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N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.
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Doenças Cardiovasculares , Hepatócitos , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/química , Análise Custo-Benefício , RNA de Cadeia Dupla , Acetilgalactosamina/química , Proteína 3 Semelhante a AngiopoietinaRESUMO
Batteries play a pivotal role in various electrochemical energy storage systems, functioning as essential components to enhance energy utilization efficiency and expedite the realization of energy and environmental sustainability. Zn-based batteries have attracted increasing attention as a promising alternative to lithium-ion batteries owing to their cost effectiveness, enhanced intrinsic safety, and favorable electrochemical performance. In this context, substantial endeavors have been dedicated to crafting and advancing high-performance Zn-based batteries. However, some challenges, including limited discharging capacity, low operating voltage, low energy density, short cycle life, and complicated energy storage mechanism, need to be addressed in order to render large-scale practical applications. In this review, we comprehensively present recent advances in designing high-performance Zn-based batteries and in elucidating energy storage mechanisms. First, various redox mechanisms in Zn-based batteries are systematically summarized, including insertion-type, conversion-type, coordination-type, and catalysis-type mechanisms. Subsequently, the design strategies aiming at enhancing the electrochemical performance of Zn-based batteries are underscored, focusing on several aspects, including output voltage, capacity, energy density, and cycle life. Finally, challenges and future prospects of Zn-based batteries are discussed.
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Heteroatom-doped layered porous carbons are recently regarded as promising electrode materials for high energy density supercapacitors because they can integrate high-level heteroatom-doping and layered nano-space together to provide huge pseudocapacitive reaction areas and accelerate ion diffusion/transport. Herein, an innovative strategy is reported to prepare N/B/O co-doped layered porous carbons via ammonium folate-reinforced self-assembly of gelatin and boric acid followed by carbonization. Biomass-derived ammonium folate not only acts as an N-riched precursor but also can fasten in the process of self-assembly via boric acid-assisted electrostatic adsorption and hydrogen bonding to promote the formation of stable 3D cross-linked networks, resulting in the obtained N/B/O co-doped layered porous carbon (BNLC-850) has a large specific surface area (1822 m2 g-1 ), hierarchical porous structure and super-high heteroatom contents (N, 12.65; B, 5.67; and O, 13.84 at.%). The BNLC-850 achieves an ultrahigh specific capacitance of 525.2 F g-1 in the alkaline electrolyte at 0.5 A g-1 , meanwhile, DFT calculations reveal that the high-level N/B/O-doping can effectively weaken the adsorption barriers of K-ions. Moreover, the BNLC-850 assembles anti-freezing flexible solid-state supercapacitors in MPEI-TF-IL gel polymer electrolyte deliver a high energy density of 41.2 Wh kg-1 , excellent flexibility, and long cycle-life at -20 °C.
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Exploring covalent triazine frameworks (CTFs) with high capacitative activity is highly desirable and challenging. Herein, the S-rich CTFs cathode is pioneeringly introduced in Zn-ion hybrid supercapacitors (ZSC), achieving outstanding capacity and energy density, and satisfactory anti-freezing flexibility. Specifically, the S-bridged CTFs are synthesized by a bifunctional template-catalytic strategy, where ZnCl2 serves as both the catalyst/solvent and in situ template to construct triazine frameworks with interconnected pores and layered gaps. The resultant CTFs (CTFS-750) are employed as a reasonable pattern-like system to more deeply scrutinize the synergistic effect of S-bridged triazine and layered porous architecture for polymer-based cathodes in Zn-ion storage. The experimental results indicate that the adsorption barriers of Zn-ions on CTFS-750 are effectively weakened, and accessible Zn2+-absorption sites provided by the CâSâC and CâN bonds have been confirmed via DFT calculations. Consequently, the CTFS-750 cathode-assembled ZSC displays an ultra-high capacity of 211.6 mAh g-1 at 1.0 A g-1, an outstanding energy density of 202.7 Wh kg-1, and attractive cycling performance. Moreover, the resulting flexible ZSC device shows superior capacity, good adaptability, and satisfactory anti-freezing behavior. This approach sheds new light on constructing advanced polymer-based cathodes at the atom level and paves the way for fabricating high-performance ZSC and beyond.
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Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.
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Doenças Mitocondriais , Pancreatite , Quercetina/análogos & derivados , Animais , Camundongos , Pancreatite/tratamento farmacológico , Doença Aguda , Simulação de Acoplamento Molecular , Mitocôndrias , Transdução de SinaisRESUMO
Environmentally friendly crosslinked polymer networks feature degradable covalent or non-covalent bonds, with many of them manifesting dynamic characteristics. These attributes enable convenient degradation, facile reprocessibility, and self-healing capabilities. However, the inherent instability of these crosslinking bonds often compromises the mechanical properties of polymer networks, limiting their practical applications. In this context, environmentally friendly dual-crosslinking polymer networks (denoted EF-DCPNs) have emerged as promising alternatives to address this challenge. These materials effectively balance the need for high mechanical properties with the ability to degrade, recycle, and/or self-heal. Despite their promising potential, investigations into EF-DCPNs remain in their nascent stages, and several gaps and limitations persist. This Review provides a comprehensive overview of the synthesis, properties, and applications of recent progress in EF-DCPNs. Firstly, synthetic routes to a rich variety of EF-DCPNs possessing two distinct types of dynamic bonds (i.e., imine, disulfide, ester, hydrogen bond, coordination bond, and other bonds) are introduced. Subsequently, complex structure- and dynamic nature-dependent mechanical, thermal, and electrical properties of EF-DCPNs are discussed, followed by their exemplary applications in electronics and biotechnology. Finally, future research directions in this rapidly evolving field are outlined.
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BACKGROUND: Muscone is a chemical monomer derived from musk. Although many studies have confirmed the cardioprotective effects of muscone, the effects of muscone on cardiac hypertrophy and its potential mechanisms are unclear.The aim of the present study was to investigate the effect of muscone on angiotensin (Ang) II-induced cardiac hypertrophy. METHODS AND RESULTS: In the present study, we found for the first time that muscone exerted inhibitory effects on Ang II-induced cardiac hypertrophy and cardiac injury in mice. Cardiac function was analyzed by echocardiography measurement, and the degree of cardiac fibrosis was determined by the quantitative real-time polymerase chain reaction (qRT-PCR), Masson trichrome staining and western blot assay. Secondly, qRT-PCR experiment showed that muscone attenuated cardiac injury by reducing the secretion of pro-inflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Moreover, western blot analysis found that muscone exerted cardio-protective effects by inhibiting phosphorylation of key proteins in the STAT3, MAPK and TGF-ß/SMAD pathways. In addition, CCK-8 and determination of serum biochemical indexes showed that no significant toxicity or side effects of muscone on normal cells and organs. CONCLUSIONS: Muscone could attenuate Ang II-induced cardiac hypertrophy, in part, by inhibiting the STAT3, MAPK, and TGF-ß/SMAD signaling pathways.
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Traumatismos Cardíacos , Transdução de Sinais , Camundongos , Animais , Angiotensina II , Fator de Crescimento Transformador beta/metabolismo , Citocinas/metabolismo , Fibrose , Cardiomegalia/induzido quimicamenteRESUMO
Methods: The potential active ingredients and corresponding potential targets of BSYS Capsule were obtained from the TCMSP, BATMAN-TCM, Swiss Target Prediction platform, and literature research. Disease targets of CNSD were explored through the GeneCards and the DisGeNET databases. The matching targets of BSYS in CNSD were identified from a Venn diagram. The protein-protein interaction (PPI) network was constructed using bioinformatics methods. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the mechanisms of BSYS. Furthermore, the neuroprotective effects of BSYS were evaluated using a cell model of hydrogen peroxide- (H2O2-) induced cell death in OLN-93 cells. Results: A total of 59 potential bioactive components of BSYS Capsule and 227 intersection targets were obtained. Topological analysis showed that AKT had the highest connectivity degrees in the PPI network. Enrichment analysis revealed that the targets of BSYS in the treatment of CNSD were the PI3K-Akt and MAPK signaling pathway, among other pathways. GO analysis results showed that the targets were associated with various biological processes, including apoptosis, reactive oxygen species metabolic process, and response to oxidative stress, among others. The experimental results demonstrated that BSYS drug-containing serum alleviated the H2O2-induced increase in LDH, MDA, and ROS levels and reversed the decrease in SOD and mitochondrial membrane potential induced by H2O2. BSYS treatment also decreased the number of TUNEL (+) cells, downregulated Bcl-2 expression, and upregulated Bax and c-caspase-3 expression by promoting Akt phosphorylation. Conclusion: BSYS Capsule alleviated H2O2-induced OLN-93 cell injury by increasing Akt phosphorylation to suppress oxidative stress and cell apoptosis. Therefore, BSYS can be potentially used for CNSD treatment. However, the results of this study are only derived from in vitro experiments, lacking the validation of in vivo animal models, which is a limitation of our study. We will further verify the underlying mechanisms of BSYS in animal experiments in the future.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Animais , Sistema Nervoso Central , Medicamentos de Ervas Chinesas/uso terapêutico , Peróxido de Hidrogênio/farmacologia , Medicina Tradicional Chinesa/métodos , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-aktRESUMO
Despite grand advances in Zn-air batteries in recently years, their commercialization remains challenging due largely to the lack of efficient bifunctional oxygen catalysts. Herein, we report the crafting of a bifunctional electrocatalyst comprising ultrafine alloyed FeNi nanoparticles encapsulated within N-doped layered carbon nanosheets (denoted FeNi/N-LCN) for high-efficiency Zn-air batteries. The FeNi/N-LCN electrocatalyst is yielded via the coordination of triphenylimidazole-containing polyaniline (TPANI) oligomer with Fe- and Ni-containing precursors, followed by hydrogen binding with melamine and subsequent pyrolysis. The as-constructed FeNi/N-LCN manifests outstanding activity and stability toward both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The primary Zn-air battery assembled with FeNi/N-LCN delivers both high specific capacity and peak power density. Remarkably, the rechargeable Zn-air battery can be repeatedly charged and discharged for 1100 h at 5 mA cm-2 and for 600 h at 10 mA cm-2, representing the highest cycling stability among various reported Zn-air batteries.
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Given health threat by global warming and increased energy consumption in regulating body temperature, it is an urgent need to construct smart temperature-regulating materials. Herein, a novel fiber-spinning asymmetric chemical assembly (FACA) method is proposed to construct nanofiber materials with asymmetric photothermal properties. The silver nanowires (AgNWs) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) with opposite thermal radiation are assembled on reduced graphene oxide (rGO) film, imparting AgNW/rGO/PVDF-HFP film with Janus structure that can realize the AgNWs side consistently keeps temperature of ca. 11 °C lower than the side of PVDF-HFP nanofiber regardless of the irradiation directions under 1 sun, suggesting the adjustable photothermal regulation. Such photothermally selective hybrid nanofiber film provides great potential as fabrics to achieve all-weather smart clothes, promoting controllable and comprehensive utilization of solar energy.
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The past decade has witnessed tremendous advances in synthesis of metal halide perovskites and their use for a rich variety of optoelectronics applications. Metal halide perovskite has the general formula ABX3, where A is a monovalent cation (which can be either organic (e.g., CH3NH3+ (MA), CH(NH2)2+ (FA)) or inorganic (e.g., Cs+)), B is a divalent metal cation (usually Pb2+), and X is a halogen anion (Cl-, Br-, I-). Particularly, the photoluminescence (PL) properties of metal halide perovskites have garnered much attention due to the recent rapid development of perovskite nanocrystals. The introduction of capping ligands enables the synthesis of colloidal perovskite nanocrystals which offer new insight into dimension-dependent physical properties compared to their bulk counterparts. It is notable that doping and ion substitution represent effective strategies for tailoring the optoelectronic properties (e.g., absorption band gap, PL emission, and quantum yield (QY)) and stabilities of perovskite nanocrystals. The doping and ion substitution processes can be performed during or after the synthesis of colloidal nanocrystals by incorporating new A', B', or X' site ions into the A, B, or X sites of ABX3 perovskites. Interestingly, both isovalent and heterovalent doping and ion substitution can be conducted on colloidal perovskite nanocrystals. In this review, the general background of perovskite nanocrystals synthesis is first introduced. The effects of A-site, B-site, and X-site ionic doping and substitution on the optoelectronic properties and stabilities of colloidal metal halide perovskite nanocrystals are then detailed. Finally, possible applications and future research directions of doped and ion-substituted colloidal perovskite nanocrystals are also discussed.
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The rational design and facile synthesis of metal organic framework (MOF)-derived carbon materials with high oxygen reduction reaction (ORR) activity still remains challenging. Herein, we report on a simple yet robust route to dual-shelled Co, N, and S co-doped hollow carbon nanocages (denoted Co-N/S-DSHCN) with outstanding ORR performance. The concurrent compositional and structural engineering of the zeolitic imidazolate framework (ZIF-67), enabled by its coating with trithiocyanuric acid (TCA), yields core-shelled precursor particles which are subsequently carbonized into Co-N/S-DSHCN. Notably, Co-N/S-DSHCN-3.5 outperforms the commercial Pt/C, representing a +25 mV onset potential (Eon) and a +43 mV half-wave potential (E1/2) in 0.1 M KOH and a comparable E1/2 to Pt/C in 0.5 M H2SO4, respectively. Such impressive ORR activities of Co-N/S-DSHCN-3.5 originate from the effective synergy of Co, N, and S co-doping (i.e., a compositional tuning) in conjunction with a unique dual-shelled hollow architecture containing hierarchical porosity (i.e., a structural tailoring).
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The key to exploiting perovskite nanocrystals (NCs) for long-term practical use in optoelectronic materials and devices lies in the ability to access stable NCs. Herein, we report the crafting of hairy perovskite NCs with a set of markedly improved stabilities by capitalizing on rationally designed star-like molecular bottlebrush trilobes as nanoreactors. An intriguing star-like molecular bottlebrush trilobe, poly(2-hydroxyethyl methacrylate)-graft-(poly(acrylic acid)-block-partially cross-linked polystyrene (denoted PHEMA-g-(PAA-b-cPS)) is synthesized. Subsequently, it is employed as a polymeric nanoreactor to direct the growth of green-emitting all-inorganic perovskite CsPbBr3 NCs intimately and stably tethered by partially cross-linked PS "hairs" (i.e., cPS-capped CsPbBr3 NCs). The resulting CsPbBr3 NCs exhibit an array of impressive stabilities against UV irradiation, moisture, heat, and water, due to permanently ligated hydrophobic cPS "hairs" on the surface of CsPbBr3 NCs as a result of the original covalent bonding between PAA and cPS blocks. More importantly, cPS-capped CsPbBr3 NCs manifest outstanding stability in various polar organic solvents. Such greatly improved stability can be attributed to the reduced surface defects enabled by the favorable interaction (i.e., coordination interaction and hydrogen bonding) between CsPbBr3 NCs and polar solvents, which dominates over their dissolution by polar solvents. Such exceptional stabilities impart the use of cPS-capped CsPbBr3 NCs as a selective probe for tracing the presence of Cl-/I- in polar organic solvents. The amphiphilic nonlinear block copolymer nanoreactor strategy can afford easy access to stable perovskite NCs of interest with controlled compositions and surface chemistry. They may find applications in solar cells, LEDs, photodetectors, lasers, bioimaging, biosensors, etc.
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Mimicking the diverse glyco-conjugate structures in nature is always the dream of scientists. Right now, hierarchical self-assembled structures of natural conjugates of peptides and sugars could not easily be achieved via linear glycopolypeptide with monosaccharides as attachments. In this work, by using a series of well-designed alternating amphiphilic glycopolypeptide brushes (AAGBs) with pendants of glycodendrons and short peptides, various self-assembled morphologies were achieved, including nanowires, nanoribbon, and compound micelles mainly depending on the number ratio of the sugar units to the amino acids species (S/F). Among these morphologies, nanowire attracted our great attention. TEM studies demonstrated that it is formed via a hierarchical self-assembly, i.e., a series of successive processes, including micellization, micelles alignment forming nanofilament, branching of the nanofilaments by micelles, and finally nanowire formation. As far as we know, such hierarchical self-assembly process with high complexity has not been observed in literature for glycopolypeptides even polypeptides, which will deepen our understanding on self-assembly mechanism of natural glyco-conjugates and expand the library of biomimetic materials.
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Glicopeptídeos/química , Manose/química , Nanofios , Tensoativos/química , Micelas , Modelos Moleculares , Estrutura MolecularRESUMO
In this study, pH- and glucose-responsive Pickering emulsions stabilized by core crosslinked polymer nanoparticles, which were constructed via reversible covalent bonds, were presented for the first time. Firstly, well-defined PDMA-b-PAPBA (poly(N,N-dimethylacrylamide)-b-poly(3-acrylamidophenylboronic acid)) diblock copolymers were synthesized via sequential reversible addition-fragmentation chain transfer (RAFT) polymerization reactions. By means of complexation of PBA units of PDMA-b-PAPBA with PVA in basic water, core crosslinked polymer nanoparticles (CCPNs) with a core-shell structure were formed. The PAPBA/PVA crosslinked network and PDMA acted as the core and shell, respectively. Because of the reversible B-O chemical bonds in the core, the as-produced CCPNs showed structural transitions in response to the external stimuli involving pH and glucose. Investigation of the interfacial activities revealed that CCPNs exhibited high emulsifying performances, and oil in water (o/w) Pickering emulsions could be formed at a low particle content. The formed Pickering emulsions showed high stability at room temperature without any disturbances, whereas de-emulsification was observed upon improving the pH or adding glucose at a given pH. This is the first report on a responsive Pickering emulsion whose stability can be manipulated by glucose, and this type of fabricated manipulative Pickering emulsions are expected to provide useful guidance in the fields of oil recovery, interfacial reactions, etc.
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In this paper, the contribution of nonpeptido small molecular linkers to the properties of sequence-defined peptidocopolymers was investigated. We synthesized four novel bioinspired peptidocopolymers (P1-P4) based on elastin motif pentapeptide (Gly-Pro-Gly-Gly-Ala) by step growth polymerization. Small molecular linkers, including tetraethylene glycol (M1), adipic acid (M2), isophthalic acid (M3), and terephthalic acid (M4) with different length and flexibility are employed to tune the conformation, physical, and mechanical properties of the corresponding peptidocopolymers P1-P4 respectively. Raman spectroscopy, solid state NMR, and circular dichroism spectroscopy were used to characterize the conformation of the four peptidocopolymers. The experimental results were further confirmed by molecular dynamics simulation of typical P2 and P4 with different repeating units. High ratio of ß-turn conformation was observed in P2 due to flexible linker M2; while affected by the hydrophobic and rigid M4 linker, P4 retained less ß-turn conformation and showed drastic difference on macroscopic properties. These simple step growth synthesis techniques provide an efficient approach toward a broad range of bioinspired peptidocopolymers, which takes a further insight into the significant effect of nonpeptido linkages toward chemical-synthesized peptidocopolymers.
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Adipatos/química , Peptidomiméticos/química , Ácidos Ftálicos/química , Polietilenoglicóis/química , Elastina/química , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Peptidomiméticos/síntese química , Polimerização , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
Purpose: Asymptomatic cerebral carotid artery stenosis (ACCAS) benefits from secondary prevention via statins and antiplatelets; nonetheless, the impact of medication alone is often limited. Evidence has suggested enhanced therapeutic outcomes when Chinese patent medicine-specifically, compound dilong capsules (CDC)-is integrated with conventional secondary prevention measures. Patients and Methods: We retrospectively analyzed 319 ACCAS patients from January 2018 to December 2022 at Xuanwu Hospital, Capital Medical University. Depending on the clinical outcomes-improvement or stabilization versus progression-patients were classified into effective or ineffective treatment groups. Patient medical records and questionnaire responses were the primary data sources. The study accounted for demographic variables, clinical history, and medication details, with the primary focus on CDC use and its duration. Treatment outcomes were gauged alongside Transcranial color-coded sonography and Carotid Doppler ultrasonography findings. We employed both univariate and multivariate statistical methods to assess the data. Results: CDC administration (aOR=2.51, 95% CI 1.39-4.54, P=0.002) and extended usage beyond six months (aOR=3.54, 95% CI 1.71-7.32, P=0.001) demonstrate a statistically significant correlation with treatment efficacy. Gender (aOR=2.54, 95% CI 1.30-5.00, P=0.007), hypertension management (aOR=0.56, 95% CI 0.33-0.95, P=0.031), and antiplatelet therapy with aspirin (aOR=9.53, 95% CI 1.15-78.89, P=0.037) or clopidogrel (aOR=9.97, 95% CI 1.10-90.12, P=0.041) also influenced the therapeutic outcome significantly. Conclusion: Incorporating CDC as part of a secondary prevention strategy for over six months can beneficially modulate and limit the progression of vascular stenosis in ACCAS. These findings underscore the value of combining traditional Chinese medicine with modern pharmacological interventions in ACCAS management.
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Purpose: The aim of this study is to investigate abdominal aortic aneurysm (AAA), a disease characterised by inflammation and progressive vasodilatation, for novel gene-targeted therapeutic loci. Methods: To do this, we used weighted co-expression network analysis (WGCNA) and differential gene analysis on samples from the GEO database. Additionally, we carried out enrichment analysis and determined that the blue module was of interest. Additionally, we performed an investigation of immune infiltration and discovered genes linked to immune evasion and mitochondrial fission. In order to screen for feature genes, we used two PPI network gene selection methods and five machine learning methods. This allowed us to identify the most featrue genes (MFGs). The expression of the MFGs in various cell subgroups was then evaluated by analysis of single cell samples from AAA. Additionally, we looked at the expression levels of the MFGs as well as the levels of inflammatory immune-related markers in cellular and animal models of AAA. Finally, we predicted potential drugs that could be targeted for the treatment of AAA. Results: Our research identified 1249 up-regulated differential genes and 3653 down-regulated differential genes. Through WGCNA, we also discovered 44 genes in the blue module. By taking the point where several strategies for gene selection overlap, the MFG (ITGAL and SELL) was produced. We discovered through single cell research that the MFG were specifically expressed in T regulatory cells, NK cells, B lineage, and lymphocytes. In both animal and cellular models of AAA, the MFGs' mRNA levels rose. Conclusion: We searched for the AAA novel targeted gene (ITGAL and SELL), which most likely function through lymphocytes of the B lineage, NK cells, T regulatory cells, and B lineage. This analysis gave AAA a brand-new goal to treat or prevent the disease.
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Breast cancer represents a substantial contributor to mortality rates among women with cancer. Chemical dynamic therapy is a promising anticancer strategy that utilizes the Fenton reaction to transform naturally occurring hydrogen peroxide (H2O2) into hydroxyl radicals (â¢OH). Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells. In this study, we proposed a Fe3O4@R837 smart nanoplatform that can trigger the Fenton reaction and induce immune responses in breast cancer treatment. Furthermore, we performed transcriptome sequencing on breast cancer samples and used the R package (limma) to analyze differential expression profiles and select differentially expressed genes (DEGs). We obtained clinical information and RNA expression matrix data from The Cancer Genome Atlas database to perform survival analysis and identify prognostic-related genes (PRGs) and molecular subtypes with distinct prognoses. We used the TIMER 2.0 web and other methods to determine the tumor immune microenvironment and immune status of different prognostic subtypes. We identified DPGs by taking the intersection of DEGs and PRGs and performed functional analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to elucidate potential mechanisms. Subsequently, we constructed a protein-protein interaction network using the STRING database to visualize the interactions between the DPGs. We screened hub genes from the DPGs using the Cytoscape plugin and identified six hub genes: CD3E, GZMK, CD27, SH2D1A, ZAP70, and TIGIT. Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.
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Neoplasias da Mama , Perfilação da Expressão Gênica , Imunoterapia , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/tratamento farmacológico , Feminino , Imunoterapia/métodos , Prognóstico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
Achieving effective hydrogen evolution/oxidation reaction (HER/HOR) across a wide pH span is of critical importance in unlocking the full potential of hydrogen energy but remains intrinsically challenging. Here, we engineer the N-coordinated Ir-Mo dual atoms on a carbon matrix by ultrafast high-temperature sintering, creating an efficient bifunctional electrocatalyst for both HER and HOR in both acidic and alkaline electrolytes. The optimized catalyst, Ir-Mo DAC/NC, demonstrates exceptional performance, with a significantly reduced HER overpotential of 11.3 mV at 10 mA/cm2 and a HOR exchange current (i0,m) of 3972 mA/mgIr in acidic conditions, surpassing the performance of Pt/C and Ir/C catalysts. In alkaline conditions, Ir-Mo DAC/NC also outperforms Pt/C, as evidenced by its low HER overpotential of 23 mV at 10 mA/cm2 and a high i0,m of 1308 mA/mgIr. Furthermore, our catalyst exhibits remarkable stability in both acidic and alkaline environments. DFT calculations results reveal that the superior electrochemical performance of Ir-Mo DAC/NC arises from the electronic synergy between Ir and Mo pairs, which regulates the interaction between the intermediates and active sites. These findings present a promising strategy for the development of dual-atom catalysts (DACs), with potential applications in the polymer fuel cells and water electrolyzers.