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1.
Sci Total Environ ; 952: 175955, 2024 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-39222819

RESUMO

The study assessed the impacts of aquatic plant silages on feeding efficiency and dairy cattle health as an alternative to conventional corn silage under high altitude conditions. Mid-lactation Holstein cows were assigned to treatment groups according to a randomized complete block design of parity, previous 105-d milk yield, and body weight. Cows (n = 8 per group) were fed with aquatic plant silage inoculated with Bacillus subtilis (BS), Yeast (YS), or conventional corn silage without inoculants (control) in addition to [standard grain feed] for 75 consecutive days. BS and YS had higher protein contents than control silage (111.20 ± 7.68, 112.10 ± 6.83 vs 76.94 ± 3.48 g/kg DM), while feeding efficiency was comparable between treatments (1.07, 0.99, and 0.90, respectively). In addition, the addition of aquatic plant silage in ruminant diets enhanced immunity and antioxidant capacity when compared with control group. Metagenomic analysis showed similar composition in rumen microbiota between YS and control groups, with higher enrichment for energy and nitrogen utilization pathways in YS-treated cows. This study highlights the use of aquatic plant silage as an alternative feed for dairy cattle with higher protein than corn silage. Our results suggest YS or BS could potentially boost immune and antioxidant functions, improving adaptation to high-altitudes and reducing demand for high input corn production on the Qinghai-Tibetan Plateau.


Assuntos
Ração Animal , Silagem , Animais , Bovinos , Ração Animal/análise , Indústria de Laticínios , Dieta/veterinária , Feminino , Zea mays , Bacillus subtilis , Fermentação , Rúmen/metabolismo
2.
J Am Chem Soc ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235449

RESUMO

Extracellular vesicles (EVs) harbor abundant glycans that mediate various functions, such as intercellular communication and disease advancement, which play significant roles in disease progression. However, the presence of EV heterogeneity in body fluids and the complex nature of the glycan structures have posed challenges for the detection of EV glycans. In this study, we provide a streamlined method integrated, membrane-specific separation with lectin-induced aggregation strategy (MESSAGE), for multiplexed profiling of EV glycans. By leveraging a rationally designed lectin-induced aggregation strategy, the expression of EV glycans is converted to size-based signals. With the assistance learning machine algorithms, the MESSAGE strategy with high sensitivity, specificity, and simplicity can be used for early cancer diagnosis and classification, as well as monitoring cancer metastasis via 20 µL plasma sample within 2 h. Furthermore, our platform holds promise for advancing the field of EV-based liquid biopsy for clinical applications, opening new possibilities for the profiling of EV glycan signatures in various disease states.

4.
Pathogens ; 13(8)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39204291

RESUMO

Mosquitoes are vectors of many important human diseases. The prolonged and widespread use of insecticides has led to the development of mosquito resistance to these insecticides. The gut microbiota is considered the master of host development and physiology; it influences mosquito biology, disease pathogen transmission, and resistance to insecticides. Understanding the role and mechanisms of mosquito gut microbiota in mosquito insecticide resistance is useful for developing new strategies for tackling mosquito insecticide resistance. We searched online databases, including PubMed, MEDLINE, SciELO, Web of Science, and the Chinese Science Citation Database. We searched all terms, including microbiota and mosquitoes, or any specific genera or species of mosquitoes. We reviewed the relationships between microbiota and mosquito growth, development, survival, reproduction, and disease pathogen transmission, as well as the interactions between microbiota and mosquito insecticide resistance. Overall, 429 studies were included in this review after filtering 8139 search results. Mosquito gut microbiota show a complex community structure with rich species diversity, dynamic changes in the species composition over time (season) and across space (environmental setting), and variation among mosquito species and mosquito developmental stages (larval vs. adult). The community composition of the microbiota plays profound roles in mosquito development, survival, and reproduction. There was a reciprocal interaction between the mosquito midgut microbiota and virus infection in mosquitoes. Wolbachia, Asaia, and Serratia are the three most studied bacteria that influence disease pathogen transmission. The insecticide resistance or exposure led to the enrichment or reduction in certain microorganisms in the resistant mosquitoes while enhancing the abundance of other microorganisms in insect-susceptible mosquitoes, and they involved many different species/genera/families of microorganisms. Conversely, microbiota can promote insecticide resistance in their hosts by isolating and degrading insecticidal compounds or altering the expression of host genes and metabolic detoxification enzymes. Currently, knowledge is scarce about the community structure of mosquito gut microbiota and its functionality in relation to mosquito pathogen transmission and insecticide resistance. The new multi-omics techniques should be adopted to find the links among environment, mosquito, and host and bring mosquito microbiota studies to the next level.

5.
Anal Chem ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155608

RESUMO

Small extracellular vesicles (sEVs) assume pivotal roles as vital messengers in intercellular communication, boasting a plethora of biological functions and promising clinical applications. However, efficient isolation and sensitive detection of sEVs continue to present formidable challenges. In this study, we report a novel method for fast isolation and highly sensitive multicolor visual detection of sEVs using aptamer-functionalized polydopamine nanospheres (SIMPLE). In the SIMPLE strategy, aptamer-functionalized polydopamine nanospheres (Apt-PDANS) with 170 nm diameters were synthesized and exhibited a remarkable ability to selectively bind to specific proteins on the surface of sEVs. The binding between sEVs and Apt-PDANS engenders an increase in the overall size of the sEVs, allowing fast isolation of sEVs by filtration (a filter membrane with a pore size of 200 nm). The fast isolation strategy not only circumvents the interference posed by unbound proteins and excessive probes as well as the intricacies associated with conventional ultracentrifugation methods but also expedites the separation of sEVs. Concurrently, the incorporation of Fe3+-doped PDANS permits the multicolor visual detection of sEVs, enabling quantitative analysis by the discernment of visual cues. The proposed strategy achieves a detection limit of 3.2 × 104 sEV mL-1 within 1 h, devoid of any reliance on instrumental apparatus. Furthermore, we showcase the potential application of this methodology in epithelial-mesenchymal transition monitoring and cancer diagnosis, while also envisioning its widespread adoption as a straightforward, rapid, sensitive, and versatile platform for disease monitoring and functional exploration.

6.
BMC Pediatr ; 24(1): 524, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138576

RESUMO

BACKGROUND: Nonsuicidal self-injury (NSSI) is a serious problem in the adolescent population worldwide. Childhood trauma and bullying have been identified as risk factors for NSSI. We explored the relationships among Childhood trauma, Bullying victimization and the severity of NSSI behaviours, and test the effect of Bullying victimization in mediating the association between Childhood trauma and the NSSI behaviours. METHODS: A total of 123 adolescents were recruited. They were diagnosed with depression or depressive episodes of bipolar disorder and had experienced NSSI in the last year. They were assessed using the Chinese version of the Childhood Trauma Questionnaire (CTQ-C), the Revised Olweus Bullying Victimization Questionnaire (OBVQ-R), and the Adolescent Self-Harm Questionnaire (ASHQ). RESULTS: Females presented a significantly greater prevalence of sexual abuse and relationship bullying than boys. Individuals in the younger age group (10-14 years) presented a greater incidence of emotional neglect, verbal bullying, relationship bullying, and total bullying, and their NSSI score was also higher than that of those in the older age group (15-19 years). Only children show a greater prevalence of sexual abuse than nononly children. Single-parent families scored higher on emotional abuse, emotional neglect, physical neglect and physical bullying than two-parent families. There was a significant positive correlation between each dimension of childhood trauma and all the dimensions of bullying, between childhood trauma and NSSI, and between bullying and NSSI. Childhood trauma can not only directly affect the severity of NSSI but also indirectly aggravate the severity of NSSI through bullying victimization. The mediating effects of bullying victimization on emotional abuse, physical abuse, emotional neglect and physical neglect were 14%, 21%, 20%, 13% and 20%, respectively. CONCLUSION: There was a significant positive correlation between childhood trauma and bullying, between childhood trauma and NSSI, and between bullying and NSSI. Childhood trauma can not only directly affect the severity of NSSI but also indirectly aggravate the severity of NSSI through bullying victimization. Bullying victimization played the partial mediating effects between Childhood trauma and NSSI.


Assuntos
Bullying , Vítimas de Crime , Comportamento Autodestrutivo , Humanos , Adolescente , Bullying/psicologia , Masculino , Feminino , Criança , Vítimas de Crime/psicologia , Comportamento Autodestrutivo/psicologia , Comportamento Autodestrutivo/epidemiologia , Experiências Adversas da Infância/psicologia , Fatores de Risco , Adulto Jovem , Maus-Tratos Infantis/psicologia , China/epidemiologia , Prevalência , Inquéritos e Questionários
7.
Biol Trace Elem Res ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958867

RESUMO

Cadmium(Cd) is a toxic heavy metal widely present in the environment, capable of accumulating in the liver and causing liver damage. In this study, the mechanism of cadmium-induced liver fibrosis in chickens was investigated from the perspective of hepatocyte epithelial-mesenchymal transition (EMT) based on the establishment of a model of chicken cadmium toxicity and a model of cadmium-stained cells in a chicken hepatocellular carcinoma cell line (LMH). The 7-day-old chickens were randomly divided into the regular group (C group) and cadmium poisoning group (Cd group), and the entire test cycle was 60 days. Three sampling time points of 20 days, 40 days, and 60 days were established. By testing the liver coefficient, histopathological and ultrastructural changes in chicken livers were observed. The enzyme activities of liver function and the expression changes of fibrosis markers (COL1A1, Fibronectin), epithelial-mesenchymal transition markers (E-cadherin, Vimentin, and α-SMA), and the critical factors of the TGF-ß/SMAD signaling pathway (TGF-ß1, SMAD 2, and SMAD 3) were detected in the liver expression changes. The results showed that at the same sampling time point, the chicken liver coefficient in group Cd was significantly higher than that in control group (P < 0.01); the activities of the liver function enzymes ALT and AST in chickens in the Cd group were significantly higher than those in the C group (P < 0.01); liver hepatocytes degenerated and necrotic, the number of erythrocytes in the blood vessels was increased, and inflammatory cells infiltrated in the sinusoidal gap; the perisinusoidal gap of the liver was enlarged, and there was an apparent aggregation of collagen fibers in the intervening period as seen by transmission electron microscopy. The results of Masson staining showed that the percentage of fiber area was significantly higher in the chickens' livers of the Cd group. The fiber area percentage was significantly higher. The results of real-time fluorescence quantitative PCR and Western Blot showed that the expression of E-cadherin in the livers of chickens in the Cd group was significantly lower than that in the C group (P < 0.01). The expression of α-SMA, Vimentin, COL1A1, Fibronectin, TGF-ß1, SMAD 2, and SMAD 3 was significantly higher than that in the C group (P < 0.01). The results of in vitro assays showed that in the LMH cell model established by adding trimethylamine N-oxide, an activator of the TGF-ß/SMAD signaling pathway, and oxidized picric acid, an inhibitor of the TGF-ß/SMAD signaling pathway, the expression of E-cadherin was significantly reduced in cadmium-stained LMH cells (P < 0.01). The expression of α-SMA, Vimentin, COL1A1, Fibronectin, TGF-ß, SMAD 2, and SMAD 3 was significantly elevated (P < 0.01). Cadmium and Trimethylamine N-oxide, an activator of the TGF-ß/SMAD signaling pathway, promoted the expression of these factors. In contrast, the inhibitor of the TGF-ß/SMAD signaling pathway, Oxymatrine, a TGF-ß/SMAD signaling pathway inhibitor, significantly slowed down these changes. These results suggest that cadmium induces hepatic epithelial-mesenchymal transition by activating the TGF-ß/SMAD signaling pathway in chicken hepatocytes, promoting hepatic fibrosis.

8.
Cell Rep ; 43(6): 114356, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38865246

RESUMO

In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light treatment, the circuit mechanisms underlying the effects of light on itch-related behaviors remain poorly understood. In this study, we demonstrate that bright light treatment reduces itch-related behaviors in mice through a visual circuit related to the lateral parabrachial nucleus (LPBN). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which subsequently inhibit CaMKIIα+ neurons in the LPBN. Activation of both the vLGN/IGL-projecting RGCs and the vLGN/IGL-to-LPBN projections is sufficient to reduce itch-related behaviors induced by various pruritogens. Importantly, we demonstrate that the antipruritic effects of bright light treatment rely on the activation of the retina-vLGN/IGL-LPBN pathway. Collectively, our findings elucidate a visual circuit related to the LPBN that underlies the antipruritic effects of bright light treatment.


Assuntos
Núcleos Parabraquiais , Prurido , Animais , Camundongos , Núcleos Parabraquiais/fisiologia , Prurido/patologia , Luz , Células Ganglionares da Retina/efeitos da radiação , Vias Visuais/efeitos da radiação , Camundongos Endogâmicos C57BL , Masculino , Antipruriginosos/farmacologia , Antipruriginosos/uso terapêutico , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos da radiação , Comportamento Animal/efeitos da radiação , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo
9.
Adv Sci (Weinh) ; 11(30): e2401059, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38863324

RESUMO

Research highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusive. Here, LHb neurons are found projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and median raphe nucleus (MnR) exhibit increased bursting following aversive stimuli exposure, correlating with distinct depressive symptoms. Enhanced bursting in DRN-projecting LHb neurons is pivotal for anhedonia and anxiety, while concurrent bursting in LHb neurons projecting to the DRN, VTA, and MnR is essential for despair. Remarkably, reducing bursting in distinct LHb neuron subpopulations underlies the therapeutic effects of BLT on specific depressive behaviors. These findings provide valuable insights into the mechanisms of depression and the antidepressant action of BLT.


Assuntos
Depressão , Modelos Animais de Doenças , Habenula , Habenula/fisiologia , Animais , Camundongos , Masculino , Depressão/terapia , Comportamento Animal , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Fototerapia/métodos , Luz , Área Tegmentar Ventral
10.
Sci China Life Sci ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38926247

RESUMO

Suppressor tRNAs are engineered or naturally occurring transfer RNA molecules that have shown promise in gene therapy for diseases caused by nonsense mutations, which result in premature termination codons (PTCs) in coding sequence, leading to truncated, often nonfunctional proteins. Suppressor tRNAs can recognize and pair with these PTCs, allowing the ribosome to continue translation and produce a full-length protein. This review introduces the mechanism and development of suppressor tRNAs, compares suppressor tRNAs with other readthrough therapies, discusses their potential for clinical therapy, limitations, and obstacles. We also summarize the applications of suppressor tRNAs in both in vitro and in vivo, offering new insights into the research and treatment of nonsense mutation diseases.

11.
Metabolites ; 14(6)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38921445

RESUMO

Wild yeast suitable for kiwifruit wine fermentation was isolated and purified, and the fermentation process was optimized to increase the alcohol content of the kiwifruit wine. Pichia kluyveri was isolated from kiwifruit pulp by lineation separating, screened by morphological characteristics in Wallerstein Laboratory Nutrient Agar (WL) medium and microscope observation, and further identified by 26S rDNA D1/D2 domain sequence analysis. Taking alcohol content and sensory evaluation as two indexes, the fermentation condition for kiwifruit wine was optimized by single factor and response surface experiment. The optimal fermentation conditions were optimized as follows: the fermentation temperature was at 24 °C, the initial pH was 3.8, the sugar dosage in second step was 8% (w/w), and the inoculating quantity of Pichia kluyveri and Saccharomyces cerevisiae was 0.15 g/L at equal proportion. Under these optimal conditions, the maximum estimated alcohol content was 15.6 vol%, and the kiwifruit wine was light green in color with strong kiwifruit aroma and mellow taste.

12.
Expert Rev Clin Immunol ; 20(10): 1261-1267, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38785065

RESUMO

OBJECTIVES: This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjögren's Syndrome-related dry eyes (SS-DE). RESEARCH DESIGN AND METHODS: In this prospective, randomized trial included, 60 individuals with SS-DE symptoms were randomized to receive topical eye drops containing either 0.1% sodium hyaluronate (Group S) or 0.05% CsA (Group C) plus IPL therapy. Before the first treatment (baseline), and at 12, 16, and 20 weeks after treatment commencement, we assessed the best corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI) score, the Schirmer I test (SIT), noninvasive tear breakup time (NBUT), corneal fluorescein staining (CFS), meibomian gland (MG) dropout, lid margin abnormality, MG expressibility, and meibum quality. RESULTS: Both groups showed significant improvements in the OSDI, NBUT, CFS, MG expressibility, and meibum quality (all p < 0.05). Group C showed a greater increase in OSDI, NBUT, MG expressibility, and meibum quality (all p < 0.05). Moreover, SIT and lid margin abnormalities significantly improved in Group C (both p < 0.05), but not in Group S. CONCLUSION: Treatment with 0.05% CsA eyedrops plus IPL therapy could significantly reduce the issues and physical discomfort of patients with SS-DE. CLINICAL TRIAL: Registered on 20 July 2021, with the registration number ChiCTR2100049059.


Assuntos
Ciclosporina , Síndromes do Olho Seco , Soluções Oftálmicas , Síndrome de Sjogren , Humanos , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Síndrome de Sjogren/terapia , Síndrome de Sjogren/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/terapia , Síndromes do Olho Seco/etiologia , Masculino , Adulto , Estudos Prospectivos , Resultado do Tratamento , Terapia de Luz Pulsada Intensa/métodos , Terapia Combinada , Administração Tópica , Idoso , Glândulas Tarsais , Lágrimas/metabolismo , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico
13.
J Agric Food Chem ; 72(18): 10304-10313, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38657164

RESUMO

Neuropeptides are involved in many biological processes in insects. However, it is unclear what role neuropeptides play in Spodoptera litura adaptation to phytochemical flavone. In this study, 63 neuropeptide precursors from 48 gene families were identified in S. litura, including two neuropeptide F genes (NPFs). NPFs played a positive role in feeding regulation in S. litura because knockdown of NPFs decreased larval diet intake. S. litura larvae reduced flavone intake by downregulating NPFs. Conversely, the flavone intake was increased if the larvae were treated with NPF mature peptides. The NPF receptor (NPFR) was susceptible to the fluctuation of NPFs. NPFR mediated NPF signaling by interacting with NPFs to regulate the larval diet intake. In conclusion, this study suggested that NPF signaling regulated diet intake to promote S. litura adaptation to flavone, which contributed to understanding insect adaptation mechanisms to host plants and provide more potential pesticidal targets for pest control.


Assuntos
Proteínas de Insetos , Larva , Neuropeptídeos , Spodoptera , Animais , Spodoptera/fisiologia , Spodoptera/metabolismo , Neuropeptídeos/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/química , Larva/crescimento & desenvolvimento , Larva/metabolismo , Larva/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/química , Flavonas/metabolismo , Flavonas/química , Comportamento Alimentar , Sequência de Aminoácidos
14.
J Steroid Biochem Mol Biol ; 240: 106478, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38430971

RESUMO

Inflammation, an important biological protective response to tissue damage or microbial invasion, is considered to be an alarming signal for the progress of varied biological complications. Based on the previous reports in the literature that proved the noticeable efficacy of pyrazole and thiazole scaffold as well as nitrogen heterocyclic based compounds against acute and chronic inflammatory disease, a new set of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazole derivatives were synthesized and evaluated their anti-inflammatory activities in vitro. Preliminary structure-activity relationship (SAR) analysis was conducted by their inhibitory activities against nitric oxide (NO) release in lipopolysaccharide (LPS)-induced RAW 264.7 cells, and the optimal compound 12b [3ß-hydroxy-pregn-5-en-17ß-yl-5'- (o- chlorophenyl)- 1'-(4''- phenyl -[1'', 3'']- thiazol-2''- yl) - 4',5'-dihydro - 1'H-pyrazol - 3'- yl] exhibited more potent anti-inflammatory activity than the positive control treatment methylprednisolone (MPS), with an IC50 value of 2.59 µM on NO production and low cytotoxicity against RAW 264.7 cells. In further mechanism study, our results showed that compound 12b significantly suppressed the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and inhibited the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) through blocking NF-κB p65 nuclear translocation and phosphorylation of IκBα. Compound 12b also attenuated LPS-induced activation of c-Jun amino-terminal kinase (JNK) and p38 phosphorylation in RAW 264.7 cells. Molecular docking study revealed the strong binding affinity of compound 12b to the active site of the COX-2 proteins, which confirmed that compound 12b acted as an anti-inflammatory mediator. These results indicate that steroidal derivatives bearing 4,5-dihydropyrazole thiazole structure might be considered for further research and scaffold optimization in designing anti-inflammatory drugs and compound 12b might be a promising therapeutic anti-inflammatory drug candidate.


Assuntos
Anti-Inflamatórios , Ciclo-Oxigenase 2 , Desenho de Fármacos , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo II , Pirazóis , Tiazóis , Animais , Camundongos , Lipopolissacarídeos/farmacologia , Células RAW 264.7 , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Tiazóis/farmacologia , Tiazóis/química , Tiazóis/síntese química , Relação Estrutura-Atividade , Óxido Nítrico/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química
15.
Small ; 20(32): e2312229, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38488721

RESUMO

δ-MnO2 is a promising cathode material for aqueous aluminium-ion batteries (AAIBs) for its layered crystalline structure with large interlayer spacing. However, the excellent Al ion storage performance of δ-MnO2 cathode remains elusive due to the frustrating structural collapse during the intercalation of high ionic potential Al ion species. Here, it is discovered that introducing heterogeneous metal dopants with high bond dissociation energy when bonded to oxygen can significantly reinforce the structural stability of δ-MnO2 frameworks. This reinforcement translates to stable cycling properties and high specific capacity in AAIBs. Vanadium-doped δ-MnO2 (V-δ-MnO2) can deliver a high specific capacity of 518 mAh g-1 at 200 mA g-1 with remarkable cycling stability for 400 cycles and improved rate capabilities (468, 339, and 285 mAh g-1 at 0.5, 1, and 2 A g-1, respectively), outperforming other doped δ-MnO2 materials and the reported AAIB cathodes. Theoretical and experimental studies indicate that V doping can substantially improve the cohesive energy of δ-MnO2 lattices, enhance their interaction with Al ion species, and increase electrical conductivity, collectively contributing to high ion storage performance. These findings provide inspiration for the development of high-performance cathodes for battery applications.

16.
Phytomedicine ; 128: 155501, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38471318

RESUMO

BACKGROUND: The discovering of an osteoclast (OC) coupling active agent, capable of suppressing OC-mediated bone resorption while concurrently stimulating osteoblast (OB)-mediated bone formation, presents a promising strategy to overcome limitations associated with existing antiresorptive agents. However, there is a lack of research on active OC coupling agents. PURPOSE: This study aims to investigate the potential of Jiangu Formula (JGF) in inhibiting OCs while maintaining the OCOB coupling function. METHODS: The anti-osteoporosis efficacy of JGF was evaluated in osteoporosis models induced by ovariectomy in C57BL/6 mouse and SD rats. The effect of JGF on OCs was evaluated by detecting its capacity to inhibit OC differentiation and bone resorption in an in vitro osteoclastogenesis model induced by RANKL. The OCOB coupling activity of JGF was evaluated by measuring the secretion levels of OC-derived coupling factors, OB differentiation activity of MC3T3-E1 interfered with conditioned medium, and the effect of JGF on OC inhibition and OB differentiation in a C3H10T1/2-RAW264.7 co-culture system. The mechanism of JGF was studied by network pharmacology and validated using western blot, immunofluorescence (IF), and ELISA. Following that, the active ingredients of JGF were explored through a chemotype-assembly approach, activity evaluation, and LC-MS/MS analysis. RESULTS: JGF inhibited bone resorption in murine osteoporosis without compromising the OCOB coupling effect on bone formation. In vitro assays showed that JGF preserved the coupling effect of OC on OB differentiation by maintaining the secretion of OC-derived coupling factors. Network analysis predicted STAT3 as a key regulation point for JGF to exert anti-osteoporosis effect. Further validation assays confirmed that JGF upregulated p-STAT3(Ser727) and its regulatory factors IL-2 in RANKL-induced RAW264.7 cells. Moreover, 23 components in JGF with anti-OC activity identified by chemotype-assembly approach and verification experiments. Notably, six compounds, including ophiopogonin D, ginsenoside Re, ginsenoside Rf, ginsenoside Rg3, ginsenoside Ro, and ononin were identified as OC-coupling compounds. CONCLUSION: This study first reported JGF as an agent that suppresses bone loss without affecting bone formation. The potential coupling mechanism of JGF involves the upregulation of STAT3 by its regulators IL-2. Additionally, the chemotype-assembly approach elucidated the activity compounds present in JGF, offering a novel strategy for developing an anti-resorption agent that preserves bone formation.


Assuntos
Reabsorção Óssea , Diferenciação Celular , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos C57BL , Osteoblastos , Osteoclastos , Osteoporose , Ratos Sprague-Dawley , Animais , Osteoclastos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Osteoporose/tratamento farmacológico , Osteoblastos/efeitos dos fármacos , Feminino , Células RAW 264.7 , Diferenciação Celular/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Ovariectomia , Ligante RANK , Ratos , Osteogênese/efeitos dos fármacos , Modelos Animais de Doenças , Fator de Transcrição STAT3/metabolismo
17.
Adv Sci (Weinh) ; 11(22): e2310146, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38526153

RESUMO

Bladder cancer (BC) is one of the most common tumors characterized by a high rate of relapse and a lack of targeted therapy. Here, YEATS domain-containing protein 4 (YEATS4) is an essential gene for BC cell viability using CRISPR-Cas9 library screening is reported, and that HUWE1 is an E3 ligase responsible for YEATS4 ubiquitination and proteasomal degradation by the Protein Stability Regulators Screening Assay. KAT8-mediated acetylation of YEATS4 impaired its interaction with HUWE1 and consequently prevented its ubiquitination and degradation. The protein levels of YEATS4 and KAT8 are positively correlated and high levels of these two proteins are associated with poor overall survival in BC patients. Importantly, suppression of YEATS4 acetylation with the KAT8 inhibitor MG149 decreased YEATS4 acetylation, reduced cell viability, and sensitized BC cells to cisplatin treatment. The findings reveal a critical role of the KAT8/YEATS4 axis in both tumor growth and cisplatin sensitivity in BC cells, potentially generating a novel therapeutic strategy for BC patients.


Assuntos
Cisplatino , Histona Acetiltransferases , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Humanos , Cisplatino/farmacologia , Linhagem Celular Tumoral , Camundongos , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Animais , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Acetilação/efeitos dos fármacos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética
18.
Nat Methods ; 21(5): 857-867, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38374262

RESUMO

Studies using antigen-presenting systems at the single-cell and ensemble levels can provide complementary insights into T-cell signaling and activation. Although crucial for advancing basic immunology and immunotherapy, there is a notable absence of synthetic material toolkits that examine T cells at both levels, and especially those capable of single-molecule-level manipulation. Here we devise a biomimetic antigen-presenting system (bAPS) for single-cell stimulation and ensemble modulation of T-cell recognition. Our bAPS uses hexapod heterostructures composed of a submicrometer cubic hematite core (α-Fe2O3) and nanostructured silica branches with diverse surface modifications. At single-molecule resolution, we show T-cell activation by a single agonist peptide-loaded major histocompatibility complex; distinct T-cell receptor (TCR) responses to structurally similar peptides that differ by only one amino acid; and the superior antigen recognition sensitivity of TCRs compared with that of chimeric antigen receptors (CARs). We also demonstrate how the magnetic field-induced rotation of hexapods amplifies the immune responses in suspended T and CAR-T cells. In addition, we establish our bAPS as a precise and scalable method for identifying stimulatory antigen-specific TCRs at the single-cell level. Thus, our multimodal bAPS represents a unique biointerface tool for investigating T-cell recognition, signaling and function.


Assuntos
Ativação Linfocitária , Linfócitos T , Linfócitos T/imunologia , Humanos , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Apresentação de Antígeno , Dióxido de Silício/química , Compostos Férricos/química , Peptídeos/química , Peptídeos/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Nanoestruturas/química , Camundongos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo
19.
Disabil Rehabil ; : 1-7, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329457

RESUMO

PURPOSE: To evaluate the effect of respiratory muscle training on improving lung function in patients with stroke-associated pneumonia. MATERIALS AND METHODS: A systematic retrieval was conducted using the databases of the Cochrane Library, PubMed, the Web of Science, Embase, ProQuest, and others. Studies involving patients who received respiratory muscle training with/without a breathing trainer and those who adopted routine post-stroke rehabilitation training were included in the systematic review. The statistical analysis was performed using RevMan 5.3 software. RESULTS: Fourteen studies were included involving 850 patients with stroke. According to the results of the meta-analysis, compared with the control group, there were statistically significant differences in forced vital capacity (FVC) measurements (mean difference (MD) = 0.93, p < 0.0001) and improvement values for FEV1/FVC (MD = 0.65, p < 0.00001) in the experimental group. The FEV1 value was higher in the experimental group than in the control group (MD = 5.89, p < 0.0001). Furthermore, respiratory muscle training was superior to routine rehabilitation training for improving the PImax of patients with stroke (MD = 9.20, p < 0.0001). The patients had better respiratory tolerance after respiratory muscle training intervention (MD = 73.40, p < 0.0001). CONCLUSIONS: The implementation of respiratory muscle training can improve FVC and FEV lung function indicators, inspiratory muscle strength and the 6-min walk test results in patients with stroke.


Respiratory training-based pulmonary rehabilitation training can improve lung function and activity tolerance of stroke patients.Pulmonary rehabilitation training is more effective than standard rehabilitation training in enhancing PImax for stroke patients.Patients receiving pulmonary rehabilitation training have better activity tolerance after intervention.

20.
J Colloid Interface Sci ; 660: 859-868, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38277842

RESUMO

The issue of heavy metal contamination in water is a global concern, and the development of highly efficient adsorbent materials is crucial for the removal and detoxification of heavy metals. Polymer-based materials have emerged as a promising class of adsorbents due to their ability to capture heavy metal pollutants and reduce them to less toxic forms. The limited surface area of conventional polymer adsorbents makes them less effective for high-capacity adsorption. Herein, we present a low-temperature steam activation approach to address this challenge. This activation approach leads to a remarkable increase of over 20 times in the surface area of concave aminophenol-formaldehyde (APF) polymer nanospheres (from 45 to 961 m2/g) while preserving their reductive functional groups. The activated concave APF nanospheres were evaluated for their adsorption capabilities towards two typical heavy metal ions (i.e., Cr(VI) and Cd(II)) in aqueous solutions. The maximum adsorption capacities achieved were 1054 mg g-1 for Cr(VI) and 342 mg g-1 for Cd(II), which are among the highest performances reported in the literature and are much higher than the capacities of the non-activated APF nanospheres. Additionally, approximately 71.5 % of Cr(VI) was simultaneously reduced to Cr(III) through the benzenoid amine pathway during adsorption, highlighting the crucial role of the steam activation strategy in enhancing the capability of polymer adsorbents.

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