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1.
J Colloid Interface Sci ; 667: 303-311, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38640650

RESUMO

Metal selenides have emerged as promising Na-storage anode materials owing to their substantial theoretical capacity and high cost-effectiveness. However, the application of metal selenides is hindered by inferior electronic conductivity, huge volume variation, and sluggish kinetics of ionic migration. In response to these challenges, herein, a hierarchical hollow tube consisting of FeSe2 nanosheets and Se quantum dots anchored within a carbon skeleton (HT-FeSe2/Se/C) is strategically engineered and synthesized. The most remarkable feature of HT-FeSe2/Se/C is the introduction of Se quantum dots, which could lead to high electron density near the Fermi level and significantly enhance the overall charge transfer capability of the electrode. Moreover, the distinctive hollow tubular structure enveloped by the carbon skeleton endows the HT-FeSe2/Se/C anode with robust structural stability and fast surface-controlled Na-storage kinetics. Consequently, the as-synthesized HT-FeSe2/Se/C demonstrates a reversible capacity of 253.5 mAh/g at a current density of 5 A/g and a high specific capacity of 343.9 mAh/g at 1 A/g after 100 cycles in sodium-ion batteries (SIBs). Furthermore, a full cell is assembled with HT-FeSe2/Se/C as the anode, and a vanadium-based cathode (Na3V2(PO4)2O2F), showcasing a high specific capacity of 118.1 mAh/g at 2 A/g. The excellent performance of HT-FeSe2/Se/C may hint at future material design strategies and advance the development and application of SIBs.

2.
Phys Chem Chem Phys ; 26(7): 6208-6215, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305386

RESUMO

Two-dimensional (2D) materials with light weight and ultra-high electrical conductivity are expected to exhibit high capacity as anodes of batteries. We have explored the curved square lattice BS2 (b-BS2) monolayer possessing a space group similar to the transition metal chloride (space group: P4̄M2). The electrochemical performance of the b-BS2 monolayer as the anode for various metal-ion batteries (Li, Na, K, Mg, Ca, and Al) has been investigated. It exhibits low diffusion energy barrier, high theoretical capacity, and low open circuit voltage for Na/K-ion batteries (SIBs/PIBs). The ultrahigh energy densities of 2146.08 and 715.36 mA h g-1 can be achieved with the stoichiometries BS2Na6 and BS2K2, respectively. Furthermore, the b-BS2 monolayer may be synthesized on the surfaces of metal substrate materials (Ag(111), Al(111), and Au(111)). These results indicate that the b-BS2 monolayer is a good candidate for the anode material of SIBs/PIBs.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38363351

RESUMO

Dexmedetomidine has been used as a sedative drug in the clinic for a long time. Many studies demonstrated that the sedative mechanism of dexmedetomidine might be related to the activation of α2-adrenoceptor (α2AR). In addition, it was reported that dexmedetomidine had some affinity for the I1-imidazoline receptor (I1R); however, the role of I1R in dexmedetomidine-induced sedative effects and its possible mechanism are poorly studied. In the present study, we found that agmatine, an I1R agonist, was able to enhance the sedative effect of dexmedetomidine in mice. Efaroxan, an α2AR and I1R antagonist, could prevent and rescue the sedative action of dexmedetomidine in mice, and its preventive effect was better than atipamezole, the specific α2AR antagonist. Knockout of imidazoline receptor antisera-selected (IRAS), the functional I1R candidate protein, suppressed the dexmedetomidine-induced sedation. Moreover, IRAS knockout led to the inhibition of agmatine and efaroxan in regulating dexmedetomidine-induced sedative effects in mice, but not of atipamezole. We then used CHO cell lines that stably expressed α2AR and IRAS to investigate the possible molecular mechanism of IRAS in regulating the dexmedetomidine-induced sedative effect. The results showed that IRAS expression significantly up-regulated dexmedetomidine-induced ERK phosphorylation, which was enhanced by agmatine and inhibited by efaroxan at low concentrations. Therefore, by taking advantage of pharmacological and genetic approaches, our finding revealed the evidence that IRAS plays an important role in the sedative effects of dexmedetomidine, and the ERK signal pathway may be involved in the mechanism of IRAS in regulating dexmedetomidine-induced sedation. This study may offer valuable insights for the advancement of novel anesthetic adjuvants.

4.
Open Life Sci ; 19(1): 20220803, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299011

RESUMO

Low-carbohydrate diets (LCDs) are frequently recommended for alleviating obesity, and the gut microbiota plays key roles in energy metabolism and weight loss. However, there is limited in-human research on how LCD changes gut microbiota. In this before-after study, 43 participants were assigned to the LCD intervention for 4 weeks. The main objective was to investigate the specific changes that occur in the participants' microbiome in response to the LCD. Changes in gut microbiota were analyzed using 16s rRNA sequencing. Body composition was measured using InBody 770. Remarkably, 35 participants (79.07%) lost more than 5% of their body weight; levels of BMI, body fat, and total cholesterol were significantly decreased, indicating the effectiveness of the LCD intervention. The richness of microbiota significantly increased after the intervention. By taking the intersection of ANOVA and linear discriminant analysis effect size (LEfSe) analysis results, we identified three phyla, three classes, four orders, five families, and six genera that were differentially enriched between baseline and week-4 time points. Among the three phyla, relative abundances of Firmicutes and Actinobacteriota decreased significantly, while Bacteroidetes increased significantly. At the genus level, Ruminococcus, Agathobacter, Streptococcus, and Bifidobacterium showed a significant reduction in relative abundances, whereas Parabacteroides and Bacteroides increased steadily. Our results demonstrate that LCD can effectively alleviate obesity and modify certain taxa of gut microbiota, providing potential insights for personalized dietary interventions against obesity.

5.
J Org Chem ; 89(3): 2039-2049, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38241277

RESUMO

The application of the DMSO/SOCl2 system enabled the intramolecular cyclization/chlorination of N,N-disubstituted 2-alkynylanilines, leading to the synthesis of a series of 3-chloroindoles with moderate to good yields. Differing from the previously reported interrupted Pummerer reaction featuring the introduction of SMe moiety, the current approach adopted an alternative pathway that realized the incorporation of chlorine atom to the indole skeleton via a desulfonylative chlorocyclization process.

6.
Eur Radiol ; 34(3): 1597-1604, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37665388

RESUMO

OBJECTIVE: This prospective observational study aimed to evaluate the efficacy of radiofrequency ablation (RFA) in treating ≤ 2 cm thyroid nodules with Bethesda IV cytology and C-TIRADS 4A categorization. Additionally, the factors influencing the completed absorption of ablation (CAA) were examined. METHODS: A total of 62 cases with 62 nodules underwent ultrasound-guided RFA and were included in the study. The volume reduction rate (VRR), CAA, and incomplete absorption of ablation (IAA) were assessed at the 1st, 3rd, 6th, and subsequent 6-month follow-ups. Clinical and ultrasound features were compared between the CAA and IAA groups at the 12th month follow-up. RESULTS: The average VRR at the 1st, 3rd, 6th, 12th month, and last follow-up were -88.6%, 16.0%, 59.7%, 82.0%, and 98.2%, respectively. More than half of the nodules achieved a 90% VRR after 1 year of RFA, with 88.7% demonstrating CAA at the end of the study (follow-up duration of 14 to 63 months). Nodules with grade 3 vascularity and those associated with chronic thyroiditis showed delayed CAA at the 12th month follow-up (p = 0.036 and 0.003, respectively). CONCLUSION: RFA is an effective technique for treating ≤ 2 cm thyroid nodules with Bethesda IV cytology and C-TIRADS 4A categorization. Nodules with grade 3 blood supply and patients with chronic thyroiditis exhibited an impact on the completed absorption following RFA. CLINICAL RELEVANCE STATEMENT: Our study has shown that radiofrequency ablation is an effective treatment for ≤ 2 cm thyroid nodules classified as Bethesda IV cytology. However, we identified that high vascularity of the nodule and chronic thyroiditis are adverse factors affecting the completed absorption of the ablation. KEY POINTS: •Radiofrequency ablation (RFA) is an effective technique for treatment of ≤ 2 cm Bethesda IV category thyroid nodules. •Higher blood supply and chronic thyroiditis influence the completed absorption after RFA.


Assuntos
Ablação por Cateter , Doença de Hashimoto , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Tireoidite , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Ablação por Radiofrequência/métodos , Resultado do Tratamento , Ultrassonografia , Estudos Retrospectivos , Ablação por Cateter/métodos
7.
J Org Chem ; 89(1): 565-575, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38115769

RESUMO

An array of biologically interesting tri/difluoromethylated chromones and their heteroatom analogues were conveniently synthesized from the reaction of chromones and their heteroatom analogues with CF3SO2Na or HCF2SO2Na in the presence of tert-butyl hydroperoxide under mild conditions. A mechanistic pathway involving the generation of the electrophilic tri/difluoromethyl radical, followed with the radical substitution of chromones and their heteroatom analogues, was postulated.

8.
Phys Chem Chem Phys ; 25(36): 24468-24474, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37655746

RESUMO

Two-dimensional (2D) materials used as anodes in metal-ion batteries have attracted increased attention due to their high specific surface area, abundant active sites and good electronic properties. Searching for 2D materials with high storage capacities and low diffusion energy barriers is one of the most effective ways to design novel anode materials. In this work, based on first-principles calculations, we design a new 2D B3S2 monolayer with high thermodynamic and dynamic stability. The obtained B3S2 monolayer has a high cohesive energy, ensuring the feasibility of experimental synthesis. These characteristics of the B3S2 monolayer prompt us to explore its application as an anode material. The B3S2 monolayer exhibits not only a metallic nature but also a low diffusion energy barrier (0.037 eV) and open-circuit voltage (0.09 V). More importantly, the B3S2 monolayer shows a very high theoretical capacity of 1658 mA h g-1 as an anode material for sodium-ion batteries, which is comparable to other similar or common 2D materials. All of these intriguing properties make the B3S2 monolayer a promising 2D anode material for sodium-ion batteries.

9.
Toxins (Basel) ; 15(8)2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37624247

RESUMO

The highly toxic plant toxin ricin is one of the most known threatening toxins. Accurate and sensitive biosensing methods for the first emergency response and intoxication treatment, are always pursued in the biodefense field. Screening affinity molecules is the fundamental mainstream approach for developing biosensing methods. Compared with common affinity molecules such as antibodies and oligonucleotide aptamers, peptides have great potential as biosensing modules with more accessible chemical synthesis capability and better batch-to-batch stability than antibodies, more abundant interaction sites, and robust sensing performance towards complex environments. However, anti-ricin peptides are so scant to be screened and discovered, and an advanced screening strategy is the utmost to tackle this issue. Here, we present a new in silico-in vitro iteration-assisted affinity maturation strategy of anti-ricin peptides. We first obtained affinity peptides targeting ricin through phage display with five panning rounds of "coating-elution-amplification-enrichment" procedures. The binding affinity and kinetic parameters characterized by surface plasmon resonance (SPR) showed that we had obtained four peptides owning dissociation constants (KD) around 2~35 µM, in which peptide PD-2-R5 has the lower KD of 4.7 µM and higher stable posture to interact with ricin. We then constructed a new strategy for affinity maturity, composing two rounds of in silico-in vitro iterations. Firstly, towards the single-site alanine scanning mutation peptide library, the molecular docking predictions match the SPR evaluation results well, laying a solid foundation for designing a full saturation mutated peptide library. Secondly, plenty of in silico saturation mutation prediction results guided the discovery of peptides PD2-R5-T3 and PD-2-R5-T4 with higher affinity from only a limited number of SPR evaluation experiments. Both evolved peptides had increased affinity by about 5~20 times, i.e., KD of 230 nM and 900 nM. A primary cellular toxicity assay indicated that both peptides could protect cells against ricin damage. We further established an SPR assay based on PD-2-R5-T3 and PD-2-R5-T4 elongated with an antifouling peptide linkage and achieved good linearity with a sensitivity of 1 nM and 0.5 nM, respectively. We hope this new affinity-mature strategy will find its favorable position in relevant peptide evolution, biosensing, and medical countermeasures for biotoxins to protect society's security and human life better.


Assuntos
Técnicas Biossensoriais , Ressonância de Plasmônio de Superfície , Humanos , Biblioteca de Peptídeos , Simulação de Acoplamento Molecular , Peptídeos , Oligonucleotídeos
10.
J Cardiovasc Pharmacol ; 82(3): 201-211, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37418294

RESUMO

ABSTRACT: Serelaxin (sRLX) has an inhibitory effect on fibrosis. However, whether the antifibrotic effects of sRLX are achieved by inhibiting the inflammatory response has not been clarified. This study aimed to investigate the role of sRLX in lipopolysaccharide (LPS)-induced inflammation in cardiac fibroblasts and elucidate the underlying mechanisms. Cardiac fibroblasts were isolated from adult rat hearts. The effect of sRLX on the inhibition of the inflammatory response after LPS induction was examined. Cell viability was measured by MMT assay. Cell proliferation was determined using the Cell Counting Kit-8. The levels of inflammatory cytokines IL-1ß, IL-6, TNF-α, and IL-10 were measured using an enzyme-linked immunosorbent assay. The mRNA levels of α-smooth muscle actin (α-SMA), collagen I/III, MMP-2, MMP-9, IL-1ß, IL-6, TNF-α, IL-10, IκBα, p-IκBα, p65 subunit of nuclear factor-kappa B (NF-κB), and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed by real-time quantitative PCR. The protein levels of α-SMA, collagen I/III, MMP-2, MMP-9, IκBα, p-IκBα, p65, p-p65, and PPAR-γ were examined by western blotting. sRLX inhibited LPS-induced IL-1ß, IL-6, TNF-α, α-SMA, and collagen I/III, and elevated the expression of IL-10, MMP-2, and MMP-9. Moreover, LPS-induced activation of NF-κB pathway was suppressed by sRLX treatment. Further studies showed that sRLX did not significantly increase the expression of PPAR-γ mRNA and protein, but activated PPAR-γ activity, and the PPAR-γ inhibitor GW9662 reversed the inhibitory effect of sRLX on IL-1ß, IL-6, and TNF-α production. These results suggest that sRLX alleviates cardiac fibrosis by stimulating PPAR-γ through a ligand-independent mechanism that subsequently abolish the expression of NF-κB signaling pathway.


Assuntos
Lipopolissacarídeos , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Inibidor de NF-kappaB alfa/metabolismo , Inibidor de NF-kappaB alfa/farmacologia , Interleucina-10 , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , PPAR gama/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Transdução de Sinais , Fibroblastos/metabolismo , RNA Mensageiro/metabolismo , Colágeno
11.
J Org Chem ; 88(15): 11083-11095, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37450647

RESUMO

A metal-free synthesis of a series of fluoroalkyl-containing oxazoles from ß-monosubstituted enamines was developed. This fluoroacyloxylation/cyclization cascade process was mediated by fluoroalkyl-containing hypervalent iodine(III) species formed in situ from the reaction of phenyliodine(III) diacetate (PIDA) and RCF2CO2H (R = H, Cl, Br, F, CF3, CH3, Ph, SAr, OAr).

12.
Artigo em Inglês | MEDLINE | ID: mdl-37428662

RESUMO

Probabilistic analysis tool is important to quantify the impacts of the uncertainties on power system operations. However, the repetitive calculations of power flow are time-consuming. To address this issue, data-driven approaches are proposed but they are not robust to the uncertain injections and varying topology. This article proposes a model-driven graph convolution neural network (MD-GCN) for power flow calculation with high-computational efficiency and good robustness to topology changes. Compared with the basic graph convolution neural network (GCN), the construction of MD-GCN considers the physical connection relationships among different nodes. This is achieved by embedding the linearized power flow model into the layer-wise propagation. Such a structure enhances the interpretability of the network forward propagation. To ensure that enough features are extracted in MD-GCN, a new input feature construction method with multiple neighborhood aggregations and a global pooling layer are developed. This allows us to integrate both global features and neighborhood features, yielding the complete features representation of the system-wide impacts on every single node. Numerical results on the IEEE 30-bus, 57-bus, 118-bus, and 1354-bus systems demonstrate that the proposed method achieves much better performance as compared to other approaches in the presence of uncertain power injections and system topology.

13.
Environ Entomol ; 52(4): 750-758, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37318359

RESUMO

Ferritins are conserved iron-binding proteins that exist in most living organisms and play an essential role in the maintenance of cellular iron homeostasis. Although ferritin has been studied in many species, little is known about its role in the whitefly, Bemisia tabaci. In this study, we identified an iron-binding protein from B. tabaci and named it BtabFer1. The full-length cDNA of BtabFer1 is 1,043 bp and encodes a protein consisting of 224 amino acids with a deduced molecular weight of 25.26 kDa, and phylogenetic analysis shows that BtabFer1 is conserved among Hemiptera insects. The expression levels of BtabFer1 in different developmental stages and tissues were analyzed by real-time PCR, and results showed that BtabFer1 was ubiquitously expressed at all developmental stages and in all examined tissues. The RNAi-mediated knockdown of BtabFer1 caused a significant reduction in survival rate, egg production, and egg hatching rate of whiteflies. Knockdown of BtabFer1 also inhibited the transcription of genes in the juvenile hormone signal transduction pathway. Taken together, these results suggest that BtabFer1 plays a critical role in the development and reproduction of whiteflies. This study can broaden our understanding of ferritin in insect fecundity and development, as well as provide baseline data for future studies.


Assuntos
Ferritinas , Hemípteros , Animais , Ferritinas/genética , Ferritinas/metabolismo , Hemípteros/genética , Hemípteros/metabolismo , Filogenia , Interferência de RNA , Reprodução
14.
J Insect Sci ; 23(3)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37335595

RESUMO

The juvenile hormone (JH) plays a vital role in the regulation of a number of physiological processes, including development, reproduction, and ovarian maturation. Isopentenyl pyrophosphate isomerase (IPPI) is a key enzyme in the biosynthetic pathway of JH. In this study, we identified an isopentenyl pyrophosphate isomerase protein from Bemisia tabaci and named it BtabIPPI. The open reading frame (ORF) of BtabIPPI is 768 bp and encodes a protein of 255 amino acids that contains a conserved domain of the Nudix family. The temporal and spatial expression profiles showed that BtabIPPI was highly expressed in the female adults.RNA interference (RNAi)-mediated silencing of BtabIPPI reduced JH titers and the relative expression of vitellogenin receptor (VgR) and JH signaling pathway genes, resulting in a dramatic reduction in fecundity and hatchability. These results indicate that the BtabIPPI gene plays an important role in the female fecundity of B. tabaci. This study will broaden our understanding of the function of IPPI in regulating insect reproduction and provide a theoretical basis for targeting IPPI for pest control in the future.


Assuntos
Isomerases de Ligação Dupla Carbono-Carbono , Hemípteros , Feminino , Animais , Hemípteros/fisiologia , Interferência de RNA , Isomerases de Ligação Dupla Carbono-Carbono/genética , Isomerases de Ligação Dupla Carbono-Carbono/metabolismo , Hemiterpenos/metabolismo
15.
Analyst ; 148(12): 2782-2792, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37195783

RESUMO

The accurate and sensitive detection of active biotoxin proteins and the determination of their kinetics are vital for the upsurge of chemical attacks but still limited. Herein, we report a liquid chromatography-tunable ultraviolet spectroscopic-quadrupole mass spectrometric detection (LC-TUV-QDa) method of active ricin. This method has the advantage of the accurate quantification of active ricin in decreased oligonucleotide (oligo) substrates as well as the produced adenine, in which the QDa detection offers the confirmative evidence of oligo and adenine products. We invented a strong cation exchange (SCX)-tip sample pretreatment way to facilitate the requirement of clean product injection without any fouling proteins. After full-method validation, a wide linear range of 1-5000 ng mL-1 was obtained with a high sensitivity of 1 ng mL-1 active ricin based on the most preferable deoxynucleobase-hybrid RNA (Rd) substrate, Rd12, and without any enrichment. We also fully depicted the kinetic parameters of ricin and its six Rd or RNA substrates and evaluated 11 nucleobase-modified oligos as substrates based on Rd12. Further, we fulfilled an improved molecular docking analysis and revealed that the binding of Rd12 to ricin was more likely to occur at pH 7.4 (typical in vitro and in vivo conditions) than at pH 4.0 (typical ex vitro conditions). With the aid of SCX-tip as a microenzymatic reactor, we can exert the catalytic activity of ricin as N-glycosidase in pH 7.4 toward its Rd12 substrate, with a comparable catalytic efficiency at pH 4.0. This is the first successful implementation of an ex vitro experiment toward oligo substrates at neutral pH, standing on the shoulder of plenty of previously reported efforts all performed under acidic conditions. This method will provide a new and powerful way to detect active ricin when tackling relevant problems in public safety and security.


Assuntos
Ricina , Ricina/análise , Cromatografia Líquida , Cinética , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Adenina , RNA , Oligonucleotídeos
16.
Front Neurol ; 14: 1139521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908594

RESUMO

The mechanism of sudden unexpected death in epilepsy (SUDEP) is elusive and many questions remain unanswered. Autopsy is generally unhelpful in providing evidence for the cause of death, as pathological changes may be on the molecular level. Although histopathological examination occasionally demonstrates pathology such as vascular malformation, old traumatic injury, and tumor, in most cases of SUDEP, the examination is negative. We examined the current status of SUDEP research by performing a bibliometric analysis of studies in the Web of Science Core Collection database published between 2002 and 2022. Our aim was to demonstrate areas of interest and frontiers of SUDEP research. A total of 1803 papers were included in the analysis. The number of published papers focused on SUDEP has been increasing since 2002. Main areas of interest include clinical manifestations, prevalence, treatment, and underlying mechanisms. Research teams from the United States and Europe are leading the way in SUDEP research, while Asia trails behind. Future studies regarding the mechanism and neuropathology of SUDEP are warranted.

17.
Environ Entomol ; 52(1): 138-147, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36462170

RESUMO

Hepatocyte nuclear factor 4 (HNF4) is essential for glucose homeostasis and lipid metabolism in insects. However, little is known about the role of HNF4 in whiteflies. In the present study, we identified a hepatocyte nuclear factor protein from Bemsia tabaci (Diptera: Drosophilidae) and named it BtabHNF4. The full-length of BtabHNF4 was 3,006 bp, encoding a sequence of 434 amino acids that contains a conserved zinc-finger DNA-binding domain (DBD) and a well-conserved ligand-binding domain (LBD). The temporal and spatial expression showed that BtabHNF4 was highly expressed in the female adult stage and abdominal tissues of B. tabaci. A leaf-mediated RNA interference method was used to explore the function of BtabHNF4 in whiteflies. Our results showed that the knockdown of BtabHNF4 influences the desiccation tolerance, egg production, and egg hatching rate of whiteflies. Additionally, BtabHNF4 silencing significantly inhibited the expression level of vitellogenin. These results expand the function of HNF4 and pave the way for understanding the molecular mechanisms of HNF4 in regulating multiple physiological processes.


Assuntos
Hemípteros , Feminino , Animais , Hemípteros/genética , Dessecação , Interferência de RNA , Fatores Nucleares de Hepatócito/genética , Fertilidade
18.
Fish Shellfish Immunol ; 128: 565-573, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35964877

RESUMO

Tripartite motif (TRIM) proteins are a multifunctional family of ubiquitin E3 ligases involved in multiple biological processes. Studies have shown that many TRIM proteins in mammals play vital roles in the host defense against viral pathogens. In the present study, we identified a novel TRIM gene (MnTrim-like) from the oriental river prawn, Macrobrachium nipponense. Predicted MnTrim-like protein contains the characteristic RING finger domain. MnTrim-like was abundantly distributed in hepatopancreas, intestine, stomach, and gills. Upon white spot syndrome virus (WSSV) challenge, transcripts of MnTrim-like in the stomach were significantly up-regulated. Knockdown of MnTrim-like increased the expression of VP28 and decreased the synthesis of several antimicrobial peptides, including two crustins and one anti-lipopolysaccharide factor. Besides, silencing of these three antimicrobial peptides (AMPs) led to an increase in the expression of VP28 and WSSV copies. Moreover, it was found that injection of recombinant MnTrim-like protein with WSSV could decrease the transcription of VP28 and the number of virus particles. These results suggest that this MnTrim-like may restrict WSSV infection by positively regulating the expression of AMPs with antiviral activities and directly interacting with viral components. This study will broaden our understanding about the function of TRIM in crustacean during viral infection.


Assuntos
Palaemonidae , Vírus da Síndrome da Mancha Branca 1 , Animais , Antivirais/metabolismo , Proteínas de Artrópodes/química , Regulação da Expressão Gênica , Imunidade Inata/genética , Mamíferos/metabolismo , Palaemonidae/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinas/genética , Vírus da Síndrome da Mancha Branca 1/fisiologia
19.
Med Chem ; 19(1): 64-74, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674304

RESUMO

BACKGROUND: Genistein has been limited in clinical application due to its low bioavailability, extremely poor liposolubility, and fast glycosylation rate, though it possesses anti-breast cancer activity. Therefore, the discovery of novel genistein derivatives is an urgency. OBJECTIVE: To enhance the anti-breast cancer activity of genistein, a series of novel fluorinated genistein derivatives were synthesized. METHODS: Their in vitro antitumor activity was investigated by the MTT assay against three cancer cell lines, via, MDA-MB-231, MCF-7, and MDA-MB-435, respectively. RESULTS: Analogs 1d, 2b, and 3b showed remarkable anticancer activities compared to tamoxifen, a clinical anti-breast cancer drug on the market. CONCLUSION: The activities against breast cancer of genistein were enhanced by introducing the 7- alkoxyl group and fluorine atom into the B-ring. Therefore, these compounds may be potential candidates for treating breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Genisteína/farmacologia , Genisteína/uso terapêutico , Neoplasias da Mama/patologia , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Linhagem Celular , Proliferação de Células , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular
20.
Front Cell Dev Biol ; 10: 785058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35178386

RESUMO

Increasing evidence indicates that the abnormal expression of N6-methyladenosine (m6A) modification is closely related to the epigenetic regulation of immune response in breast cancer (BC). However, the potential roles of m6A modification in the tumor microenvironment (TME) of BC remain unclear. For addressing this issue, we comprehensively analyzed the m6A modification patterns in 983 samples and correlated these modification patterns with TME immune cell infiltration, based on 23 kinds of m6A regulators. Principal component analysis (PCA) was used to construct the m6A scoring system to quantify the modification pattern of m6A of BC individuals. Consequently, three different m6A modification patterns were identified, and the infiltrating characteristics of TME cells were consistent with the three immune phenotypes, including immune rejection, immune inflammation, and immune desert. Besides, our analysis showed that the prognosis of patients could be predicted by evaluating the m6A modification pattern in the tumor. The low m6Ascore corresponded to increased mutation burden and immune activation, while stroma activation and lack of immune infiltration were observed in high m6Ascore subtypes. In addition, a low m6Ascore was associated with enhanced response to anti-PD-1/PD-L1 immunotherapy. In conclusion, the m6A modification pattern was closely related to the BC immune landscape. This well-validated score model of the m6A modification patterns will provide a valuable tool to depict the tumor immune state and guide effective tumor immunotherapy for combating BC.

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