BACKGROUND Vestibular dysfunction(VH)is a common concomitant symptom of late peri-pheral vestibular lesions,which can be trauma,poisoning,infection,heredity,and neurodegeneration,but about 50%of the causes are unknown...BACKGROUND Vestibular dysfunction(VH)is a common concomitant symptom of late peri-pheral vestibular lesions,which can be trauma,poisoning,infection,heredity,and neurodegeneration,but about 50%of the causes are unknown.The study uses the information-motivation-behavioral skills(IMB)model for health education,effectively improve the quality of life,increase their self-confidence,reduce anxiety and depression,and effectively improve the psychological state of patients.AIM To explore the effect of health education based on the IMB model on the degree of vertigo,disability,anxiety and depression in patients with unilateral vestibular hypofunction.METHODS The clinical data of 80 patients with unilateral vestibular hypofunction from January 2019 to December 2021 were selected as the retrospective research objects,and they were divided into the control group and the observation group with 40 cases in each group according to different nursing methods.Among them,the control group was given routine nursing health education and guidance,and the observation group was given health education and guidance based on the IMB model.The changes in self-efficacy,anxiety and depression,and quality of life of patients with unilateral VH were compared between the two groups.RESULTS There was no significant difference in General Self-Efficacy Scale(GSES)scale scores between the two groups of patients before nursing(P>0.05),which was comparable;after nursing,the GSES scale scores of the two groups were higher than those before nursing.The nursing group was higher than the control group,and the difference was statistically significant(P<0.05).There was no significant difference in the scores of Hospital Anxiety and Depression Scale(HADS)and anxiety and depression subscales between the two groups before nursing(P>0.05).After nursing,the HADS score,anxiety,and depression subscale scores of the two groups of patients were lower than those before nursing,and the nursing group was lower than the control group,and the difference was statistically significant(P<0.05).After nursing,the Dizziness Handicap Inventory(DHI)scale and DHI-P,DHI-E and DHI-F scores in the two groups were decreased,and the scores in the nursing group were lower than those in the control group,and the difference was statistically significant(P<0.05).CONCLUSION Health education based on the IMB model can effectively improve patients'quality of life,increase self-efficacy of patients with unilateral vestibular hypofunction,enhance patients'confidence,enable patients to resume normal work and life as soon as possible,reduce patients'anxiety and depression,and effectively improve patients'psychological status.展开更多
Glass catfish(Kryptopterus vitreolus)are notable in the aquarium trade for their highly transparent body pattern.This transparency is due to the loss of most reflective iridophores and light-absorbing melanophores in ...Glass catfish(Kryptopterus vitreolus)are notable in the aquarium trade for their highly transparent body pattern.This transparency is due to the loss of most reflective iridophores and light-absorbing melanophores in the main body,although certain black and silver pigments remain in the face and head.To date,however,the molecular mechanisms underlying this transparent phenotype remain largely unknown.To explore the genetic basis of this transparency,we constructed a chromosome-level haplotypic genome assembly for the glass catfish,encompassing 32 chromosomes and 23344 protein-coding genes,using PacBio and Hi-C sequencing technologies and standard assembly and annotation pipelines.Analysis revealed a premature stop codon in the putative albinism-related tyrp1b gene,encoding tyrosinase-related protein 1,rendering it a nonfunctional pseudogene.Notably,a synteny comparison with over 30 other fish species identified the loss of the endothelin-3(edn3b)gene in the glass catfish genome.To investigate the role of edn3b,we generated edn3b^(−/−)mutant zebrafish,which exhibited a remarkable reduction in black pigments in body surface stripes compared to wild-type zebrafish.These findings indicate that edn3b loss contributes to the transparent phenotype of the glass catfish.Our high-quality chromosome-scale genome assembly and identification of key genes provide important molecular insights into the transparent phenotype of glass catfish.These findings not only enhance our understanding of the molecular mechanisms underlying transparency in glass catfish,but also offer a valuable genetic resource for further research on pigmentation in various animal species.展开更多
Largemouth bass(Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence ...Largemouth bass(Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence through selective pressure, leaving nucleotide signals that can be detected at the genomic level. In this study,we sequenced 149 largemouth bass fish, including protospecies(imported from the US) and improved breeds(four domestic breeding populations from China). We detected genomic regions harboring certain genes associated with improved traits, which may be useful molecular markers for practical domestication, breeding, and selection. Subsequent analyses of genetic diversity and population structure revealed that the improved breeds have undergone more rigorous genetic changes. Through selective signal analysis, we identified hundreds of putative selective sweep regions in each largemouth bass line. Interestingly, we predicted 103 putative candidate genes potentially subjected to selection,including several associated with growth(psst1 and grb10), early development(klf9, sp4, and sp8), and immune traits(pkn2, sept2, bcl6, and ripk2). These candidate genes represent potential genomic landmarks that could be used to improve important traits of biological and commercial interest. In summary, this study provides a genome-wide map of genetic variations and selection footprints in largemouth bass, which may benefit genetic studies and accelerate genetic improvement of this economically important fish.展开更多
This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening....This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.展开更多
The Dianchi golden-line barbel,Sinocyclocheilus grahami(Regan,1904),is one of the“Four Famous Fishes”of Yunnan Province,China.Given its economic value,this species has been artificially bred successfully since 2007,...The Dianchi golden-line barbel,Sinocyclocheilus grahami(Regan,1904),is one of the“Four Famous Fishes”of Yunnan Province,China.Given its economic value,this species has been artificially bred successfully since 2007,with a nationally selected breed(“S.grahami,Bayou No.1”)certified in 2018.For the future utilization of this species,its growth rate,disease resistance,and wild adaptability need to be improved,which could be achieved with the help of molecular markerassisted selection(MAS).In the current study,we constructed the first chromosome-level genome of S.grahami,assembled 48 pseudo-chromosomes,and obtained a genome size of 1.49 Gb.We also performed QTL-seq analysis of S.grahami using the highest and lowest bulks(i.e.,largest and smallest size)in both a sibling and random population.We screened two quantitative trait loci(QTLs)(Chr3,14.9-39.1 Mb and Chr17,4.1-27.4 Mb)as major growth-related locations.Several candidate genes(e.g.,map2k5,stat1,phf21a,sox6,and smad6)were also identified,with functions related to growth,such as cell differentiation,neuronal development,skeletal muscle development,chondrogenesis,and immunity.These results built a solid foundation for in-depth MAS studies on the growth traits of S.grahami.展开更多
Melanoma is the most lethal type of skin cancer,originating from the malignant transformation of melanocyte.While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating...Melanoma is the most lethal type of skin cancer,originating from the malignant transformation of melanocyte.While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect,the prognosis of patients with melanoma is still suboptimal.During tumor progression,melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment.SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide(NAD+),with versatile biological functions in maintaining cell homeostasis.Nevertheless,whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive.Herein,we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response.We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress.Then,we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo.Mechanistically,SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumorpromoting cytokines.SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal,which relieved the transcriptional repression on IRE1αand induced the activation of the IRE1α-XBP1 axis.Moreover,SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis.Additionally,the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated.Taken together,SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.展开更多
Orange spotted grouper(Epinephelus coioides)is an important mariculture fish,and genomic breeding of this grouper species has been hindered due to lack of efficient genotyping tools.Here,we developed a single nucleoti...Orange spotted grouper(Epinephelus coioides)is an important mariculture fish,and genomic breeding of this grouper species has been hindered due to lack of efficient genotyping tools.Here,we developed a single nucleotide polymorphism(SNP)genotyping technology based on multiplex PCR enrichment capture sequencing,which mainly aims at target area for high-throughput sequencing,and 741 SNPs were designed for genomic selection(GS)of growth and ammonia tolerance traits at the same time.The multiplex PCR enrichment capture sequencing assay showed that the genotyping efficiency was more than 99%in the orange-spotted grouper and the predictive accuracy of body weight and ammonia tolerance traits was 82%and 96%,respectively.More importantly,the average identity of the sequences with these SNPs aligned to the genomes of giant grouper(E.lanceolatus)and brown-marbled grouper(E.fuscoguttatus)were both over 96%.Test data showed that the SNP genotyping efficiency was more than 94%in both giant grouper and brown-marbled grouper.In summary,these results indicated that the development of SNP loci and genotyping approach based on the multiple PCR enrichment capture sequencing are suitable for GS of growth and ammonia tolerance traits in various grouper species,and it would provide technical support for practical grouper breeding.展开更多
The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"gro...The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"group.In Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"group.In Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.展开更多
Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the mo...Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.展开更多
Progranulin(PGRN)is a growth factor that is involved in the progression of multiple tumors.However,the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear.The expression level of PGRN was...Progranulin(PGRN)is a growth factor that is involved in the progression of multiple tumors.However,the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear.The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma(NSCLC)patients.The proliferation,apoptosis,migration,and invasion of NSCLC cells were assessed by the MTT assay,Western blot,degree of wound healing,and Transwell assays.A nude mouse xenograft model was used to validate the role of PGRN in vivo.The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma;by contrast,no difference was observed in female patients.The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520(derived from lung squamous cell carcinoma)cells,whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549(derived from lung adenocarcinoma)cells.Copanlisib(targeting PI3K)inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein;the PI3K agonist 740 YeP partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells.PGRN increased the expression of Ki-67,PCNA,and Bcl-2 in vivo.PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis;PGRN positivity correlated with lung adenocarcinoma.PGRN is a potential biomarker for the treatment and diagnosis of NSCLC,especially in lung adenocarcinoma.展开更多
With the rapid development of next-generation sequencing technologies and bioinformatics, over 50 ray-finned fish genomes by far have been sequenced with high quality. The genomic work provides abundant genetic resour...With the rapid development of next-generation sequencing technologies and bioinformatics, over 50 ray-finned fish genomes by far have been sequenced with high quality. The genomic work provides abundant genetic resources for deep understanding of divergence, evolution and adaptation in the fish genomes. They are also instructive for identification of candidate genes for functional verification, molecular breeding, and development of novel marine drugs. As an example of other omics data, the Fish-T1 K project generated a big database of fish transcriptomes to integrate with these published fish genomes for potential applications. In this review, we highlight the above-mentioned recent investigations and core topics on the ray-finned fish genome research, with a main goal to obtain a deeper understanding of fish biology for theoretical and practical applications.展开更多
The orange-spotted grouper, Epinephelus coioides, is one of the most popular fish in China and Southeast Asian countries because of its important economic value. However, molecular mechanism underlying the growth of o...The orange-spotted grouper, Epinephelus coioides, is one of the most popular fish in China and Southeast Asian countries because of its important economic value. However, molecular mechanism underlying the growth of orange-spotted grouper has never been fully understood. Herein, we performed a genome-wide association study (GWAS) on a natural population of 198 individuals aiming to screen the whole genome of orange-spotted grouper for identification of growth-related loci by restriction-site associated DNA sequencing. In this research, 261,366 single nucleotide polymorphisms (SNPs) were developed, in which 110 SNPs were identified to be correlated with growth and 20 SNPs were further confirmed to be associated with both body weight and total length. From these identified SNPs, we annotated a total of 34 genes, including adgrb2, csnkzal, cers5, co122al, creb5, dndl, dzankl, dnail, npy2r, fat3, lrrk2, lrp5, map3k9, and so on. Among these candidate genes, npy2r (neuropeptide Y receptor Y2) was reported to play a critical role in growth of the orange-spotted grouper. In addition, population structure, principal component analysis, kinship matrix and linkage disequilibrium were examined to verify the accuracy and reliability of our GWAS results. Our data will also provide a valuable genetic resource for further marker-assisted selection program to improve growth quality in groupers.展开更多
As a living fossil, the endangered Chinese sturgeon(Acipenser sinensis) has been considered a national treasure in China. Here,the famous Gezhouba Dam and Three Gorges Dam on the Yangtze River were built in 1988 and 2...As a living fossil, the endangered Chinese sturgeon(Acipenser sinensis) has been considered a national treasure in China. Here,the famous Gezhouba Dam and Three Gorges Dam on the Yangtze River were built in 1988 and 2006, for economic purposes.The natural population of Chinese sturgeon has declined since then, as these dams block its migratory route to the original spawning grounds in the middle reaches of the Yangtze River. In 2013 and 2014, there was an absence of spawning where it typically happened near the Gezhouba Dam. Nevertheless, from April to June in 2015, over 1,000 larvae with different body lengths(10–35 cm) were detected along the Shanghai Yangtze Estuary; but only little is currently known about the population genetic structure of the Chinese sturgeon. Herein, we inferred population genetic parameters from 462 available Chinese sturgeon specimens based on a 421-bp fragment of the mitochondrial DNA(mtDNA) D-loop region and 1,481,620 SNPs(singlenucleotide polymorphisms) generated by restriction site-associated DNA sequencing(RAD-seq). For the D-loop dataset, 15 haplotypes were determined. Randomly picked 23 individuals, representing the 15 D-loop haplotype groups, were subsequently used for further RAD-seq validation. The average nucleotide diversity calculated from the mtDNA and RAD datasets was 0.0086 and 0.000478, respectively. The overall effective female population size was calculated to be 1,255 to 2,607, and the long-term effective population size was estimated to range from 11,950 to 119,500. We observed that the genetic variability and the effective female population size of the current population in the Yangtze River are severely low, which are similar to the data reported over 10 years ago. The deduced relatively small effective population of female fish, limiting the genetic connectivity among Chinese sturgeon, should be considered a serious threat to this endangered species.展开更多
Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previo...Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that BMP4 signif-icantly inhibits hepatic steatosis and lowers serum triglycerides,playing a protective role against the progression of non-alcoholic fatty liver disease(NAFLD).However,the direct impact of BMP4 on hepatic glucose metabolism is poorly understood.Here,we investigated the regulatory roles of BMP4 in hepatic glucose metabolism.Through a comprehensive analysis of the 14 types of BMPs,we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation,reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism.Mechanistically,we demonstrated that BMP4 reduced the hepatic glucose lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.Collectively,our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism.This knowledge should aid us to understand the molecular pathogenesis of NAFLD,and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism.展开更多
On June 17 of 2016,a group of scientists from Chinese Academy of Fishery Sciences(CAFS)and Shenzhen BGI Fisheries Sci&Tech Co.Ltd.(BGI Fisheries)met together in Shenzhen,China to launch a novel project,the China ...On June 17 of 2016,a group of scientists from Chinese Academy of Fishery Sciences(CAFS)and Shenzhen BGI Fisheries Sci&Tech Co.Ltd.(BGI Fisheries)met together in Shenzhen,China to launch a novel project,the China Aquatic 10-100-1,000 Genomics Program,to conduct molecular breeding of-10 aquaculture species and sequence genomes of-100 and transcriptomes of-1,000 aquatic species.展开更多
Objective:Capsaicin(CPS)is a major component of the red pepper,and its anti-tumor property has been confirmed.However,the underlying mechanism of this anti-tumor effect has not been fully clarified,so we conducted thi...Objective:Capsaicin(CPS)is a major component of the red pepper,and its anti-tumor property has been confirmed.However,the underlying mechanism of this anti-tumor effect has not been fully clarified,so we conducted this study to evaluate the role of mitochondrial fission and subsequent mitochondrial dysfunction in CPS-induced apoptosis of melanoma cells.Methods:Two melanoma cell lines and melanocytes were treated with CPS alone or in combination with ruthenium red(a transient receptor potential vanilloid 1[TRPV]antagonist),Z-VAD-FMK(a pan-caspase inhibitor),or N-acetyl-Lcysteine(an antioxidant).Cell vitality was tested using a cell counting kit-8 assay.The expression levels of related proteins were examined by Western blotting.Apoptosis,intracellular reactive oxygen species,mitochondrial membrane potential,adenosine triphosphate levels,and mitochondrial dynamics were analyzed by flow cytometry,luminometry,and confocal laser microscopy,respectively,and compared between groups.Results:CPS treatment significantly inhibited the vitality of melanoma cells(For A2058 cells:0 vs.120 mmol/L:[100.00%±0%]vs.[51.02%±6.40%],P<0.05;For WM35 cells:0 vs.120 mmol/L:[100.00%±0%]vs.[51.80%±3.45%],P<0.05)but exerted less impact on normal melanocytes.CPS promoted melanoma cell apoptosis through TRPV channels and the caspase cascade.CPS treatment then led to TRPV channel-dependent mitochondrial dysfunction with an increase in reactive oxygen species generation(For A2058 cells:CPS vs.CPS+RR:[2.34±0.30]vs.[1.34±0.12],P<0.05;For WM35 cells:CPS vs.CPS+RR:[2.25±0.25]vs.[1.65±0.13],P<0.05),dissipation of the mitochondrial membrane potential(Control vs.CPS:[1.00±0]vs.[0.61±0.08],P<0.05),and adenosine triphosphate reduction(P<0.05).In addition,reactive oxygen species generation contributed to CPS-induced melanoma cell apoptosis.Mitochondrial fission was subsequently proved to connect CPS treatment to mitochondrial dysfunction,which was also TRPV channel-dependent,thereby inducing melanoma cell apoptosis.Conclusion:Our study highlights the role of mitochondrial fission and its related mitochondrial dysfunction in mediating the pro-apoptotic effect of CPS in melanoma.These findings deepen our understanding of the mechanisms underlying the anti-tumor activity of CPS and indicate the clinical relevancy of extending the use of this agent for cancer therapy.展开更多
Cone snail venoms have been considered a valuable treasure for international scientists and businessmen, mainly due to theirpharmacological applications in development of marine drugs for treatment of various human di...Cone snail venoms have been considered a valuable treasure for international scientists and businessmen, mainly due to theirpharmacological applications in development of marine drugs for treatment of various human diseases. To date, around 800Conus species are recorded, and each of them produces over 1,000 venom peptides (termed as conopeptides or conotoxins).This reflects the high diversity and complexity of cone snails, although most of their venoms are still uncharacterized.Advanced multiomics (such as genomics, transcriptomics, and proteomics) approaches have been recently developed to minediverse Conus venom samples, with the main aim to predict and identify potentially interesting conopeptides in an efficientway. Some bioinformatics techniques have been applied to predict and design novel conopeptide sequences, related targets, andtheir binding modes. This review provides an overview of current knowledge on the high diversity of conopeptides andmultiomics advances in high-throughput prediction of novel conopeptide sequences, as well as molecular modeling and designof potential drugs based on the predicted or validated interactions between these toxins and their molecular targets.展开更多
文摘BACKGROUND Vestibular dysfunction(VH)is a common concomitant symptom of late peri-pheral vestibular lesions,which can be trauma,poisoning,infection,heredity,and neurodegeneration,but about 50%of the causes are unknown.The study uses the information-motivation-behavioral skills(IMB)model for health education,effectively improve the quality of life,increase their self-confidence,reduce anxiety and depression,and effectively improve the psychological state of patients.AIM To explore the effect of health education based on the IMB model on the degree of vertigo,disability,anxiety and depression in patients with unilateral vestibular hypofunction.METHODS The clinical data of 80 patients with unilateral vestibular hypofunction from January 2019 to December 2021 were selected as the retrospective research objects,and they were divided into the control group and the observation group with 40 cases in each group according to different nursing methods.Among them,the control group was given routine nursing health education and guidance,and the observation group was given health education and guidance based on the IMB model.The changes in self-efficacy,anxiety and depression,and quality of life of patients with unilateral VH were compared between the two groups.RESULTS There was no significant difference in General Self-Efficacy Scale(GSES)scale scores between the two groups of patients before nursing(P>0.05),which was comparable;after nursing,the GSES scale scores of the two groups were higher than those before nursing.The nursing group was higher than the control group,and the difference was statistically significant(P<0.05).There was no significant difference in the scores of Hospital Anxiety and Depression Scale(HADS)and anxiety and depression subscales between the two groups before nursing(P>0.05).After nursing,the HADS score,anxiety,and depression subscale scores of the two groups of patients were lower than those before nursing,and the nursing group was lower than the control group,and the difference was statistically significant(P<0.05).After nursing,the Dizziness Handicap Inventory(DHI)scale and DHI-P,DHI-E and DHI-F scores in the two groups were decreased,and the scores in the nursing group were lower than those in the control group,and the difference was statistically significant(P<0.05).CONCLUSION Health education based on the IMB model can effectively improve patients'quality of life,increase self-efficacy of patients with unilateral vestibular hypofunction,enhance patients'confidence,enable patients to resume normal work and life as soon as possible,reduce patients'anxiety and depression,and effectively improve patients'psychological status.
基金supported by the National Key Research and Development Program of China(2022YFE0139700,2023YFE0205100)Key Laboratory of Tropical and Subtropical Fishery Resources Application and Cultivation,Ministry of Agriculture and Rural Affairs,Pearl River Fisheries Research Institute,Chinese Academy of Fishery Sciences(20220202)+3 种基金Guangdong Provincial Special Fund for Modern Agriculture Industry Technology Innovation Team(2023KJ150)China-ASEAN Maritime Cooperation Fund(CAMC-2018F)National Freshwater Genetic Resource Center(FGRC18537)Guangdong Rural Revitalization Strategy Special Provincial Organization and Implementation Project Funds(2022-SBH-00-001)。
文摘Glass catfish(Kryptopterus vitreolus)are notable in the aquarium trade for their highly transparent body pattern.This transparency is due to the loss of most reflective iridophores and light-absorbing melanophores in the main body,although certain black and silver pigments remain in the face and head.To date,however,the molecular mechanisms underlying this transparent phenotype remain largely unknown.To explore the genetic basis of this transparency,we constructed a chromosome-level haplotypic genome assembly for the glass catfish,encompassing 32 chromosomes and 23344 protein-coding genes,using PacBio and Hi-C sequencing technologies and standard assembly and annotation pipelines.Analysis revealed a premature stop codon in the putative albinism-related tyrp1b gene,encoding tyrosinase-related protein 1,rendering it a nonfunctional pseudogene.Notably,a synteny comparison with over 30 other fish species identified the loss of the endothelin-3(edn3b)gene in the glass catfish genome.To investigate the role of edn3b,we generated edn3b^(−/−)mutant zebrafish,which exhibited a remarkable reduction in black pigments in body surface stripes compared to wild-type zebrafish.These findings indicate that edn3b loss contributes to the transparent phenotype of the glass catfish.Our high-quality chromosome-scale genome assembly and identification of key genes provide important molecular insights into the transparent phenotype of glass catfish.These findings not only enhance our understanding of the molecular mechanisms underlying transparency in glass catfish,but also offer a valuable genetic resource for further research on pigmentation in various animal species.
基金supported by the Key-Area Research and Development Program of Guangdong Province(2021B0202020001)China Agriculture Research System of MOF and MARA(CARS-46)+2 种基金Central Public-interest Scientific Institution Basal Research Fund of CAFS(2020TD23,2020ZJTD-02)Project of Construction of Guangdong Aquatic Seed Industry Demonstration Base 2021Special Funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District(KJYF202101-02)。
文摘Largemouth bass(Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence through selective pressure, leaving nucleotide signals that can be detected at the genomic level. In this study,we sequenced 149 largemouth bass fish, including protospecies(imported from the US) and improved breeds(four domestic breeding populations from China). We detected genomic regions harboring certain genes associated with improved traits, which may be useful molecular markers for practical domestication, breeding, and selection. Subsequent analyses of genetic diversity and population structure revealed that the improved breeds have undergone more rigorous genetic changes. Through selective signal analysis, we identified hundreds of putative selective sweep regions in each largemouth bass line. Interestingly, we predicted 103 putative candidate genes potentially subjected to selection,including several associated with growth(psst1 and grb10), early development(klf9, sp4, and sp8), and immune traits(pkn2, sept2, bcl6, and ripk2). These candidate genes represent potential genomic landmarks that could be used to improve important traits of biological and commercial interest. In summary, this study provides a genome-wide map of genetic variations and selection footprints in largemouth bass, which may benefit genetic studies and accelerate genetic improvement of this economically important fish.
基金supported in part by the National Natural Science Foundation of China,No.81072072,31070933the guidance project of Xuzhou Science and Technology Bureau,No.X22D1056
文摘This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.
基金This study was supported by the National Natural Science Foundation of China(31672282,U1702233,U1902202)Program of the Chinese Academy of Sciences(XDA24030505,XDA23080500,KFJ-STS-QYZD-101)Program of Yunnan Provincial Science and Technology Department(202003AD150017,2018FY001-007)。
文摘The Dianchi golden-line barbel,Sinocyclocheilus grahami(Regan,1904),is one of the“Four Famous Fishes”of Yunnan Province,China.Given its economic value,this species has been artificially bred successfully since 2007,with a nationally selected breed(“S.grahami,Bayou No.1”)certified in 2018.For the future utilization of this species,its growth rate,disease resistance,and wild adaptability need to be improved,which could be achieved with the help of molecular markerassisted selection(MAS).In the current study,we constructed the first chromosome-level genome of S.grahami,assembled 48 pseudo-chromosomes,and obtained a genome size of 1.49 Gb.We also performed QTL-seq analysis of S.grahami using the highest and lowest bulks(i.e.,largest and smallest size)in both a sibling and random population.We screened two quantitative trait loci(QTLs)(Chr3,14.9-39.1 Mb and Chr17,4.1-27.4 Mb)as major growth-related locations.Several candidate genes(e.g.,map2k5,stat1,phf21a,sox6,and smad6)were also identified,with functions related to growth,such as cell differentiation,neuronal development,skeletal muscle development,chondrogenesis,and immunity.These results built a solid foundation for in-depth MAS studies on the growth traits of S.grahami.
基金The research leading to these results has received funding from National Natural Science Foundation of China(No.81902791,82173395)Support Program of Young Talents in Shaanxi Province(No.20200303,No.2022SF-178)Young Eagle Project of Fourth Military Medical University(No.2019cyjhgwn).
文摘Melanoma is the most lethal type of skin cancer,originating from the malignant transformation of melanocyte.While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect,the prognosis of patients with melanoma is still suboptimal.During tumor progression,melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment.SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide(NAD+),with versatile biological functions in maintaining cell homeostasis.Nevertheless,whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive.Herein,we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response.We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress.Then,we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo.Mechanistically,SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumorpromoting cytokines.SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal,which relieved the transcriptional repression on IRE1αand induced the activation of the IRE1α-XBP1 axis.Moreover,SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis.Additionally,the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated.Taken together,SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.
基金National Natural Science Foundation of China(No.31872572)Natural Science Foundation for Fundamental Research in Shenzhen(No.JCYJ20190812105801661)Shenzhen Dapeng Special Program for Industrial Development(No.KJYF202101-01).
文摘Orange spotted grouper(Epinephelus coioides)is an important mariculture fish,and genomic breeding of this grouper species has been hindered due to lack of efficient genotyping tools.Here,we developed a single nucleotide polymorphism(SNP)genotyping technology based on multiplex PCR enrichment capture sequencing,which mainly aims at target area for high-throughput sequencing,and 741 SNPs were designed for genomic selection(GS)of growth and ammonia tolerance traits at the same time.The multiplex PCR enrichment capture sequencing assay showed that the genotyping efficiency was more than 99%in the orange-spotted grouper and the predictive accuracy of body weight and ammonia tolerance traits was 82%and 96%,respectively.More importantly,the average identity of the sequences with these SNPs aligned to the genomes of giant grouper(E.lanceolatus)and brown-marbled grouper(E.fuscoguttatus)were both over 96%.Test data showed that the SNP genotyping efficiency was more than 94%in both giant grouper and brown-marbled grouper.In summary,these results indicated that the development of SNP loci and genotyping approach based on the multiple PCR enrichment capture sequencing are suitable for GS of growth and ammonia tolerance traits in various grouper species,and it would provide technical support for practical grouper breeding.
文摘The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"group.In Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"group.In Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303,DE020140 to TCH and RRR)the U.S.Department of Defense(OR130096 to JMW)+1 种基金the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(RRR,TCH),the Scoliosis Research Society(TCH and MJL)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH).
文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.
基金This research was supported by Chongqing Technology Innovation and application development special fund(No.cstc2019jscx-msxmX0095)National Natural Science Foundation of China(No.NSFC 81672103)The authors are responsible for the results and opinions provided by this research,and the sponsor is not responsible for the content published.
文摘Progranulin(PGRN)is a growth factor that is involved in the progression of multiple tumors.However,the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear.The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma(NSCLC)patients.The proliferation,apoptosis,migration,and invasion of NSCLC cells were assessed by the MTT assay,Western blot,degree of wound healing,and Transwell assays.A nude mouse xenograft model was used to validate the role of PGRN in vivo.The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma;by contrast,no difference was observed in female patients.The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520(derived from lung squamous cell carcinoma)cells,whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549(derived from lung adenocarcinoma)cells.Copanlisib(targeting PI3K)inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein;the PI3K agonist 740 YeP partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells.PGRN increased the expression of Ki-67,PCNA,and Bcl-2 in vivo.PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis;PGRN positivity correlated with lung adenocarcinoma.PGRN is a potential biomarker for the treatment and diagnosis of NSCLC,especially in lung adenocarcinoma.
基金supported by Shenzhen Special Program for Development of Emerging Strategic Industries (JSGG20170412153411369)Shenzhen Special Program for Upgrading Key Links to Strategies for the Emerging and Future Industries (20170428173357698)
文摘With the rapid development of next-generation sequencing technologies and bioinformatics, over 50 ray-finned fish genomes by far have been sequenced with high quality. The genomic work provides abundant genetic resources for deep understanding of divergence, evolution and adaptation in the fish genomes. They are also instructive for identification of candidate genes for functional verification, molecular breeding, and development of novel marine drugs. As an example of other omics data, the Fish-T1 K project generated a big database of fish transcriptomes to integrate with these published fish genomes for potential applications. In this review, we highlight the above-mentioned recent investigations and core topics on the ray-finned fish genome research, with a main goal to obtain a deeper understanding of fish biology for theoretical and practical applications.
基金supported by National Natural Science Foundation of China (31370047)Shenzhen Scientific R&D Grant (GJHS20160331150703934)Shenzhen Dapeng Special Program for Industrial Development (KY20160102, KY20170205)
文摘The orange-spotted grouper, Epinephelus coioides, is one of the most popular fish in China and Southeast Asian countries because of its important economic value. However, molecular mechanism underlying the growth of orange-spotted grouper has never been fully understood. Herein, we performed a genome-wide association study (GWAS) on a natural population of 198 individuals aiming to screen the whole genome of orange-spotted grouper for identification of growth-related loci by restriction-site associated DNA sequencing. In this research, 261,366 single nucleotide polymorphisms (SNPs) were developed, in which 110 SNPs were identified to be correlated with growth and 20 SNPs were further confirmed to be associated with both body weight and total length. From these identified SNPs, we annotated a total of 34 genes, including adgrb2, csnkzal, cers5, co122al, creb5, dndl, dzankl, dnail, npy2r, fat3, lrrk2, lrp5, map3k9, and so on. Among these candidate genes, npy2r (neuropeptide Y receptor Y2) was reported to play a critical role in growth of the orange-spotted grouper. In addition, population structure, principal component analysis, kinship matrix and linkage disequilibrium were examined to verify the accuracy and reliability of our GWAS results. Our data will also provide a valuable genetic resource for further marker-assisted selection program to improve growth quality in groupers.
基金supported by National Natural Science Foundation of China (31370047, U1301252)Shenzhen Scientific R & D Grant (GJHS20160331150703934)+1 种基金Shenzhen Dapeng Special Program for Industrial Development (KY20160102)Zhenjiang Leading Talent Program for Innovation and Entrepreneurship
文摘As a living fossil, the endangered Chinese sturgeon(Acipenser sinensis) has been considered a national treasure in China. Here,the famous Gezhouba Dam and Three Gorges Dam on the Yangtze River were built in 1988 and 2006, for economic purposes.The natural population of Chinese sturgeon has declined since then, as these dams block its migratory route to the original spawning grounds in the middle reaches of the Yangtze River. In 2013 and 2014, there was an absence of spawning where it typically happened near the Gezhouba Dam. Nevertheless, from April to June in 2015, over 1,000 larvae with different body lengths(10–35 cm) were detected along the Shanghai Yangtze Estuary; but only little is currently known about the population genetic structure of the Chinese sturgeon. Herein, we inferred population genetic parameters from 462 available Chinese sturgeon specimens based on a 421-bp fragment of the mitochondrial DNA(mtDNA) D-loop region and 1,481,620 SNPs(singlenucleotide polymorphisms) generated by restriction site-associated DNA sequencing(RAD-seq). For the D-loop dataset, 15 haplotypes were determined. Randomly picked 23 individuals, representing the 15 D-loop haplotype groups, were subsequently used for further RAD-seq validation. The average nucleotide diversity calculated from the mtDNA and RAD datasets was 0.0086 and 0.000478, respectively. The overall effective female population size was calculated to be 1,255 to 2,607, and the long-term effective population size was estimated to range from 11,950 to 119,500. We observed that the genetic variability and the effective female population size of the current population in the Yangtze River are severely low, which are similar to the data reported over 10 years ago. The deduced relatively small effective population of female fish, limiting the genetic connectivity among Chinese sturgeon, should be considered a serious threat to this endangered species.
基金The reported study was supported in part by research grants from the 2017 Chongqing Postdoctoral Innovation Talent Support Program(Chongqing Human Resources and Social Security Bureau No.356)(JMF)the 64th China Postdoctoral Science Fund(No.2018M643426)(JMF)+4 种基金the 2019 Chongqing Support Program for Entrepreneurship and Innovation(Chongqing Human Resources and Social Security Bureau No.288)(JMF)the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(KJQN201900410)(JMF)the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission(CY200409)(JMF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)(JMF)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906).
文摘Liver is an important organ for regulating glucose and lipid metabolism.Recent studies have shown that bone morphogenetic proteins(BMPs)may play important roles in regu-lating glucose and lipid metabolism.Inour previous studies,we demonstrated that BMP4 signif-icantly inhibits hepatic steatosis and lowers serum triglycerides,playing a protective role against the progression of non-alcoholic fatty liver disease(NAFLD).However,the direct impact of BMP4 on hepatic glucose metabolism is poorly understood.Here,we investigated the regulatory roles of BMP4 in hepatic glucose metabolism.Through a comprehensive analysis of the 14 types of BMPs,we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation,reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism.Mechanistically,we demonstrated that BMP4 reduced the hepatic glucose lewels through the activation of mTORC2 signaling pathway in vitro and in wivo.Collectively,our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism.This knowledge should aid us to understand the molecular pathogenesis of NAFLD,and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism.
基金supported by Special Project on the Integration of Industry,Education and Research of Guangdong Province (2013B090800017)Shenzhen Special Program for Future Industrial Development(JSGG20141020113728803)Quality Inspection Programs of Scientific Research Project(2015IK246)
文摘On June 17 of 2016,a group of scientists from Chinese Academy of Fishery Sciences(CAFS)and Shenzhen BGI Fisheries Sci&Tech Co.Ltd.(BGI Fisheries)met together in Shenzhen,China to launch a novel project,the China Aquatic 10-100-1,000 Genomics Program,to conduct molecular breeding of-10 aquaculture species and sequence genomes of-100 and transcriptomes of-1,000 aquatic species.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81625020,81402736,and 81902791)the Key Research and Development Program of Shaanxi Province(No.2019sf-079).
文摘Objective:Capsaicin(CPS)is a major component of the red pepper,and its anti-tumor property has been confirmed.However,the underlying mechanism of this anti-tumor effect has not been fully clarified,so we conducted this study to evaluate the role of mitochondrial fission and subsequent mitochondrial dysfunction in CPS-induced apoptosis of melanoma cells.Methods:Two melanoma cell lines and melanocytes were treated with CPS alone or in combination with ruthenium red(a transient receptor potential vanilloid 1[TRPV]antagonist),Z-VAD-FMK(a pan-caspase inhibitor),or N-acetyl-Lcysteine(an antioxidant).Cell vitality was tested using a cell counting kit-8 assay.The expression levels of related proteins were examined by Western blotting.Apoptosis,intracellular reactive oxygen species,mitochondrial membrane potential,adenosine triphosphate levels,and mitochondrial dynamics were analyzed by flow cytometry,luminometry,and confocal laser microscopy,respectively,and compared between groups.Results:CPS treatment significantly inhibited the vitality of melanoma cells(For A2058 cells:0 vs.120 mmol/L:[100.00%±0%]vs.[51.02%±6.40%],P<0.05;For WM35 cells:0 vs.120 mmol/L:[100.00%±0%]vs.[51.80%±3.45%],P<0.05)but exerted less impact on normal melanocytes.CPS promoted melanoma cell apoptosis through TRPV channels and the caspase cascade.CPS treatment then led to TRPV channel-dependent mitochondrial dysfunction with an increase in reactive oxygen species generation(For A2058 cells:CPS vs.CPS+RR:[2.34±0.30]vs.[1.34±0.12],P<0.05;For WM35 cells:CPS vs.CPS+RR:[2.25±0.25]vs.[1.65±0.13],P<0.05),dissipation of the mitochondrial membrane potential(Control vs.CPS:[1.00±0]vs.[0.61±0.08],P<0.05),and adenosine triphosphate reduction(P<0.05).In addition,reactive oxygen species generation contributed to CPS-induced melanoma cell apoptosis.Mitochondrial fission was subsequently proved to connect CPS treatment to mitochondrial dysfunction,which was also TRPV channel-dependent,thereby inducing melanoma cell apoptosis.Conclusion:Our study highlights the role of mitochondrial fission and its related mitochondrial dysfunction in mediating the pro-apoptotic effect of CPS in melanoma.These findings deepen our understanding of the mechanisms underlying the anti-tumor activity of CPS and indicate the clinical relevancy of extending the use of this agent for cancer therapy.
基金Hainan Provincial Natural Science Foundation of China(820RC636)Special Scientific Research Project of Hainan Academician Innovation Platform(YSPTZX202132)Hainan Province Science and Technology Special Fund(ZDYF2021SHFZ222).
文摘Cone snail venoms have been considered a valuable treasure for international scientists and businessmen, mainly due to theirpharmacological applications in development of marine drugs for treatment of various human diseases. To date, around 800Conus species are recorded, and each of them produces over 1,000 venom peptides (termed as conopeptides or conotoxins).This reflects the high diversity and complexity of cone snails, although most of their venoms are still uncharacterized.Advanced multiomics (such as genomics, transcriptomics, and proteomics) approaches have been recently developed to minediverse Conus venom samples, with the main aim to predict and identify potentially interesting conopeptides in an efficientway. Some bioinformatics techniques have been applied to predict and design novel conopeptide sequences, related targets, andtheir binding modes. This review provides an overview of current knowledge on the high diversity of conopeptides andmultiomics advances in high-throughput prediction of novel conopeptide sequences, as well as molecular modeling and designof potential drugs based on the predicted or validated interactions between these toxins and their molecular targets.