The ＇double T-DNA＇ binary vector p13HSR which harbored two independent T-DNAs, containing hygromycin phosphotransferase gene （hpf） in one T-DNA region and three target genes （hLF, SB401, RZ10） in another T-DNA r...The ＇double T-DNA＇ binary vector p13HSR which harbored two independent T-DNAs, containing hygromycin phosphotransferase gene （hpf） in one T-DNA region and three target genes （hLF, SB401, RZ10） in another T-DNA region, was used to generate selectable marker-free transgenic rice by Agrobacterium-mediated transformation. The regenerated plants with both the three target genes and the selectable marker gene hpt were selected for anther culture. RT-PCR analysis indicated that target genes were inserted in rice genomic DNA and successfully transcribed. It took only one year to obtain double haploid selectable marker-free transgenic plants containing the three target genes with co-transformation followed by anther culture technique, and the efficiency was 12.2%. It was also noted that one or two target genes derived from the binary vector were lost in some transgenic rice plants.展开更多
In order to obtain marker-free transgenic rice with improved disease resistance, the AP1 gene of Capsicum annuum and hygromycin-resistance gene （HPT） were cloned into the two separate T-DNA regions of the binary vec...In order to obtain marker-free transgenic rice with improved disease resistance, the AP1 gene of Capsicum annuum and hygromycin-resistance gene （HPT） were cloned into the two separate T-DNA regions of the binary vector pSB130, respectively, and introduced into the calli derived from the immature seeds of two elite japonica rice varieties, Guangling Xiangjing and Wuxiangjing 9, mediated by Agrobacterium-mediated transformation. Many cotransgenic rice lines containing both the AP1 gene and the marker gene were regenerated and the integration of both transgenes in the transgenic rice plants was confirmed by either PCR or Southern blotting technique. Several selectable marker-free transgenic rice plants were subsequently obtained from the progeny of the cotransformants, and confirmed by both PCR and Southern blotting analysis. These transgenic rice lines were tested in the field and their resistance to disease was carefully investigated, the results showed that after inoculation the resistance to either bacterial blight or sheath blight of the selected transgenic lines was improved when compared with those of wild type.展开更多
Pichia membranefaciens, which was isolated from the surface of peach fruits, showed effective biocontrol capabilityagainst rhizopus rot of peach fruits. Aminoglycoside antibiotic G418 can inhibit the growth of P. memb...Pichia membranefaciens, which was isolated from the surface of peach fruits, showed effective biocontrol capabilityagainst rhizopus rot of peach fruits. Aminoglycoside antibiotic G418 can inhibit the growth of P. membranefaciens. Theminimal inhibitory concentration of G418 to P. membranefaciens in YPD medium was 100g mL-1. We constructed aphosphoglycerate kinase (PGK) promoter-driven neoR expression cassette, which was called pFL61-neo. The biocontrolyeast P. membranefaciens was transformed with pFL61-neo by lithium acetate method. Expression vector pFL61-neoconferred P. membranefaciens drug resistance to 100g mL-1 G418. The transformant could keep a high percentage ofplasmid-containing of transformant with 67.87% after 50 generations in non-selective medium. The result showed that P.membranefaciens could recognize the promoter and terminator of PGK and direct the expression of heterologous neoRgene. Expression vector pFL61-neo could exist stably in P. membranefaciens. Therefore, it is feasible to utilize G418-resistance as a dominant selectable marker for heterogenous gene expression in antagonist P. membranefaciens.展开更多
Flavobacterium columnare, the etiological agent of colunmaris disease, is one of the most important and widespread bacterial pathogens of freshwater fish. In this study, we constructed two artificial selectable marke...Flavobacterium columnare, the etiological agent of colunmaris disease, is one of the most important and widespread bacterial pathogens of freshwater fish. In this study, we constructed two artificial selectable markers （chloramphenicol and spectinomycin resistance） for gene transfer in F. columnare. These two new artificial selectable markers, which were created by placing the chloramphenicol or spectinomycin resistance gene under the control of the native acs regulatory region of F. columnare, were functional in both F. columnare and Escherichia coli. The integrative/conjugative plasmids constructed by using these markers were introduced into F. columnare G4 via electroporation or conjugation. The integrated plasmid DNA was confirmed by Southern blotting and PCR analysis. These two markers can be employed in future investigations into gene deletion and the pathogenicity of virulence factors in F. columnare.展开更多
To study the efficiency of generating selectable marker-free （SMF） transgenic rice, two transformation methods were employed for four rice varieties （Wuxiangjing 9, Longtefu, Xieqingzao and Zhenshan 97）. One metho...To study the efficiency of generating selectable marker-free （SMF） transgenic rice, two transformation methods were employed for four rice varieties （Wuxiangjing 9, Longtefu, Xieqingzao and Zhenshan 97）. One method is by using a single twin T-DNA binary vector pYH592 in one Agrobacterium strain, which is composed of two separate T-DNA regions （one carrying an antisense Wx gene and the other carrying a HPTgene）. The other one, named as two-strain/two-vector system, is by using two separate binary vectors in two separate Agrobacterium cultures. The results indicated that the average co-transformation frequencies of the antisense Wx gene and the HPT gene were 10.1% and 45.0%, respectively, for the four rice varieties. And the SMF transgenic plants selected from the offsprings of co-transformants were 55.6% and 60.0% in the two-strain/two-vector and twin T-DNA vector binary systems, respectively.展开更多
Soybean is one of the crops most difficult to be manipulated in vitro. Although several soybean marker genes, all the selectable markers used were from bacteria origin. To find suitable selectable marker gene from pla...Soybean is one of the crops most difficult to be manipulated in vitro. Although several soybean marker genes, all the selectable markers used were from bacteria origin. To find suitable selectable marker gene from plant origin for soybean transformation, a mutant acetolactate synthase （ALS） gene from Arabidopsis thaliana was tested for Agrobacterium-mediated soybean embryo axis transformation with the herbicide Arsenal as the selective agent. Transgenic soybean plants were obtained after the herbicide se- lection and the To transgenic lines showed resistance to the herbicide at a concentration of 100 g/ha. ALS enzyme assay of To transgenic line also showed higher activity compared to the wild type control plant. PCR analysis of the T1 transgenic lines confirmed the integration and segregation of the transgene. Taken together, our results showed that the mutant ALS gene is a suitable selectable marker for soybean transformation.展开更多
In this paper,we establish and study a single-species logistic model with impulsive age-selective harvesting.First,we prove the ultimate boundedness of the solutions of the system.Then,we obtain conditions for the asy...In this paper,we establish and study a single-species logistic model with impulsive age-selective harvesting.First,we prove the ultimate boundedness of the solutions of the system.Then,we obtain conditions for the asymptotic stability of the trivial solution and the positive periodic solution.Finally,numerical simulations are presented to validate our results.Our results show that age-selective harvesting is more conducive to sustainable population survival than non-age-selective harvesting.展开更多
To explore the formation mechanism of anisotropy in Ti-6Al-4V alloy fabricated by selective laser melting(SLM),the compressive mechanical properties,microhardness,microstructure,and crystallographic orientation of the...To explore the formation mechanism of anisotropy in Ti-6Al-4V alloy fabricated by selective laser melting(SLM),the compressive mechanical properties,microhardness,microstructure,and crystallographic orientation of the alloy across different planes were investigated.The anisotropy of SLM-fabricated Ti-6Al-4V alloys was analyzed,and the electron backscatter diffraction technique was used to investigate the influence of different grain types and orientations on the stress-strain distribution at various scales.Results reveal that in room-temperature compression tests at a strain rate of 10^(-3) s^(-1),both the compressive yield strength and microhardness vary along the deposition direction,indicating a certain degree of mechanical property anisotropy.The alloy exhibits a columnar microstructure;along the deposition direction,the grains appear equiaxed,and they have internal hexagonal close-packed(hcp)α/α'martensitic structure.α'phase has a preferential orientation approximately along the<0001>direction.Anisotropy arises from the high aspect ratio of columnar grains,along with the weak texture of the microstructure and low symmetry of the hcp crystal structure.展开更多
A novel wavelength selectable fiber ring laser was proposed. Superimposed fiber Bragg gratings with uniform reflectivity were made to serve as comb-like filter. Optical tunable filter combined with the comb filter rea...A novel wavelength selectable fiber ring laser was proposed. Superimposed fiber Bragg gratings with uniform reflectivity were made to serve as comb-like filter. Optical tunable filter combined with the comb filter realized fast and accurately wavelength selectivity. The SMSR at each wavelength is more than 50dB.展开更多
A novel cascaded DFB laser,which consists of two serial gratings to provide selectable wavelengths,is presented and analyzed by the transfer matrix method.In this method,efficient facet reflectivity is derived from th...A novel cascaded DFB laser,which consists of two serial gratings to provide selectable wavelengths,is presented and analyzed by the transfer matrix method.In this method,efficient facet reflectivity is derived from the transfer matrix built for each serial section and is then used to simulate the performance of the novel cascaded DFB laser through self-consistently solving the gain equation,the coupled wave equation and the current continuity equations.The simulations prove the feasibility of this kind of wavelength selectable laser and a corresponding designed device with two selectable wavelengths of 1.51μm and 1.53μm is realized by experiments on InP-based multiple quantum well structure.展开更多
BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their effi...BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their efficacy is limited.This study investigated whether combining SSRIs with traditional Chinese medicine(TCM)Free San could enhance their therapeutic effects.AIM To evaluate the clinical efficacy and safety of combining SSRIs with Free San in treating PSD,and to assess its impact on HPA axis function.METHODS Ninety-two patients with PSD were enrolled and randomly divided into control groups(n=46)and study groups(n=46).The control group received the SSRI paroxetine alone,whereas the study group received paroxetine combined with Free San for 4 weeks.Hamilton Depression Scale and TCM syndrome scores were assessed before and after treatment.Serum serotonin,norepinephrine,cortisol,cor-ticotropin-releasing hormone,and adrenocorticotropic hormone were measured.The treatment responses and adverse reactions were recorded.RESULTS After treatment,the Hamilton Depression Scale and TCM syndrome scores were significantly lower in the study group than in the control group(P<0.05).Serum serotonin and norepinephrine levels were significantly higher in the study group than in the control group,whereas cortisol,corticotropin-releasing hormone,and adrenocorticotropic hormone levels were significantly lower(P<0.05).The total efficacy rates were 84.78%and 65.22%in the study and control groups,respectively(P<0.05).No significant differences in adverse reactions were observed between the two groups(P>0.05).CONCLUSION Combining SSRIs with Free San can enhance therapeutic efficacy,improve depressive symptoms,and regulate HPA axis function in patients with PSD with good safety and clinical application value.展开更多
GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a ...GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.展开更多
Electrocatalytic nitrate reduction reaction(NO3RR)represents a sustainable and environmentally benign route for ammonia(NH3)synthesis.However,NO3RR is still limited by the competition from hydrogen evolution reaction(...Electrocatalytic nitrate reduction reaction(NO3RR)represents a sustainable and environmentally benign route for ammonia(NH3)synthesis.However,NO3RR is still limited by the competition from hydrogen evolution reaction(HER)and the high energy barrier in the hydrogenation step of nitrogen-containing intermediates.Here,we report a selective etching strategy to construct Ru M nanoalloys(M=Fe,Co,Ni,Cu)uniformly dispersed on porous nitrogen-doped carbon substrates for efficient neutral NH3electrosynthesis.Density functional theory calculations confirm that the synergic effect between Ru and transition metal M modulates the electronic structure of the alloy,significantly lowering the energy barrier for the conversion of*NO_(2)to*HNO_(2).Experimentally,the optimized Ru Fe-NC catalyst achieves 100%Faraday efficiency with a high yield rate of 0.83 mg h^(-1)mg^(-1)catat a low potential of-0.1 V vs.RHE,outperforming most reported catalysts.In situ spectroscopic analyses further demonstrate that the Ru M-NC effectively promotes the hydrogenation of nitrogen intermediates while inhibiting the formation of hydrogen radicals,thereby reducing HER competition.The Ru FeNC assembled Zn-NO_(3)^(-)battery achieved a high open-circuit voltage and an outstanding power density and capacity,which drive selective NO_(3)^(-)conversion to NH3.This work provides a powerful synergistic design strategy for efficient NH3electrosynthesis and a general framework for the development of advanced multi-component catalysts for sustainable nitrogen conversion.展开更多
Developing biomass platform compounds into high value-added chemicals is a key step in renewable resource utilization.Herein,we report porous carbon-supported Ni-ZnO nanoparticles catalyst(Ni-ZnO/AC)synthesized via lo...Developing biomass platform compounds into high value-added chemicals is a key step in renewable resource utilization.Herein,we report porous carbon-supported Ni-ZnO nanoparticles catalyst(Ni-ZnO/AC)synthesized via low-temperature coprecipitation,exhibiting excellent performance for the selective hydrogenation of 5-hydroxymethylfurfural(HMF).A linear correlation is first observed between solvent polarity(E_(T)(30))and product selectivity within both polar aprotic and protic solvent classes,suggesting that solvent properties play a vital role in directing reaction pathways.Among these,1,4-dioxane(aprotic)favors the formation of 2,5-bis(hydroxymethyl)furan(BHMF)with 97.5%selectivity,while isopropanol(iPrOH,protic)promotes 2,5-dimethylfuran production with up to 99.5%selectivity.Mechanistic investigations further reveal that beyond polarity,proton-donating ability is critical in facilitating hydrodeoxygenation.iPrOH enables a hydrogen shuttle mechanism where protons assist in hydroxyl group removal,lowering the activation barrier.In contrast,1,4-dioxane,lacking hydrogen bond donors,stabilizes BHMF and hinders further conversion.Density functional theory calculations confirm a lower activation energy in iPrOH(0.60 eV)compared to 1,4-dioxane(1.07 eV).This work offers mechanistic insights and a practical strategy for solvent-mediated control of product selectivity in biomass hydrogenation,highlighting the decisive role of solvent-catalyst-substrate interactions.展开更多
BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initi...BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initiation,progression,metastasis,therapeutic resistance,and disease recurrence.Cancer stem cells possess selfrenewal capacity,multipotent differentiation potential,and enhanced tumorigenic activity,but their molecular characteristics and regulatory mechanisms require further investigation.AIM To comprehensively characterize the molecular features of BCSCs through multiomics approaches,construct a prognostic prediction model based on stem cellrelated genes,reveal cell-cell communication networks within the tumor microenvironment,and provide theoretical foundation for personalized treatment strategies.METHODS Flow cytometry was employed to detect the expression of BCSC surface markers(CD34,CD45,CD29,CD90,CD105).Transcriptomic analysis was performed to identify differentially expressed genes.Least absolute shrinkage and selection operator regression analysis was utilized to screen key prognostic genes and construct a risk scoring model.Single-cell RNA sequencing and spatial transcriptomics were applied to analyze tumor heterogeneity and spatial gene expression patterns.Cell-cell communication network analysis was conducted to reveal interactions between stem cells and the microenvironment.RESULTS Flow cytometric analysis revealed the highest expression of CD105(96.30%),followed by CD90(68.43%)and CD34(62.64%),while CD29 showed lower expression(7.16%)and CD45 exhibited the lowest expression(1.19%).Transcriptomic analysis identified 3837 significantly differentially expressed genes(1478 upregulated and 2359 downregulated).Least absolute shrinkage and selection operator regression analysis selected 10 key prognostic genes,and the constructed risk scoring model effectively distinguished between high-risk and low-risk patient groups(P<0.001).Single-cell analysis revealed tumor cellular heterogeneity,and spatial transcriptomics demonstrated distinct spatial expression gradients of stem cell-related genes.MED18 gene showed significantly higher expression in malignant tissues(P<0.001)and occupied a central position in cell-cell communication networks,exhibiting significant correlations with tumor cells,macrophages,fibroblasts,and endothelial cells.CONCLUSION This study comprehensively characterized the molecular features of BCSCs through multi-omics approaches,identified reliable surface markers and key regulatory genes,and constructed a prognostic prediction model with clinical application value.展开更多
Lithium-oxygen(Li-O2)batteries are perceived as a promising breakthrough in sustainable electrochemical energy storage,utilizing ambient air as an energy source,eliminating the need for costly cathode materials,and of...Lithium-oxygen(Li-O2)batteries are perceived as a promising breakthrough in sustainable electrochemical energy storage,utilizing ambient air as an energy source,eliminating the need for costly cathode materials,and offering the highest theoretical energy density(~3.5 k Wh kg^(-1))among discussed candidates.Contributing to the poor cycle life of currently reported Li-O_(2)cells is singlet oxygen(1O_(2))formation,inducing parasitic reactions,degrading key components,and severely deteriorating cell performance.Here,we harness the chirality-induced spin selectivity effect of chiral cobalt oxide nanosheets(Co_(3)O_(4)NSs)as cathode materials to suppress 1O_(2)in Li-O_(2)batteries for the first time.Operando photoluminescence spectroscopy reveals a 3.7-fold and 3.23-fold reduction in 1O_(2)during discharge and charge,respectively,compared to conventional carbon paperbased cells,consistent with differential electrochemical mass spectrometry results,which indicate a near-theoretical charge-to-O_(2)ratio(2.04 e-/O_(2)).Density functional theory calculations demonstrate that chirality induces a peak shift near the Fermi level,enhancing Co 3d-O 2p hybridization,stabilizing reaction intermediates,and lowering activation barriers for Li_(2)O_(2)formation and decomposition.These findings establish a new strategy for improving the stability and energy efficiency of sustainable Li-O_(2)batteries,abridging the current gap to commercialization.展开更多
Gibberellic acid(GA3)is a vital plant growth hormone widely used in agriculture.Currently,GA3 production relies on liquid fermentation by the filamentous fungus Fusarium fujikuroi.However,the lack of an effective sele...Gibberellic acid(GA3)is a vital plant growth hormone widely used in agriculture.Currently,GA3 production relies on liquid fermentation by the filamentous fungus Fusarium fujikuroi.However,the lack of an effective selection marker recycling system hampers the application of metabolic engineering technology in F.fujikuroi,as multiple-gene editing and positive-strain screening still rely on a limited number of antibiotics.In this study,we developed a strategy using pyr4-blaster and CRISPR/Cas9 tools for recycling orotidine-5'-phosphate decarboxylase(Pyr4)selection markers.We demonstrated the effectiveness of this method for iterative gene integration and large gene-cluster deletion.We also successfully improved GA3 titers by overexpressing geranylgeranyl pyrophosphate synthase and truncated 3-hydroxy-3-methyl glutaryl coenzyme A reductase,which rewired the GA3 biosynthesis pathway.These results highlight the efficiency of our established system in recycling selection markers during iterative gene editing events.Moreover,the selection marker recycling system lays the foundation for further research on metabolic engineering for GA3 industrial production.展开更多
The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role i...The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.展开更多
Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to prote...Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.展开更多
文摘The ＇double T-DNA＇ binary vector p13HSR which harbored two independent T-DNAs, containing hygromycin phosphotransferase gene （hpf） in one T-DNA region and three target genes （hLF, SB401, RZ10） in another T-DNA region, was used to generate selectable marker-free transgenic rice by Agrobacterium-mediated transformation. The regenerated plants with both the three target genes and the selectable marker gene hpt were selected for anther culture. RT-PCR analysis indicated that target genes were inserted in rice genomic DNA and successfully transcribed. It took only one year to obtain double haploid selectable marker-free transgenic plants containing the three target genes with co-transformation followed by anther culture technique, and the efficiency was 12.2%. It was also noted that one or two target genes derived from the binary vector were lost in some transgenic rice plants.
基金This paper is translated from its Chinese version in Scientia Agricultura Sinica.This study was supported by the Government of Jiangsu Province,China(BG2002301 and JH02-106)National Transgenic Plant R&D Project(JY03-B-10)+1 种基金National Natural Science Foundation of China(30170567)Department of Education of Jiangsu Goverment,China(K05015).
文摘In order to obtain marker-free transgenic rice with improved disease resistance, the AP1 gene of Capsicum annuum and hygromycin-resistance gene （HPT） were cloned into the two separate T-DNA regions of the binary vector pSB130, respectively, and introduced into the calli derived from the immature seeds of two elite japonica rice varieties, Guangling Xiangjing and Wuxiangjing 9, mediated by Agrobacterium-mediated transformation. Many cotransgenic rice lines containing both the AP1 gene and the marker gene were regenerated and the integration of both transgenes in the transgenic rice plants was confirmed by either PCR or Southern blotting technique. Several selectable marker-free transgenic rice plants were subsequently obtained from the progeny of the cotransformants, and confirmed by both PCR and Southern blotting analysis. These transgenic rice lines were tested in the field and their resistance to disease was carefully investigated, the results showed that after inoculation the resistance to either bacterial blight or sheath blight of the selected transgenic lines was improved when compared with those of wild type.
基金supported by the National Science Fund for Distinguished Young Scholars of China(30225030)the National Natural Science Foundation of China(30430480).
文摘Pichia membranefaciens, which was isolated from the surface of peach fruits, showed effective biocontrol capabilityagainst rhizopus rot of peach fruits. Aminoglycoside antibiotic G418 can inhibit the growth of P. membranefaciens. Theminimal inhibitory concentration of G418 to P. membranefaciens in YPD medium was 100g mL-1. We constructed aphosphoglycerate kinase (PGK) promoter-driven neoR expression cassette, which was called pFL61-neo. The biocontrolyeast P. membranefaciens was transformed with pFL61-neo by lithium acetate method. Expression vector pFL61-neoconferred P. membranefaciens drug resistance to 100g mL-1 G418. The transformant could keep a high percentage ofplasmid-containing of transformant with 67.87% after 50 generations in non-selective medium. The result showed that P.membranefaciens could recognize the promoter and terminator of PGK and direct the expression of heterologous neoRgene. Expression vector pFL61-neo could exist stably in P. membranefaciens. Therefore, it is feasible to utilize G418-resistance as a dominant selectable marker for heterogenous gene expression in antagonist P. membranefaciens.
基金Supported by the National Basic Research Program of China(973Program)(No.2009CB118703)
文摘Flavobacterium columnare, the etiological agent of colunmaris disease, is one of the most important and widespread bacterial pathogens of freshwater fish. In this study, we constructed two artificial selectable markers （chloramphenicol and spectinomycin resistance） for gene transfer in F. columnare. These two new artificial selectable markers, which were created by placing the chloramphenicol or spectinomycin resistance gene under the control of the native acs regulatory region of F. columnare, were functional in both F. columnare and Escherichia coli. The integrative/conjugative plasmids constructed by using these markers were introduced into F. columnare G4 via electroporation or conjugation. The integrated plasmid DNA was confirmed by Southern blotting and PCR analysis. These two markers can be employed in future investigations into gene deletion and the pathogenicity of virulence factors in F. columnare.
基金supported by the National Transgenic Research Project (Grant Nos. 2008ZX08001-006 and 2008ZX08010-002)the National Natural Science Foundation (Grant No. 30770131)+1 种基金the Program for New Century Excellent Talents in University (Grant No. NCET-07-0736)the Jiangsu Province Government (Grant Nos. BK2007510, 06KJA21018 and K05015) of China
文摘To study the efficiency of generating selectable marker-free （SMF） transgenic rice, two transformation methods were employed for four rice varieties （Wuxiangjing 9, Longtefu, Xieqingzao and Zhenshan 97）. One method is by using a single twin T-DNA binary vector pYH592 in one Agrobacterium strain, which is composed of two separate T-DNA regions （one carrying an antisense Wx gene and the other carrying a HPTgene）. The other one, named as two-strain/two-vector system, is by using two separate binary vectors in two separate Agrobacterium cultures. The results indicated that the average co-transformation frequencies of the antisense Wx gene and the HPT gene were 10.1% and 45.0%, respectively, for the four rice varieties. And the SMF transgenic plants selected from the offsprings of co-transformants were 55.6% and 60.0% in the two-strain/two-vector and twin T-DNA vector binary systems, respectively.
基金Supported by the National Natural Science Foundation of China （No. 30370133）.
文摘Soybean is one of the crops most difficult to be manipulated in vitro. Although several soybean marker genes, all the selectable markers used were from bacteria origin. To find suitable selectable marker gene from plant origin for soybean transformation, a mutant acetolactate synthase （ALS） gene from Arabidopsis thaliana was tested for Agrobacterium-mediated soybean embryo axis transformation with the herbicide Arsenal as the selective agent. Transgenic soybean plants were obtained after the herbicide se- lection and the To transgenic lines showed resistance to the herbicide at a concentration of 100 g/ha. ALS enzyme assay of To transgenic line also showed higher activity compared to the wild type control plant. PCR analysis of the T1 transgenic lines confirmed the integration and segregation of the transgene. Taken together, our results showed that the mutant ALS gene is a suitable selectable marker for soybean transformation.
基金Supported by the National Natural Science Foundation of China(12261018)Universities Key Laboratory of Mathematical Modeling and Data Mining in Guizhou Province(2023013)。
文摘In this paper,we establish and study a single-species logistic model with impulsive age-selective harvesting.First,we prove the ultimate boundedness of the solutions of the system.Then,we obtain conditions for the asymptotic stability of the trivial solution and the positive periodic solution.Finally,numerical simulations are presented to validate our results.Our results show that age-selective harvesting is more conducive to sustainable population survival than non-age-selective harvesting.
基金National Natural Science Foundation of China(51504138,51674118,52271177)Hunan Provincial Natural Science Foundation of China(2023JJ50181)Supported by State Key Laboratory of Materials Processing and Die&Mould Technology,Huazhong University of Science and Technology(P2024-022)。
文摘To explore the formation mechanism of anisotropy in Ti-6Al-4V alloy fabricated by selective laser melting(SLM),the compressive mechanical properties,microhardness,microstructure,and crystallographic orientation of the alloy across different planes were investigated.The anisotropy of SLM-fabricated Ti-6Al-4V alloys was analyzed,and the electron backscatter diffraction technique was used to investigate the influence of different grain types and orientations on the stress-strain distribution at various scales.Results reveal that in room-temperature compression tests at a strain rate of 10^(-3) s^(-1),both the compressive yield strength and microhardness vary along the deposition direction,indicating a certain degree of mechanical property anisotropy.The alloy exhibits a columnar microstructure;along the deposition direction,the grains appear equiaxed,and they have internal hexagonal close-packed(hcp)α/α'martensitic structure.α'phase has a preferential orientation approximately along the<0001>direction.Anisotropy arises from the high aspect ratio of columnar grains,along with the weak texture of the microstructure and low symmetry of the hcp crystal structure.
文摘A novel wavelength selectable fiber ring laser was proposed. Superimposed fiber Bragg gratings with uniform reflectivity were made to serve as comb-like filter. Optical tunable filter combined with the comb filter realized fast and accurately wavelength selectivity. The SMSR at each wavelength is more than 50dB.
基金Project supported by the National Natural Science Foundation of China(Nos.60776051,60376033)the Beijing Municipal Natural Science Foundation of China(No.4082007)the Beijing Municipal Education Committee of China(Nos.KM200910005001, KM200710005015).
文摘A novel cascaded DFB laser,which consists of two serial gratings to provide selectable wavelengths,is presented and analyzed by the transfer matrix method.In this method,efficient facet reflectivity is derived from the transfer matrix built for each serial section and is then used to simulate the performance of the novel cascaded DFB laser through self-consistently solving the gain equation,the coupled wave equation and the current continuity equations.The simulations prove the feasibility of this kind of wavelength selectable laser and a corresponding designed device with two selectable wavelengths of 1.51μm and 1.53μm is realized by experiments on InP-based multiple quantum well structure.
基金Supported by Open Project of Jiangsu Province Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Prevention and Treatment of Geriatric Diseases,No.202232.
文摘BACKGROUND Post-stroke depression(PSD)is associated with hypothalamic-pituitary-adrenal(HPA)axis dysfunction and neurotransmitter deficits.Selective serotonin reuptake inhibitors(SSRIs)are commonly used,but their efficacy is limited.This study investigated whether combining SSRIs with traditional Chinese medicine(TCM)Free San could enhance their therapeutic effects.AIM To evaluate the clinical efficacy and safety of combining SSRIs with Free San in treating PSD,and to assess its impact on HPA axis function.METHODS Ninety-two patients with PSD were enrolled and randomly divided into control groups(n=46)and study groups(n=46).The control group received the SSRI paroxetine alone,whereas the study group received paroxetine combined with Free San for 4 weeks.Hamilton Depression Scale and TCM syndrome scores were assessed before and after treatment.Serum serotonin,norepinephrine,cortisol,cor-ticotropin-releasing hormone,and adrenocorticotropic hormone were measured.The treatment responses and adverse reactions were recorded.RESULTS After treatment,the Hamilton Depression Scale and TCM syndrome scores were significantly lower in the study group than in the control group(P<0.05).Serum serotonin and norepinephrine levels were significantly higher in the study group than in the control group,whereas cortisol,corticotropin-releasing hormone,and adrenocorticotropic hormone levels were significantly lower(P<0.05).The total efficacy rates were 84.78%and 65.22%in the study and control groups,respectively(P<0.05).No significant differences in adverse reactions were observed between the two groups(P>0.05).CONCLUSION Combining SSRIs with Free San can enhance therapeutic efficacy,improve depressive symptoms,and regulate HPA axis function in patients with PSD with good safety and clinical application value.
基金partially supported by grants PID2020-115096RB-I00 and PID2023-148273NB-I00 from Ministerio de Ciencia y Universidad (MICIU/AEI)(to EMS)。
文摘GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.
基金financially supported by National Natural Science Foundation of China(22466010)Guizhou Provincial Basic Research Program(Natural Science)ZK[2023]47 and key program ZD[2025]075+6 种基金Innovation and Entrepreneurship Project for overseas Talents in Guizhou Province[2022]02Specific Natural Science Foundation of Guizhou University(X202207)the national undergraduate innovation and entrepreneurship training program(gzugc2023006gzusc2024012)SRT project of Guizhou university(2023SRT0292023SRT024)supported by Shanghai Technical Service Center of Science and Engineering Computing,Shanghai University。
文摘Electrocatalytic nitrate reduction reaction(NO3RR)represents a sustainable and environmentally benign route for ammonia(NH3)synthesis.However,NO3RR is still limited by the competition from hydrogen evolution reaction(HER)and the high energy barrier in the hydrogenation step of nitrogen-containing intermediates.Here,we report a selective etching strategy to construct Ru M nanoalloys(M=Fe,Co,Ni,Cu)uniformly dispersed on porous nitrogen-doped carbon substrates for efficient neutral NH3electrosynthesis.Density functional theory calculations confirm that the synergic effect between Ru and transition metal M modulates the electronic structure of the alloy,significantly lowering the energy barrier for the conversion of*NO_(2)to*HNO_(2).Experimentally,the optimized Ru Fe-NC catalyst achieves 100%Faraday efficiency with a high yield rate of 0.83 mg h^(-1)mg^(-1)catat a low potential of-0.1 V vs.RHE,outperforming most reported catalysts.In situ spectroscopic analyses further demonstrate that the Ru M-NC effectively promotes the hydrogenation of nitrogen intermediates while inhibiting the formation of hydrogen radicals,thereby reducing HER competition.The Ru FeNC assembled Zn-NO_(3)^(-)battery achieved a high open-circuit voltage and an outstanding power density and capacity,which drive selective NO_(3)^(-)conversion to NH3.This work provides a powerful synergistic design strategy for efficient NH3electrosynthesis and a general framework for the development of advanced multi-component catalysts for sustainable nitrogen conversion.
基金the National Nature Science Foundation of China for Excellent Young Scientists Fund(32222058)Fundamental Research Foundation of CAF(CAFYBB2022QB001).
文摘Developing biomass platform compounds into high value-added chemicals is a key step in renewable resource utilization.Herein,we report porous carbon-supported Ni-ZnO nanoparticles catalyst(Ni-ZnO/AC)synthesized via low-temperature coprecipitation,exhibiting excellent performance for the selective hydrogenation of 5-hydroxymethylfurfural(HMF).A linear correlation is first observed between solvent polarity(E_(T)(30))and product selectivity within both polar aprotic and protic solvent classes,suggesting that solvent properties play a vital role in directing reaction pathways.Among these,1,4-dioxane(aprotic)favors the formation of 2,5-bis(hydroxymethyl)furan(BHMF)with 97.5%selectivity,while isopropanol(iPrOH,protic)promotes 2,5-dimethylfuran production with up to 99.5%selectivity.Mechanistic investigations further reveal that beyond polarity,proton-donating ability is critical in facilitating hydrodeoxygenation.iPrOH enables a hydrogen shuttle mechanism where protons assist in hydroxyl group removal,lowering the activation barrier.In contrast,1,4-dioxane,lacking hydrogen bond donors,stabilizes BHMF and hinders further conversion.Density functional theory calculations confirm a lower activation energy in iPrOH(0.60 eV)compared to 1,4-dioxane(1.07 eV).This work offers mechanistic insights and a practical strategy for solvent-mediated control of product selectivity in biomass hydrogenation,highlighting the decisive role of solvent-catalyst-substrate interactions.
基金the Natural Science Foundation of Yongchuan District,No.2023yc-jckx20021.
文摘BACKGROUND Breast cancer is one of the most prevalent malignancies affecting women worldwide,with approximately 2.3 million new cases diagnosed annually.Breast cancer stem cells(BCSCs)play pivotal roles in tumor initiation,progression,metastasis,therapeutic resistance,and disease recurrence.Cancer stem cells possess selfrenewal capacity,multipotent differentiation potential,and enhanced tumorigenic activity,but their molecular characteristics and regulatory mechanisms require further investigation.AIM To comprehensively characterize the molecular features of BCSCs through multiomics approaches,construct a prognostic prediction model based on stem cellrelated genes,reveal cell-cell communication networks within the tumor microenvironment,and provide theoretical foundation for personalized treatment strategies.METHODS Flow cytometry was employed to detect the expression of BCSC surface markers(CD34,CD45,CD29,CD90,CD105).Transcriptomic analysis was performed to identify differentially expressed genes.Least absolute shrinkage and selection operator regression analysis was utilized to screen key prognostic genes and construct a risk scoring model.Single-cell RNA sequencing and spatial transcriptomics were applied to analyze tumor heterogeneity and spatial gene expression patterns.Cell-cell communication network analysis was conducted to reveal interactions between stem cells and the microenvironment.RESULTS Flow cytometric analysis revealed the highest expression of CD105(96.30%),followed by CD90(68.43%)and CD34(62.64%),while CD29 showed lower expression(7.16%)and CD45 exhibited the lowest expression(1.19%).Transcriptomic analysis identified 3837 significantly differentially expressed genes(1478 upregulated and 2359 downregulated).Least absolute shrinkage and selection operator regression analysis selected 10 key prognostic genes,and the constructed risk scoring model effectively distinguished between high-risk and low-risk patient groups(P<0.001).Single-cell analysis revealed tumor cellular heterogeneity,and spatial transcriptomics demonstrated distinct spatial expression gradients of stem cell-related genes.MED18 gene showed significantly higher expression in malignant tissues(P<0.001)and occupied a central position in cell-cell communication networks,exhibiting significant correlations with tumor cells,macrophages,fibroblasts,and endothelial cells.CONCLUSION This study comprehensively characterized the molecular features of BCSCs through multi-omics approaches,identified reliable surface markers and key regulatory genes,and constructed a prognostic prediction model with clinical application value.
基金supported by Basic Science Research Program(Priority Research Institute)through the NRF of Korea funded by the Ministry of Education(2021R1A6A1A10039823)by the Korea Basic Science Institute(National Research Facilities and Equipment Center)grant funded by the Ministry of Education(2020R1A6C101B194)。
文摘Lithium-oxygen(Li-O2)batteries are perceived as a promising breakthrough in sustainable electrochemical energy storage,utilizing ambient air as an energy source,eliminating the need for costly cathode materials,and offering the highest theoretical energy density(~3.5 k Wh kg^(-1))among discussed candidates.Contributing to the poor cycle life of currently reported Li-O_(2)cells is singlet oxygen(1O_(2))formation,inducing parasitic reactions,degrading key components,and severely deteriorating cell performance.Here,we harness the chirality-induced spin selectivity effect of chiral cobalt oxide nanosheets(Co_(3)O_(4)NSs)as cathode materials to suppress 1O_(2)in Li-O_(2)batteries for the first time.Operando photoluminescence spectroscopy reveals a 3.7-fold and 3.23-fold reduction in 1O_(2)during discharge and charge,respectively,compared to conventional carbon paperbased cells,consistent with differential electrochemical mass spectrometry results,which indicate a near-theoretical charge-to-O_(2)ratio(2.04 e-/O_(2)).Density functional theory calculations demonstrate that chirality induces a peak shift near the Fermi level,enhancing Co 3d-O 2p hybridization,stabilizing reaction intermediates,and lowering activation barriers for Li_(2)O_(2)formation and decomposition.These findings establish a new strategy for improving the stability and energy efficiency of sustainable Li-O_(2)batteries,abridging the current gap to commercialization.
基金supported by National key research and development program of China(2021YFC2104300)Natural Science Foundation of Jiangsu Province(BK20210573,20230381)+2 种基金Project of Leading Innovative Talents in Short-term Jiangxi Province(jxsq2023102172)Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project TSBICIP-PTJS-003-04Postgraduate Research&Practice Innovation Program of Jiangsu Province KYCX23_1788.
文摘Gibberellic acid(GA3)is a vital plant growth hormone widely used in agriculture.Currently,GA3 production relies on liquid fermentation by the filamentous fungus Fusarium fujikuroi.However,the lack of an effective selection marker recycling system hampers the application of metabolic engineering technology in F.fujikuroi,as multiple-gene editing and positive-strain screening still rely on a limited number of antibiotics.In this study,we developed a strategy using pyr4-blaster and CRISPR/Cas9 tools for recycling orotidine-5'-phosphate decarboxylase(Pyr4)selection markers.We demonstrated the effectiveness of this method for iterative gene integration and large gene-cluster deletion.We also successfully improved GA3 titers by overexpressing geranylgeranyl pyrophosphate synthase and truncated 3-hydroxy-3-methyl glutaryl coenzyme A reductase,which rewired the GA3 biosynthesis pathway.These results highlight the efficiency of our established system in recycling selection markers during iterative gene editing events.Moreover,the selection marker recycling system lays the foundation for further research on metabolic engineering for GA3 industrial production.
基金supported by the National Natural Science Foundation of China,Nos.92049120 and 81870897STI2030-Major Projects,No.2021ZD0204001+6 种基金Guangdong Key Project for Development of New Tools for the Diagnosis and Treatment of Autism,No.2018B030335001the Natural Science Foundation of Jiangsu Province,No.BK20181436the National Major Scientific and Technological Special Project for Significant New Drug Development,No.2019ZX09301102the Discipline Construction Program of the Second Affiliated Hospital of Soochow University,No.XKTJ-TD202003Sino-German Cooperation Mobility Programme,No.M-0679the Science and Technology Project of Suzhou,No.SKY2022161Research Project of Neurological Diseases of the Second Affiliated Hospital of Soochow University Medical Center,No.ND2023A01(all to QHM)。
文摘The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.
基金supported by:Fondazione Telethon-Italy(No.GGP19128 to AP)Fondazione Cariplo-Italy(No.2021-1544 to RC)+14 种基金Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica(AriSLA)-Italy(No.MLOpathy to APTarget-RAN to AP)Association Française contre les Myopathies-France(AFM Telethon No.23236 to AP)Kennedy’s Disease Association-USA(2018 grant to RC2020 grant to MG)Ministero dell’Universitàe della Ricerca(MIUR)-Italy(PRIN-Progetti di ricerca di interesse nazionale(No.2017F2A2C5 to APNo.2022EFLFL8 to APNo.2020PBS5MJ to VCNo.2022KSJZF5 to VC)PRIN-Progetti di ricerca di interesse nazionale-bando 2022,PNRR finanziato dall’Unione europea-Next Generation EU,componente M4C2,investimento 1.1(No.P2022B5J32 to RC and No.P20225R4Y5 to VC)CN3:RNA-Codice Proposta:CN_00000041Tematica Sviluppo di terapia genica e farmaci con tecnologia a RNA(Centro Nazionale di Ricerca-CN3 National Center for Gene Therapy and Drugs based on RNA Technology to AP)Progetto Dipartimenti di Eccellenza(to DiSFeB)Ministero della Salute,Agenzia Italiana del Farmaco(AIFA)-Italy(Co_ALS to AP)Universitàdegli Studi di Milano(piano di sviluppo della ricerca(PSR)UNIMI-linea B(to RC and BT).
文摘Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.
