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Degradable biomedical elastomers (DBE), characterized by controlled biodegradability, excellent biocompatibility, tailored elasticity, and favorable network design and processability, have become indispensable in tissue repair. This review critically examines the recent advances of biodegradable elastomers for tissue repair, focusing mainly on degradation mechanisms and evaluation, synthesis and crosslinking methods, microstructure design, processing techniques, and tissue repair applications. The review explores the material composition and cross-linking methods of elastomers used in tissue repair, addressing chemistry-related challenges and structural design considerations. In addition, this review focuses on the processing methods of two- and three-dimensional structures of elastomers, and systematically discusses the contribution of processing methods such as solvent casting, electrostatic spinning, and three-/four-dimensional printing of DBE. Furthermore, we describe recent advances in tissue repair using DBE, and include advances achieved in regenerating different tissues, including nerves, tendons, muscle, cardiac, and bone, highlighting their efficacy and versatility. The review concludes by discussing the current challenges in material selection, biodegradation, bioactivation, and manufacturing in tissue repair, and suggests future research directions. This concise yet comprehensive analysis aims to provide valuable insights and technical guidance for advances in DBE for tissue engineering.
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Materiais Biocompatíveis , Elastômeros , Medicina Regenerativa , Engenharia Tecidual , Humanos , Elastômeros/química , Materiais Biocompatíveis/química , AnimaisRESUMO
Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.
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Produtos Agrícolas/classificação , Produtos Agrícolas/genética , Variação Genética , Genoma de Planta/genética , Oryza/classificação , Oryza/genética , Ásia , Evolução Molecular , Genes de Plantas/genética , Genética Populacional , Genômica , Haplótipos , Mutação INDEL/genética , Filogenia , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Three-dimensional (3D) electronic systems with their potential for enhanced functionalities often require complex fabrication processes. This paper presents a water-based, stimuli-responsive approach for creating self-assembled 3D electronic systems, particularly suited for biorelated applications. We utilize laser scribing to programmatically shape a water-responsive bilayer, resulting in smart 3D electronic substrates. Control over the deformation direction, actuation time, and surface curvature of rolling structures is achieved by adjusting laser-scribing parameters, as validated through experiments and numerical simulations. Additionally, self-locking structures maintain the integrity of the 3D systems. This methodology enables the implementation of spiral twining electrodes for electrophysiological signal monitoring in plants. Furthermore, the integration of self-rolling electrodes onto peripheral nerves in a rodent model allows for stimulation and recording of in vivo neural activities with excellent biocompatibility. These innovations provide viable paths to next-generation 3D biointegrated electronic systems for life science studies and medical applications.
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Eletrônica , Água , Eletrodos , Nervos Periféricos , Fenômenos EletrofisiológicosRESUMO
The development of sustainable technologies for efficient nitrate removal has attracted increasing attention, because excessive nitrate emissions can result in serious environmental, economic, and health effects. Herein, we propose to utilize FeSiBC metallic glass (MG) powders as a potential solution for nitrate removal. In terms of removal efficiency and reusability, our results show that the MG powders, as special zero-valent iron carriers, are 2-3 orders of magnitude more efficient in nitrate removal than the previous studies, while maintaining more than 50% nitrate removal efficiency after 9 cycles of reaction. Moreover, the optimal FeSiBC MG dosage, pH value, and temperature for nitrate removal are determined. The mechanism of nitrate removal is also revealed. The present study offers a promising approach to remediate nitrate, one of the world's most widespread water pollutants.
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In this work, the potential application of the fluorescence dye Thioflavin-T (ThT), which can specifically bind to amyloid, as a powerful tool for monitoring secondary structural transitions of silk fibroin (SF) induced by pH in low solution concentrations was examined. Results showed that ThT emission intensities substantially increased when pH decreased from 6.8 to 4.8. This increase may be ascribed to conformational transitions from random coil to ß-sheet. The morphology and secondary structure of SF were also investigated via TEM, AFM and circular dichroism spectroscopy. The information obtained herein can be utilized not only for the development of convenient and efficient noninvasive method for monitoring the assembly behavior of SF in aqueous solution but also for in vitro fluorescence imaging.
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Benzotiazóis , Fibroínas/química , Corantes Fluorescentes , Espectrometria de Fluorescência/métodos , Água , Concentração de Íons de Hidrogênio , Conformação Proteica , SoluçõesRESUMO
BACKGROUND: Third-generation sequencing platforms, such as PacBio sequencing, have been developed rapidly in recent years. PacBio sequencing generates much longer reads than the second-generation sequencing (or the next generation sequencing, NGS) technologies and it has unique sequencing error patterns. An effective read simulator is essential to evaluate and promote the development of new bioinformatics tools for PacBio sequencing data analysis. RESULTS: We developed a new PacBio Sequencing Simulator (PaSS). It can learn sequence patterns from PacBio sequencing data currently available. In addition to the distribution of read lengths and error rates, we included a context-specific sequencing error model. Compared to existing PacBio sequencing simulators such as PBSIM, LongISLND and NPBSS, PaSS performed better in many aspects. Assembly tests also suggest that reads simulated by PaSS are the most similar to experimental sequencing data. CONCLUSION: PaSS is an effective sequence simulator for PacBio sequencing. It will facilitate the evaluation and development of new analysis tools for the third-generation sequencing data.
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Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA , Software , Animais , Arabidopsis/genética , Caenorhabditis elegans/genética , Simulação por Computador , Escherichia coli/genéticaRESUMO
Insulin resistance (IR) continues to pose a major threat to public health due to its role in the pathogenesis of metabolic syndrome and its ever-increasing prevalence on a global scale. The aim of the current study was to investigate the efficacy of Anxa2 in obesity-induced IR through the mediation of the NF-κB signaling pathway. Microarray analysis was performed to screen differentially expressed genes associated with obesity. To verify whether Anxa2 was differentially expressed in IR triggered by obesity, IR mouse models were established in connection with a high-fat diet (HFD). In the mouse IR model, the role of differentially expressed Anxa2 in glycometabolism and IR was subsequently detected. To investigate the effect of Anxa2 on IR and its correlation with inflammation, a palmitic acid (PA)-induced IR cell model was established, with the relationship between Anxa2 and the NF-κB signaling pathway investigated accordingly. Anxa2 was determined to be highly expressed in IR. Silencing Anxa2 was shown to inhibit IR triggered by obesity. When Anxa2 was knocked down, elevated expression of phosphorylated insulin receptor substrate 1 (IRS1), IRS1 and peroxisome proliferator-activated receptor coactivator-1a, and glucose tolerance and insulin sensitivity along with 2-deoxy-d-glucose uptake was detected, whereas decreased expression of suppressor of cytokine signaling 3, IL-6, IL-1ß, TNF-α, and p50 was observed. Taken together, the current study ultimately demonstrated that Anxa2 may be a novel drug strategy for IR disruption, indicating that Anxa2 gene silencing is capable of alleviating PA or HFD-induced IR and inflammation through its negative regulatory role in the process of p50 nuclear translocation of the NF-κB signaling pathway.
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Anexina A2/deficiência , Anexina A2/genética , Resistência à Insulina/fisiologia , NF-kappa B/metabolismo , Obesidade/genética , Obesidade/metabolismo , Células 3T3-L1 , Animais , Anexina A2/antagonistas & inibidores , Dieta Hiperlipídica/efeitos adversos , Vetores Genéticos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Diversity-generating retroelements (DGRs) are a unique family of retroelements that generate sequence diversity of DNA to benefit their hosts by introducing variations and accelerating the evolution of target proteins. They exist widely in bacteria, archaea, phage and plasmid. However, our understanding about DGRs in natural environments was still very limited. RESULTS: We developed an efficient computational algorithm to identify DGRs, and applied it to characterize DGRs in more than 80,000 sequenced bacterial genomes as well as more than 4,000 human metagenome datasets. In total, we identified 948 non-redundant DGRs, which expanded the number of known DGRs in bacterial genomes and human microbiomes by about 55%, and provided a much more comprehensive reference for the study of DGRs. Phylogenetic analysis was done for identified DGRs. The putative target genes of DGRs were searched, and the functions of these target genes were investigated with a comprehensive alignment against the nr database. CONCLUSIONS: DGR system is a powerful and universal mechanism to generate diversity. DGR evolution is closely associated with the living environment and their cassette structures. Furthermore, it may impact a wide range of functional processes in addition to receptor-binding. These results significantly improved our understanding about DGRs.
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Evolução Molecular , Variação Genética , Genômica , Metagenoma/genética , Retroelementos/genética , Algoritmos , Bactérias/genética , Humanos , Microbiota/genéticaRESUMO
BACKGROUND: Obesity is one of the leading causes of insulin resistance. Accumulating reports have highlighted that serum amyloid A-1 (SAA1) is a potential candidate that is capable of attenuating insulin resistance. Hence, we conducted the current study with aims of investigating our proposed hypothesis that silencing SAA1 could inhibit the progression of obesity-induced insulin resistance through the NF-κB pathway. METHODS: Gene expression microarray analysis was initially performed to screen differentially expressed genes (DEGs) associated with obesity. Palmitate (PA)-induced insulin resistance Huh7 cell models and high-fat diet (HFD)-induced mouse models were established to elucidate the effect of SAA1/Saa1 on insulin resistance. The NF-κB pathway-related expression was subsequently determined through the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. RESULTS: Saa1 was identified as an obesity-related gene based on the microarray data of GSE39549. Saa1 was determined to be highly expressed in HFD-induced insulin resistance mouse models. PA-induced Huh7 cells, treated with silenced SAA1 or NF-κB pathway inhibition using BAY 11-7082, displayed a marked decrease in both Saa1 and SOCS3 as well as an elevation in 2DG, IRS1 and the extent of IRS1 phosphorylation. HFD mice treated with silenced Saa1 or inhibited NF-κB pathway exhibited improved fasting blood glucose (FBG) levels as well as fasting plasma insulin (FPI) levels, glucose tolerance and systemic insulin sensitivity. Saa1/SAA1 was determined to show a stimulatory effect on the transport of the NF-κBp65 protein from the cytoplasm to the nucleus both in vivo and in vitro, suggesting that Saa1/SAA1 could activate the NF-κB pathway. CONCLUSION: Taken together, our key findings highlight a novel mechanism by which silencing of SAA1 hinders PA or HFD-induced insulin resistance through inhibition of the NF-κB pathway.
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Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina/fisiologia , NF-kappa B/metabolismo , Ácido Palmítico/efeitos adversos , Proteína Amiloide A Sérica/metabolismo , Animais , Glicemia/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Jejum/sangue , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina/genética , Camundongos , Camundongos Endogâmicos C57BL , Análise Serial de Proteínas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Amiloide A Sérica/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
Metaproteomics provides a direct measure of the functional information by investigating all proteins expressed by a microbiota. However, due to the complexity and heterogeneity of microbial communities, it is very hard to construct a sequence database suitable for a metaproteomic study. Using a public database, researchers might not be able to identify proteins from poorly characterized microbial species, while a sequencing-based metagenomic database may not provide adequate coverage for all potentially expressed protein sequences. To address this challenge, we propose a metagenomic taxonomy-guided database-search strategy (MT), in which a merged database is employed, consisting of both taxonomy-guided reference protein sequences from public databases and proteins from metagenome assembly. By applying our MT strategy to a mock microbial mixture, about two times as many peptides were detected as with the metagenomic database only. According to the evaluation of the reliability of taxonomic attribution, the rate of misassignments was comparable to that obtained using an a priori matched database. We also evaluated the MT strategy with a human gut microbial sample, and we found 1.7 times as many peptides as using a standard metagenomic database. In conclusion, our MT strategy allows the construction of databases able to provide high sensitivity and precision in peptide identification in metaproteomic studies, enabling the detection of proteins from poorly characterized species within the microbiota.
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Mineração de Dados/métodos , Metagenômica/normas , Microbiota , Proteínas/análise , Proteômica/normas , Classificação/métodos , Simulação por Computador , Bases de Dados de ProteínasRESUMO
BACKGROUND/AIMS: This study sought to investigate the expression and prognostic value of peripheral blood microRNA-448 (miR-448) and its target gene SIRT1 after laparoscopic bariatric surgery in obese type 2 diabetic mellitus (T2DM) patients. METHODS: Obese T2DM patients were selected and treated with laparoscopic bariatric surgery. Enzyme-linked immunosorbent assay (ELISA) was used to measure SIRT1 protein expression. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to determine the mRNA expression of the related gene. Endothelial progenitor cells (EPCs) were grouped into blank, negative control (NC), miR-448 mimic, miR-448 inhibitor, siRNA-SIRT1 and miR-448 inhibitor + siRNA-SIRT1 groups. Transwell assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were applied to determine cell invasion and cell viability. A tube formation assay and an adherence test were utilized to assess the angiogenic and adhesive capacities of the cells. RESULTS: In peripheral blood, the expression of miR-448 was reduced, whereas the mRNA and protein expression of SIRT1 was increased after surgery compared to before surgery. miR-448 expression was lower and mRNA and protein expression of SIRT1 was higher in the effective group than in the ineffective group after surgery. SIRT1 is a target gene of miR-448. miR-448 can suppress viability and invasion, and it reflects the angiogenic and adhesive capacity of EPCs and the protein expression of relative genes in EPCs through targeting SIRT1. CONCLUSION: The results demonstrated that miR-448 and its target gene SIRT1 can serve as prognostic indicators for obese T2DM patients after laparoscopic bariatric surgery.
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Diabetes Mellitus Tipo 2/diagnóstico , MicroRNAs/genética , Obesidade Mórbida/diagnóstico , Sirtuína 1/genética , Adulto , Idoso , Antagomirs/metabolismo , Cirurgia Bariátrica , Células Cultivadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Laparoscopia , Modelos Logísticos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Prognóstico , Interferência de RNA , Sirtuína 1/análise , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , Regulação para CimaRESUMO
Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical pursuit. Currently used traditional block-shaped or mesh patches, typically incorporating a positive Poisson's ratio, often fall short of matching the deformation characteristics of cardiac tissue satisfactorily, thus often diminishing their repairing capability. By introducing auxeticity into the cardiac patches, this study is trying to present a beneficial approach to address these shortcomings of the traditional patches. The patches, featuring the auxetic effect, offer unparalleled conformity to the cardiac complex mechanical challenges. Initially, scaffolds demonstrating the auxetic effect were designed by merging chiral rotation and concave angle units, followed by integrating scaffolds with a composite hydrogel through thermally triggering, ensuring excellent biocompatibility closely mirroring heart tissue. Tensile tests revealed that auxetic patches possessed superior elasticity and strain capacity exceeding cardiac tissue's physiological activity. Notably, Model III showed an equivalent modulus ratio and Poisson's ratio closely toward cardiac tissue, underscoring its outstanding mechanical potential as cardiac patches. Cyclic tensile loading tests demonstrated that Model III withstood continuous heartbeats, showcasing outstanding cyclic loading and recovery capabilities. Numerical simulations further elucidated the deformation and failure mechanisms of these patches, leading to an exploration of influence on mechanical properties with alternative design parameters, which enabled the customization of mechanical strength and Poisson's ratio. Therefore, this research presents substantial potential for designing cardiac auxetic patches that can emulate the deformation properties of cardiac tissue and possess adjustable mechanical parameters.
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With the advancement of wearable and implantable medical devices, hydrogel flexible bioelectronic devices have attracted significant interest due to exhibiting tissue-like mechanical compliance, biocompatibility, and low electrical resistance. In this study, the development and comprehensive performance evaluation of poly(acrylic acid)/ N,N'-bis(acryloyl) cystamine/ 1-butyl-3-ethenylimidazol-1-ium:bromide (PAA/NB/IL) hydrogels designed for flexible sensor applications are introduced. Engineered through a combination of physical and chemical cross-linking strategies, these hydrogels exhibit strong mechanical properties, high biocompatibility, and effective sensing capabilities. At 95 % strain, the compressive modulus of PAA/NB/IL 100 reach up to 3.66 MPa, with the loading-unloading process showing no significant hysteresis loop, indicating strong mechanical stability and elasticity. An increase in the IL content was observed to enlarge the porosity of the hydrogels, thereby influencing their swelling behavior and sensing functionality. Biocompatibility assessments revealed that the hemolysis rate was below 5 %, ensuring their suitability for biomedical applications. Upon implantation in rats, a minimal acute inflammatory response was observed, comparable to that of the biocompatibility control poly(ethylene glycol) diacrylate (PEGDA). These results suggest that PAA/NB/IL hydrogels hold promise as biomaterials for biosensors, offering a balance of mechanical integrity, physiological compatibility, and sensing sensitivity, thereby facilitating advanced healthcare monitoring solutions.
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Resinas Acrílicas , Materiais Biocompatíveis , Técnicas Biossensoriais , Hidrogéis , Hidrogéis/química , Animais , Ratos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Resinas Acrílicas/química , Humanos , Propriedades de Superfície , Cistamina/química , Tamanho da Partícula , Imidazóis/química , Hemólise/efeitos dos fármacosRESUMO
Soft robots with good deformability and adaptability have important prospects in the bionics and intelligence field. However, current research into soft robots is primarily limited to the study of actuators and ignores the integrated use of functional devices and actuators. To enrich the functions of soft robots and expand their application fields, it is necessary to integrate various functional electronic devices into soft robots to perform diverse functions during dynamic deformation. Therefore, this paper discusses methods and strategies to manufacture optical stimuli-responsive soft actuators and integrate them into functional devices for soft robots. Specifically, laser cutting allows us to fabricate an optically responsive actuator structure, e.g., the curling direction can be controlled by adjusting the direction of the cutting line. Actuators with different bending curvatures, including nonbending, can be obtained by adjusting the cutting depth, cutting width, and the spacing of the cutting line, which makes it easy to obtain a folded structure. Thus, various actuators with complex shape patterns can be obtained. In addition, we demonstrate a fabrication scheme for a worm-like soft robot integrated with functional devices (LEDs are used in this paper). The local nonbending design provides an asymmetric structure that provides driving power and avoids damage to the functional circuit caused by the large deformation during movement. The integration of drive and function provides a new path for the application of soft robots in the intelligence and bionics field.
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Effectively and completely eliminating residual tumor cells is the key to reducing the risk of tumor metastasis and recurrence. Designing an "ideal" nanoplatform for programmable cancer therapy has great prospects for completely eliminating residual tumor cells. Herein, an intelligent nanoplatform of disulfiram (DSF)-loaded CuS-tannic acid nanohexahedrons (denoted as "DSF-CuS@TA") with thermal- and pH-sensitive degradation, as well as near-infrared (NIR-II) phototherapeutics properties, was constructed. And then, it was employed for in situ DSF toxification activation programmable "triple attack" cancer therapy. After accumulating in the tumor, DSF-CuS@TA first releases the loaded Cu(DTC)2, and simultaneously degrades and releases Cu2+ and DSF under mildly acidic stimulation to trigger instant intratumoral Cu(DTC)2 chelation, thereby achieving the "first strike." Next, under irradiation by a NIR-II laser, light energy is converted into heat to generate NIR-II photothermal therapy, thereby achieving the second strike. Subsequently, under thermal stimulation, DSF-CuS@TA degrades further, triggering the chelation of Cu(DTC)2 for a second time to reach the third strike. As expected, in vitro and in vivo studies showed that the synergistic integration of DSF-based programmed chemotherapy and NIR-II phototherapeutics could achieve effective tumor removal. Therefore, we propose a novel type of programmed therapy against cancer by designing a nanoplatform via "nontoxicity-to-toxicity" chemical chelation transformation.
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A new compound 3-acetyloxy-epicycloeucalenol-24-one (1), with 11 known compounds 3α-acetyloxy-4α,14α-dimethyl-9ß,19-cycloergost-24-oic acid (2), 3-epicycloeucalenol (3), 3-epicycloeucalenyl-24-one (4), 3-epicycloeucalenyl acetate (5), 4ß,14α-dimethyl-5α-ergosta-9ß,19-cyclo-24(31)-en-3ß-hydroxy-4α-carboxylic acid (6), cycloeucalenone (7), friedelin (8), epifriedelanol (9), lup-20 (29)-en-3ß,30-diol (10), betulin (11), lupeol (12), was isolated from the stems and leaves of Quercus variabilis Blume. Seven compounds (1-7) showed anti-inflammatory activity.
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Anti-Inflamatórios/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Quercus/química , Triterpenos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Orelha/patologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Folhas de Planta/química , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologia , Xilenos/toxicidadeRESUMO
Hydrogels are essential biomaterials due to their favorable biocompatibility, mechanical properties similar to human soft tissue extracellular matrix, and tissue repair properties. In skin wound repair, hydrogels with antibacterial functions are especially suitable for dressing applications, so novel antibacterial hydrogel wound dressings have attracted widespread attention, including the design of components, optimization of preparation methods, strategies to reduce bacterial resistance, etc. In this review, we discuss the fabrication of antibacterial hydrogel wound dressings and the challenges associated with the crosslinking methods and chemistry of the materials. We have investigated the advantages and limitations (antibacterial effects and antibacterial mechanisms) of different antibacterial components in the hydrogels to achieve good antibacterial properties, and the response of hydrogels to stimuli such as light, sound, and electricity to reduce bacterial resistance. Conclusively, we provide a systematic summary of antibacterial hydrogel wound dressings findings (crosslinking methods, antibacterial components, antibacterial methods) and an outlook on long-lasting antibacterial effects, a broader antibacterial spectrum, diversified hydrogel forms, and the future development prospects of the field.
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To help researchers in the field of biology, medicine, chemistry, and materials science to use lipidomic data conveniently, there is an urgent need to develop a platform that provides a systematic knowledgebase of human lipid metabolism and lipidome-centric omics analysis tools. DBLiPro is a user-friendly webserver allowing for access to human metabolism-related lipids and proteins knowledge database and an interactive bioinformatics integrative analysis workflow for lipidomics, transcriptomics, and proteomics data. In DBLiPro, there are 3109 lipid-associated proteins (LAPs) and 2098 lipid metabolites in the knowledge base section, which were obtained from Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG) and were further annotated by information from other public resources in the knowledge base section, such as RaftProt and PubChem. DBLiPro offers a step-by-step interactive analysis workflow for lipidomics, transcriptomics, proteomics, and their integrating multi-omics analysis focusing on the human lipid metabolism. In summary, DBLiPro is capable of helping users discover key molecules (lipids and proteins) in human lipid metabolism and investigate lipid-protein functions underlying mechanisms based on their own omics data. The DBLiPro is freely available at http://lipid.cloudna.cn/home.
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Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.
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Nanopartículas , Neoplasias da Próstata , Masculino , Humanos , Proteína X Associada a bcl-2 , Apoptose , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Zinco/farmacologia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Synthetic estrogens are the most hazardous and persistent environmental estrogenic contaminants, with few reports on their biodegradation. Pseudomonas citronellolis SJTE-3 degraded natural steroids efficiently and metabolized 17α-ethynylestradiol (EE2) with the addition of different easily used energy sources (glucose, peptone, ethanol, yeast extract, fulvic acid and ammonia). Over 92% of EE2 (1 mg/L) and 55% of EE2 (10 mg/L) in culture were removed in seven days with the addition of 0.1% ethanol, and the EE2-biotransforming efficiency increased with the increasing ethanol concentrations. Two novel intermediate metabolites of EE2 (C22H22O and C18H34O2) were identified with high-performance liquid chromatography (HPLC) and GC-Orbitrap/MS. Comparative analysis and genome mining revealed strain SJTE-3 contained a unique genetic basis for EE2 metabolism, and the putative EE2-degrading genes exhibited dispersed distribution. The EE2 metabolism of strain SJTE-3 was inducible and the transcription of eight genes were significantly induced by EE2. Three genes (sdr3, yjcH and cyp2) encoding a short-chain dehydrogenase, a membrane transporter and a cytochrome P450 hydroxylase, respectively, were vital for EE2 metabolism in strain SJTE-3; their over-expression accelerated EE2 metabolic processes and advanced the generation of intermediate metabolites. This work could promote the study of bacterial EE2 metabolism mechanisms and facilitate efficient bioremediation for EE2 pollution.