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Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease:beyond the role of amyloid beta 被引量:2
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作者 Madia Lozupone Francesco Panza 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期80-83,共4页
The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully unders... The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype. 展开更多
关键词 Alzheimer's disease AMYLOID-BETA apolipoprotein E DEMENTIA glymphatic transport LIPIDS neuropsychiatric symptoms neurovascular unit tau protein
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Optimizing the Bacillus thuringiensis(Bt)protein concentration in cotton:Coordinated application of exogenous amino acids and EDTA to reduce spatiotemporal variability in boll and leaf toxins 被引量:1
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作者 Zhenyu Liu Shu Dong +8 位作者 Yuting Liu Hanjia Li Fuqin Zhou Junfeng Ding Zixu Zhao Yinglong Chen Xiang Zhang Yuan Chen Dehua Chen 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第10期3419-3436,共18页
During the boll formation stage,cotton bolls exhibit the lowest expression of Bacillus thuringiensis(Bt)insecticidal proteins.Resistance to insects varies notably among different organs,which poses challenges for cont... During the boll formation stage,cotton bolls exhibit the lowest expression of Bacillus thuringiensis(Bt)insecticidal proteins.Resistance to insects varies notably among different organs,which poses challenges for controlling cotton bollworms.Consequently,an experimental strategy was designed in the 2020-2021 cotton growing season to coordinate the enhancement of protein synthesis and the attenuation of degradation.Two Bt cultivars of Gossypium hirsutum,namely the hybrid Sikang 3 and the conventional Sikang 1,were used as test materials.Three treatments were applied at the peak flowering period:CK(the control),T1(amino acids),and T2(amino acids and EDTA).The results show that,in comparison to the CK group,the Bt protein contents were significantly increased in both cotton bolls and their subtending leaves under the T1 and T2 treatments.The maximum levels of increase observed were 67.5%in cotton bolls and 21.7%in leaves.Moreover,the disparity in Bt protein content between cotton bolls and their subtending leaves notably decreased by 31.2%.Correlation analysis suggested that the primary physiological mechanisms for augmenting Bt protein content involve increased protein synthesis and reduced protein catabolism,which are independent of Bt gene expression levels.Stepwise regression and path analysis revealed that elevating the soluble protein content and transaminase activity,while reducing the catabolic enzyme activities,are instrumental in enhancing the Bt protein content.Consequently,the coordinated application of amino acids and EDTA emerges as a strategy that can improve the overall resistance of Bt cotton and mitigate the spatiotemporal variations in Bt toxin concentrations in both cotton bolls and leaves. 展开更多
关键词 Gossypium hirsutum Bt cotton insecticidal protein bolls and their subtending leaves nitrogen metabolism
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Systematic Analysis of Post-Translational Modifications for Increased Longevity of Biotherapeutic Proteins
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作者 Justin Kim Karanveer Sadiora 《Computational Molecular Bioscience》 2024年第3期125-145,共21页
Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and... Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins. 展开更多
关键词 Post-Translational Modification protein-Based Therapeutics Therapeutic Half-Life protein Aggregation protein Reception
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Structural and Functional Annotation of Hypothetical Protein of Fusobacterium nucleatum Strain MJR7757B: An in Silico Approach
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作者 Md. Isrfil Hossen Fouzia Mostafa +3 位作者 Nusrat Jahan Jannatul Ferdaus Amgad Albahi Sayed Mashequl Bari 《Computational Molecular Bioscience》 2024年第1期17-33,共17页
Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, H... Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, HMPREF3221_01179, derived from F. nucleatum strain MJR7757B, employing various computational methods to anticipate both its structure and functional characteristics. NCBI conserved domain analysis, NCBI BLASTp and MEGA Phylogenetic tree study characterize the target protein as an outer membrane efflux protein (ToIC family) which facilitate the bacterial transmembrane transport. With a molecular weight of 52120.02 Da, an isoelectric point (pI) of 8.33, and an instability index of 29.47, the protein is anticipated to exhibit good solubility in the extracellular space and crucial stability for pharmaceutical applications. The protein’s structure meets quality standards during the construction and refinement of its 3D model. The efflux inhibitor Arginine beta-naphthylamide exhibits a significant binding affinity (-7.1 kcal/mol) to the binding site of the target protein. The in-silico analysis improves the understanding of the protein and facilitates future investigations into therapeutic medication. 展开更多
关键词 Fusobacterium nucleatum In Silico BACTERIA Hypothetical protein Molecular Docking
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Selection and application of four QTLs for grain protein content in modern wheat cultivars
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作者 Zihui Liu Xiangjun Lai +4 位作者 Yijin Chen Peng Zhao Xiaoming Wang Wanquan Ji Shengbao Xu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第8期2557-2570,共14页
The grain protein content(GPC)is the key parameter for wheat grain nutritional quality.This study conducted a resampling GWAS analysis using 406 wheat accessions across eight environments,and identified four previousl... The grain protein content(GPC)is the key parameter for wheat grain nutritional quality.This study conducted a resampling GWAS analysis using 406 wheat accessions across eight environments,and identified four previously reported GPC QTLs.An analysis of 87 landraces and 259 modern cultivars revealed the loss of superior GPC haplotypes,especially in Chinese cultivars.These haplotypes were preferentially adopted in different agroecological zones and had broad effects on wheat yield and agronomic traits.Most GPC QTLs did not significantly reduce yield,suggesting that high GPC can be achieved without a yield penalty.The results of this study provide a reference for future GPC breeding in wheat using the four identified QTLs. 展开更多
关键词 BREEDING grain protein content haplotype selection and application WHEAT
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Effects of galactooligosaccharide glycation on the functional properties of soy protein isolate and its application in noodles
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作者 Meiyue Wang Guanhao Bu +3 位作者 Yufei Xing Mengke Ren Yang Wang Yijing Xie 《Grain & Oil Science and Technology》 CAS 2024年第3期159-167,共9页
Soybean protein has high nutritional value, but its functional properties are easily affected by external factors,which limits its application in food industry. In the study, soybean protein isolate(SPI) was modified ... Soybean protein has high nutritional value, but its functional properties are easily affected by external factors,which limits its application in food industry. In the study, soybean protein isolate(SPI) was modified by dry heat glycation of galactooligosaccharides(GOS). The gel properties, antioxidant properties and structural changes of SPI-GOS conjugates were investigated. The application of SPI-GOS conjugates in noodles was also explored. The results observed that the glycation degree of SPI increased with the increasing reaction time. SDS-PAGE and spectral analysis showed the changes of spatial conformation of SPI after glycation. The antioxidant activity of SPI increased after glycation and DPPH radical scavenging activity of SPI-GOS peaked at 48 h of reaction. The hardness, elasticity and resilience of soybean protein gel reached their relative maximum at 48 h, 48 h and 12 h of glycation reaction, respectively. Moreover, the appropriate addition of glycated SPI improved the quality of noodles. The noodles with 4% addition of SPI-GOS had higher hardness, elasticity and tensile properties. This study will provide an effective method to modify soybean protein and expand the use of soybean protein in food industry. 展开更多
关键词 Soy protein isolate Glycation GALACTOOLIGOSACCHARIDE Functional properties NOODLES
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A Review on Characteristics, Extraction Methods and Applications of Renewable Insect Protein
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作者 Adelya Khayrova Sergey Lopatin Valery Varlamov 《Journal of Renewable Materials》 EI CAS 2024年第5期923-950,共28页
Due to the expected rise in the world population,an increase in the requirements for quality and safety of food and feed is expected,which leads to the growing demand for new sources of sustainable and renewable prote... Due to the expected rise in the world population,an increase in the requirements for quality and safety of food and feed is expected,which leads to the growing demand for new sources of sustainable and renewable protein.Insect protein is gaining importance as a renewable material for several reasons,reflecting its potential contribu-tions to sustainability,resource efficiency,and environmental conservation.Some insect species are known to be able to efficiently convert organic waste into high-value products such as protein,requiring less land and water compared to traditional livestock.In addition,insect farming produces fewer greenhouse gas emissions,contri-buting to mitigating climate change.Insects are considered as a major potential alternative to animal or plant protein due to their many nutritional benefits,including high protein,mineral,and vitamin contents.On average,the protein content of insects ranges between 35%and 60%dry weight,which exceeds plant protein sources,such as cereal,soybeans,and lentils.As the acceptance of insect protein grows and technologies advance,the food and feed industries continue to explore and expand their applications,offering consumers diverse and sustainable pro-tein choices.In this review,we discuss the recentfindings relating to insect protein focusing on its characteristics,extraction methods,applications,and opportunities along with some trade-offs and uncertainties. 展开更多
关键词 Circular economy waste utilisation protein INSECT Hermetia illucens
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Antihypertensive effects of whey protein hydrolysate involve reshaping the gut microbiome in spontaneously hypertension rats
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作者 Peipei Dou Xiaoyi Li +6 位作者 Xiaoxiao Zou Kai Wang Lei Yao Zhuo Sun Hui Hong Yongkang Luo Yuqing Tan 《Food Science and Human Wellness》 SCIE CAS CSCD 2024年第4期1974-1986,共13页
Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated... Novel angiotensin-converting enzyme(ACE)inhibitory peptides were identified from whey protein hydrolysates(WPH)in vitro in our previous study and the antihypertensive abilities of WPH in vivo were further investigated in the current study.Results indicated that WPH significantly inhibited the development of high blood pressure and tissue injuries caused by hypertension.WPH inhibited ACE activity(20.81%,P<0.01),and reduced renin concentration(P<0.05),thereby reducing systolic blood pressure(SBP)(12.63%,P<0.05)in spontaneously hypertensive rats.The increased Akkermansia,Bacteroides,and Lactobacillus abundance promoted high short chain fatty acid content in feces after WPH intervention.These changes jointly contributed to low blood pressure.The heart weight and cardiomyocyte injuries(hypertrophy and degeneration)were alleviated by WPH.The proteomic results revealed that 19 protein expressions in the heart mainly associated with the wingless/integrated(Wnt)signaling pathway and Apelin signaling pathway were altered after WPH supplementation.Notably,WPH alleviated serum oxidative stress,indicated by the decreased malondialdehyde content(P<0.01),enhanced total antioxidant capacity(P<0.01)and superoxide dismutase activity(P<0.01).The current study suggests that WPH exhibit promising antihypertensive abilities in vivo and could be a potential alternative for antihypertensive dietary supplements. 展开更多
关键词 Whey protein hydrolysate ANTIHYPERTENSION Short chain fatty acids Gut microbiome
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Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics
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作者 Patanachai K.Limpikirati Sorrayut Mongkoltipparat +7 位作者 Thinnaphat Denchaipradit Nathathai Siwasophonpong Wudthipong Pornnopparat Parawan Ramanandana Phumrapee Pianpaktr Songsak Tongchusak Maoxin Tim Tian Trairak Pisitkun 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第6期785-804,共20页
In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding ... In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control. 展开更多
关键词 Biopharmaceutical analysis Biopharmaceutical quality control Biopharmaceutical specifications Monoclonal antibodies protein therapeutics Regulatory science
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Better understanding of c-reactive protein and leukocytes in psychiatric inpatients with affective disorders:A biopsychosocial approach
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作者 Felix Kölblinger Elena MD Schönthaler +6 位作者 Andreas Baranyi Tatjana Stross Frederike T Fellendorf Dirk von Lewinski Robert Queissner Eva Z Reininghaus Nina Dalkner 《World Journal of Clinical Cases》 SCIE 2024年第19期3824-3836,共13页
BACKGROUND Affective disorders(AD)have been linked to inflammatory processes,although the underlying mechanisms of this relationship are still not fully elucidated.It is hypothesized that demographic,somatic,lifestyle... BACKGROUND Affective disorders(AD)have been linked to inflammatory processes,although the underlying mechanisms of this relationship are still not fully elucidated.It is hypothesized that demographic,somatic,lifestyle,and personality variables predict inflammatory parameters in AD.AIM To identify biopsychosocial factors contributing to inflammation in AD measured with two parameters,C-reactive protein(CRP)and leukocytes.METHODS This observational study investigated 186 hospital inpatients diagnosed with AD using demographic parameters,serum inflammatory markers,somatic variables,psychological questionnaires,and lifestyle parameters.Hierarchical regression analyses were used to predict inflammatory markers from demographic,somatic,lifestyle,and personality variables.RESULTS Analyses showed that 33.8%of the variance of CRP was explained by body mass index and other somatic medication(e.g.anti-diabetics),age and education,and age of affective disorder diagnosis.For leukocytes,20.1%of the variance was explained by smoking,diet,metabolic syndrome(MetS),and anti-inflammatory medication(e.g.non-steroidal anti-inflammatory drugs).Other psychiatric or behavioural variables did not reach significance.CONCLUSION Metabolic components seem important,with mounting evidence for a metabolic affective disorder subtype.Lifestyle modifications and psychoeducation should be employed to prevent or treat MetS in AD. 展开更多
关键词 Affective disorders C-reactive protein Leukocytes Metabolic syndrome Health behaviour PERSONALITY
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Jiaohong pills attenuate neuroinflammation and amyloid-βprotein-induced cognitive deficits by modulating the mitogen-activated protein kinase/nuclear factor kappa-B pathway
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作者 Hong Zhang Weiyan Cai +9 位作者 Lijinchuan Dong Qing Yang Qi Li Qingsen Ran Li Liu Yajie Wang Yujie Li Xiaogang Weng Xiaoxin Zhu Ying Chen 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第3期222-233,共12页
Background:Jiaohong pills(JHP)consist of Pericarpium Zanthoxyli(PZ)and Radix Rehmanniae,two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive dec... Background:Jiaohong pills(JHP)consist of Pericarpium Zanthoxyli(PZ)and Radix Rehmanniae,two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment.However,the precise mechanisms underlying the beneficial effects remain elusive.Here,research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease.Methods:BV-2 cell inflammation was induced by lipopolysaccharide.AD mice were administered amyloid-β(Aβ).Behavioral experiments were used to evaluate learning and memory ability.The levels of nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)were detected using enzymelinked immunosorbent assay(ELISA).The protein expressions of inducible nitric oxide synthase(iNOS)and the phosphorylation level of mitogen-activated protein kinase(MAPK)and nuclear factor kappa-B(NF-κB)were detected using Western blot.Nissl staining was used to detect neuronal degeneration.Results:The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO,IL-1β,TNF-α,and iNOS;increased the expression level of IL-10;and significantly decreased the phosphorylation levels of MAPK and NF-κB.These inhibitory effects were further confirmed in the AD mouse model.Meanwhile,JHP improved learning and memory function in AD mice,reduced neuronal damage,and enriched the Nissl bodies in the hippocampus.Moreover,IL-1βand TNF-αin the cortex were significantly downregulated after JHP administration,whereas IL-10showed increased expression.Conclusions:It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF-κB signaling pathway. 展开更多
关键词 amyloid-β(Aβ)protein BV2 NEUROINFLAMMATION Pericarpium Zanthoxyli Radix Rehmanniae
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Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer malignant behaviors by activation of target of rapamycin kinase/autophagy signaling
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作者 Juan Sun Jin-Xiu Zhang +8 位作者 Meng-Shi Li Meng-Bin Qin Ruo-Xi Cheng Qing-Ru Wu Qiu-Ling Chen Dan Yang Cun Liao Shi-Quan Liu Jie-An Huang 《World Journal of Gastroenterology》 SCIE CAS 2024年第26期3229-3246,共18页
BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorecta... BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.AIM To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis.After overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were assayed.Tumor cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro results.RESULTS MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis.Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC cells.At the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO cells.In contrast,the opposite results were observed in tumor cells with MOB3B knockdown.The nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.CONCLUSION Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling. 展开更多
关键词 Colorectal cancer Monopolar spindle-binding protein 3B Mechanistic target of rapamycin kinase AUTOPHAGY Prognosis
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Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma
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作者 Yan Li William Lee +3 位作者 Zhen-Gang Zhao Yi Liu Hao Cui Hao-Yu Wang 《World Journal of Clinical Oncology》 2024年第1期130-144,共15页
BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell... BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC. 展开更多
关键词 Hepatocellular carcinoma Fatty acid binding protein Novel target AMPLIFICATION Correlated expression
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Potential regulatory mechanism and clinical significance of synaptotagmin binding cytoplasmic RNA interacting protein in colorectal cancer
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作者 Hui Li He-Qing Huang +8 位作者 Zhi-Guang Huang Rong-Quan He Ye-Ying Fang Rui Song Jia-Yuan Luo Da-Tong Zeng Kai Qin Dan-Ming Wei Gang Chen 《World Journal of Clinical Oncology》 2024年第11期1412-1427,共16页
BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetica... BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetically targeting some genes.Our study will examine the expression,potential effect,biological function and clinical value of SYNCRIP in CRC.AIM To examine the expression,potential effect,biological function and clinical value METHODS The expression of SYNCRIP was examined by immunohistochemistry arrays and high-throughput data.The effect of SYNCRIP gene in CRC cell growth was evaluated by CRISPR-Cas9 technology.The target genes of SYNCRIP were calculated using various algorithms,and the molecular mechanism of SYNCRIP in CRC was explored by mutation analysis and pathway analysis.The clinical value of SYNCRIP in prognosis and radiotherapy was revealed via evidence-based medicine methods.RESULTS The protein and mRNA levels of SYNCRIP were both highly expressed in CRC samples compared to nontumorous tissue based on 330 immunohistochemistry arrays and 3640 CRC samples.Cells grew more slowly in eleven CRC cell lines after knocking out the SYNCRIP gene.SYNCRIP could epigenetically target genes to promote the occurrence and development of CRC by boosting the cell cycle and affecting the tumor microenvironment.In addition,CRC patients with high SYNCRIP expression are more sensitive to radiotherapy.CONCLUSION SYNCRIP is upregulated in CRC,and highly expressed SYNCRIP can accelerate CRC cell division by exerting its epigenetic regulatory effects.In addition,SYNCRIP is expected to become a potential biomarker to predict the effect of radiotherapy. 展开更多
关键词 Synaptotagmin binding cytoplasmic RNA interacting protein Colorectal cancer Radiotherapy Cell mitosis Immune microenvironment
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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice
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作者 Zhengwei Hu Jing Yang +7 位作者 Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu 《Neural Regeneration Research》 SCIE CAS 2025年第1期253-264,共12页
The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed... The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease. 展开更多
关键词 adeno-associated virus Alzheimer’s disease apP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy
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Targeting neuronal PAS domain protein 2 and KN motif/ankyrin repeat domains 1:Advances in type 2 diabetes therapy
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作者 Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng 《World Journal of Diabetes》 SCIE 2024年第11期2173-2176,共4页
This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore t... This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment strategies.We offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D. 展开更多
关键词 Type 2 diabetes Neuronal PAS domain protein 2 KN motif and ankyrin repeat domain 1 β-cell dysfunction Therapeutic target
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活性碳负载纳米金属氧化物对AP热分解的催化性能
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作者 石小兵 谢五喜 +5 位作者 李洋 黄海涛 胥会祥 李勇宏 曾丽媛 庞维强 《火炸药学报》 EI CAS CSCD 北大核心 2024年第5期475-484,I0006,共11页
采用水热法制备了两种纳米金属氧化物(纳米CuO和纳米Fe_(2)O_(3)颗粒),将纳米CuO和纳米Fe_(2)O_(3)负载在活性碳上,制备成CuO@C、Fe_(2)O_(3)@C复合材料,并将其作为催化剂与高氯酸铵(AP)混合制备成混合物样品AP/CuO、AP/CuO@C、AP/Fe_(2... 采用水热法制备了两种纳米金属氧化物(纳米CuO和纳米Fe_(2)O_(3)颗粒),将纳米CuO和纳米Fe_(2)O_(3)负载在活性碳上,制备成CuO@C、Fe_(2)O_(3)@C复合材料,并将其作为催化剂与高氯酸铵(AP)混合制备成混合物样品AP/CuO、AP/CuO@C、AP/Fe_(2)O_(3)、AP/Fe_(2)O_(3)@C;通过扫描电子显微镜(SEM)、差示扫描量热仪(DSC)、热重-微分热重分析(TG-DTG)和热重-红外光谱(TG-FTIR)联用等技术研究了4种催化剂对AP热分解的催化机理及分解动力学特性。结果表明,4种催化剂均将AP的两步分解反应催化为单放热峰,在5 K/min升温速率下,AP的分解峰温较纯AP分别提前90.1、73.4、65.4和69℃;AP/CuO@C分解主要气相产物有HCl、CO_(2)、N_(2)O、HNO_(3)和NO_(2),其中NO_(2)含量最高;AP/Fe_(2)O_(3)@C分解主要气相产物中CO_(2)含量显著提升,NO_(2)含量稍有降低。 展开更多
关键词 物理化学 水热法 催化性能 ap 分解动力学 气相产物 金属氧化物 活性炭 燃烧催化剂
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面向一致覆盖的无蜂窝和传统蜂窝共存网络AP部署优化
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作者 姜静 陶莎 +3 位作者 王伟 褚宏云 Worakrin Sutthiphan 李春国 《电子与信息学报》 EI CAS CSCD 北大核心 2024年第6期2352-2360,共9页
为了解决传统蜂窝网络中用户体验剧烈波动的问题,无蜂窝和传统蜂窝共存网络将大量接入点(Access Point,AP)部署到传统蜂窝网络中,显著改善边缘用户和盲区的覆盖信号质量。因此用户在覆盖区域的任何位置均获得良好、一致的用户体验,即一... 为了解决传统蜂窝网络中用户体验剧烈波动的问题,无蜂窝和传统蜂窝共存网络将大量接入点(Access Point,AP)部署到传统蜂窝网络中,显著改善边缘用户和盲区的覆盖信号质量。因此用户在覆盖区域的任何位置均获得良好、一致的用户体验,即一致覆盖是提升共存网络性能的首要目标。而AP部署方案是共存网络中用户传输速率和覆盖的决定性因素,该文提出了面向一致覆盖的AP部署优化方法。首先根据共存网络的联合传输模型推导得到用户的下行可达速率,然后以最大化平均吞吐量为目标,将AP部署建模为比率和规划问题,并基于分式规划和引入辅助变量将其转换为凸优化问题,进而通过迭代求解AP的最优位置。仿真结果表明,相比传统蜂窝网络,所提方案可显著提高边缘和盲区的平均吞吐量。 展开更多
关键词 无线通信 无蜂窝和传统蜂窝共存网络 一致覆盖 联合传输 ap部署
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金钗石斛AP2/ERF基因家族的鉴定和表达分析
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作者 于相丽 刘雅银 +1 位作者 李勇慧 周晓君 《江苏农业科学》 北大核心 2024年第17期47-57,共11页
对金钗石斛AP2/ERF转录因子基因家族在全基因组上进行鉴定及生物信息学分析,为进一步阐明金钗石斛AP2/ERF转录因子的功能研究奠定理论基础。利用BLASTP比对金钗石斛蛋白,并通过在线网站NCBI CDD、InterPro和SMART进一步鉴定,共获得97个... 对金钗石斛AP2/ERF转录因子基因家族在全基因组上进行鉴定及生物信息学分析,为进一步阐明金钗石斛AP2/ERF转录因子的功能研究奠定理论基础。利用BLASTP比对金钗石斛蛋白,并通过在线网站NCBI CDD、InterPro和SMART进一步鉴定,共获得97个金钗石斛AP2/ERF基因,然后通过ProtParam分析金钗石斛AP2/ERF家族蛋白的理化性质、亲疏水性,使用MEGA11.0软件构建进化树,利用Map Gene Chrome、GSDS、MEME、PlantCARE在线工具分析AP2/ERF转录因子的基因定位、基因结构和保守基序,并预测基因上游的顺式作用元件,利用TBTools分析并可视化AP2/ERF基因在各部位的表达情况。结果表明,金钗石斛AP2/ERF转录因子家族的成员,大部分定位在细胞核中,相对分子质量介于2726.88~71682.81 u之间,氨基酸数量介于94~659个之间,等电点介于4.45~10.44之间。进化树分析显示,AP2/ERF家族成员分为AP2、RAV、ERF及DREB 4个亚家族。97条基因不均匀地分布在19条染色体上,各个亚族都有独特基序,AP2/ERF基因启动子上游区域光响应作用元件种类最多,数量也最多。大多数DnAP2s基因在根中的表达量最大,不同的居群DnAP2s基因表达有较大不同。鉴定得到97个金钗石斛AP2/ERF蛋白,DnAP2s基因在根茎叶花中表达具有差异性,地理分布导致不同居群的遗传多样性水平不同。 展开更多
关键词 金钗石斛 ap2/ERF基因家族 生物信息学 表达分析
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非能动补水对AP1000乏燃料池局部硼稀释的影响分析
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作者 苏夏 《科技创新与应用》 2024年第7期68-71,共4页
AP1000非能动电厂在事故后采用非能动补水的方式为乏燃料池提供冷却,同时临界安全分析要求乏池硼浓度高于最低允许硼浓度,以保证足够的次临界裕度。基于AP1000乏燃料池设计,采用CFD流体分析软件,使用多孔介质模型和组分输运模型模拟非... AP1000非能动电厂在事故后采用非能动补水的方式为乏燃料池提供冷却,同时临界安全分析要求乏池硼浓度高于最低允许硼浓度,以保证足够的次临界裕度。基于AP1000乏燃料池设计,采用CFD流体分析软件,使用多孔介质模型和组分输运模型模拟非硼化水源补水对燃料贮存区域的非均匀硼稀释影响。分析结果表明,燃料贮存区的局部硼浓度受到非硼化水源的稀释作用有所降低。在有效控制补水的前提下,局部硼浓度最低降至约2 140 ppm,高于允许的最低硼浓度值,不影响乏燃料临界安全。 展开更多
关键词 乏燃料池 非能动补水 局部硼稀释 影响分析 ap1000
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