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1.
Cell Mol Life Sci ; 80(3): 63, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36781473

RESUMO

Adipose tissue CD11c+ myeloid cell is an independent risk factor associated with obesity and metabolic disorders. However, the underlying molecular basis remains elusive. Here, we demonstrated that liver kinase B1 (Lkb1), a key bioenergetic sensor, is involved in CD11c+ cell-mediated immune responses in diet-induced obesity. Loss of Lkb1 in CD11c+ cells results in obesity resistance but lower glucose tolerance, which accompanies tissue-specific immune abnormalities. The accumulation and CD80's expression of Lkb1 deficient adipose-tissue specific dendritic cells but not macrophages is restrained. Additionally, the balance of IL-17A and IFN-γ remarkably tips towards the latter in fat T cells and CD11c- macrophages. Mechanistically, IFN-γ promotes apoptosis of preadipocytes and inhibits their adipogenesis while IL-17A promotes the adipogenesis in vitro, which might account in part for the fat gain resistant phenotype. In summary, these findings reveal that Lkb1 is essential for fat CD11c+ dendritic cells responding to HFD exposure and provides new insights into the IL-17A/IFN-γ balance in HFD-induced obesity.


Assuntos
Proteínas Quinases Ativadas por AMP , Intolerância à Glucose , Resistência à Insulina , Obesidade , Animais , Camundongos , Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/metabolismo , Inflamação/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/complicações , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Interferon gama/metabolismo
2.
Nano Lett ; 23(3): 1010-1016, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36693172

RESUMO

Inspired by natural photosynthesis, light has become an emerging ionic behavior regulator and ion-pumping source. Nanoprocessing technology has allowed the bridge between the light-regulated nanofluids and the optoelectronic properties of two-dimensional (2D) materials, which inspires applications like energy harvesting and enhances fundamental understandings in nanofluidics. However, unlike light-induced ion pumping based on densely layered membranes with multiple nanochannels, experimental implementation on atomically thin materials featuring only a single nanochannel remains challenging. Here, we report light-induced ion pumping based on a single artificial heterojunction nanopore. Under light illumination, the induced current through a single nanopore reaches tens of picoamperes. The hole-electron separation originating from the optoelectrical property of a van der Waals PN junction is proposed to capture the light-driven ion transport. Further, different methods are adopted to modify the ion behavior and response time, presenting potential applications in fluidic photoenergy harvesting, photoelectric ion transport control, and bionic artificial neurons.

3.
Nano Lett ; 23(10): 4464-4470, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37154839

RESUMO

Classical nanofluidic frameworks account for the confined fluid and ion transport under an electrostatic field at the solid-liquid interface, but the electronic property of the solid is often overlooked. Harvesting the interaction of the nanofluidic transport with the electron transport in solid requires a route effectively coupling ion and electron dynamics. Here we report a nanofluidic analogy of Coulomb drag for exploring the dynamic ion-electron interactions at the liquid-graphene interface. An induced electric current in graphene by ionic flow with no bias directly applied to the graphene channel is observed experimentally, featuring an opposite electron current direction to the ion current. Our experiments and ab initio calculations show that the current generation stems from the confined ion-electron interactions via a nanofluidic Coulomb drag mechanism. Our findings may open up a new dimension for nanofluidics and transport control by ion-electron coupling.

4.
J Clin Psychol ; 78(7): 1354-1375, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35191525

RESUMO

OBJECTIVE: The present study tested the efficacy of an unguided internet-based Acceptance and Commitment Therapy (iACT) program for depression, and identified the psychological characteristics of participants who benefitted the most from the program. METHOD: Undergraduate students with mild to severe symptoms of depression were randomized to the iACT group (n = 95) or the waiting-list group (WLC group; n = 87). Depressive symptoms and positive mental health were assessed at baseline (T0 ), at the end of the 6-week program (T1 ), and at a 3-month follow-up (T2 ). RESULTS: Compared with the WLC group, the iACT group showed significantly more improvement in depressive symptoms (d = 1.27) and positive mental health (d = 0.59), both at T1 and T2 . Latent Profile Analysis identified three classes of participants: Sensitive-to-Relationship, Low-Reactive-Depression, and Endogenous-Depression group. In general, the treatment was particularly suitable for the Sensitive-to-Relationship class. CONCLUSION: The iACT was effective in treating the depressive symptoms of undergraduates, especially suitable for the clients with high baseline depression, high externality, high resistance, and high sensitivity to relationships.


Assuntos
Terapia de Aceitação e Compromisso , Depressão/psicologia , Depressão/terapia , Humanos , Internet , Estudantes , Resultado do Tratamento , Universidades
5.
Angew Chem Int Ed Engl ; 61(2): e202112150, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-34751999

RESUMO

Probing proton transport is of vital importance for understanding cellular transport, surface catalysis and fuel cells. Conventional proton transport measurements rely on the use of electrochemical conductivity and do not allow for the direct visualization of proton transport pathways. The development of novel experimental techniques to spatiotemporally resolve proton transport is in high demand. Here, building upon the general conversion of aqueous proton flux into spatially resolved fluorescence signals, we optically visualize proton transport through nanopores and along hydrophilic interfaces. We observed that the fluorescence intensity increased at negative voltage due to lateral transport. Thanks to the temporal resolution of optical imaging, our technique further empowers the analysis of proton transport dynamics.


Assuntos
Água
6.
Exp Cell Res ; 392(2): 112003, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32278689

RESUMO

Dendritic cells (DCs) play a central role in autoimmunity, immune homeostasis, and presentation of tumor antigens to T cells in order to prime antitumor responses. The number of tumor-infiltrating DCs is associated with survival and prognosis in cancer. Twist1 is a well-known regulator of tumor initiation and promotion, but whether and how DC-derived Twist1 regulates antitumor responses remains poorly understood. Here, we generated a mouse line with Twist1 conditionally depleted in DCs and found that Twist1-deficiency in DCs did not affect the DCs and T cell homeostasis under steady-state conditions; however, in melanoma models, the proportion of conventional DCs (cDCs) in draining lymph nodes (DLNs) was significantly decreased. Accordingly, a decreased ratio and number of tumor-infiltrating cDCs were observed, which reduced the recruitment of tumor-infiltrating T cells. Furthermore, production of IFN-γ, a crucial antitumor factor, by T cells, was dramatically decreased, which can further dampen the T cell antitumor functions. Collectively, our data indicate that Twist1 in DCs regulates antitumor functions by maintain the number of tumor-infiltrating DCs and T cells, and their antitumor activity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Imunidade Celular/imunologia , Linfócitos do Interstício Tumoral/imunologia , Melanoma Experimental/imunologia , Proteína 1 Relacionada a Twist/fisiologia , Animais , Antígenos de Neoplasias/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Knockout
7.
Arch Insect Biochem Physiol ; 106(2): e21762, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33415772

RESUMO

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of primary silkworm pathogens and causes a serious damage of cocoon losses every year. Recent years, many works have been done to clarify the silkworm anti-BmNPV mechanism, and a significant progress has been made in screening and studying of genes and proteins related to BmNPV infection, but several of them lacked the proofs in vivo. In this study, to further validate the function of seven newly reported genes in vivo, including BmAtlatin-n, Bmferritin-heavy chain (BmFerHCH), Bmthymosin (BmTHY), Bmseroin1, Bmseroin2, Bmnuclear hormone receptors 96 (BmNHR96), and BmE3 ubiquitin-protein ligase SINA-like 10 (BmSINAL10), the response of them in the midgut, fat body, and hemolymph of differentially resistant strains (resistant strain YeA and susceptible strain YeB) at 48 h following BmNPV infection were analyzed. The results showed that the relative stable or upregulated expression level of BmAtlatin-n, BmTHY, Bmseroin1, and Bmseroin2 in YeA resistant strain following BmNPV infection further indicated their antiviral role in vivo, compared with susceptible YeB strain. Moreover, the significant downregulation of BmFerHCH, BmNHR96, and BmSINAL10 in both strains following BmNPV infection revealed their role in benefiting virus infection, as well as the upregulation of BmFerHCH in YeB midgut and BmSINAL10 in YeB hemolymph. These data could be used to complementary the proofs of the function of these genes in response to BmNPV infection.


Assuntos
Bombyx/genética , Bombyx/virologia , Genes de Insetos , Interações Hospedeiro-Patógeno , Nucleopoliedrovírus/fisiologia , Animais , Bombyx/crescimento & desenvolvimento , Bombyx/metabolismo , Corpo Adiposo/metabolismo , Trato Gastrointestinal/metabolismo , Hemolinfa/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/virologia
8.
Arch Insect Biochem Physiol ; 107(3): e21793, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33949719

RESUMO

Apoptosis, as one kind of innate immune system, is involved in host response against pathogens innovation. Caspases play a vital role in the execution stage of host cell apoptosis. It has been reported that Bmcaspase-1 (Bmcas-1) has a close relationship with Bombyx mori nucleopolyhedrovirus (BmNPV) infection for its differentially expressed patterns after viral infection. However, its underlying response mechanism is still unclear. The significant differential expression of Bmcas-1 in different tissues of differentially resistant strains revealed its vital role in BmNPV infection. To further validate its role in BmNPV infection, budded virus (BV)-eGFP was analyzed after knockdown and overexpression of Bmcas-1 by small interfering RNA and the pIZT-mCherry vector, respectively. The reproduction of BV-eGFP obviously increased at 72 h after knockdown of Bmcas-1, and decreased after overexpression in BmN cells. Moreover, the conserved functional domain of Cas-1 among different species and the closed evolutionary relationship of Cas-1 in Lepidoptera hinted that Bmcas-1 might be associated with apoptosis, and this was also validated by the apoptosis inducer, Silvestrol, and the inhibitor, Z-DEVD-FMK. Therefore, Bmcas-1 plays an essential antiviral role by activating apoptosis, and this result lays a fundament for clarifying the molecular mechanism of silkworm in response against BmNPV infection and breeding of resistant strains.


Assuntos
Apoptose , Bombyx/virologia , Caspase 1/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Nucleopoliedrovírus/imunologia , Animais , Bombyx/enzimologia , Bombyx/imunologia , Caspase 1/imunologia , Proteínas de Fluorescência Verde
9.
Exp Cell Res ; 384(2): 111650, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31563695

RESUMO

Liver kinase B1 (Lkb1) in dendritic cells (DCs) plays a key role in maintaining immunity homeostasis and adaptive immunity by controlling the CD4+Foxp3+T regulatory cell (CD4+Tregs) pool and T cells activation. However, the function of Lkb1 in DCs for the regulation of CD8+Foxp3+T regulatory cells (CD8+Tregs) has not been addressed. Herein, we found that Lkb1-deficient DCs could lead to excessive CD8+Tregs expansion in multiple organs. We found that OX40 expression was significantly higher in Lkb1-deficient DCs compared with that in wild-type (WT) mice, suggesting a potential pathway of CD8+Treg expansion. Moreover, we found that CD8+Tregs from mice with conditional deletion Lkb1 in DCs (KO) displayed an activated phenotype and expressed higher levels of specific markers, including ICOS and CD103. Interestingly, compared with the WT mice without lipopolysaccharide(LPS) treatment, we found that CD8+Tregs population increased in the WT mice with LPS treatment which can selectively delete Lkb1 protein in DCs. However, there was no significant difference in CD8+Tregs population in the KO mice between LPS treatment group and non-LPS treatment. Collectively, our findings identified Lkb1 in DCs as a crucial regulator of CD8+Treg expansion.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Fatores de Transcrição Forkhead/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Linfócitos T Reguladores/imunologia , Proteínas Quinases Ativadas por AMP , Animais , Antígenos CD/imunologia , Proliferação de Células/fisiologia , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Cadeias alfa de Integrinas/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
10.
Cell Physiol Biochem ; 36(4): 1406-18, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26159807

RESUMO

BACKGROUND/AIMS: Tuberous sclerosis complex 1 (Tsc1) has been shown to regulate M1/M2 polarization of macrophages, but the precise roles of Tsc1 in the function and stability of macrophages are not fully understood. Here we show that Tsc1 is required for regulating the survival, migration and phagocytosis of macrophages. METHODS: Mice with Tsc1 homozygous deletion in myeloid cells (LysMCreTsc1(flox/flox); Tsc1 KO) were obtained by crossing Tsc1(flox/flox) mice with mice expressing Cre recombinase under the control of Lysozyme promoter (LysMCre). The apoptosis and growth of macrophages were determined by flow cytometry and Real-time PCR (RT-PCR). The phagocytosis was determined using a Vybrant™ phagocytosis assay kit. The migration of macrophages was determined using transwell migration assay. RESULTS: Peritoneal macrophages of Tsc1 KO mice exhibited increased apoptosis and enlarged cell size. Both M1 and M2 phenotypes in Tsc1-deficient macrophages were elevated in steady-state as well as in inflammatory conditions. Tsc1-deficient macrophages demonstrated impaired migration and reduced expression of chemokine receptors including CCR2 and CCR5. Phagocytosis activity and ROS production were enhanced in Tsc1-deficient macrophages. Furthermore, pharmacological inhibition of the mammalian target of rapamycin complex 1 (mTORC1) partially reversed the aberrance of Tsc1-deficient macrophages. CONCLUSION: Tsc1 plays a critical role in regulating macrophage survival, function and polarization via inhibition of mTORC1 activity.


Assuntos
Deleção de Genes , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Animais , Movimento Celular , Sobrevivência Celular , Células Cultivadas , Quimiocinas/genética , Feminino , Regulação da Expressão Gênica , Ativação Linfocitária , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Knockout , Complexos Multiproteicos/metabolismo , Células Mieloides/citologia , Células Mieloides/metabolismo , Fagocitose , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína 1 do Complexo Esclerose Tuberosa
11.
Arch Esp Urol ; 77(1): 72-78, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38374016

RESUMO

OBJECTIVE: This study aims to analyse factors influencing bone metastasis in prostate cancer and the diagnostic value of serum prostate-specific antigen (PSA), and D-dimer (D-D) combined with cystatin C (CysC) in bone metastasis of prostate cancer. METHODS: Data of 116 patients with prostate cancer admitted to our hospital were retrospectively analysed. They were divided into two groups: Bone metastasis group (46 cases) and non-bone metastasis group (70 cases). Univariate and multivariate logistic regression analyses were used to determine factors influencing bone metastasis in prostate cancer. The values of serum PSA, D-D and CysC were identified using a receiver operating characteristic diagnostic curve. RESULTS: Of the 116 patients, 46 had bone metastases and 70 had non-bone metastases. Among 46 patients with bone metastasis, 8 cases (17.39%) had single bone metastasis and 38 cases (82.61%) had multiple bone metastasis. Based on the univariate analysis, bone metastasis was associated with increases in Gleason score, clinical stage, lymph node metastasis, systemic inflammatory response index, fibrinogen to albumin ratio and alkaline phosphatase and fibrinogen levels. The Gleason score was higher than 8 points, the clinical stages ranged from T3 to T4 and the serum levels of PSA, D-D and CysC were higher in the bone metastasis group (p < 0.05). The combined value of serum PSA, D-D and CysC in the diagnosis of bone metastasis in prostate cancer was higher than the three indicators alone. CONCLUSIONS: Lymph node metastasis in T3-T4 clinical stages with Gleason score >8 was a risk factor for bone metastasis in prostate cancer (all p < 0.05). The risk of bone metastasis in patients with prostate cancer increases with increasing Gleason clinical stage and the occurrence of lymph node metastasis. Serum PSA, D-D and CysC have certain diagnostic value in the diagnosis of bone metastasis, and their combination has the highest value.


Assuntos
Neoplasias Ósseas , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico , Metástase Linfática , Cistatina C , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Neoplasias Ósseas/secundário , Estadiamento de Neoplasias
12.
Psychol Trauma ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38330350

RESUMO

OBJECTIVE: Both theoretical and empirical studies suggest that negative cognitive biases significantly influence the onset and persistence of posttraumatic stress disorder (PTSD) symptoms. However, the interplay among these cognitive biases and their conjoint contribution to the long-term trajectory of posttraumatic stress symptoms remains underexplored. This study delves into the interplay among attention, appraisal, and memory biases within a provisional PTSD population and evaluates the predictive effects of two integrative models (weakest link, additive approach) on posttraumatic stress symptoms reported 2 months later. METHOD: Sixty Chinese participants (Mage = 20.17, SDage = 2.11) with provisional PTSD undertook the scrambled sentences test (appraisal bias) with their eye movements recorded (attention bias) and then the free recall task (memory bias). Posttraumatic stress symptom was assessed at baseline and 2-month follow-up. RESULTS: Selective attention bias toward negative words was positively associated with the negative appraisal of scrambled sentences, which subsequently showed a strong association with negative memory bias. Regarding the progression of posttraumatic stress symptoms, the additive approach was found to be a more reliable predictor of self-reported posttraumatic stress symptoms at 2 months than the weak link approach. CONCLUSIONS: This study provides initial evidence supporting the combined cognitive biases hypothesis in provisional PTSD. It also underscores potential avenues to enhance cognitive bias modification techniques. Replication of these findings in broader clinical samples is essential. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

13.
Environ Sci Pollut Res Int ; 30(38): 88387-88405, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37436633

RESUMO

A better reconciliation of haze pollution and economic growth has become the social consensus in China. The development of China's economy and air quality will be significantly impacted by its efforts to create high-speed rail (HSR). Based on panel data from 265 prefecture-level cities in China from 2003 to 2019, this paper investigates how the opening of HSR affects the spatial mismatch of haze pollution and economic growth by using the spatial mismatch index model, multi-period difference-in-differences (DID) model, and intermediary effect model. We find that the spatial mismatch in China has an overall decreasing trend. And its spatial agglomeration is dominated by low levels. Further empirical analysis shows that HSR opening can effectively restrain the spatial mismatch. Even after some robustness tests and endogenous treatment, the conclusion is still valid. In addition, population density, FDI, and industrial structure are also explicit factors affecting the spatial mismatch. Second, there is significant heterogeneity in the impact. This is reflected in the fact that HSR opening can suppress the spatial mismatch of service-oriented cities and the eastern region, while other cities and regions have no noticeable effect. Third, spatial transfer of haze pollution (STHP) and balanced development of economic growth (BEG) are two important conduction paths for the opening of HSR to affect the spatial mismatch. Specifically, HSR opening can constrain the spatial mismatch by inhibiting STHP and BEG. Based on the above findings, recommendations related to promoting a better harmony between haze pollution and economic growth are proposed.


Assuntos
Poluição do Ar , Desenvolvimento Econômico , Poluição Ambiental/análise , Poluição do Ar/análise , Cidades , China
14.
Braz J Anesthesiol ; 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37453497

RESUMO

BACKGROUND: Acute Kidney Injury (AKI) is a common complication after cardiac surgery and has been associated with poor outcomes. Dexmedetomidine (DEX) has been shown to confer direct renoprotection based on some animal and clinical studies, but data from other trials came to the opposite conclusion following cardiac surgery. This meta-analysis was conducted to evaluate the effects of perioperative DEX administration on the occurrence of AKI and the outcomes after cardiac surgery. METHODS: We searched databases including EMBASE, PubMed, and Cochrane CENTRAL for Randomized Controlled Trials (RCTs) focused on DEX for AKI in adult patients after cardiac surgery. The primary outcome was incidence of AKI. Secondary outcomes were Mechanical Ventilation (MV) duration, Intensive Care Unit (ICU) Length Of Stay (LOS), hospital LOS and mortality. RESULTS: Fifteen trials enrolling 2907 study patients were collected in the meta-analyses. Compared with controls, DEX reduced the incidence of postoperative AKI (Odds Ratio [OR = 0.66]; 95% Confidence Interval [95% CI 0.48-0.91]; p = 0.01), and there was no significant difference between groups in postoperative mortality (OR = 0.63; 95% CI 0.32-1.26; p = 0.19), MV duration (Weighted Mean Difference [WMD = -0.44]; 95% CI -1.50-0.63; p = 0.42), ICU LOS (WMD = -1.19; 95% CI -2.89-0.51; p = 0.17), and hospital LOS (WMD = -0.31; 95% CI -0.76-0.15; p = 0.19). CONCLUSIONS: Perioperative DEX reduced the incidence of postoperative AKI in adult patients undergoing cardiac surgery. No significant decrease existed in mortality, MV duration, ICU LOS and hospital LOS owing to DEX administration.

15.
Nat Commun ; 14(1): 2895, 2023 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-37210427

RESUMO

The sequencing of single protein molecules using nanopores is faced with a huge challenge due to the lack of resolution needed to resolve single amino acids. Here we report the direct experimental identification of single amino acids in nanopores. With atomically engineered regions of sensitivity comparable to the size of single amino acids, MoS2 nanopores provide a sub-1 Dalton resolution for discriminating the chemical group difference of single amino acids, including recognizing the amino acid isomers. This ultra-confined nanopore system is further used to detect the phosphorylation of individual amino acids, demonstrating its capability for reading post-translational modifications. Our study suggests that a sub-nanometer engineered pore has the potential to be applied in future chemical recognition and de novo protein sequencing at the single-molecule level.


Assuntos
Aminoácidos , Nanoporos , Aminoácidos/química , Molibdênio/química , Proteínas , Sequência de Aminoácidos
16.
J Med Chem ; 66(12): 8011-8029, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37272653

RESUMO

Bombesin receptor subtype-3 (BB3, BRS-3) is an orphan Gαq protein-coupled receptor. The characterization of novel synthetic ligands for BB3 is an alternative and attractive strategy to study its diverse physiological functions. Here, we uncovered the intimate pairing of DMAKO-00 and its derivatives with BB3. Dimethyl shikonin oxime 5a (DSO-5a) was identified as the most potent agonist for BB3 (pEC50 = 8.422 in IP-1 accumulation), which was 898-fold more potent than DMAKO-00. Importantly, without brain penetration, DSO-5a improved glucose tolerance in C57BL/6 mice through BB3 and ameliorated glucose homeostasis in diabetic db/db mice. We further revealed that DSO-5a upregulated PPAR-gamma activity via BB3 through a quantitative proteomics approach. Collectively, our study demonstrated that DSO-5a, a representative compound of DMAKO-00 derivatives, is a potent, selective, and low-brain-penetrating agonist for BB3, and BB3 is a promising treatment target for type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Receptores da Bombesina , Camundongos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Camundongos Endogâmicos C57BL , Glucose , Bombesina
17.
Insects ; 14(6)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37367321

RESUMO

Bombyx mori nucleopolyhedrovirus (BmNPV) is a serious threat to sericulture. Nevertheless, no effective control strategy is currently available. The innate immunity of silkworm is critical in the antiviral process. Exploring its molecular mechanism provides theoretical support for the prevention and treatment of BmNPV. Insect hormone receptors play an essential role in regulating host immunity. We found a correlation between Bombyx mori ecdysone receptor B1 (BmEcR-B1) and BmNPV infection, whereas the underlying mechanism remains unclear. In this study, the expression patterns and sequence characteristics of BmEcR-B1 and its isoform, BmEcR-A, were initially analyzed. BmEcR-B1 was found to be more critical than BmEcR-A in silkworm development and responses to BmNPV. Moreover, RNAi and an overexpression in BmN cells showed BmEcR-B1 had antiviral effects in the presence of 20-hydroxyecdysone (20E); Otherwise, it had no antiviral activity. Furthermore, BmEcR-B1 was required for 20E-induced apoptosis, which significantly suppressed virus infection. Finally, feeding 20E had no significant negative impacts on larval growth and the cocoon shell, suggesting the regulation of this pathway has practical value in controlling BmNPV in sericulture. The findings of this study provide important theoretical support for understanding the mechanism of the silkworm innate immune system in response to BmNPV infection.

18.
Behav Res Ther ; 171: 104440, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37992482

RESUMO

Due to the COVID-19 pandemic and its extensive effects, the incidence of posttraumatic stress disorder (PTSD) symptoms is rapidly increasing in China. This research aimed to assess the efficacy and acceptability of a mobile application delivering Acceptance and Commitment Therapy (ACT) in reducing PTSD symptoms. 221 Chinese individuals with elevated PTSD symptoms were randomly assigned to app-delivered ACT (ACT condition), app-delivered mindfulness (MI condition), or a waitlist (WL condition). Assessments were performed pre- and post-intervention. The results showed that participants in both the ACT and MI groups had significantly greater improvements across mental health outcomes compared to the WL group. No significant differences were observed between the ACT and MI groups except for psychological flexibility, which improved more in ACT than MI (d = -0.37). Compared to WL, the ACT group showed a greater improvement in PTSD symptoms (d = -0.79), anxiety (d = -0.62), depression (d = -0.51), posttraumatic growth (d = 0.46), and psychological flexibility (d = 0.76). The drop-out rates in the ACT and MI were 25.76% and 39.71%, respectively. Participants in the ACT condition reported medium program satisfaction. The study suggests app-delivered ACT is efficacious in reducing PTSD symptoms and improving overall mental health among Chinese adults.


Assuntos
Terapia de Aceitação e Compromisso , Aplicativos Móveis , Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Pandemias , Ansiedade/terapia
19.
Gen Hosp Psychiatry ; 84: 47-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37385139

RESUMO

PURPOSE: This meta-analysis was to assess the efficacy of digital psychological interventions to improve physical symptoms (i.e., fatigue, pain, disturbed sleep, and physical well-being) among cancer patients, as well as to evaluate the variables that possibly moderate intervention effects. METHODS: Nine databases were searched for the literature up to February 2023. Two reviewers independently conducted a quality assessment. Effect sizes were reported as the standardized mean difference (Hedge's g) and estimated using a random-effects model. RESULTS: The meta-analysis included 44 randomized clinical trials comprising 7200 adults with cancer. Digital psychological interventions were associated with significant improvements in short-term fatigue (g = -0.33; 95% CI, -0.58 to -0.07) and disturbed sleep (g = -0.36; 95% CI, -0.57 to -0.15), but with non-significant changes in pain (g = -0.23; 95% CI, -0.68 to 0.21) and physical well-being (g = 0.31; 95% CI, -0.18 to 0.80). Additionally, no alleviation in long-term physical symptoms was observed. In subgroup analysis, results suggest that the country significantly moderated the effectiveness of digital psychological interventions in alleviating fatigue. CONCLUSIONS: Digital psychological interventions can be effective for improving short-term fatigue and disturbed sleep in patients with cancer. Clinicians could consider digital psychological interventions as a possible and efficient addition to better manage some of the physical symptoms during and after cancer treatment.


Assuntos
Neoplasias , Intervenção Psicossocial , Adulto , Humanos , Ansiedade/terapia , Neoplasias/complicações , Dor , Fadiga/etiologia , Fadiga/terapia
20.
Internet Interv ; 30: 100585, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36426200

RESUMO

Background: As a result of the COVID-19 pandemic and its far-reaching impact, the prevalence of posttraumatic stress disorder (PTSD) symptoms is increasing significantly in China. Yet access to reliable and effective psychological treatment is still limited during the pandemic. The widespread adoption of mobile technologies may provide a new way to address this gap. In this research we will develop an Acceptance and Commitment Therapy (ACT) based intervention delivered by mobile application and will test its usability, efficacy, and mechanism of its effects in relieving PTSD symptoms. Methods: A total of 147 Chinese participants with a diagnosis of PTSD according to the Clinician Administered PTSD Scale (CAPS-5) will be randomly assigned to an intervention group (app-delivered ACT), an active comparison group (app-delivered mindfulness), or a waitlist group. Participants in the intervention group or comparison group will use their respective apps for one month. Online self-report questionnaires will be used to assess the primary outcome of PTSD symptoms and the secondary outcomes symptoms of depression, symptoms of anxiety, and posttraumatic growth. The potential mediating variable to be tested is psychological flexibility and its components. These assessments will be conducted at baseline, at five times during treatment, at the end of treatment, and at 1- and 3-month follow-ups. Discussion: As far as we know, this study is the first randomized controlled trial to investigate the usability, efficacy, and mechanism of an app-delivered ACT intervention for PTSD. Furthermore, the research will assess the effect of treatment in reducing dropout rates, explore effective therapeutic components, and investigate mechanisms of symptom change, which will be valuable in improving the efficacy and usability of PTSD interventions.Trial registration: ChiCTR2200058408.

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