can stably express high levels without being affected by the carbon source,which hinders the construction and modification of cell factories containing long metabolic pathways.This study mapped a gene expression intensity library of central metabolic pathways in P.pastoris under methanol and glucose conditions.Through modification of the upstream sequences of promoters,an artificial promoter PS2 was developed with a strong intensity up to 90%of PGAP.By using this promoter,we successfully constructed a hybrid pathway that integrates theβ-alanine and malonyl-CoA pathways for the production of 3-hydroxypro-pionic acid.Further combining rational metabolic engineering strategies,such as optimizing gene copy numbers and blocking byproduct synthesis pathways,the engineered strains CHP9 and CHP20 achieved 3-HP titers of 23 g/L and 22 g/L by using methanol as the sole carbon source.These results indicate that adaptive strength of promoters can facilitate efficient chemical biosynthesis in methanol bioconversion by mitigating glucose repression effects.This work preliminarily explored the expression patterns of genes in the central metabolic pathways of P.pastoris,identified and characterized the intensities of various endogenous promoters,and extended the enabling toolbox for P.pastoris.This result also lays a foundation for the construction of mi-crobial cell factories and the industrial production of 3-HP via methanol bioconversion.展开更多
Rice straw and sugar cane industrial waste are a plentiful source of lignocellulosic biomass with a high poly-saccharide content,that is hydrolyzed into sugar for microbial growth and their metabolites.3-Hydroxypropio...Rice straw and sugar cane industrial waste are a plentiful source of lignocellulosic biomass with a high poly-saccharide content,that is hydrolyzed into sugar for microbial growth and their metabolites.3-Hydroxypropionic acid(3-HP)is a promising chemical building block that can be produced from renewable resources.The malonyl-CoA pathway is one of the biosynthetic routes for 3-HP production by expressing the malonyl-CoA reductase gene(mcr).However,the problem of the activity imbalance between the C and N-terminal causes a low con-version rate of malonyl-CoA to 3-hydroxypropionic acid.This study aimed to balance the bi-functional MCR enzyme by dissecting MCR into two fragments and enhancing the supply of intermediates to increase the pro-duction of 3-HP.The recombinant strain harboring the dissected mcr gene showed a 21-fold increase in 3-HP titer compared to the strain carrying the full-length mcr gene.The addition of cerulenin and acetate to the fermented medium enhanced 3-HP yield by 8 times,in which recombinant yeast produced 3-HP up to 10 g/L(0.201 gproduct/gsubstrate).The results of using rice straw hydrolysate as a carbon source indicated that Saccharomyces cerevisiae S2 produced 3-HP of 4.02 g/L,which was 0.074 gproduct/gglucose in the diluted hydrolysate.These findings provide an alternative and sustainable strategy for utilizing lignocellulosic biomass for future 3-HP production at an industrial scale.展开更多
Syngas,which contains large amount of CO2 as well as H2 and CO,can be convert to acetic acid chemically or biologically.Nowadays,acetic acid become a cost-effective nonfood-based carbon source for value-added biochemi...Syngas,which contains large amount of CO2 as well as H2 and CO,can be convert to acetic acid chemically or biologically.Nowadays,acetic acid become a cost-effective nonfood-based carbon source for value-added biochemical production.In this study,acetic acid and CO2 were used as substrates for the biosynthesis of 3-hydroxypropionic acid(3-HP)in metabolically engineered Escherichia coli carrying heterogeneous acetyl-CoA carboxylase(Acc)from Corynebacterium glutamicum and codon-optimized malonyl-CoA reductase(MCR)from Chloroflexus aurantiacus.Strategies of metabolic engineering included promoting glyoxylate shunt pathway,inhibiting fatty acid synthesis,dynamic regulating of TCA cycle,and enhancing the assimilation of acetic acid.The engineered strain LNY07(M*DA)accumulated 15.8 g/L of 3-HP with the yield of 0.71 g/g in 48 h by whole-cell biocatalysis.Then,syngas-derived acetic acid was used as substrate instead of pure acetic acid.The concentration of 3-HP reached 11.2 g/L with the yield of 0.55 g/g in LNY07(M*DA).The results could potentially contribute to the future development of an industrial bioprocess of 3-HP production from syngas-derived acetic acid.展开更多
3-Hydroxypropionic Acid(3-HP)is recognized as a high value-added chemical with a broad range of applications.Among the various biosynthetic pathways for 3-HP production,theβ-alanine pathway is particularly noteworthy...3-Hydroxypropionic Acid(3-HP)is recognized as a high value-added chemical with a broad range of applications.Among the various biosynthetic pathways for 3-HP production,theβ-alanine pathway is particularly noteworthy due to its capacity to generate 3-HP from glucose at a high theoretical titer.In this study,theβ-alanine biosynthesis pathway was introduced and optimized in Corynebacterium glutamicum.By strategically regulating the supply of precursors,we successfully engineered a strain capable of efficiently synthesizing 3-HP through theβ-alanine pathway,utilizing glucose as the substrate.The engineered strain CgP36 produced 47.54 g/L 3-HP at a yield of 0.295 g/g glucose during the fed-batch fermentation in a 5 L fermenter,thereby attaining the highest 3-HP titer obtained from glucose via theβ-alanine pathway.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
Background:The purpose of this report is to summarize the evidence supporting supplementation of n-3 polyunsaturated fatty acids(n-3 PUFAs)in adult cancer patients,and to offer a better understanding of the appropriat...Background:The purpose of this report is to summarize the evidence supporting supplementation of n-3 polyunsaturated fatty acids(n-3 PUFAs)in adult cancer patients,and to offer a better understanding of the appropriate use of n-3 PUFAs in the clinical setting.Methods:Numerous databases were searched for guidelines,clinical decision-making documents,systematic reviews,expert consensus statements,and best evidence summaries about the use of n-3 PUFAs in cancer patients from the inception of the database to December 31,2023.Evidence grading and recommendation rating were conducted.The data extracted included the timing of supplementation,symptom management,disease prevention,cost-effectiveness,route of administration,application scenarios,dosage,and safety.Results:The collected data show that n-3 PUFAs are safe for patients receiving chemotherapy who are at risk of malnutrition and cachexia.Moreover,n-3 PUFA supplementation can alleviate the adverse symptoms associated with chemotherapy,extend survival,and improve the quality of life of patients with cancer.Conclusions:The administration of supplementary n-3 PUFAs should be considered based on the patient’s disease stage,treatment plan,nutritional status,and tolerance,as well as the dosage,route and application scenarios.Promoting the clinical use of n-3 PUFAs may improve the outcomes for patients with cancer.展开更多
In order to reveal the effect of 2-hydroxy-3-naphthyl hydroxamic acid(H205)on the flotation behavior and action mechanism of bastnaesite,single-mineral flotation experiments of bastnaesite were conducted.The flotation...In order to reveal the effect of 2-hydroxy-3-naphthyl hydroxamic acid(H205)on the flotation behavior and action mechanism of bastnaesite,single-mineral flotation experiments of bastnaesite were conducted.The flotation recovery of bastnaesites can be achieved more than 90%when the aeration rate is 40 mL/min,the rotational speed is 200 r/min,the H205 dosage is 120 mg/L,and the pulp pH ranges from 7 to 9.The action mechanism of H205 on the surface of bastnaesite was studied by simultaneous thermogravimetry and differential scanning calorimetry(TG-DSC),Zeta potential measurements,Fourier transform-infrared spectra(FT-IR)and X-ray photoelectron spectroscopy(XPS).These analysis results show that under suitable flotation conditions,H205 has an obvious adsorption phenomenon on the surface of bastnaesite.The adsorption involves electrostatic interactions and chemical interactions,namely H205 has a strong collecting ability of bastnaesite due to the synergism of electrostatic adsorption and chemical adsorption.This study systematically reveals the flotation behavior and adsorption mechanism of H205 on the surface of bastnaesite,and provides useful theoretical guidance for efficient flotation separation of bastnaesite.展开更多
BACKGROUND The incidence of malignant tumors in the digestive system is increasing and is a threat to human health.However,the long duration from tumor detection to radical resection,stress responses due to surgical t...BACKGROUND The incidence of malignant tumors in the digestive system is increasing and is a threat to human health.However,the long duration from tumor detection to radical resection,stress responses due to surgical trauma,and insufficient nu-tritional intake increases the risk of malnutrition,immune function reduction,postoperative complications,and intestinal dysfunction among patients.AIM To systematically investigate the association of parenteral nutrition enriched with n-3 polyunsaturated fatty acids(PUFAs)with the nutritional status of patients after gastrointestinal treatment.METHODS Randomized controlled trials associated with PUFA-enriched parenteral nutrition administration in patients with digestive system malignancies were retrieved from online databases such as PubMed,EMBASE,ScienceDirect,Cochrane Li-brary,China Knowledge Network,China VIP,Wanfang,and China Biomedical Literature Database,with the retrieval time from database inception to present.Two researchers independently extracted data.Each article’s bias risk was ass-essed by referring to the Cochrane Handbook version 5.3 criteria and RevMan5.4 was used for data analysis.RESULTS This meta-analysis involved six randomized controlled trials involving a total of 505 cases.Random-effects model analysis indicated remarkably better impro-vements in various inflammatory factors in the study group(P<0.05).Meta-analysis of nutritional indicators revealed that the study group had higher total protein,albumin,and prealbumin levels,as well as lower transferrin levels compared to the control group(P<0.05).Meanwhile,meta-analysis of T-cell subsets revealed no remarkable inter-group difference in post-treatment CD8+cells(P>0.05).Moreover,the meta-analysis identified a notably lower incidence of adverse reactions in the study group(P<0.05).CONCLUSION Administration of PUFAs helps improve the nutritional status of patients with digestive malignancies in the perioperative period.It promotes immune function recovery,reduces the inflammatory response,and decreases the risk of adverse effects.These beneficial effects make it worth investigating and promoting their use in ap-propriate patient populations.However,further validation via high-quality studies with long intervention time and extended follow-up periods is required.展开更多
Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products.CoSe_(2)is a promising nonprecious,efficient cocatalyst for photooxidation,which can facilitate the separati...Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products.CoSe_(2)is a promising nonprecious,efficient cocatalyst for photooxidation,which can facilitate the separation of photogenerated electron–holes,increase the reaction rates,and enhance photocatalytic efficiency.In this work,we synthesized a stable and efficient photocatalysis system of CoSe_(2)/g-C_(3)N_(4)through attaching CoSe_(2)on g-C_(3)N_(4)sheets,with a yield of 50.12%for the selective photooxidation of xylose to xylonic acid.Under light illumination,the photogenerated electrons were prone to migrating from g-C_(3)N_(4)to CoSe_(2)due to the higher work function of CoSe_(2),resulting in the accelerated separation of photogenerated electron–holes and the promoted photooxidation.Herein,this study reveals the unique function of CoSe_(2),which can significantly promote oxygen adsorption,work as an electron sink and accelerate the generation of ·O_(2)^(-),thereby improving the selectivity toward xylonic acid over other by-products.This work provides useful insights into the design of selective photocatalysts by engineering g-C_(3)N_(4)for biomass high-value utilization.展开更多
Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell...Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell carcinoma(ESCC)cells to cisplatin(DDP)is not well understood.Methods:Cell counting kit-8 assay examined how GA affected KYSE30 and TE-1 cell viability.5-Ethynyl-2′-deoxyuridine and TdT-mediated dUTP Nick-End labeling staining detected cell proliferation and apoptosis.Clone formation assay,flow cytometry,Carboxyfluorescein diacetate succinimidyl ester fluorescent probes,and Transwell assay determined cell biological properties,and 2′,7′-Dichlorofluorescin diacetate(DCFH-DA)fluorescent probes detected oxidative stress levels.Signal transducer and activator of transcription 3(STAT3)/Notch pathway protein levels after GA and/or Interleukin-6(IL-6)intervention were examined through Western blot.Furthermore,a model for subcutaneous graft tumors was established in nude mice.Results:GA exerted suppressive effects on cell proliferation,and caused apoptosis of KYSE30 and TE-1 cells.IL-6 intervention activated the STAT3/Notch pathway and promoted the malignant biological properties of ESCC cells.In contrast,GA attenuated the effects of IL-6,while STAT3 or Notch inhibitor further enhanced the effects of GA,suggesting that GA inhibited the IL-6/STAT3/Notch pathway.Not only that,GA promoted oxidative stress and enhanced cell sensitivity to DDP both in vitro and in vivo.Conclusion:GA suppresses the malignant progression of ESCC and enhances cell sensitivity to DDP by hindering the IL-6/STAT3/Notch pathway.展开更多
BACKGROUND Gastric cancer(GC)is a type of cancer which causes high cancer-related mortality.Surgical operation and systematic chemical therapies are primary choices for the treatment of GC patients with advanced stage...BACKGROUND Gastric cancer(GC)is a type of cancer which causes high cancer-related mortality.Surgical operation and systematic chemical therapies are primary choices for the treatment of GC patients with advanced stages,however,the 5-year overall survival is only around 30%.AIM To investigate the role of mesenchymal stem cell(MSC)-derived long non-coding RNAs(lncRNA)NKILA in fatty acid oxidation and chemoresistance in GC cells,mediated through the miR-485-5p/STAT3 pathway.METHODS GC cell lines(AGS and MKN45)were co-cultured with human bone marrowderived MSCs were cultured.The MSC identity was confirmed by flow cytometry(CD73,CD90,CD105>95%positive,CD34,CD45 negative).Co-culture of GC cells and MSCs was performed in Transwell plates,where MSCs were placed in the upper chamber and GC cells in the lower chamber for 72 hours.For transfections,pcDNA-NKILA vectors,shSTAT3,and miR-485-5p mimics were utilized.Colony formation,apoptosis assays(Annexin V/PI staining),sphere formation,and flow cytometry were performed to evaluate cell proliferation,stemness,and chemoresistance.qPCR was used to analyze gene expression(Sox2,Oct4,CD133,LIN28,NKILA),and Western blotting assessed protein levels of stemness markers.Luciferase reporter assays were conducted to confirm miR-485-5p/STAT3 interactions,and biotin-labeled RNA pulldown was used to assess RNA-protein binding.Fatty acid oxidation was evaluated using a CPT1 activity assay andβ-oxidation rate detection.ATP levels were measured to assess the energetic status of GC cells.Clinical GC tissue samples were collected from patients at our hospital for validation.RESULTS MSCs were found to enhance the stemness and chemoresistance of GC cells.Co-culturing MKN45 and AGS cells with MSCs significantly increased sphere-forming ability and the expression of key cancer stem cell markers(SOX2,Oct4,LIN28,CD133),indicating that MSCs promote stem-like properties.Flow cytometry confirmed an enrichment of CD44+and CD133+subpopulations in MSC-treated GC cells.Additionally,MSC co-culture reduced chemotherapy-induced apoptosis and enhanced cell proliferation,suggesting a protective role in chemotherapy resistance.MSC-derived lncRNA NKILA further promoted stemness and chemoresistance,enhancing expression of stem cell markers and protecting cells from oxaliplatin and 5-FU-induced apoptosis.MSC co-culture also induced fatty acid oxidation in GC cells,as shown by increased CPT1 activity,β-oxidation rates,and ATP levels.NKILA mediated these effects by upregulating STAT3,which was confirmed to regulate fatty acid oxidation and chemoresistance.NKILA’s interaction with miR-485-5p further promoted STAT3 expression and fatty acid oxidation,reinforcing its role in maintaining stemness and enhancing chemoresistance.CONCLUSION MSCs enhance the stemness and chemoresistance of GC cells by secreting lncRNA NKILA,which promotes fatty acid oxidation through STAT3 activation.NKILA modulates the miR-485-5p/STAT3 axis,thereby increasing energy metabolism and supporting cancer stem cell properties.Targeting NKILA or the miR-485-5p/STAT3 pathway offers potential therapeutic strategies to overcome chemoresistance in GC.展开更多
Reducing the amount of aluminum chloride needed for the catalytic preparation of high quality mesophase and carbon materials is important and we have found that using terephthalic acid(PTA)as a co-catalyst serves this...Reducing the amount of aluminum chloride needed for the catalytic preparation of high quality mesophase and carbon materials is important and we have found that using terephthalic acid(PTA)as a co-catalyst serves this purpose.By adding 3%(mass fraction)AlCl_(3)and 0.9%(mass fraction)PTA to the coal tar pitch,approximately 90%mesophase was synthesized.The product(M-3-0.9)had a high stacking order(L_(c)=3.1 nm,n=10.14)and aromaticity(0.942).By adding PTA,a larger anisotropy content was produced using a smaller amount of AlCl_(3).The PTA participated in the polycondensation reaction through its own benzene ring structure to increase the catalytic activity.However,when its content was higher than 1.5%,the number of oxygen-containing groups in the product increased which was unfavorable for the aromatic lamellar stacking and gave rise to more isotropic structures.The work opens up a new way to prepare mesophase by a catalytic method.展开更多
Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of high...Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of highβ-oxidation consumption,oxidative susceptibility,and low conversion efficiency.The current study investigated how flax lignans with different degrees of polymerization and glycosylation affect the conversion of ALA to n-3 LCPUFAs in mice over 35 days of administering sunflower phospholipid-stabilized flaxseed oil nanoemulsions.Results showed that flax lignan macromolecules(FLM)increased hepatic protein expression of elongase of very long chain fatty acid 5(Elovl5,24.2%)and fatty acid desaturase 2(Fads2,44.7%),thereby positively regulating ALA conversion pathways and raising serum eicosapentaenoic acid(EPA)levels(52.7%)via liver lipid re-efflux.Secoisolariciresinol diglucoside(SDG)enhanced ALA desaturation by upregulating hepatic protein expression of Fads1(30.4%)and Fads2(45.6%),increasing serum EPA levels(55.9%)and hepatic docosahexaenoic acid(DHA)levels(10%).Secoisolariciresinol(SECO)elevated hepatic protein expression of Elovl2(30.7%),Elovl5(11.7%),Fads1(37.9%),and Fads2(24.1%),but also increased carnitine palmitoyltransferase 1a(45.2%),leading to decreased ALA,EPA,and DHA levels in serum and liver.Therefore,in comparison,FLM and SDG emerge as the dominant structural units that positively regulate the conversion of ALA.These findings lay a groundwork for designing precise dietary delivery systems to enhance the conversion to n-3 LCPUFAs.展开更多
Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a pr...Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a promising strategy.In this study,both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1,but the former has a lower IC_(50)than the latter.Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5,and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells.Furthermore,knockdown of STAT3 expression inhibited proliferation and migration of glioma cells.Next,the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1,p-ERK1/2,p300 were increased by oleanonic acid.The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells.In addition,the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6.Furthermore,oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts,but not in nude mice bearing intracerebral SIRT6-knockdown U87xenografts.In conclusion,oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.展开更多
基金supported by Youth Fund Project of National Natural Science Foundation of China(22308352)China Postdoctoral Science Foundation(2023 M733450)DICP innovation grant(DICP I202335).
文摘Enabling tools are essential for facilitating the methanol bioconversion in Pichia pastoris.However,there is still a relative lack of promoters that can stably express high levels without being affected by the carbon source,which hinders the construction and modification of cell factories containing long metabolic pathways.This study mapped a gene expression intensity library of central metabolic pathways in P.pastoris under methanol and glucose conditions.Through modification of the upstream sequences of promoters,an artificial promoter PS2 was developed with a strong intensity up to 90%of PGAP.By using this promoter,we successfully constructed a hybrid pathway that integrates theβ-alanine and malonyl-CoA pathways for the production of 3-hydroxypro-pionic acid.Further combining rational metabolic engineering strategies,such as optimizing gene copy numbers and blocking byproduct synthesis pathways,the engineered strains CHP9 and CHP20 achieved 3-HP titers of 23 g/L and 22 g/L by using methanol as the sole carbon source.These results indicate that adaptive strength of promoters can facilitate efficient chemical biosynthesis in methanol bioconversion by mitigating glucose repression effects.This work preliminarily explored the expression patterns of genes in the central metabolic pathways of P.pastoris,identified and characterized the intensities of various endogenous promoters,and extended the enabling toolbox for P.pastoris.This result also lays a foundation for the construction of mi-crobial cell factories and the industrial production of 3-HP via methanol bioconversion.
基金funded by Thailand Science Research and Innova-tion Fund Chulalongkorn University(DIS_FF_68_319_2300_087)Research and Researchers for Industries(RRI)jointly administered by Thailand Research Fund[grant numbers PHD61I0031]Innovation Institute,PTT Public Company Limited provided financial support for this research.
文摘Rice straw and sugar cane industrial waste are a plentiful source of lignocellulosic biomass with a high poly-saccharide content,that is hydrolyzed into sugar for microbial growth and their metabolites.3-Hydroxypropionic acid(3-HP)is a promising chemical building block that can be produced from renewable resources.The malonyl-CoA pathway is one of the biosynthetic routes for 3-HP production by expressing the malonyl-CoA reductase gene(mcr).However,the problem of the activity imbalance between the C and N-terminal causes a low con-version rate of malonyl-CoA to 3-hydroxypropionic acid.This study aimed to balance the bi-functional MCR enzyme by dissecting MCR into two fragments and enhancing the supply of intermediates to increase the pro-duction of 3-HP.The recombinant strain harboring the dissected mcr gene showed a 21-fold increase in 3-HP titer compared to the strain carrying the full-length mcr gene.The addition of cerulenin and acetate to the fermented medium enhanced 3-HP yield by 8 times,in which recombinant yeast produced 3-HP up to 10 g/L(0.201 gproduct/gsubstrate).The results of using rice straw hydrolysate as a carbon source indicated that Saccharomyces cerevisiae S2 produced 3-HP of 4.02 g/L,which was 0.074 gproduct/gglucose in the diluted hydrolysate.These findings provide an alternative and sustainable strategy for utilizing lignocellulosic biomass for future 3-HP production at an industrial scale.
基金supported by the Natural Science Foundation of Shanghai(19ZR1472700)the Fok Ying-Tong Education Foundation,China(Grant No.161017)+2 种基金the National Natural Science Foundation of China(Grant No.21776083)the Fundamental Research Funds for the Central Universities(Grant No.22221818014)supported by Open Funding Project of the CAS Key Laboratory of Synthetic Biology.
文摘Syngas,which contains large amount of CO2 as well as H2 and CO,can be convert to acetic acid chemically or biologically.Nowadays,acetic acid become a cost-effective nonfood-based carbon source for value-added biochemical production.In this study,acetic acid and CO2 were used as substrates for the biosynthesis of 3-hydroxypropionic acid(3-HP)in metabolically engineered Escherichia coli carrying heterogeneous acetyl-CoA carboxylase(Acc)from Corynebacterium glutamicum and codon-optimized malonyl-CoA reductase(MCR)from Chloroflexus aurantiacus.Strategies of metabolic engineering included promoting glyoxylate shunt pathway,inhibiting fatty acid synthesis,dynamic regulating of TCA cycle,and enhancing the assimilation of acetic acid.The engineered strain LNY07(M*DA)accumulated 15.8 g/L of 3-HP with the yield of 0.71 g/g in 48 h by whole-cell biocatalysis.Then,syngas-derived acetic acid was used as substrate instead of pure acetic acid.The concentration of 3-HP reached 11.2 g/L with the yield of 0.55 g/g in LNY07(M*DA).The results could potentially contribute to the future development of an industrial bioprocess of 3-HP production from syngas-derived acetic acid.
基金supported by the National Key Research and Development Program of China(2021YFC2100700)the National Natural Science Foundation of China(NSFC-21776208).
文摘3-Hydroxypropionic Acid(3-HP)is recognized as a high value-added chemical with a broad range of applications.Among the various biosynthetic pathways for 3-HP production,theβ-alanine pathway is particularly noteworthy due to its capacity to generate 3-HP from glucose at a high theoretical titer.In this study,theβ-alanine biosynthesis pathway was introduced and optimized in Corynebacterium glutamicum.By strategically regulating the supply of precursors,we successfully engineered a strain capable of efficiently synthesizing 3-HP through theβ-alanine pathway,utilizing glucose as the substrate.The engineered strain CgP36 produced 47.54 g/L 3-HP at a yield of 0.295 g/g glucose during the fed-batch fermentation in a 5 L fermenter,thereby attaining the highest 3-HP titer obtained from glucose via theβ-alanine pathway.
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Background:The purpose of this report is to summarize the evidence supporting supplementation of n-3 polyunsaturated fatty acids(n-3 PUFAs)in adult cancer patients,and to offer a better understanding of the appropriate use of n-3 PUFAs in the clinical setting.Methods:Numerous databases were searched for guidelines,clinical decision-making documents,systematic reviews,expert consensus statements,and best evidence summaries about the use of n-3 PUFAs in cancer patients from the inception of the database to December 31,2023.Evidence grading and recommendation rating were conducted.The data extracted included the timing of supplementation,symptom management,disease prevention,cost-effectiveness,route of administration,application scenarios,dosage,and safety.Results:The collected data show that n-3 PUFAs are safe for patients receiving chemotherapy who are at risk of malnutrition and cachexia.Moreover,n-3 PUFA supplementation can alleviate the adverse symptoms associated with chemotherapy,extend survival,and improve the quality of life of patients with cancer.Conclusions:The administration of supplementary n-3 PUFAs should be considered based on the patient’s disease stage,treatment plan,nutritional status,and tolerance,as well as the dosage,route and application scenarios.Promoting the clinical use of n-3 PUFAs may improve the outcomes for patients with cancer.
基金Project supported by the Natural Science Foundation Innovation Group Project of Hubei Province(2023AFA044)the National Natural Science Foundation of China(52222405)+1 种基金the Science and Technology Research Project of Education Department of Hubei Province(Q20221505)the China Postdoctoral Science(2023M731041)。
文摘In order to reveal the effect of 2-hydroxy-3-naphthyl hydroxamic acid(H205)on the flotation behavior and action mechanism of bastnaesite,single-mineral flotation experiments of bastnaesite were conducted.The flotation recovery of bastnaesites can be achieved more than 90%when the aeration rate is 40 mL/min,the rotational speed is 200 r/min,the H205 dosage is 120 mg/L,and the pulp pH ranges from 7 to 9.The action mechanism of H205 on the surface of bastnaesite was studied by simultaneous thermogravimetry and differential scanning calorimetry(TG-DSC),Zeta potential measurements,Fourier transform-infrared spectra(FT-IR)and X-ray photoelectron spectroscopy(XPS).These analysis results show that under suitable flotation conditions,H205 has an obvious adsorption phenomenon on the surface of bastnaesite.The adsorption involves electrostatic interactions and chemical interactions,namely H205 has a strong collecting ability of bastnaesite due to the synergism of electrostatic adsorption and chemical adsorption.This study systematically reveals the flotation behavior and adsorption mechanism of H205 on the surface of bastnaesite,and provides useful theoretical guidance for efficient flotation separation of bastnaesite.
基金Supported by the Guangxi Medical and Health Key(Cultivation)Discipline Construction ProjectGuilin Scientific Research and Technology Development Program Project,No.20210227-7-8.
文摘BACKGROUND The incidence of malignant tumors in the digestive system is increasing and is a threat to human health.However,the long duration from tumor detection to radical resection,stress responses due to surgical trauma,and insufficient nu-tritional intake increases the risk of malnutrition,immune function reduction,postoperative complications,and intestinal dysfunction among patients.AIM To systematically investigate the association of parenteral nutrition enriched with n-3 polyunsaturated fatty acids(PUFAs)with the nutritional status of patients after gastrointestinal treatment.METHODS Randomized controlled trials associated with PUFA-enriched parenteral nutrition administration in patients with digestive system malignancies were retrieved from online databases such as PubMed,EMBASE,ScienceDirect,Cochrane Li-brary,China Knowledge Network,China VIP,Wanfang,and China Biomedical Literature Database,with the retrieval time from database inception to present.Two researchers independently extracted data.Each article’s bias risk was ass-essed by referring to the Cochrane Handbook version 5.3 criteria and RevMan5.4 was used for data analysis.RESULTS This meta-analysis involved six randomized controlled trials involving a total of 505 cases.Random-effects model analysis indicated remarkably better impro-vements in various inflammatory factors in the study group(P<0.05).Meta-analysis of nutritional indicators revealed that the study group had higher total protein,albumin,and prealbumin levels,as well as lower transferrin levels compared to the control group(P<0.05).Meanwhile,meta-analysis of T-cell subsets revealed no remarkable inter-group difference in post-treatment CD8+cells(P>0.05).Moreover,the meta-analysis identified a notably lower incidence of adverse reactions in the study group(P<0.05).CONCLUSION Administration of PUFAs helps improve the nutritional status of patients with digestive malignancies in the perioperative period.It promotes immune function recovery,reduces the inflammatory response,and decreases the risk of adverse effects.These beneficial effects make it worth investigating and promoting their use in ap-propriate patient populations.However,further validation via high-quality studies with long intervention time and extended follow-up periods is required.
基金financial support by National Key Research and Development Project(Grant No.2023YFE0109600)Guangzhou Key Research and Development Program(Grant No.2023B03J1330)+5 种基金National Program for Support of Topnotch Young Professionals(Grant No.x2qsA4210090)Guangzhou Basic and Applied Basic Research Foundation(Grant No.2024A04J3413)National Natural Science Foundation of China(Grant No.32201499)State Key Laboratory of Pulp and Paper Engineering(Grant Nos.2023PY01 and 202215)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2023A1515012519 and 2023B1515040013)China Postdoctoral Science Foundation(Grant No.2023M732021).
文摘Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products.CoSe_(2)is a promising nonprecious,efficient cocatalyst for photooxidation,which can facilitate the separation of photogenerated electron–holes,increase the reaction rates,and enhance photocatalytic efficiency.In this work,we synthesized a stable and efficient photocatalysis system of CoSe_(2)/g-C_(3)N_(4)through attaching CoSe_(2)on g-C_(3)N_(4)sheets,with a yield of 50.12%for the selective photooxidation of xylose to xylonic acid.Under light illumination,the photogenerated electrons were prone to migrating from g-C_(3)N_(4)to CoSe_(2)due to the higher work function of CoSe_(2),resulting in the accelerated separation of photogenerated electron–holes and the promoted photooxidation.Herein,this study reveals the unique function of CoSe_(2),which can significantly promote oxygen adsorption,work as an electron sink and accelerate the generation of ·O_(2)^(-),thereby improving the selectivity toward xylonic acid over other by-products.This work provides useful insights into the design of selective photocatalysts by engineering g-C_(3)N_(4)for biomass high-value utilization.
基金Mechanistic Investigation into the Extraction,Purification,and Anti-Esophageal Cancer Effects of Gallic Acid Derived from Rhodiola crenulata(YLUKLM2023001).
文摘Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell carcinoma(ESCC)cells to cisplatin(DDP)is not well understood.Methods:Cell counting kit-8 assay examined how GA affected KYSE30 and TE-1 cell viability.5-Ethynyl-2′-deoxyuridine and TdT-mediated dUTP Nick-End labeling staining detected cell proliferation and apoptosis.Clone formation assay,flow cytometry,Carboxyfluorescein diacetate succinimidyl ester fluorescent probes,and Transwell assay determined cell biological properties,and 2′,7′-Dichlorofluorescin diacetate(DCFH-DA)fluorescent probes detected oxidative stress levels.Signal transducer and activator of transcription 3(STAT3)/Notch pathway protein levels after GA and/or Interleukin-6(IL-6)intervention were examined through Western blot.Furthermore,a model for subcutaneous graft tumors was established in nude mice.Results:GA exerted suppressive effects on cell proliferation,and caused apoptosis of KYSE30 and TE-1 cells.IL-6 intervention activated the STAT3/Notch pathway and promoted the malignant biological properties of ESCC cells.In contrast,GA attenuated the effects of IL-6,while STAT3 or Notch inhibitor further enhanced the effects of GA,suggesting that GA inhibited the IL-6/STAT3/Notch pathway.Not only that,GA promoted oxidative stress and enhanced cell sensitivity to DDP both in vitro and in vivo.Conclusion:GA suppresses the malignant progression of ESCC and enhances cell sensitivity to DDP by hindering the IL-6/STAT3/Notch pathway.
文摘BACKGROUND Gastric cancer(GC)is a type of cancer which causes high cancer-related mortality.Surgical operation and systematic chemical therapies are primary choices for the treatment of GC patients with advanced stages,however,the 5-year overall survival is only around 30%.AIM To investigate the role of mesenchymal stem cell(MSC)-derived long non-coding RNAs(lncRNA)NKILA in fatty acid oxidation and chemoresistance in GC cells,mediated through the miR-485-5p/STAT3 pathway.METHODS GC cell lines(AGS and MKN45)were co-cultured with human bone marrowderived MSCs were cultured.The MSC identity was confirmed by flow cytometry(CD73,CD90,CD105>95%positive,CD34,CD45 negative).Co-culture of GC cells and MSCs was performed in Transwell plates,where MSCs were placed in the upper chamber and GC cells in the lower chamber for 72 hours.For transfections,pcDNA-NKILA vectors,shSTAT3,and miR-485-5p mimics were utilized.Colony formation,apoptosis assays(Annexin V/PI staining),sphere formation,and flow cytometry were performed to evaluate cell proliferation,stemness,and chemoresistance.qPCR was used to analyze gene expression(Sox2,Oct4,CD133,LIN28,NKILA),and Western blotting assessed protein levels of stemness markers.Luciferase reporter assays were conducted to confirm miR-485-5p/STAT3 interactions,and biotin-labeled RNA pulldown was used to assess RNA-protein binding.Fatty acid oxidation was evaluated using a CPT1 activity assay andβ-oxidation rate detection.ATP levels were measured to assess the energetic status of GC cells.Clinical GC tissue samples were collected from patients at our hospital for validation.RESULTS MSCs were found to enhance the stemness and chemoresistance of GC cells.Co-culturing MKN45 and AGS cells with MSCs significantly increased sphere-forming ability and the expression of key cancer stem cell markers(SOX2,Oct4,LIN28,CD133),indicating that MSCs promote stem-like properties.Flow cytometry confirmed an enrichment of CD44+and CD133+subpopulations in MSC-treated GC cells.Additionally,MSC co-culture reduced chemotherapy-induced apoptosis and enhanced cell proliferation,suggesting a protective role in chemotherapy resistance.MSC-derived lncRNA NKILA further promoted stemness and chemoresistance,enhancing expression of stem cell markers and protecting cells from oxaliplatin and 5-FU-induced apoptosis.MSC co-culture also induced fatty acid oxidation in GC cells,as shown by increased CPT1 activity,β-oxidation rates,and ATP levels.NKILA mediated these effects by upregulating STAT3,which was confirmed to regulate fatty acid oxidation and chemoresistance.NKILA’s interaction with miR-485-5p further promoted STAT3 expression and fatty acid oxidation,reinforcing its role in maintaining stemness and enhancing chemoresistance.CONCLUSION MSCs enhance the stemness and chemoresistance of GC cells by secreting lncRNA NKILA,which promotes fatty acid oxidation through STAT3 activation.NKILA modulates the miR-485-5p/STAT3 axis,thereby increasing energy metabolism and supporting cancer stem cell properties.Targeting NKILA or the miR-485-5p/STAT3 pathway offers potential therapeutic strategies to overcome chemoresistance in GC.
文摘Reducing the amount of aluminum chloride needed for the catalytic preparation of high quality mesophase and carbon materials is important and we have found that using terephthalic acid(PTA)as a co-catalyst serves this purpose.By adding 3%(mass fraction)AlCl_(3)and 0.9%(mass fraction)PTA to the coal tar pitch,approximately 90%mesophase was synthesized.The product(M-3-0.9)had a high stacking order(L_(c)=3.1 nm,n=10.14)and aromaticity(0.942).By adding PTA,a larger anisotropy content was produced using a smaller amount of AlCl_(3).The PTA participated in the polycondensation reaction through its own benzene ring structure to increase the catalytic activity.However,when its content was higher than 1.5%,the number of oxygen-containing groups in the product increased which was unfavorable for the aromatic lamellar stacking and gave rise to more isotropic structures.The work opens up a new way to prepare mesophase by a catalytic method.
基金supported by grants from the National Natural Science Foundation of China(32072267)China Agriculture Research System(CARS-14)+1 种基金National Key Research and Development Program of China(2023YFD2100404)the Innovation Group Project of Hubei Province(2023AFA042).
文摘Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of highβ-oxidation consumption,oxidative susceptibility,and low conversion efficiency.The current study investigated how flax lignans with different degrees of polymerization and glycosylation affect the conversion of ALA to n-3 LCPUFAs in mice over 35 days of administering sunflower phospholipid-stabilized flaxseed oil nanoemulsions.Results showed that flax lignan macromolecules(FLM)increased hepatic protein expression of elongase of very long chain fatty acid 5(Elovl5,24.2%)and fatty acid desaturase 2(Fads2,44.7%),thereby positively regulating ALA conversion pathways and raising serum eicosapentaenoic acid(EPA)levels(52.7%)via liver lipid re-efflux.Secoisolariciresinol diglucoside(SDG)enhanced ALA desaturation by upregulating hepatic protein expression of Fads1(30.4%)and Fads2(45.6%),increasing serum EPA levels(55.9%)and hepatic docosahexaenoic acid(DHA)levels(10%).Secoisolariciresinol(SECO)elevated hepatic protein expression of Elovl2(30.7%),Elovl5(11.7%),Fads1(37.9%),and Fads2(24.1%),but also increased carnitine palmitoyltransferase 1a(45.2%),leading to decreased ALA,EPA,and DHA levels in serum and liver.Therefore,in comparison,FLM and SDG emerge as the dominant structural units that positively regulate the conversion of ALA.These findings lay a groundwork for designing precise dietary delivery systems to enhance the conversion to n-3 LCPUFAs.
基金supported by the National Natural Science Foundation of China(81560059,81760058,8160042,and 31800891)。
文摘Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a promising strategy.In this study,both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1,but the former has a lower IC_(50)than the latter.Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5,and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells.Furthermore,knockdown of STAT3 expression inhibited proliferation and migration of glioma cells.Next,the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1,p-ERK1/2,p300 were increased by oleanonic acid.The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells.In addition,the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6.Furthermore,oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts,but not in nude mice bearing intracerebral SIRT6-knockdown U87xenografts.In conclusion,oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.
